Comparison of random forest and parametric imputation models for imputing missing data using MICE: a CALIBER study.

Multivariate imputation by chained equations (MICE) is commonly used for imputing missing data in epidemiologic research. The "true" imputation model may contain nonlinearities which are not included in default imputation models. Random forest imputation is a machine learning technique which can accommodate nonlinearities and interactions and does not require a particular regression model to be specified. We compared parametric MICE with a random forest-based MICE algorithm in 2 simulation studies. The first study used 1,000 random samples of 2,000 persons drawn from the 10,128 stable angina patients in the CALIBER database (Cardiovascular Disease Research using Linked Bespoke Studies and Electronic Records; 2001-2010) with complete data on all covariates. Variables were artificially made "missing at random," and the bias and efficiency of parameter estimates obtained using different imputation methods were compared. Both MICE methods produced unbiased estimates of (log) hazard ratios, but random forest was more efficient and produced narrower confidence intervals. The second study used simulated data in which the partially observed variable depended on the fully observed variables in a nonlinear way. Parameter estimates were less biased using random forest MICE, and confidence interval coverage was better. This suggests that random forest imputation may be useful for imputing complex epidemiologic data sets in which some patients have missing data

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Fluid-structure interaction for heart attack prediction

Cardiovascular disease is one of the largest and most economically burdensome challenges of modern society. Despite continuous imaging, intervention and pharmacological improvements, this burden continues to grow. Biomechanical stress is known to play a role in the natural history of the largest facet of this burden, coronary atherosclerosis. Yet a detailed understanding or capability to determine these stresses in any great detail eludes both clinical research and practice. With consistent improvements in computational power and numerical complexity enabling advancements in coronary simulation, this thesis now aims to address this challenge through the development of fluid-structure interaction (FSI) frameworks. Beginning with a detailed reconstruction of an entire vessel from invasive coronary angiography (ICA), including all epicardial branches and replication of the unique dynamic coupling between coronary arteries and cardiac function, traditional stress measures were assessed, namely wall shear (WSS) and von Mises stress. The reconstruction approach was then further enhanced with high-resolution intravascular optical coherence tomography (OCT) to assess changes in plaque morphology between two time points and their associations with baseline biomechanical stress. To expand the detail in biomechanical results a further 11 multidirectional and topological WSS metrics were developed for use in FSI simulations for the first time. Their relationship with coronary dynamics was also assessed to determine if dynamic factors may play a role in atherosclerosis development. Taking inspiration from these WSS metrics, several novel structural metrics were then proposed to specifically provide information on the directional properties of the Cauchy stress tensor in coronary simulations. These metrics were assessed against changes in the coronary vasculature in six patients. Finally, to combine the developed knowledge, a complete FSI framework, including a novel patientspecific dynamic profile (PDP), was proposed to culminate with a biomechanical stress profiling index (BSPI) which used a total of 66 metrics to target key changes in lipid plaques and vessel remodeling. This holistic modelling approach significantly builds upon current biomechanical simulation knowledge, with preliminary results already suggesting mechanisms of plaque destabilisation and remodelling not previously identified. It is hoped the details encompassed in the BSPI will provide both a better understanding of the natural history of atherosclerosis and lead to novel approaches to prevent its significant morbidity, mortality, and economic burden when studied in larger patient cohorts.Thesis (Ph.D.) -- University of Adelaide, School of Electrical and Mechanical Engineering, 202

Chiral Co3Y propeller-shaped chemosensory platforms based on 19F-NMR

Two propeller-shaped chiral CoIII3YIII complexes built from fluorinated ligands are synthesized and characterized by single-crystal X-Ray diffraction (SXRD), IR, UV-Vis, Circular Dichroism (CD), Elemental analysis, Thermogravimetric analysis (TGA), Electron Spray Ionization Mass Spectroscopy (ESI-MS) and NMR (1H, 13C and 19F). This work explores the sensing and discrimination abilities of these complexes, thus providing an innovative sensing method using a 19F NMR chemosensory system and opening new directions in 3d/4f chemistry. Control experiments and theoretical studies shed light on the sensing mechanism, while the scope and limitations of this method are discussed and presented

Chiral Co₃Y Propeller-Shaped Chemosensory Platforms Based on ¹⁹F-NMR

Two propeller-shaped chiral CoIII3YIII complexes built from fluorinated ligands are synthesized and characterized by single-crystal X-ray diffraction (SXRD), IR, UV–vis, circular dichroism (CD), elemental analysis, thermogravimetric analysis (TGA), electron spray ionization mass spectroscopy (ESI-MS), and NMR (1H, 13C, and 19F). This work explores the sensing and discrimination abilities of these complexes, thus providing an innovative sensing method using a 19F NMR chemosensory system and opening new directions in 3d/4f chemistry. Control experiments and theoretical studies shed light on the sensing mechanism, while the scope and limitations of this method are discussed and presented

Chiral Co3Y propeller-shaped chemosensory platforms based on 19F-NMR

Two propeller-shaped chiral CoIII3YIII complexes built from fluorinated ligands are synthesized and characterized by single-crystal X-Ray diffraction (SXRD), IR, UV-Vis, Circular Dichroism (CD), Elemental analysis, Thermogravimetric analysis (TGA), Electron Spray Ionization Mass Spectroscopy (ESI-MS) and NMR (1H, 13C and 19F). This work explores the sensing and discrimination abilities of these complexes, thus providing an innovative sensing method using a 19F NMR chemosensory system and opening new directions in 3d/4f chemistry. Control experiments and theoretical studies shed light on the sensing mechanism, while the scope and limitations of this method are discussed and presented