Discrete Event Simulation Implemented in a Virtual Environment

Virtual reality (VR) technology provides a human-computer interface that allows participants to interact naturally with digital objects which are represented as three-dimensional images that occupy positions in a three-dimensional world. Related to problems of engineering design and manufacturing, this new technology offers engineers the ability to work with computer models in a three-dimensional, immersive environment. This paper describes a virtual reality application where the results of a discrete event simulation of a manufacturing cell are integrated with a virtual model of the cell to produce a virtual environment. The program described in this paper, the VRFactory, combines results from a commercial discrete event simulation program, SLAM II, with a virtual environment. This allows the user to investigate, using three-dimensional computer models, how various changes to the manufacturing cell affect part production. This investigation is performed while immersed in a computer-generated three-dimensional representation of the cell. Existing discrete event programming software allows only two-dimensional views of the factory as the parts progress through the simulation. Parts are shown only as primitive geometric shapes on the computer monitor and instantaneously move from one station to the next. The virtual environment implementation of the SLAM II results allows users to experience the simulation in a fully immersive three-dimensional digital environment. The virtual environment used here is a CAVE™-like projection screen-based facility called the C2, which is located at Iowa State University. This paper describes the creation of the VR model of the manufacturing cell, the animation of the environment and the implementation of the results of the discrete event simulation

Discrete Event Simulation Implemented in a Virtual Environment

Virtual reality (VR) technology provides a human-computer interface that allows participants to interact naturally with digital objects which are represented as three-dimensional images that occupy positions in a three-dimensional world. Related to problems of engineering design and manufacturing, this new technology offers engineers the ability to work with computer models in a three-dimensional, immersive environment. This paper describes a virtual reality application where the results of a discrete event simulation of a manufacturing cell are integrated with a virtual model of the cell to produce a virtual environment. The program described in this paper, the VRFactory, combines results from a commercial discrete event simulation program, SLAM II, with a virtual environment. This allows the user to investigate, using three-dimensional computer models, how various changes to the manufacturing cell affect part production. This investigation is performed while immersed in a computer-generated three-dimensional representation of the cell. Existing discrete event programming software allows only two-dimensional views of the factory as the parts progress through the simulation. Parts are shown only as primitive geometric shapes on the computer monitor and instantaneously move from one station to the next. The virtual environment implementation of the SLAM II results allows users to experience the simulation in a fully immersive three-dimensional digital environment. The virtual environment used here is a CAVE™-like projection screen-based facility called the C2, which is located at Iowa State University. This paper describes the creation of the VR model of the manufacturing cell, the animation of the environment and the implementation of the results of the discrete event simulation.This article is from Journal of Mechanical Design 125 (2003): 428–433, doi:10.1115/1.1587745. Posted with permission.</p

Reversible Airflow Obstruction Predicts Future Chronic Obstructive Pulmonary Disease Development in the SPIROMICS Cohort: An Observational Cohort Study.

Rationale: Chronic obstructive pulmonary disease (COPD) is defined by fixed spirometric ratio, FEV1/FVC &lt; 0.70 after inhaled bronchodilators. However, the implications of variable obstruction (VO), in which the prebronchodilator FEV1/FVC ratio is less than 0.70 but increases to 0.70 or more after inhaled bronchodilators, have not been determined. Objectives: We explored differences in physiology, exacerbations, and health status in participants with VO compared with reference participants without obstruction. Methods: Data from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort were obtained. Participants with VO were compared with reference participants without obstruction. Measurements and Main Results: We assessed differences in baseline radiographic emphysema and small airway disease at study entry, baseline, and change in lung function by spirometry, functional capacity by 6-minute walk, health status using standard questionnaires, exacerbation rates, and progression to COPD between the two groups. All models were adjusted for participant characteristics, asthma history, and tobacco exposure. We assessed 175 participants with VO and 603 reference participants without obstruction. Participants with VO had 6.2 times the hazard of future development of COPD controlling for other factors (95% confidence interval, 4.6-8.3; P &lt; 0.001). Compared with reference participants, the VO group had significantly lower baseline pre- and post-bronchodilator (BD) FEV1, and greater decline over time in post-BD FEV1, and pre- and post-BD FVC. There were no significant differences in exacerbations between groups. Conclusions: Significant risk for future COPD development exists for those with pre- but not post-BD airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT01969344)

Exome-Based Mapping and Variant Prioritization for Inherited Mendelian Disorders.

Exome sequencing in families affected by rare genetic disorders has the potential to rapidly identify new disease genes (genes in which mutations cause disease), but the identification of a single causal mutation among thousands of variants remains a significant challenge. We developed a scoring algorithm to prioritize potential causal variants within a family according to segregation with the phenotype, population frequency, predicted effect, and gene expression in the tissue(s) of interest. To narrow the search space in families with multiple affected individuals, we also developed two complementary approaches to exome-based mapping of autosomal-dominant disorders. One approach identifies segments of maximum identity by descent among affected individuals; the other nominates regions on the basis of shared rare variants and the absence of homozygous differences between affected individuals. We showcase our methods by using exome sequence data from families affected by autosomal-dominant retinitis pigmentosa (adRP), a rare disorder characterized by night blindness and progressive vision loss. We performed exome capture and sequencing on 91 samples representing 24 families affected by probable adRP but lacking common disease-causing mutations. Eight of 24 families (33%) were revealed to harbor high-scoring, most likely pathogenic (by clinical assessment) mutations affecting known RP genes. Analysis of the remaining 17 families identified candidate variants in a number of interesting genes, some of which have withstood further segregation testing in extended pedigrees. To empower the search for Mendelian-disease genes in family-based sequencing studies, we implemented them in a cross-platform-compatible software package, MendelScan, which is freely available to the research community. Am J Hum Genet 2014 Mar 6; 94:373-384

Effects of torcetrapib in patients at high risk for coronary events

BACKGROUND: Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. METHODS: We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P <0.001 for both comparisons), in addition to an increase of 5.4 mm Hg in systolic blood pressure, a decrease in serum potassium, and increases in serum sodium, bicarbonate, and aldosterone (P <0.001 for all comparisons). There was also an increased risk of cardiovascular events (hazard ratio, 1.25; 95% confidence interval [CI], 1.09 to 1.44; P=0.001) and death from any cause (hazard ratio, 1.58; 95% CI, 1.14 to 2.19; P=0.006). Post hoc analyses showed an increased risk of death in patients treated with torcetrapib whose reduction in potassium or increase in bicarbonate was greater than the median change. CONCLUSIONS: Torcetrapib therapy resulted in an increased risk of mortality and morbidity of unknown mechanism. Although there was evidence of an off-target effect of torcetrapib, we cannot rule out adverse effects related to CETP inhibition. (ClinicalTrials.gov number, NCT00134264 [ClinicalTrials.gov].

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

BackgroundForced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD.ObjectiveTo determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD.Study design and methodsThe SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease.ResultsLower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC).InterpretationThe %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD