Artificial intelligence for dementia research methods optimization

Artificial intelligence (AI) and machine learning (ML) approaches are increasingly being used in dementia research. However, several methodological challenges exist that may limit the insights we can obtain from high-dimensional data and our ability to translate these findings into improved patient outcomes. To improve reproducibility and replicability, researchers should make their well-documented code and modeling pipelines openly available. Data should also be shared where appropriate. To enhance the acceptability of models and AI-enabled systems to users, researchers should prioritize interpretable methods that provide insights into how decisions are generated. Models should be developed using multiple, diverse datasets to improve robustness, generalizability, and reduce potentially harmful bias. To improve clarity and reproducibility, researchers should adhere to reporting guidelines that are co-produced with multiple stakeholders. If these methodological challenges are overcome, AI and ML hold enormous promise for changing the landscape of dementia research and care

Hand Transplants and Bodily Integrity

In this article, we present an analysis of bodily integrity in hand transplants from a phenomenological narrative perspective, while drawing on two contrasting case stories. We consider bodily integrity as the subjective bodily experience of wholeness which, instead of referring to actual bodily intactness, involves a positive identification with one's physical body. Bodily mutilations, such as the loss of a hand, may severely affect one's bodily integrity. A possible restoration of one's experience of wholeness requires a process of re-identification. Medical interventions, such as a hand transplant, may improve the possibility of a successful re-identification. However, since the experience of wholeness does not refer simply to physical intactness or impairment, the choice for medical intervention should not be based merely upon the degree of physical mutilation. It should also be based upon the degree to which a person fails in re-identifying with his or her mutilated body. We argue that a normalizing operation is only ethically justifiable if the intervention enables the person to be the body he or she has

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc