Ethical and social implications of using predictive modeling for Alzheimer´s disease prevention:a systematic literature review

BACKGROUND: The therapeutic paradigm in Alzheimer's disease (AD) is shifting from symptoms management toward prevention goals. Secondary prevention requires the identification of individuals without clinical symptoms, yet "at-risk" of developing AD dementia in the future, and thus, the use of predictive modeling. OBJECTIVE: The objective of this study was to review the ethical concerns and social implications generated by this new approach. METHODS: We conducted a systematic literature review in Medline, Embase, PsycInfo, and Scopus, and complemented it with a gray literature search between March and July 2018. Then we analyzed data qualitatively using a thematic analysis technique. RESULTS: We identified thirty-one ethical issues and social concerns corresponding to eight ethical principles: (i) respect for autonomy, (ii) beneficence, (iii) non-maleficence, (iv) equality, justice, and diversity, (v) identity and stigma, (vi) privacy, (vii) accountability, transparency, and professionalism, and (viii) uncertainty avoidance. Much of the literature sees the discovery of disease-modifying treatment as a necessary and sufficient condition to justify AD risk assessment, overlooking future challenges in providing equitable access to it, establishing long-term treatment outcomes and social consequences of this approach, e.g., medicalization. The ethical/social issues associated specifically with predictive models, such as the adequate predictive power and reliability, infrastructural requirements, data privacy, potential for personalized medicine in AD, and limiting access to future AD treatment based on risk stratification, were covered scarcely. CONCLUSION: The ethical discussion needs to advance to reflect recent scientific developments and guide clinical practice now and in the future, so that necessary safeguards are implemented for large-scale AD secondary prevention.</p

The DOE Wide Area Measurement System (WAMS) Project: Demonstration of dynamic information technology for the future power system

In 1989 the Bonneville Power Administration (BPA) and the Western Area Power Administration (WAPA) joined the US Department of Energy (DOE) in an assessment of longer-term research and development needs for future electric power system operation. The effort produced a progressively sharper vision of a future power system in which enhanced control and operation are the primary means for serving new customer demands, in an environment where increased competition, a wider range of services and vendors, and much narrower operating margins all contribute to increased system efficiencies and capacity. Technology and infrastructure for real time access to wide area dynamic information were identified as critical path elements in realizing that vision. In 1995 the DOE accordingly launched the Wide Area Measurement System (WAMS) Project jointly with the two Power Marketing Administrations (PMAs) to address these issues in a practical operating environment--the western North America power system. The Project draws upon many years of PMA effort and related collaboration among the western utilities, plus an expanding infrastructure that includes regionally involved contractors, universities, and National Laboratories plus linkages to the Electric Power Research Institute (EPRI). The WAMS project also brings added focus and resources to the evolving Western System Dynamic Information Network, or WesDINet. This is a collective response of the Western Systems Coordinating Council (WSCC) member utilities to their shared needs for direct information about power system characteristics, model fidelity, and operational performance. The WAMS project is a key source of the technology and backbone communications needed to make WesDINet a well integrated, cost effective enterprise network demonstrating the role of dynamic information technology in the emerging utility environment

AI reflections in 2020

We invited authors of selected Comments and Perspectives published in Nature Machine Intelligence in the latter half of 2019 and first half of 2020 to describe how their topic has developed, what their thoughts are about the challenges of 2020, and what they look forward to in 2021.Postprint (author's final draft

Challenges for Optimizing Real-World Evidence in Alzheimer’s Disease: The ROADMAP Project

ROADMAP is a public-private advisory partnership to evaluate the usability of multiple data sources, including real-world evidence, in the decision-making process for new treatments in Alzheimer’s disease, and to advance key concepts in disease and pharmacoeconomic modeling. ROADMAP identified key disease and patient outcomes for stakeholders to make informed funding and treatment decisions, provided advice on data integration methods and standards, and developed conceptual cost-effectiveness and disease models designed in part to assess whether early treatment provides long-term benefit

Comparison of RNA-Seq and Microarray Gene Expression Platforms for the Toxicogenomic Evaluation of Liver From Short-Term Rat Toxicity Studies

Gene expression profiling is a useful tool to predict and interrogate mechanisms of toxicity. RNA-Seq technology has emerged as an attractive alternative to traditional microarray platforms for conducting transcriptional profiling. The objective of this work was to compare both transcriptomic platforms to determine whether RNA-Seq offered significant advantages over microarrays for toxicogenomic studies. RNA samples from the livers of rats treated for 5 days with five tool hepatotoxicants (α-naphthylisothiocyanate/ANIT, carbon tetrachloride/CCl4, methylenedianiline/MDA, acetaminophen/APAP, and diclofenac/DCLF) were analyzed with both gene expression platforms (RNA-Seq and microarray). Data were compared to determine any potential added scientific (i.e., better biological or toxicological insight) value offered by RNA-Seq compared to microarrays. RNA-Seq identified more differentially expressed protein-coding genes and provided a wider quantitative range of expression level changes when compared to microarrays. Both platforms identified a larger number of differentially expressed genes (DEGs) in livers of rats treated with ANIT, MDA, and CCl4 compared to APAP and DCLF, in agreement with the severity of histopathological findings. Approximately 78% of DEGs identified with microarrays overlapped with RNA-Seq data, with a Spearman’s correlation of 0.7 to 0.83. Consistent with the mechanisms of toxicity of ANIT, APAP, MDA and CCl4, both platforms identified dysregulation of liver relevant pathways such as Nrf2, cholesterol biosynthesis, eiF2, hepatic cholestasis, glutathione and LPS/IL-1 mediated RXR inhibition. RNA-Seq data showed additional DEGs that not only significantly enriched these pathways, but also suggested modulation of additional liver relevant pathways. In addition, RNA-Seq enabled the identification of non-coding DEGs that offer a potential for improved mechanistic clarity. Overall, these results indicate that RNA-Seq is an acceptable alternative platform to microarrays for rat toxicogenomic studies with several advantages. Because of its wider dynamic range as well as its ability to identify a larger number of DEGs, RNA-Seq may generate more insight into mechanisms of toxicity. However, more extensive reference data will be necessary to fully leverage these additional RNA-Seq data, especially for non-coding sequences

The ethics of digital well-being: a multidisciplinary perspective

This chapter serves as an introduction to the edited collection of the same name, which includes chapters that explore digital well-being from a range of disciplinary perspectives, including philosophy, psychology, economics, health care, and education. The purpose of this introductory chapter is to provide a short primer on the different disciplinary approaches to the study of well-being. To supplement this primer, we also invited key experts from several disciplines—philosophy, psychology, public policy, and health care—to share their thoughts on what they believe are the most important open questions and ethical issues for the multi-disciplinary study of digital well-being. We also introduce and discuss several themes that we believe will be fundamental to the ongoing study of digital well-being: digital gratitude, automated interventions, and sustainable co-well-being

MANGO ? Modal Analysis for Grid Operation: A Method for Damping Improvement through Operating Point Adjustment

Small signal stability problems are one of the major threats to grid stability and reliability in the U.S. power grid. An undamped mode can cause large-amplitude oscillations and may result in system breakups and large-scale blackouts. There have been several incidents of system-wide oscillations. Of those incidents, the most notable is the August 10, 1996 western system breakup, a result of undamped system-wide oscillations. Significant efforts have been devoted to monitoring system oscillatory behaviors from measurements in the past 20 years. The deployment of phasor measurement units (PMU) provides high-precision, time-synchronized data needed for detecting oscillation modes. Measurement-based modal analysis, also known as ModeMeter, uses real-time phasor measurements to identify system oscillation modes and their damping. Low damping indicates potential system stability issues. Modal analysis has been demonstrated with phasor measurements to have the capability of estimating system modes from both oscillation signals and ambient data. With more and more phasor measurements available and ModeMeter techniques maturing, there is yet a need for methods to bring modal analysis from monitoring to actions. The methods should be able to associate low damping with grid operating conditions, so operators or automated operation schemes can respond when low damping is observed. The work presented in this report aims to develop such a method and establish a Modal Analysis for Grid Operation (MANGO) procedure to aid grid operation decision making to increase inter-area modal damping. The procedure can provide operation suggestions (such as increasing generation or decreasing load) for mitigating inter-area oscillations

Ethical principles in machine learning and artificial intelligence: cases from the field and possible ways forward

Decision-making on numerous aspects of our daily lives is being outsourced to machine-learning algorithms and artificial intelligence (AI), motivated by speed and efficiency in the decision process. Machine learning (ML) approaches - one of the typologies of algorithms underpinning artificial intelligence - are typically developed as black boxes. The implication is that ML code scripts are rarely scrutinised; interpretability is usually sacrificed in favour of usability and effectiveness. Room for improvement in practices associated with programme development have also been flagged along other dimensions, including inter alia fairness, accuracy, accountability, and transparency. In this contribution, the production of guidelines and dedicated documents around these themes is discussed. The following applications of AI-driven decision making are outlined: a) Risk assessment in the criminal justice system, and b) autonomous vehicles, highlighting points of friction across ethical principles. Possible ways forward towards the implementation of governance on AI are finally examined