Evolutionary optimisation of network flow plans for emergency movement in the built environment

Planning for emergency evacuation, and, more generally, for emergency movement involving both evacuation (egress) of occupants and ingress of first responders, presents important and challenging problems. A number of the current issues that arise during emergency incidents are due to the uncertainty and transiency of environmental conditions. In general, movement plans are formulated at building design-time, and those involved, such as building occupants and emergency responders, are left to adapt routing plans to actual events as they unfold. In the context of next-generation emergency response systems, it has been proposed to dynamically plan and route individuals during an emergency event, replanning to take account of changes in the environment. In this work, an emergency movement problem, the Maximal Safest Escape (MSE) problem, is formulated in terms that model the uncertain and transient environmental conditions as a flow problem in time-dependent networks with time-varying and stochastic edge travel-times and capacities (STV Networks). The objective of the MSE problem is to find flow patterns with the a priori maximal probability of successfully conveying all supply from the source to the sink in some given STV Network. The MSE and its deterministic counterpart are proved to be NP-hard. Furthermore, due to inherent complexity in evaluating the exact quality of candidate solutions, a simulation approximation method is presented based on well-known Monte-Carlo sampling methods. Given the complexity of the problem, and using the approximation method for evaluating solutions, it is proposed to tackle the MSE problem using a metaheuristic approach based on an existing framework that integrates Evolutionary Algorithms (EA) with a state-of-the-art statistical ranking and selection method, the Optimal Computing Budget Allocation (OCBA). Several improvements are proposed for the framework to reduce the computational demand of the ranking method. Empirically, the approach is compared with a simple fitness averaging approach and conditions under which the integrated framework is more efficient are investigated. The performance of the EA is compared against upper and lower bounds on optimal solutions. An upper bound is established through the “wait-and-see” bound, and a lower bound by a naıve random search algorithm (RSA). An experimental design is presented that allows for a fair comparison between the EA and the RSA. While there is no guarantee that the EA will find optimal solutions, this work demonstrates that the EA can still find useful solutions; useful solutions are those that are at least better than some baseline, here the lower bound, in terms of solution quality and computational effort. Experimentally, it is demonstrated that the EA performs significantly better than the baseline. Also, the EA finds solutions relatively close to the upper bound; however, it is difficult to establish how optimistic the upper bounds. The main approach is also compared against an existing approach developed for solving a related problem wrapped in a heuristic procedure in order to apply the approach to the MSE. Empirical results show that the heuristic approach requires significantly less computation time, but finds solutions of significantly lower quality. Overall, this work introduces and empirically verifies the efficacy of a metaheuristic based on a framework integrating EAs with a state-of-the-art statistical ranking and selection technique, the OCBA, for a novel flow problem in STV Networks. It is suggested that the lessons learned during the course of this work, along with the specific techniques developed, may be relevant for addressing other flow problems of similar complexity

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The Frederick Law Olmsted Symposium (2014) - Welcome

Opening welcome of the Frederick Law Olmsted Symposium on June 2, 2014 at the Georgia Tech Hotel and Conference Center.Dr. Gary S. May is the Dean of the College of Engineering at the Georgia Institute of Technology.Reginald DesRoches, PhD, is the Karen and John Huff School Chair, School of Civil and Environmental Engineering, College of Engineering at the Georgia Institute of Technology.Steven P. French, FAICP, is Dean and John Portman Chair in the College of Architecture at the Georgia Institute of Technology.Runtime: 12:50 minutesThis symposium is a celebration of the creation of the Frederick Law Olmsted Chair in the School of Civil and Environmental Engineering at the Georgia Institute of Technology. It serves as a special opportunity to gather in one place leading experts in the area of sustainable urban infrastructure for a discussion of state of the art research and practice as it relates to the theme of this unique Endowed Chair. Each speaker will touch upon topics that are different, yet complementary in the following thematic areas: Public Health, Urban Ecology, Transportation, Risk & Resilience, and Public Policy

Evolutionary optimisation of network flow plans for emergency movement in the built environment

Planning for emergency evacuation, and, more generally, for emergency movement involving both evacuation (egress) of occupants and ingress of first responders, presents important and challenging problems. A number of the current issues that arise during emergency incidents are due to the uncertainty and transiency of environmental conditions. In general, movement plans are formulated at building design-time, and those involved, such as building occupants and emergency responders, are left to adapt routing plans to actual events as they unfold. In the context of next-generation emergency response systems, it has been proposed to dynamically plan and route individuals during an emergency event, replanning to take account of changes in the environment. In this work, an emergency movement problem, the Maximal Safest Escape (MSE) problem, is formulated in terms that model the uncertain and transient environmental conditions as a flow problem in time-dependent networks with time-varying and stochastic edge travel-times and capacities (STV Networks). The objective of the MSE problem is to find flow patterns with the a priori maximal probability of successfully conveying all supply from the source to the sink in some given STV Network. The MSE and its deterministic counterpart are proved to be NP-hard. Furthermore, due to inherent complexity in evaluating the exact quality of candidate solutions, a simulation approximation method is presented based on well-known Monte-Carlo sampling methods. Given the complexity of the problem, and using the approximation method for evaluating solutions, it is proposed to tackle the MSE problem using a metaheuristic approach based on an existing framework that integrates Evolutionary Algorithms (EA) with a state-of-the-art statistical ranking and selection method, the Optimal Computing Budget Allocation (OCBA). Several improvements are proposed for the framework to reduce the computational demand of the ranking method. Empirically, the approach is compared with a simple fitness averaging approach and conditions under which the integrated framework is more efficient are investigated. The performance of the EA is compared against upper and lower bounds on optimal solutions. An upper bound is established through the “wait-and-see” bound, and a lower bound by a naıve random search algorithm (RSA). An experimental design is presented that allows for a fair comparison between the EA and the RSA. While there is no guarantee that the EA will find optimal solutions, this work demonstrates that the EA can still find useful solutions; useful solutions are those that are at least better than some baseline, here the lower bound, in terms of solution quality and computational effort. Experimentally, it is demonstrated that the EA performs significantly better than the baseline. Also, the EA finds solutions relatively close to the upper bound; however, it is difficult to establish how optimistic the upper bounds. The main approach is also compared against an existing approach developed for solving a related problem wrapped in a heuristic procedure in order to apply the approach to the MSE. Empirical results show that the heuristic approach requires significantly less computation time, but finds solutions of significantly lower quality. Overall, this work introduces and empirically verifies the efficacy of a metaheuristic based on a framework integrating EAs with a state-of-the-art statistical ranking and selection technique, the OCBA, for a novel flow problem in STV Networks. It is suggested that the lessons learned during the course of this work, along with the specific techniques developed, may be relevant for addressing other flow problems of similar complexity.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Evolutionary optimisation of network flow plans for emergency movement in the built environment

Planning for emergency evacuation, and, more generally, for emergency movement involving both evacuation (egress) of occupants and ingress of first responders, presents important and challenging problems. A number of the current issues that arise during emergency incidents are due to the uncertainty and transiency of environmental conditions. In general, movement plans are formulated at building design-time, and those involved, such as building occupants and emergency responders, are left to adapt routing plans to actual events as they unfold. In the context of next-generation emergency response systems, it has been proposed to dynamically plan and route individuals during an emergency event, replanning to take account of changes in the environment. In this work, an emergency movement problem, the Maximal Safest Escape (MSE) problem, is formulated in terms that model the uncertain and transient environmental conditions as a flow problem in time-dependent networks with time-varying and stochastic edge travel-times and capacities (STV Networks). The objective of the MSE problem is to find flow patterns with the a priori maximal probability of successfully conveying all supply from the source to the sink in some given STV Network. The MSE and its deterministic counterpart are proved to be NP-hard. Furthermore, due to inherent complexity in evaluating the exact quality of candidate solutions, a simulation approximation method is presented based on well-known Monte-Carlo sampling methods. Given the complexity of the problem, and using the approximation method for evaluating solutions, it is proposed to tackle the MSE problem using a metaheuristic approach based on an existing framework that integrates Evolutionary Algorithms (EA) with a state-of-the-art statistical ranking and selection method, the Optimal Computing Budget Allocation (OCBA). Several improvements are proposed for the framework to reduce the computational demand of the ranking method. Empirically, the approach is compared with a simple fitness averaging approach and conditions under which the integrated framework is more efficient are investigated. The performance of the EA is compared against upper and lower bounds on optimal solutions. An upper bound is established through the “wait-and-see” bound, and a lower bound by a naıve random search algorithm (RSA). An experimental design is presented that allows for a fair comparison between the EA and the RSA. While there is no guarantee that the EA will find optimal solutions, this work demonstrates that the EA can still find useful solutions; useful solutions are those that are at least better than some baseline, here the lower bound, in terms of solution quality and computational effort. Experimentally, it is demonstrated that the EA performs significantly better than the baseline. Also, the EA finds solutions relatively close to the upper bound; however, it is difficult to establish how optimistic the upper bounds. The main approach is also compared against an existing approach developed for solving a related problem wrapped in a heuristic procedure in order to apply the approach to the MSE. Empirical results show that the heuristic approach requires significantly less computation time, but finds solutions of significantly lower quality. Overall, this work introduces and empirically verifies the efficacy of a metaheuristic based on a framework integrating EAs with a state-of-the-art statistical ranking and selection technique, the OCBA, for a novel flow problem in STV Networks. It is suggested that the lessons learned during the course of this work, along with the specific techniques developed, may be relevant for addressing other flow problems of similar complexity.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Capacity-Building Toward a Patient-Centered Research Translation Model: Lessons from Sickle Cell Disease Management

Introduction: Research discoveries on chronic diseases, such as sickle cell disease (SCD), are seldom translated into practical application for patient consumption. Those managing chronic diseases in rural communities are even more disadvantaged than their urban counterparts, due to limited access to health education, availability of health care services, and confronting challenges associated with navigating health care (Lee et al., 2019). As was evidenced during the COVID-19 pandemic, less than 10% of populations disproportionately represented in chronic disease, have access to efficacious intervention and even fewer are aware of information emerging from research that hold promise to prevent, improve, and enhance health outcomes (Brownson et al., 2018, Kerner et al., 2017, Morris et al., 2011). Methods: This study—designed in collaboration with stakeholders from the Tennessee Sickle Cell Disease Network (TN-SCDN) and the Sickle Cell Foundation of Tennessee—aimed to build the translation and dissemination capacity readiness of an academic-patient-community-based stakeholder partnership network to improve health management and health outcomes of rural and urban African American residents in Tennessee managing chronic diseases, particularly SCD. To discern existing dissemination capacity readiness and practices, the research team conducted a series of qualitative-focused sessions—a semi-structured focus group (general insight), a community leader-facilitated education forum (research translation-focused knowledge), and a community engagement studio (research dissemination-focused preferences)—to understand patient perspectives more deeply on the challenges of receiving research findings and barriers to using these findings. Community stakeholders received training on guidelines and procedures and research ethics. Each session provided insight for a research dissemination model for researchers to employ. Qualitative sessions, conducted virtually due to the COVID-19 pandemic, included African American adults (N=24) who identified as patients living with SCD or caregivers of a SCD patient. All sessions were facilitated by community stakeholders, who also served as experts in the protocol design process. Sessions were video recorded, transcribed, and summarized into structured memos for the purposes of review and discussion by the research team. Results: Content analysis resulted in key themes across a variety of dissemination and translation topics; exemplar quotes showcase the lived experiences of SCD patients and their caregivers, with regard to patient-provider communication, comfort understanding of research articles, and methods of implementation for research findings into care practices, including pain management. Conclusions: Findings bring visibility to issues germane to addressing COVID-19. We also highlight preferred methods of learning about, accessing, disseminating and sharing research findings are also discussed. Unique challenges and advantages of virtual sessions. Future studies will employ and test these findings for the purposes of adapting insight to the dissemination and translation of research involving other chronic diseases