Structure-based protein and small molecule generation using EGNN and diffusion models: A comprehensive review.

Recent breakthroughs in deep learning have revolutionized protein sequence and structure prediction. These advancements are built on decades of protein design efforts, and are overcoming traditional time and cost limitations. Diffusion models, at the forefront of these innovations, significantly enhance design efficiency by automating knowledge acquisition. In the field of de novo protein design, the goal is to create entirely novel proteins with predetermined structures. Given the arbitrary positions of proteins in 3-D space, graph representations and their properties are widely used in protein generation studies. A critical requirement in protein modelling is maintaining spatial relationships under transformations (rotations, translations, and reflections). This property, known as equivariance, ensures that predicted protein characteristics adapt seamlessly to changes in orientation or position. Equivariant graph neural networks offer a solution to this challenge. By incorporating equivariant graph neural networks to learn the score of the probability density function in diffusion models, one can generate proteins with robust 3-D structural representations. This review examines the latest deep learning advancements, specifically focusing on frameworks that combine diffusion models with equivariant graph neural networks for protein generation.

Provision and evaluation of explanations within an automated planning-based approach to solving the multimorbidity problem.

The multimorbidity problem involves the identification and mitigation of adverse interactions that occur when multiple computer interpretable guidelines are applied concurrently to develop a treatment plan for a patient diagnosed with multiple diseases. Solving this problem requires decision support approaches which are difficult to comprehend for physicians. As such, the rationale for treatment plans generated by these approaches needs to be provided. OBJECTIVE: To develop an explainability component for an automated planning-based approach to the multimorbidity problem, and to assess the fidelity and interpretability of generated explanations using a clinical case study. METHODS: The explainability component leverages the task-network model for representing computer interpretable guidelines. It generates post-hoc explanations composed of three aspects that answer why specific clinical actions are in a treatment plan, why specific revisions were applied, and how factors like medication cost, patient's adherence, etc. influence the selection of specific actions. The explainability component is implemented as part of MitPlan, where we revised our planning-based approach to support explainability. We developed an evaluation instrument based on the system causability scale and other vetted surveys to evaluate the fidelity and interpretability of its explanations using a two dimensional comparison study design. RESULTS: The explainability component was implemented for MitPlan and tested in the context of a clinical case study. The fidelity and interpretability of the generated explanations were assessed using a physician-focused evaluation study involving 21 participants from two different specialties and two levels of experience. Results show that explanations provided by the explainability component in MitPlan are of acceptable fidelity and interpretability, and that the clinical justification of the actions in a treatment plan is important to physicians. CONCLUSION: We created an explainability component that enriches an automated planning-based approach to solving the multimorbidity problem with meaningful explanations for actions in a treatment plan. This component relies on the task-network model to represent computer interpretable guidelines and as such can be ported to other approaches that also use the task-network model representation. Our evaluation study demonstrated that explanations that support a physician's understanding of the clinical reasons for the actions in a treatment plan are useful and important.

Knowledge transfer in lifelong machine learning: a systematic literature review.

Lifelong Machine Learning (LML) denotes a scenario involving multiple sequential tasks, each accompanied by its respective dataset, in order to solve specific learning problems. In this context, the focus of LML techniques is on utilizing already acquired knowledge to adapt to new tasks efficiently. Essentially, LML concerns about facing new tasks while exploiting the knowledge previously gathered from earlier tasks not only to help in adapting to new tasks but also to enrich the understanding of past ones. By understanding this concept, one can better grasp one of the major obstacles in LML, known as Knowledge Transfer (KT). This systematic literature review aims to explore state-of-the-art KT techniques within LML and assess the evaluation metrics and commonly utilized datasets in this field, thereby keeping the LML research community updated with the latest developments. From an initial pool of 417 articles from four distinguished databases, 30 were deemed highly pertinent for the information extraction phase. The analysis recognizes four primary KT techniques: Replay, Regularization, Parameter Isolation, and Hybrid. This study delves into the characteristics of these techniques across both neural network (NN) and non-neural network (non-NN) frameworks, highlighting their distinct advantages that have captured researchers' interest. It was found that the majority of the studies focused on supervised learning within an NN modelling framework, particularly employing Parameter Isolation and Hybrid for KT. The paper concludes by pinpointing research opportunities, including investigating non-NN models for Replay and exploring applications outside of computer vision (CV).

Annealed fractional Lévy-Ito diffusion models for protein generation.

Protein generation has numerous applications in designing therapeutic antibodies and creating new drugs. Still, it is a demanding task due to the inherent complexities of protein structures and the limitations of current generative models. Proteins possess intricate geometry, and sampling their conformational space is challenging due to its high dimensionality. This paper introduces novel Markovian and non-Markovian generative diffusion models based on fractional stochastic differential equations and the Lévy distribution, allowing for a more effective exploration of the conformational space. The approach is applied to a dataset of 40,000 proteins and evaluated in terms of Fréchet distance, fidelity, and diversity, outperforming the state-of-the-art by 25.4%, 35.8%, and 11.8%, respectively.

Multivariable Prediction Models for Traumatic Spinal Cord Injury: A Systematic Review.

Background: Traumatic spinal cord injuries (TSCI) greatly affect the lives of patients and their families. Prognostication may improve treatment strategies, health care resource allocation, and counseling. Multivariable clinical prediction models (CPMs) for prognosis are tools that can estimate an absolute risk or probability that an outcome will occur. Objectives: We sought to systematically review the existing literature on CPMs for TSCI and critically examine the predictor selection methods used. Methods: We searched MEDLINE, PubMed, Embase, Scopus, and IEEE for English peer-reviewed studies and relevant references that developed multivariable CPMs to prognosticate patient-centered outcomes in adults with TSCI. Using narrative synthesis, we summarized the characteristics of the included studies and their CPMs, focusing on the predictor selection process. Results: We screened 663 titles and abstracts; of these, 21 full-text studies (2009-2020) consisting of 33 distinct CPMs were included. The data analysis domain was most commonly at a high risk of bias when assessed for methodological quality. Model presentation formats were inconsistently included with published CPMs; only two studies followed established guidelines for transparent reporting of multivariable prediction models. Authors frequently cited previous literature for their initial selection of predictors, and stepwise selection was the most frequent predictor selection method during modelling. Conclusion: Prediction modelling studies for TSCI serve clinicians who counsel patients, researchers aiming to risk-stratify participants for clinical trials, and patients coping with their injury. Poor methodological rigor in data analysis, inconsistent transparent reporting, and a lack of model presentation formats are vital areas for improvement in TSCI CPM research.

Using Unsupervised Machine Learning to Predict Quality of Life After Total Knee Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) are an important metric to assess total knee arthroplasty (TKA) patients. The purpose of this study was to use a machine learning (ML) algorithm to identify patient features that impact PROMs after TKA. METHODS: Data from 636 TKA patients enrolled in our patient database between 2018 and 2022, were retrospectively reviewed. Their mean age was 68 years (range, 39 to 92), 56.7% women, and mean body mass index of 31.17 (range, 16 to 58). Patient demographics and the Functional Comorbidity Index were collected alongside Patient-Reported Outcome Measures Information System Global Health v1.2 (PROMIS GH-P) physical component scores preoperatively, at 3 months, and 1 year after TKA. An unsupervised ML algorithm (spectral clustering) was used to identify patient features impacting PROMIS GH-P scores at the various time points. RESULTS: The algorithm identified 5 patient clusters that varied by demographics, comorbidities, and pain scores. Each cluster was associated with predictable trends in PROMIS GH-P scores across the time points. Notably, patients who had the worst preoperative PROMIS GH-P scores (cluster 5) had the most improvement after TKA, whereas patients who had higher global health rating preoperatively had more modest improvement (clusters 1, 2, and 3). Two out of Five patient clusters (cluster 4 and 5) showed improvement in PROMIS GH-P scores that met a minimally clinically important difference at 1-year postoperative. CONCLUSIONS: The unsupervised ML algorithm identified patient clusters that had predictable changes in PROMs after TKA. It is a positive step toward providing precision medical care for each of our arthroplasty patients.

A data-driven approach to categorize patients with traumatic spinal cord injury: cluster analysis of a multicentre database.

Background: Conducting clinical trials for traumatic spinal cord injury (tSCI) presents challenges due to patient heterogeneity. Identifying clinically similar subgroups using patient demographics and baseline injury characteristics could lead to better patient-centered care and integrated care delivery. Purpose: We sought to (1) apply an unsupervised machine learning approach of cluster analysis to identify subgroups of tSCI patients using patient demographics and injury characteristics at baseline, (2) to find clinical similarity within subgroups using etiological variables and outcome variables, and (3) to create multi-dimensional labels for categorizing patients. Study design: Retrospective analysis using prospectively collected data from a large national multicenter SCI registry. Methods: A method of spectral clustering was used to identify patient subgroups based on the following baseline variables collected since admission until rehabilitation: location of the injury, severity of the injury, Functional Independence Measure (FIM) motor, and demographic data (age, and body mass index). The FIM motor score, the FIM motor score change, and the total length of stay were assessed on the subgroups as outcome variables at discharge to establish the clinical similarity of the patients within derived subgroups. Furthermore, we discussed the relevance of the identified subgroups based on the etiological variables (energy and mechanism of injury) and compared them with the literature. Our study also employed a qualitative approach to systematically describe the identified subgroups, crafting multi-dimensional labels to highlight distinguishing factors and patient-focused insights. Results: Data on 334 tSCI patients from the Rick Hansen Spinal Cord Injury Registry was analyzed. Five significantly different subgroups were identified (p-value ≤0.05) based on baseline variables. Outcome variables at discharge superimposed on these subgroups had statistically different values between them (p-value ≤0.05) and supported the notion of clinical similarity of patients within each subgroup. Conclusion: Utilizing cluster analysis, we identified five clinically similar subgroups of tSCI patients at baseline, yielding statistically significant inter-group differences in clinical outcomes. These subgroups offer a novel, data-driven categorization of tSCI patients which aligns with their demographics and injury characteristics. As it also correlates with traditional tSCI classifications, this categorization could lead to improved personalized patient-centered care.

A community-of-practice-based evaluation methodology for knowledge intensive computational methods and its application to multimorbidity decision support.

OBJECTIVE: The study has dual objectives. Our first objective (1) is to develop a community-of-practice-based evaluation methodology for knowledge-intensive computational methods. We target a whitebox analysis of the computational methods to gain insight on their functional features and inner workings. In more detail, we aim to answer evaluation questions on (i) support offered by computational methods for functional features within the application domain; and (ii) in-depth characterizations of the underlying computational processes, models, data and knowledge of the computational methods. Our second objective (2) involves applying the evaluation methodology to answer questions (i) and (ii) for knowledge-intensive clinical decision support (CDS) methods, which operationalize clinical knowledge as computer interpretable guidelines (CIG); we focus on multimorbidity CIG-based clinical decision support (MGCDS) methods that target multimorbidity treatment plans. MATERIALS AND METHODS: Our methodology directly involves the research community of practice in (a) identifying functional features within the application domain; (b) defining exemplar case studies covering these features; and (c) solving the case studies using their developed computational methods-research groups detail their solutions and functional feature support in solution reports. Next, the study authors (d) perform a qualitative analysis of the solution reports, identifying and characterizing common themes (or dimensions) among the computational methods. This methodology is well suited to perform whitebox analysis, as it directly involves the respective developers in studying inner workings and feature support of computational methods. Moreover, the established evaluation parameters (e.g., features, case studies, themes) constitute a re-usable benchmark framework, which can be used to evaluate new computational methods as they are developed. We applied our community-of-practice-based evaluation methodology on MGCDS methods. RESULTS: Six research groups submitted comprehensive solution reports for the exemplar case studies. Solutions for two of these case studies were reported by all groups. We identified four evaluation dimensions: detection of adverse interactions, management strategy representation, implementation paradigms, and human-in-the-loop support. Based on our whitebox analysis, we present answers to the evaluation questions (i) and (ii) for MGCDS methods. DISCUSSION: The proposed evaluation methodology includes features of illuminative and comparison-based approaches; focusing on understanding rather than judging/scoring or identifying gaps in current methods. It involves answering evaluation questions with direct involvement of the research community of practice, who participate in setting up evaluation parameters and solving exemplar case studies. Our methodology was successfully applied to evaluate six MGCDS knowledge-intensive computational methods. We established that, while the evaluated methods provide a multifaceted set of solutions with different benefits and drawbacks, no single MGCDS method currently provides a comprehensive solution for MGCDS. CONCLUSION: We posit that our evaluation methodology, applied here to gain new insights into MGCDS, can be used to assess other types of knowledge-intensive computational methods and answer other types of evaluation questions. Our case studies can be accessed at our GitHub repository (https://github.com/william-vw/MGCDS).

Using graph rewriting to operationalize medical knowledge for the revision of concurrently applied clinical practice guidelines.

Clinical practice guidelines (CPGs) are patient management tools that synthesize medical knowledge into an actionable format. CPGs are disease specific with limited applicability to the management of complex patients suffering from multimorbidity. For the management of these patients, CPGs need to be augmented with secondary medical knowledge coming from a variety of knowledge repositories. The operationalization of this knowledge is key to increasing CPGs' uptake in clinical practice. In this work, we propose an approach to operationalizing secondary medical knowledge inspired by graph rewriting. We assume that the CPGs can be represented as task network models, and provide an approach for representing and applying codified medical knowledge to a specific patient encounter. We formally define revisions that model and mitigate adverse interactions between CPGs and we use a vocabulary of terms to instantiate these revisions. We demonstrate the application of our approach using synthetic and clinical examples. We conclude by identifying areas for future work with the vision of developing a theory of mitigation that will facilitate the development of comprehensive decision support for the management of multimorbid patients.

ProtInteract: A deep learning framework for predicting protein-protein interactions.

Proteins mainly perform their functions by interacting with other proteins. Protein-protein interactions underpin various biological activities such as metabolic cycles, signal transduction, and immune response. However, due to the sheer number of proteins, experimental methods for finding interacting and non-interacting protein pairs are time-consuming and costly. We therefore developed the ProtInteract framework to predict protein-protein interaction. ProtInteract comprises two components: first, a novel autoencoder architecture that encodes each protein's primary structure to a lower-dimensional vector while preserving its underlying sequence attributes. This leads to faster training of the second network, a deep convolutional neural network (CNN) that receives encoded proteins and predicts their interaction under three different scenarios. In each scenario, the deep CNN predicts the class of a given encoded protein pair. Each class indicates different ranges of confidence scores corresponding to the probability of whether a predicted interaction occurs or not. The proposed framework features significantly low computational complexity and relatively fast response. The contributions of this work are twofold. First, ProtInteract assimilates the protein's primary structure into a pseudo-time series. Therefore, we leverage the nature of the time series of proteins and their physicochemical properties to encode a protein's amino acid sequence into a lower-dimensional vector space. This approach enables extracting highly informative sequence attributes while reducing computational complexity. Second, the ProtInteract framework utilises this information to identify protein interactions with other proteins based on its amino acid configuration. Our results suggest that the proposed framework performs with high accuracy and efficiency in predicting protein-protein interactions.

Why did AI get this one wrong? - Tree-based explanations of machine learning model predictions.

Increasingly complex learning methods such as boosting, bagging and deep learning have made ML models more accurate, but harder to interpret and explain, culminating in black-box machine learning models. Model developers and users alike are often presented with a trade-off between performance and intelligibility, especially in high-stakes applications like medicine. In the present article we propose a novel methodological approach for generating explanations for the predictions of a generic machine learning model, given a specific instance for which the prediction has been made. The method, named AraucanaXAI, is based on surrogate, locally-fitted classification and regression trees that are used to provide post-hoc explanations of the prediction of a generic machine learning model. Advantages of the proposed XAI approach include superior fidelity to the original model, ability to deal with non-linear decision boundaries, and native support to both classification and regression problems. We provide a packaged, open-source implementation of the AraucanaXAI method and evaluate its behaviour in a number of different settings that are commonly encountered in medical applications of AI. These include potential disagreement between the model prediction and physician's expert opinion and low reliability of the prediction due to data scarcity.

Protein-protein interaction prediction with deep learning: A comprehensive review.

Most proteins perform their biological function by interacting with themselves or other molecules. Thus, one may obtain biological insights into protein functions, disease prevalence, and therapy development by identifying protein-protein interactions (PPI). However, finding the interacting and non-interacting protein pairs through experimental approaches is labour-intensive and time-consuming, owing to the variety of proteins. Hence, protein-protein interaction and protein-ligand binding problems have drawn attention in the fields of bioinformatics and computer-aided drug discovery. Deep learning methods paved the way for scientists to predict the 3-D structure of proteins from genomes, predict the functions and attributes of a protein, and modify and design new proteins to provide desired functions. This review focuses on recent deep learning methods applied to problems including predicting protein functions, protein-protein interaction and their sites, protein-ligand binding, and protein design.

A scoping review of complication prediction models in spinal surgery: An analysis of model development, validation and impact.

Background: Predictive analytics are being used increasingly in the field of spinal surgery with the development of models to predict post-surgical complications. Predictive models should be valid, generalizable, and clinically useful. The purpose of this review was to identify existing post-surgical complication prediction models for spinal surgery and to determine if these models are being adequately investigated with internal/external validation, model updating and model impact studies. Methods: This was a scoping review of studies pertaining to models for the prediction of post-surgical complication after spinal surgery published over 10 years (2010-2020). Qualitative data was extracted from the studies to include study classification, adherence to Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines and risk of bias (ROB) assessment using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). Model evaluation was determined using area under the curve (AUC) when available. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used as a basis for the search methodology in four different databases. Results: Thirty studies were included in the scoping review and 80% (24/30) included model development with or without internal validation. Twenty percent (6/30) were exclusively external validation studies and only one study included an impact analysis in addition to model development and internal validation. Two studies referenced the TRIPOD guidelines and there was a high ROB in 100% of the studies using the PROBAST tool. Conclusions: The majority of post-surgical complication prediction models in spinal surgery have not undergone standardized model development and internal validation or adequate external validation and impact evaluation. As such there is uncertainty as to their validity, generalizability, and clinical utility. Future efforts should be made to use existing tools to ensure standardization in development and rigorous evaluation of prediction models in spinal surgery.

Developing a pneumonia diagnosis ontology from multiple knowledge sources.

Background: Pneumonia is difficult to differentiate from other pulmonary diseases because it shares many symptoms with these diseases. Diagnosing pneumonia in clinical practice would benefit from having access to a codified representation of clinical knowledge. An ontology represents a well-established paradigm for such codification. Objectives: The goal of this research is to create Pneumonia Diagnosis Ontology (PNADO) that brings together the medical knowledge dispersed among multiple medical knowledge sources. Material and Methods: We used several clinical practice guidelines (CPGs) describing the pneumonia diagnostic process as a starting point in developing PNADO. Preliminary version of PNADO was subsequently expanded to cover a broader range of the concepts by reusing ontologies from Open Biological and Biomedical Ontology (OBO) Foundry and BioPortal. PNADO was evaluated by examining relevant concepts from the pneumonia-specific systematic reviews, using patient data from the MIMIC-III clinical dataset, and by clinical domain experts. Results: PNADO is a comprehensive ontology and has a rich set of classes and properties that cover different types of pneumonia, pathogens, symptoms, clinical signs, laboratory tests and imaging, clinical findings, complications, and diagnoses. Conclusion: PNADO unifies pneumonia diagnostic concepts from multiple knowledge sources. It is available in the BioPortal repository.

A Health eLearning Ontology and Procedural Reasoning Approach for Developing Personalized Courses to Teach Patients about Their Medical Condition and Treatment.

We propose a methodological framework to support the development of personalized courses that improve patients' understanding of their condition and prescribed treatment. Inspired by Intelligent Tutoring Systems (ITSs), the framework uses an eLearning ontology to express domain and learner models and to create a course. We combine the ontology with a procedural reasoning approach and precompiled plans to operationalize a design across disease conditions. The resulting courses generated by the framework are personalized across four patient axes-condition and treatment, comprehension level, learning style based on the VARK (Visual, Aural, Read/write, Kinesthetic) presentation model, and the level of understanding of specific course content according to Bloom's taxonomy. Customizing educational materials along these learning axes stimulates and sustains patients' attention when learning about their conditions or treatment options. Our proposed framework creates a personalized course that prepares patients for their meetings with specialists and educates them about their prescribed treatment. We posit that the improvement in patients' understanding of prescribed care will result in better outcomes and we validate that the constructs of our framework are appropriate for representing content and deriving personalized courses for two use cases: anticoagulation treatment of an atrial fibrillation patient and lower back pain management to treat a lumbar degenerative disc condition. We conduct a mostly qualitative study supported by a quantitative questionnaire to investigate the acceptability of the framework among the target patient population and medical practitioners.

MitPlan: A planning approach to mitigating concurrently applied clinical practice guidelines.

As the population ages, patients' complexity and the scope of their care is increasing. Over 60% of the population is 65 years of age or older and suffers from multi-morbidity, which is associated with two times as many patient-physician encounters. Yet clinical practice guidelines (CPGs) are developed to treat a single disease. To reconcile these two competing issues, previously we developed a framework for mitigation, i.e., identifying and addressing adverse interactions in multi-morbid patients managed according to multiple CPGs. That framework relies on first-order logic (FOL) to represent CPGs and secondary medical knowledge and FOL theorem proving to establish valid patient management plans. In the work presented here, we leverage our earlier research and simplify the mitigation process by representing it as a planning problem using the Planning Domain Definition Language (PDDL). This new framework, called MitPlan, identifies and addresses adverse interactions using durative planning actions that embody clinical actions (including medication administration and patient testing), supports a physician-defined length of planning horizons, and optimizes plans based on patient preferences and action costs. It supports a variety of criteria when developing management plans, including the total cost of prescribed treatment and the cost of the revisions to be introduced. The solution to MitPlan's planning problem is a sequence of timed actions that are easy to interpret when creating a management plan. We demonstrate MitPlan's capabilities using illustrative and clinical case studies.

Towards a framework for comparing functionalities of multimorbidity clinical decision support: A literature-based feature set and benchmark cases.

Multimorbidity, the coexistence of two or more health conditions, has become more prevalent as mortality rates in many countries have declined and their populations have aged. Multimorbidity presents significant difficulties for Clinical Decision Support Systems (CDSS), particularly in cases where recommendations from relevant clinical guidelines offer conflicting advice. A number of research groups are developing computer-interpretable guideline (CIG) modeling formalisms that integrate recommendations from multiple Clinical Practice Guidelines (CPGs) for knowledge-based multimorbidity decision support. In this paper we describe work towards the development of a framework for comparing the different approaches to multimorbidity CIG-based clinical decision support (MGCDS). We present (1) a set of features for MGCDS, which were derived using a literature review and evaluated by physicians using a survey, and (2) a set of benchmarking case studies, which illustrate the clinical application of these features. This work represents the first necessary step in a broader research program aimed at the development of a benchmark framework that allows for standardized and comparable MGCDS evaluations, which will facilitate the assessment of functionalities of MGCDS, as well as highlight important gaps in the state-of-the-art. We also outline our future work on developing the framework, specifically, (3) a standard for reporting MGCDS solutions for the benchmark case studies, and (4) criteria for evaluating these MGCDS solutions. We plan to conduct a large-scale comparison study of existing MGCDS based on the comparative framework.

An ontology-driven framework to support the dynamic formation of an interdisciplinary healthcare team.

BACKGROUND AND PURPOSE: Teamwork has become a modus operandi in healthcare and delivery of patient care by an interdisciplinary healthcare team (IHT) is now a prevailing modality of care. We argue that a formal and automated support framework is needed for an IHT to properly leverage information technology resources. Such a framework should allow for patient preferences and expand a representation of a clinical workflow with a formal model of dynamic formation of a team, especially with regards to team leader- and membership, and the assignment of tasks to team members. Our goal was to develop such a support framework, present its prototype software implementation and verify the implementation using a proof-of-concept use case. Specifically, we focused on clinical workflows for in-patient tertiary care and on patient preferences with regards to selecting team members and team leaders. MATERIALS AND METHODS: Drawing on the research on clinical teamwork we defined the conceptual foundations for the proposed framework. Then, we designed its architecture and used ontology-driven design and first-order logic with associated reasoning methods to create and operationalize architectural elements. Finally, we incorporated existing solutions for business workflow modeling and execution as a backend for implementing the proposed framework. RESULTS: We developed a Team and Workflow Management Framework (TWMF) with semantic components that allow for formalizing and operationalizing team formation in in-patient tertiary care setting and support provider-related patient preferences. We also created a prototype software implementation of TWMF using the IBM Business Process Manager platform. This implementation was evaluated in several simulated patient scenarios. CONCLUSIONS: TWMF integrates existing workflow technologies and extends them with the capabilities to support dynamic formation of an IHT. Results of this research can be used to support real-time execution of clinical workflows, or to simulate their execution in order to assess the impact of various conditions (e.g., patterns of work shifts, staffing) on IHT operations.

Business school teams up with clinical innovators: An opportunity for health system transformation.

Healthcare represents one of the largest sectors in the economy with the health spending on average accounting for about 9% of GDP in OECD countries. Canada was projected in 2018 to spend about 11% of its GDP on healthcare with an expected health expenditure growth of 4.2%. Addressing this issue asks for a redesign of health delivery system and associated cultural shift allowing for incorporation of industry and business best practices. To make this redesign happen, system transformation requires seeking out new institutional mechanisms, partnerships, and forums where industry leaders in business and healthcare can develop a top-down approach with a shared vision, shared best practices, and support coming from a bottom-up approach through pilots and scaling-up initiatives. In this article, we describe one successful partnership initiative-Telfer Health Transformation Exchange at the Telfer School of Management at the University of Ottawa.

How Do Spinal Surgeons Perceive The Impact of Factors Used in Post-Surgical Complication Risk Scores?

When deciding about surgical treatment options, an important aspect of the decision-making process is the potential risk of complications. A risk assessment performed by a spinal surgeon is based on their knowledge of the best available evidence and on their own clinical experience. The objective of this work is to demonstrate the differences in the way spine surgeons perceive the importance of attributes used to calculate risk of post-operative and quantify the differences by building individual formal models of risk perceptions. We employ a preference-learning method - ROR-UTADIS - to build surgeon-specific additive value functions for risk of complications. Comparing these functions enables the identification and discussion of differences among personal perceptions of risk factors. Our results show there exist differences in surgeons' perceived factors including primary diagnosis, type of surgery, patient's age, body mass index, or presence of comorbidities.