Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

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

Stereoselective hydrosilylation of terminal alkynes catalyzed by [Cp*IrCl2]2: A computational and experimental study

10.1021/om0609158Organometallics2651157-1160ORGN

[Cp*IrCl2]2-assisted C=C bond cleavage with water: An experimental and computational study

10.1021/om0610445Organometallics2651173-1177ORGN

Synthetic, X-ray diffraction, electrochemical, and density functional theoretical studies of (indenyl)ruthenium complexes containing dithiolate ligands

10.1002/ejic.200700070European Journal of Inorganic Chemistry243827-3840EJIC

Design.Lives Lab: a case to introduce solution-focused design methodology for participatory design for social inclusion

The Design.Lives project is collaboration between the disciplines of design and sociology. This paper unfolds our latest attempt on the practice of design participation through educating young designers. We discuss a three-week Design.Lives Lab, a workshop for practicing our approach in a design education context. The design lab was inspired and informed by solution-focused approach and employed three tactics namely confrontational, empathy and the imagination of replacement so as to bring forth reflectivity on the role of designers and users. We finally found that these three tactics are significant in opening up the design community and sensitizing novice designers to the power of pre-reflexive being and dispositions. Our attempt has shown the significance and effectiveness of using solutionfocused approach as a design methodology