Law of Large Numbers: The Theory, Applications and Technology-Based Education

Modern approaches for technology-based blended education utilize a variety of recently developed novel pedagogical, computational and network resources. Such attempts employ technology to deliver integrated, dynamically-linked, interactive-content and heterogeneous learning environments, which may improve student comprehension and information retention. In this paper, we describe one such innovative effort of using technological tools to expose students in probability and statistics courses to the theory, practice and usability of the Law of Large Numbers (LLN). We base our approach on integrating pedagogical instruments with the computational libraries developed by the Statistics Online Computational Resource (www.SOCR.ucla.edu). To achieve this merger we designed a new interactive Java applet and a corresponding demonstration activity that illustrate the concept and the applications of the LLN. The LLN applet and activity have common goals – to provide graphical representation of the LLN principle, build lasting student intuition and present the common misconceptions about the law of large numbers. Both the SOCR LLN applet and activity are freely available online to the community to test, validate and extend (Applet: http://socr.ucla.edu/htmls/exp/Coin_Toss_LLN_Experiment.html, and Activity: http://wiki.stat.ucla.edu/socr/index.php/SOCR_EduMaterials_Activities_LLN)

Machine learning-based lifetime breast cancer risk reclassification compared with the BOADICEA model: impact on screening recommendations

BACKGROUND: The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screening practices. METHODS: We used three different ML algorithms and the BOADICEA model to estimate lifetime breast cancer risk in a sample of 112,587 individuals from 2481 families from the Oncogenetic Unit, Geneva University Hospitals. Performance of algorithms was evaluated using the area under the receiver operating characteristic (AU-ROC) curve. Risk reclassification was compared for 36,146 breast cancer-free women of ages 20-80. The impact on recommendations for mammography surveillance was based on the Swiss Surveillance Protocol. RESULTS: The predictive accuracy of ML-based algorithms (0.843 </= AU-ROC </= 0.889) was superior to BOADICEA (AU-ROC = 0.639) and reclassified 35.3% of women in different risk categories. The largest reclassification (20.8%) was observed in women characterised as 'near population' risk by BOADICEA. Reclassification had the largest impact on screening practices of women younger than 50. CONCLUSION: ML-based reclassification of lifetime breast cancer risk occurred in approximately one in three women. Reclassification is important for younger women because it impacts clinical decision- making for the initiation of screening

Randomization‐based statistical inference: A resampling and simulation infrastructure

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143752/1/test12156_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143752/2/test12156.pd

Mapping Connectivity Damage in the Case of Phineas Gage

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a “tamping iron” was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25–36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized “average” brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis : a pilot project of the ENIGMA–DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/)

e-MIR2: a public online inventory of medical informatics resources

Background. Over the last years, the number of available informatics resources in medicine has grown exponentially. While specific inventories of such resources have already begun to be developed for Bioinformatics (BI), comparable inventories are as yet not available for Medical Informatics (MI) field, so that locating and accessing them currently remains a hard and time-consuming task. Description. We have created a repository of MI resources from the scientific literature, providing free access to its contents through a web-based service. Relevant information describing the resources is automatically extracted from manuscripts published in top-ranked MI journals. We used a pattern matching approach to detect the resources? names and their main features. Detected resources are classified according to three different criteria: functionality, resource type and domain. To facilitate these tasks, we have built three different taxonomies by following a novel approach based on folksonomies and social tagging. We adopted the terminology most frequently used by MI researchers in their publications to create the concepts and hierarchical relationships belonging to the taxonomies. The classification algorithm identifies the categories associated to resources and annotates them accordingly. The database is then populated with this data after manual curation and validation. Conclusions. We have created an online repository of MI resources to assist researchers in locating and accessing the most suitable resources to perform specific tasks. The database contained 282 resources at the time of writing. We are continuing to expand the number of available resources by taking into account further publications as well as suggestions from users and resource developers

A pilot study of application of the Stroke Riskometer mobile app for assessment of the course and clinical outcomes of COVID-19 among hospitalised patients

Early determination of COVID-19 severity and health outcomes could facilitate better treatment of patients. Different methods and tools have been developed for predicting outcomes of COVID-19, but they are difficult to use in routine clinical practice. Methods: We conducted a prospective cohort study of inpatients aged 20-92 years, diagnosed with COVID-19 to determine whether their individual 5-year absolute risk of stroke at the time of hospital admission predicts the course of COVID-19 severity and mortality. The risk of stroke was determined by the Stroke Riskometer mobile application. Results: We examined 385 patients hospitalised with COVID-19 (median age 61 years). The participants were categorised based on COVID-19 severity: 271 (70.4%) to the “Not severe” and 114 (29.6%) to the “Severe” groups. The median risk of stroke the next day after hospitalisation was significantly higher among patients in the Severe group (2.83 [95% CI 2.35-4.68]) vs the Not severe group (1.11 [95% CI 1.00–1.29]). The median risk of stroke and median systolic blood pressure (SBP) were significantly higher among non-survivors (12.04 [95% CI 2.73-21.19]) and (150 [95% CI 140-170]) vs survivors (1.31 [95% CI 1.14-1.52]), 134 [95% CI 130-135]), respectively. Those who spent more than 2.5 hours a week on physical activity were 3.1 times more likely to survive from COVID-19. Those who consumed more than one standard alcohol drink a day, or suffered with atrial fibrillation, or had poor memory were 2.5, 2.3, and 2.6 times more likely not to survive from COVID-19, respectively. Conclusions: High risk of stroke, physical inactivity, alcohol intake, high SBP, and atrial fibrillation are associated with severity and mortality of COVID-19. Our findings suggest that the Stroke Riskometer app could be used as a simple predictive tool of COVID-19 severity and mortality

EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA)

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multimorbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research