Conceptual graph-based knowledge representation for supporting reasoning in African traditional medicine

Although African patients use both conventional or modern and traditional healthcare simultaneously, it has been proven that 80% of people rely on African traditional medicine (ATM). ATM includes medical activities stemming from practices, customs and traditions which were integral to the distinctive African cultures. It is based mainly on the oral transfer of knowledge, with the risk of losing critical knowledge. Moreover, practices differ according to the regions and the availability of medicinal plants. Therefore, it is necessary to compile tacit, disseminated and complex knowledge from various Tradi-Practitioners (TP) in order to determine interesting patterns for treating a given disease. Knowledge engineering methods for traditional medicine are useful to model suitably complex information needs, formalize knowledge of domain experts and highlight the effective practices for their integration to conventional medicine. The work described in this paper presents an approach which addresses two issues. First it aims at proposing a formal representation model of ATM knowledge and practices to facilitate their sharing and reusing. Then, it aims at providing a visual reasoning mechanism for selecting best available procedures and medicinal plants to treat diseases. The approach is based on the use of the Delphi method for capturing knowledge from various experts which necessitate reaching a consensus. Conceptual graph formalism is used to model ATM knowledge with visual reasoning capabilities and processes. The nested conceptual graphs are used to visually express the semantic meaning of Computational Tree Logic (CTL) constructs that are useful for formal specification of temporal properties of ATM domain knowledge. Our approach presents the advantage of mitigating knowledge loss with conceptual development assistance to improve the quality of ATM care (medical diagnosis and therapeutics), but also patient safety (drug monitoring)

Knowledge-based incremental induction of clinical algorithms

The current approaches for the induction of medical procedural knowledge suffer from several drawbacks: the structures produced may not be explicit medical structures, they are only based on statistical measures that do not necessarily respect medical criteria which can be essential to guarantee medical correct structures, or they are not prepared to deal with the incremental arrival of new data. In this thesis we propose a methodology to automatically induce medically correct clinical algorithms (CAs) from hospital databases. These CAs are represented according to the SDA knowledge model. The methodology considers relevant background knowledge and it is able to work in an incremental way. The methodology has been tested in the domains of hypertension, diabetes mellitus and the comborbidity of both diseases. As a result, we propose a repository of background knowledge for these pathologies and provide the SDA diagrams obtained. Later analyses show that the results are medically correct and comprehensible when validated with health care professionals

Early development of decision support systems based on artificial intelligence: an application to postoperative complications and a cross-specialty reporting guideline for early-stage clinical evaluation

Background: Complications after major surgery occur in a similar manner internationally but the success of response process in preventing death varies widely depending on speed and appropriateness. Artificial intelligence (AI) offers new opportunities to provide support to the decision making of clinicians in this stressful situation when uncertainty is high. However, few AI systems have been robustly and successfully tested in real-world clinical settings. Whilst preparing to develop an AI decision support algorithm and planning to evaluate it in real-world settings, a lack of appropriate guidance on reporting early clinical evaluation of such systems was identified. Objectives: The objectives of this work were twofold: i) to develop a prototype of AI system to improve the management of postoperative complications; and ii) to understand expert consensus on reporting standards for early-stage evaluation of AI systems in live clinical settings. Methods: I conducted and thematically analysed interviews with clinicians to identify their main challenges and support needs when managing postoperative complications. I then systematically reviewed the literature on the impact of AI-based decision support systems on clinicians’ diagnostic performance. A model based on unsupervised clustering and providing prescription recommendations was developed, optimised, and tested on an internal hold out dataset. Finally, I conducted a Delphi process, to reach expert consensus on minimum reporting standards for the early-stage clinical evaluation of AI systems in live clinical settings. Results: 12 interviews were conducted with junior and senior clinicians identifying 54 themes about challenges, common errors, strategies, and support needs when managing postoperative complications. 37 studies were included in the systematic review, which found no robust evidence of a positive association between the use of AI decision support systems and improved clinician diagnostic performance. The developed algorithm showed no improvement in recall at position ten compared to a list of the most common prescriptions in the study population. When considering the prevalence of the individual prescriptions, the algorithm showed a 12% relative increase in performance compared to the same baseline. 151 experts participated in the Delphi study, representing 18 countries and 20 stakeholder groups. The final DECIDE-AI checklist comprises 27 items, accompanied by Explanation & Elaboration sections for each. Conclusion: The proposed algorithm offers a proof of concept for an AI system to improve the management of postoperative complications. However, it needs further development and evaluation before claiming clinical utility. The DECIDE-AI guideline provides a practicable checklist for researchers reporting on the implementation of AI decision support systems in clinical settings, and merits future iterative evaluation-update cycles in practice

Manufacturing Barriers to Biologics Competition and Innovation

As finding breakthrough small-molecule drugs gets harder, drug companies are increasingly turning to “large molecule” biologics. Although biologics represent many of the most promising new therapies for previously intractable diseases, they are extremely expensive. Moreover, the pathway for generic-type competition set up by Congress in 2010 is unlikely to yield significant cost savings. In this Article, we provide a fresh diagnosis of, and prescription for, this major public policy problem. We argue that the key cause is pervasive trade secrecy in the complex area of biologics manufacturing. Under the current regime, this trade secrecy, combined with certain features of FDA regulation, not only creates high barriers to entry of indefinite duration but also undermines efforts to advance fundamental knowledge. In sharp contrast, offering incentives for information disclosure to originator manufacturers would leverage the existing interaction of trade secrecy and the regulatory state in a positive direction. Although trade secrecy, particularly in complex areas like biologics manufacturing, often involves tacit knowledge that is difficult to codify and thus transfer, in this case regulatory requirements that originator manufacturers submit manufacturing details have already codified the relevant tacit knowledge. Incentivizing disclosure of these regulatory submissions would not only spur competition but it would provide a rich source of information upon which additional research, including fundamental research into the science of manufacturing, could build. In addition to provide fresh diagnosis and prescription in the specific area of biologics, the Article contributes to more general scholarship on trade secrecy and tacit knowledge. Prior scholarship has neglected the extent to which regulation can turn tacit knowledge not only into codified knowledge but into precisely the type of codified knowledge that is most likely to be useful and accurate. The Article also draws a link to the literature on adaptive regulation, arguing that greater regulatory flexibility is necessary and that more fundamental knowledge should spur flexibility. A vastly shortened version of the central argument that manufacturing trade secrecy hampers biosimilar development was published at 348 Science 188 (2015), available online

Unsupervised learning methods for identifying and evaluating disease clusters in electronic health records

Introduction Clustering algorithms are a class of algorithms that can discover groups of observations in complex data and are often used to identify subtypes of heterogeneous diseases in electronic health records (EHR). Evaluating clustering experiments for biological and clinical significance is a vital but challenging task due to the lack of consensus on best practices. As a result, the translation of findings from clustering experiments to clinical practice is limited. Aim The aim of this thesis was to investigate and evaluate approaches that enable the evaluation of clustering experiments using EHR. Methods We conducted a scoping review of clustering studies in EHR to identify common evaluation approaches. We systematically investigated the performance of the identified approaches using a cohort of Alzheimer's Disease (AD) patients as an exemplar comparing four different clustering methods (K-means, Kernel K-means, Affinity Propagation and Latent Class Analysis.). Using the same population, we developed and evaluated a method (MCHAMMER) that tested whether clusterable structures exist in EHR. To develop this method we tested several cluster validation indexes and methods of generating null data to see which are the best at discovering clusters. In order to enable the robust benchmarking of evaluation approaches, we created a tool that generated synthetic EHR data that contain known cluster labels across a range of clustering scenarios. Results Across 67 EHR clustering studies, the most popular internal evaluation metric was comparing cluster results across multiple algorithms (30% of studies). We examined this approach conducting a clustering experiment on AD patients using a population of 10,065 AD patients and 21 demographic, symptom and comorbidity features. K-means found 5 clusters, Kernel K means found 2 clusters, Affinity propagation found 5 and latent class analysis found 6. K-means 4 was found to have the best clustering solution with the highest silhouette score (0.19) and was more predictive of outcomes. The five clusters found were: typical AD (n=2026), non-typical AD (n=1640), cardiovascular disease cluster (n=686), a cancer cluster (n=1710) and a cluster of mental health issues, smoking and early disease onset (n=1528), which has been found in previous research as well as in the results of other clustering methods. We created a synthetic data generation tool which allows for the generation of realistic EHR clusters that can vary in separation and number of noise variables to alter the difficulty of the clustering problem. We found that decreasing cluster separation did increase cluster difficulty significantly whereas noise variables increased cluster difficulty but not significantly. To develop the tool to assess clusters existence we tested different methods of null dataset generation and cluster validation indices, the best performing null dataset method was the min max method and the best performing indices we Calinksi Harabasz index which had an accuracy of 94%, Davies Bouldin index (97%) silhouette score ( 93%) and BWC index (90%). We further found that when clusters were identified using the Calinski Harabasz index they were more likely to have significantly different outcomes between clusters. Lastly we repeated the initial clustering experiment, comparing 10 different pre-processing methods. The three best performing methods were RBF kernel (2 clusters), MCA (4 clusters) and MCA and PCA (6 clusters). The MCA approach gave the best results highest silhouette score (0.23) and meaningful clusters, producing 4 clusters; heart and circulatory( n=1379), early onset mental health (n=1761), male cluster with memory loss (n = 1823), female with more problem (n=2244). Conclusion We have developed and tested a series of methods and tools to enable the evaluation of EHR clustering experiments. We developed and proposed a novel cluster evaluation metric and provided a tool for benchmarking evaluation approaches in synthetic but realistic EHR

Biasing Brands

The dominant search-costs model of trademark law posits that consumers choose products to satisfy their preferences by analytically mapping those preferences to product information that trademarks efficiently provide. This Article tests these descriptive claims against empirical and theoretical research in marketing and consumer psychology, particularly the concept of brand equity : the value to a firm or its customers of a brand and of the firm\u27s efforts to build and maintain that brand. Internally complex brand equity models, juxtaposed with empirical findings in related psychology and marketing research, challenge the descriptive accuracy of the search-costs model. In particular, branding efforts can influence consumer decision-making not only by informing and persuading consumers, but also by altering the way consumers evaluate product information and consumption experiences. In a word, branding can bias consumers. The phenomenon of brand bias suggests that the search-costs model is incomplete and that trademark protection can only reliably promote economic efficiency in a legal environment where complementary regulations, such as those prevalent in food and drug law, mitigate the opportunities for producers to extract rents by manipulating consumer psychology. The Article concludes by situating trademark law in this broader web of consumer protection law

Confronting the Ghost: Legal Strategies to Oust Medical Ghostwriters

Articles published in medical journals contribute significantly to public health by disseminating medical information to physicians, thereby influencing prescribing practices. However, the information guiding treatment decisions becomes distorted by selective publishing and medical ghostwriting, which negatively affects overall patient care. Although there is general consensus in the medical community that these practices of publication bias represent a moral failing, the issue is rarely framed as a wrong that necessitates legal consequences. This Note takes the stance that medical ghostwriting constitutes an act prohibited under the Racketeer Influenced and Corrupt Organizations Act (RICO) and argues that physicians fraudulently named as authors should be held civilly liable under RICO. This Note explores civil RICO, its origin, its legislative and judicial history, and the evolution of RICO to areas beyond traditional organized crime. By applying the elements of civil RICO to medical ghostwriting, this Note argues that physicians named as authors who knowingly fail to fulfill journal authorship criteria should be held accountable for their role in disseminating misleading medical information. This Note argues that, at the very least, current regulations governing the medical publication framework should be better enforced and revised to mandate authorship disclosure

Linking patient data to scientific knowledge to support contextualized mining

Tese de mestrado, Bioinformática e Biologia Computacional, Universidade de Lisboa, Faculdade de Ciências, 2022ICU readmissions are a critical problem associated with either serious conditions, ill nesses, or complications, representing a 4 times increase in mortality risk and a financial burden to health institutions. In developed countries 1 in every 10 patients discharged comes back to the ICU. As hospitals become more and more data-oriented with the adop tion of Electronic Health Records (EHR), there as been a rise in the development of com putational approaches to support clinical decision. In recent years new efforts emerged, using machine learning approaches to make ICU readmission predictions directly over EHR data. Despite these growing efforts, machine learning approaches still explore EHR data directly without taking into account its mean ing or context. Medical knowledge is not accessible to these methods, who work blindly over the data, without considering the meaning and relationships the data objects. Ontolo gies and knowledge graphs can help bridge this gap between data and scientific context, since they are computational artefacts that represent the entities in a domain and how the relate to each other in a formalized fashion. This opportunity motivated the aim of this work: to investigate how enriching EHR data with ontology-based semantic annotations and applying machine learning techniques that explore them can impact the prediction of 30-day ICU readmission risk. To achieve this, a number of contributions were developed, including: (1) An enrichment of the MIMIC-III data set with annotations to several biomedical ontologies; (2) A novel ap proach to predict ICU readmission risk that explores knowledge graph embeddings to represent patient data taking into account the semantic annotations; (3) A variant of the predictive approach that targets different moments to support risk prediction throughout the ICU stay. The predictive approaches outperformed both state-of-the-art and a baseline achieving a ROC-AUC of 0.815 (an increase of 0.2 over the state of the art). The positive results achieved motivated the development of an entrepreneurial project, which placed in the Top 5 of the H-INNOVA 2021 entrepreneurship award

Patterns in the politics of drugs and tobacco: The Supreme Court and issue attention by policymakers and the press

Past research has demonstrated lasting effects of important Supreme Court decisions on issue attention in the national media. In this light, the Court has served as an important agenda setter. We significantly expand on these findings by arguing that these salient Court decisions can raise the perceived importance of political issues and induce heightened, short-term policy attention in the broader political system. Using measures of media attention, congressional policy actions, and presidential policy actions, we utilize dynamic vector autoregressive modelling to examine the Court’s impact on issue attention in the macro policy system regarding tobacco and drug policy. Overall, this study suggests that the Supreme Court’s most important decisions might significantly affect broader issue attention in the American political system