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Counterfactual strategies for Markov decision processes
No full textCounterfactuals are widely used in AI to explain how minimal changes to a model’s input can cause a different output. However, established methods for computing counterfactuals focus on one-step decision-making, and are not applicable for sequential decision-making. This paper fills this gap by introducing counterfactuals for Markov decision processes (MDPs), i.e., discrete-time Markov models with non-determinism. During MDP execution, a strategy decides which of the enabled actions (with known probabilistic effects) to execute next. Given an initial strategy that reaches an undesired outcome with a probability above some limit, we identify minimal changes to the initial strategy
to reduce that probability below the limit. We encode such counterfactual strategies as solutions to non-linear optimization problems, and further extend this encoding to synthesize diverse counterfactual strategies. We evaluate our approach on four real-world datasets and demonstrate its suitability for providing algorithmic recourse in sophisticated sequential decision-making tasks
Replicating community dynamics reveals how initial composition shapes the functional outcomes of bacterial communities
No full textBacterial communities play key roles in global biogeochemical cycles, industry, agriculture, human health, and animal husbandry. There is therefore great interest in understanding bacterial community dynamics so that they can be controlled and engineered to optimise ecosystem services. We assess the reproducibility and predictability of bacterial community dynamics by creating a frozen archive of hundreds of naturally-occurring bacterial communities that we repeatedly revive and track in a standardised, complex resource environment. Replicate communities follow reproducible trajectories and the community dynamics closely map to ecosystem functioning. However, even under standardised conditions, the communities exhibit tipping-points, where small differences in initial community composition create divergent compositional and functional outcomes. The predictability of community trajectories therefore requires detailed knowledge of rugged compositional landscapes where ecosystem properties are not the inevitable result of prevailing environmental conditions but can be tilted toward different outcomes depending on the initial community composition. Our results shed light on the relationship between composition and function, opening new avenues to understand the feasibility and limitations of function prediction in complex microbial communities
A feasibility cluster RCT involving SPECTROM staff training programme to help reduce the overmedication of adults with intellectual disabilities
No full textIntroduction
We coproduced SPECTROM (Short-term Psycho-Education for Carers To Help Reduce the OverMedication of people with intellectual disabilities) (https://spectrom.wixsite.com/project) training for support staff (direct care workers) to help reduce the overmedication of people with intellectual disabilities.
Methods
A multisite feasibility cluster randomized controlled trial involving SPECTROM training.
Results
Overall, 39 clusters were recruited (26 in the SPECTROM training and 13 in the control group). Antipsychotic medicine dose was reduced among 19% of prescriptions in the training group at 6 months post-training follow-up compared with 6% in the non-training group. PKQ-R (Psychotropic Knowledge Questionnaire-Revised) and MAVAS-R-ID (Management of Aggression and Violence Attitude Scale-Revised-Intellectual Disabilities) scores showed a statistically significant improvement at 4 weeks of follow-up (p < .001). The focus groups revealed that the trainees found the SPECTROM acceptable, practical, and relevant to their practice.
Conclusions
The findings of the current feasibility study support progression to a larger and more definitive RCT.
Trial Registration
Name of the registry: ISRCTN; Trial registration number: ISRCTN71712166; date of registration: 24.01.24; URL of trial registry: https://doi.org/10.1186/ISRCTN7171216
Neuropathological stages of neuronal, astrocytic and oligodendrocytic alpha-synuclein pathology in Parkinson’s disease
No full textAlpha-synucleinopathies are neurodegenerative diseases characterized by the spread of alpha-synuclein (α-syn) aggregates throughout the central nervous system in a stereotypical manner. These diseases include Lewy body disease (LBD), which encompass Dementia with Lewy bodies (DLB), Parkinson’s Disease (PD), and Parkinson’s Disease Dementia (PDD), and Multiple System Atrophy (MSA). LBD and MSA chiefly contain α-syn aggregates in neurons and oligodendrocytes, respectively, although glial α-syn pathology in LBD is increasingly being recognized. Semi-quantitative and machine learning-based quantifications of neuronal, oligodendrocytic and astrocytic α-syn pathology were implemented on a cohort of LBD and MSA post-mortem tissue samples. The neuroanatomical distribution of each cell-type specific α-syn pathology was evaluated using conditional probability matrices and Subtype and Stage Inference (SuStaIn) algorithm. We revealed extensive glial α-syn pathology in LBD, emphasizing the disease- and region-specific profile of astrocytic α-syn pathology, which was absent in MSA and minimal in the substantia nigra of LBD. Furthermore, we have described distinct morphologies of astrocytic α-syn pathology, which were found to correlate with the density of astrocytic α-syn inclusions. Astrocytic α-syn pathology was mainly centered in the amygdala and exhibited a unique stereotypical progression whilst oligodendrocytes displayed a distribution akin to the established neuronal progression pattern. SuStaIn modeling was further used to test for heterogeneity in the spatiotemporal progression, revealing that a subset of cases might follow an alternative pattern. Based on these findings, we introduce a novel multimodal progression framework that integrates, for the first time, the temporal and spatial progression of astrocytic and oligodendrocytic α-syn pathology alongside neuronal pathology in PD, providing further information regarding the role of neurons and glia in disease pathogenesis
Spatiotemporal heterogeneity in malaria transmission across Indonesia: analysis of routine surveillance data 2010-2019
No full textBackground
Indonesia faces challenges in achieving its goal of eliminating malaria by 2030, with cases stagnating between 2015 and 2019. This study analysed regional epidemiological trends and demographic changes in malaria cases from 2010 to 2019, considering differences in surveillance across the country.
Methods
We analysed national and sub-national malaria routine surveillance data using generalised additive and generalised linear models to assess temporal trends in case reporting, test positivity, demographics, and parasite species distribution while accounting for surveillance variations.
Results
After adjusting for increased testing from 2015 onwards, we estimated declining malaria incidence in six of seven Indonesian regions. These regions showed a demographic shift toward older, predominantly male cases, suggesting a transition from household to occupational transmission. In contrast, Papua maintained high transmission with cases concentrated in children. Despite comprising only 2% of Indonesia’s population, Papua’s contribution to national malaria cases rose from 40 to 90% (2010–2019).
Conclusion
While most Indonesian regions progress toward elimination by addressing mobile and migrant populations and P. vivax transmission, Papua shows different patterns with persistently high transmission among children. Achieving nationwide elimination requires enhanced control measures, improved healthcare access, and strengthened multisectoral collaboration to address these region-specific challenges
Metal-centred states control carrier lifetimes in transition metal oxide photocatalysts
No full textEfficient sunlight-to-energy conversion requires materials that can generate long-lived charge carriers upon illumination. However, the targeted design of semiconductors possessing intrinsically long lifetimes remains a key challenge. Here using a series of transition metal oxides, we establish a link between carrier lifetime and electronic configuration in transition metal-based semiconductors. We identify a subpicosecond relaxation mechanism via metal-centred ligand field states that compromise quantum yields in open d-shell transition metal oxides (for example, Fe2O3, Co3O4, Cr2O3 and NiO), which is more reminiscent of molecular complexes than crystalline semiconductors. We found that materials with spin-forbidden ligand field transitions could partially mitigate this relaxation pathway, explaining why Fe2O3 achieves higher photoelectrochemical activity than other visible light-absorbing transition metal oxides. However, achieving high yields of long-lived charges requires transition metal oxides with d0 or d10 electronic configurations (for example, TiO2 and BiVO4), where ligand field states are absent. These trends translate to transition metal-containing semiconductors beyond oxides, enabling the design of photoabsorbers with better-controlled recombination channels in photovoltaics, photocatalysis and communication devices
Transcytosis of LDL across arterial endothelium: mechanisms and therapeutic targets
No full textTransport of LDL (low-density lipoprotein) from plasma to arterial intima is thought to be rate limiting in the development of atherosclerosis. Its variation likely determines where lesions develop within arteries and might account for some of the currently unexplained difference in disease susceptibility between individuals. It may also be critical in the development of lipid-rich, unstable plaques. Mechanisms have been controversial but recent evidence suggests that caveolar transcytosis across endothelial cells is the dominant pathway. Receptors involved are LDLR (LDL receptor), SR-B1 (scavenger receptor class B type 1), and ALK1 (activin receptor-like kinase 1). The role of LDLR is influenced by IL-1β (interleukin-1β); the role of SR-B1 by HDL (high-density lipoprotein), DOCK4 (dedicator of cytokinesis 4), GPER (G-protein–coupled estrogen receptor), and HMGB1 (high mobility group box 1); and the role of ALK1 by BMP (bone morphogenetic protein) 9. Additionally, BMP4 stimulates transcytosis and FSTL1 (follistatin-like 1 protein) inhibits it. Fundamental transcytotic mechanisms include caveola formation, undocking, trafficking, and docking; they are influenced by cholesterol-lowering agents, MYDGF (myeloid-derived growth factor), MFSD2a (major facilitator superfamily domain containing 2a) in the blood-brain barrier, and inhibitors of dynamin-2 and tubulin polymerization. The relative merits of different therapeutic approaches are discussed, with statins, colchicine, benzimidazoles, and metformin being existing drugs that might be repurposed and salidroside and glycyrrhizic acid being nutraceuticals worth investigating. Finally, we discuss evidence against the ferry-boat model of transcytosis, the contributions of receptor-mediated, fluid-phase, and active transcytosis, and where inhibition of transcytosis might be most beneficial
The impact of patient-reported factors of endoscopic screening experience on attendance at future examinations and distal colorectal cancer incidence
No full textBackground
Endoscopic examinations can reduce colorectal cancer (CRC) burden through early detection and removal of precancerous lesions; however, after initial endoscopy, some patients do not attend subsequent examinations.
Aims
To investigate the impact of patient experience of endoscopic screening on attendance at future examinations and distal CRC incidence.
Methods
In a cohort study including 40,141 participants who received flexible sigmoidoscopy (FS) screening in the UK FS Screening Trial, median follow-up was 16.8 years. We examined family history of CRC, bowel preparation quality, segment of bowel reached, and responses to patient-reported post-examination questionnaires. We estimated multivariable odds ratios (OR) for attendance at future examinations by logistic regression and hazard ratios (HR) for associations between patient experience at FS and distal CRC incidence.
Results
Of those recommended a future endoscopy, 7.1% did not attend repeat FS, 3.4% did not attend colonoscopy, 18.3% did not attend surveillance, and 0.5% developed distal CRC. Symptoms of faintness/dizziness (OR = 5.10 95%CI 1.49–17.42) were associated with non-attendance at repeat FS. Non-attendance at surveillance was associated with whether participants felt they had made the right decision to take the tests; that taking the tests was tempting fate; that they needed the tests; or that they would rather have let nature take its course. A FS more painful than expected (HR = 0.57 95%CI 0.37–0.88) was inversely associated with distal CRC incidence.
Conclusions
We identified aspects of patient experience at endoscopy that could be used to improve attendance at future endoscopic examinations, which in turn could reduce CRC incidence. Trial registration number: ISRCTN28352761. Trial registration date: April 2000
Essential components and validation of multi-specialty robotic surgical training curricula: a systematic review
No full textIntroduction:
The rapid adoption of robotic surgical systems has overtook the development of standardized training and competency assessment for surgeons, resulting in an unmet educational need in this field. This systematic review aims to identify the essential components and evaluate the validity of current robotic training curricula across all surgical specialties.
Methods:
A systematic search of MEDLINE, EMBASE, Emcare, and CINAHL databases was conducted to identify the studies reporting on multi-specialty or specialty-specific surgical robotic training curricula, between January 2000 and January 2024. We extracted the data according to Kirkpatrick’s curriculum evaluation model and Messick’s concept of validity. The quality of studies was assessed using the Medical Education Research Study Quality Instrument (MERSQI).
Results:
From the 3687 studies retrieved, 66 articles were included. The majority of studies were single-center (n = 52, 78.8%) and observational (n = 58, 87.9%) in nature. The most commonly reported curriculum components include didactic teaching (n = 48, 72.7%), dry laboratory skills (n = 46, 69.7%), and virtual reality (VR) simulation (n = 44, 66.7%). Curriculum assessment methods varied, including direct observation (n = 44, 66.7%), video assessment (n = 26, 39.4%), and self-assessment (6.1%). Objective outcome measures were used in 44 studies (66.7%). None of the studies were fully evaluated according to Kirkpatrick’s model, and five studies (7.6%) were fully evaluated according to Messick’s framework. The studies were generally found to have moderate methodological quality with a median MERSQI of 11.
Conclusions:
Essential components in robotic training curricula identified were didactic teaching, dry laboratory skills, and VR simulation. However, variability in assessment methods used and notable gaps in curricula validation remain evident. This highlights the need for standardized evidence-based development, evaluation, and reporting of robotic curricula to ensure the effective and safe adoption of robotic surgical systems