Engaging children and young people on the potential role of artificial intelligence in medicine

INTRODUCTION: There is increasing interest in Artificial Intelligence (AI) and its application to medicine. Perceptions of AI are less well-known, notably amongst children and young people (CYP). This workshop investigates attitudes towards AI and its future applications in medicine and healthcare at a specialised paediatric hospital using practical design scenarios. METHOD: Twenty-one members of a Young Persons Advisory Group for research contributed to an engagement workshop to ascertain potential opportunities, apprehensions, and priorities. RESULTS: When presented as a selection of practical design scenarios, we found that CYP were more open to some applications of AI in healthcare than others. Human-centeredness, governance and trust emerged as early themes, with empathy and safety considered as important when introducing AI to healthcare. Educational workshops with practical examples using AI to help, but not replace humans were suggested to address issues, build trust, and effectively communicate about AI. CONCLUSION: Whilst policy guidelines acknowledge the need to include children and young people to develop AI, this requires an enabling environment for human-centred AI involving children and young people with lived experiences of healthcare. Future research should focus on building consensus on enablers for an intelligent healthcare system designed for the next generation, which fundamentally, allows co-creation. IMPACT: Children and young people (CYP) want to be included to share their insights about the development of research on the potential role of Artificial Intelligence (AI) in medicine and healthcare and are more open to some applications of AI than others. Whilst it is acknowledged that a research gap on involving and engaging CYP in developing AI policies exists, there is little in the way of pragmatic and practical guidance for healthcare staff on this topic. This requires research on enabling environments for ongoing digital cooperation to identify and prioritise unmet needs in the application and development of AI

Filamin repeat segments required for photosensory signalling in Dictyostelium discoideum

<p>Abstract</p> <p>Background</p> <p>Filamin is an actin binding protein which is ubiquitous in eukaryotes and its basic structure is well conserved – an N-terminal actin binding domain followed by a series of repeated segments which vary in number in different organisms. <it>D. discoideum </it>is a well established model organism for the study of signalling pathways and the actin cytoskeleton and as such makes an excellent organism in which to study filamin. Ddfilamin plays a putative role as a scaffolding protein in a photosensory signalling pathway and this role is thought to be mediated by the unusual repeat segments in the rod domain.</p> <p>Results</p> <p>To study the role of filamin in phototaxis, a filamin null mutant, HG1264, was transformed with constructs each of which expressed wild type filamin or a mutant filamin with a deletion of one of the repeat segments. Transformants expressing the full length filamin to wild type levels completely rescued the phototaxis defect in HG1264, however if filamin was expressed at lower than wild type levels the phototaxis defect was not restored. The transformants lacking any one of the repeat segments 2–6 retained defective phototaxis and thermotaxis phenotypes, whereas transformants expressing filaminΔ1 exhibited a range of partial complementation of the phototaxis phenotype which was related to expression levels. Immunofluorescence microscopy showed that filamin lacking any of the repeat segments still localised to the same actin rich areas as wild type filamin. Ddfilamin interacts with RasD and IP experiments demonstrated that this interaction did not rely upon any single repeat segment or the actin binding domain.</p> <p>Conclusion</p> <p>This paper demonstrates that wild type levels of filamin expression are essential for the formation of functional photosensory signalling complexes and that each of the repeat segments 2–6 are essential for filamins role in phototaxis. By contrast, repeat segment 1 is not essential provided the mutated filamin lacking repeat segment 1 is expressed at a high enough level. The defects in photo/thermosensory signal transduction caused by the absence of the repeats are due neither to mislocalisation of filamin nor to the loss of RasD recruitment to the previously described photosensory signalling complex.</p

The erythromycin breath test as a predictor of cyclosporine blood levels

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109915/1/cptclpt1990126.pd

A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations

A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a simplified model of cell metabolism, growth and proliferation, suitable for inclusion in a multicell simulator, now under development (Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the proliferation dynamics of tumor cells which adapt their behaviour to respond to changes in the biochemical composition of the environment. This modeling of nutrient metabolism and cell cycle at a mesoscopic scale level leads to a continuous flow of information between the two disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with modern computers and tested experimentally.Comment: 58 pages, 7 figures, 3 tables, pdf onl

A conserved role for LRRK2 and Roco proteins in the regulation of mitochondrial activity

Parkinson’s Disease (PD) is the second most common neurodegenerative disease world-wide. Mutations in the multidomain protein Leucine Rich Repeat Kinase 2 (LRRK2) are the most frequent cause of hereditary PD. Furthermore, recent data suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in PD pathogenesis. Isolated mitochondria of tissue samples from PD patients carrying LRRK2 mutations display a significant impairment of mitochondrial function. However, due to the complexity of the mitochondrial signaling network, the role of LRRK2 in mitochondrial metabolism is still not well understood. Previously we have shown that D. discoideum Roco4 is a suitable model to study the activation mechanism of LRRK2 in vivo. To get more insight in the LRRK2 pathways regulating mitochondrial activity we used this Roco4 model system in combination with murine RAW macrophages. Here we show that both Dictyostelium roco4 knockout and cells expressing PD-mutants show behavioral and developmental phenotypes that are characteristic for mitochondrial impairment. Mitochondrial activity measured by Seahorse technology revealed that the basal respiration of D. discoideum roco4- cells is significantly increased compared to the WT strain, while the basal and maximal respiration values of cells overexpressing Roco4 are reduced compared to the WT strain. Consistently, LRRK2 KO RAW 264.7 cells exhibit higher maximal mitochondrial respiration activity compared to the LRRK2 parental RAW264.7 cells. Measurement on isolated mitochondria from LRRK2 KO and parental RAW 264.7 cells revealed no difference in activity compared to the parental cells. Furthermore, neither D. discoideum roco4- nor LRRK2 KO RAW 264.7 showed a difference in either the number or the morphology of mitochondria compared to their respective parental strains. This suggests that the observed effects on the mitochondrial respiratory in cells are indirect and that LRRK2/Roco proteins most likely require other cytosolic cofactors to elicit mitochondrial effects

Issues raised developing AQuRate (an authoring tool that uses the question and test interoperability version 2 specification)

The IMS Question & Test Interoperability (QTI) specification has existed for many years, and there are a few tools for authoring questions in early versions of the specification. However, the new QTIv2 specification was unsupported in any existing authoring environment. The AQuRate project was funded by JISC’s capital project program to fill this gap. AQuRate is one of three JISC projects, which together aimed to support the whole e-assessment process, from authoring (AQuRate at Kingston University) to storage (Minibix at Cambridge) and finally to a delivery/assessment development (ASDEL at Southampton). This paper considers issues raised during the creation of the tool: data modelling, graphical user interface design, and use cases. It ends raising issues currently effecting on-going development

A predictive model for creep deformation following vertebral compression fractures

Many vertebral compression fractures continue to collapse over time, resulting in spinal deformity and chronic back pain. Currently, there is no adequate screening strategy to identify patients at risk of progressive vertebral collapse. This study developed a mathematical model to describe the quantitative relationship between initial bone damage and progressive (“creep”) deformation in human vertebrae. The model uses creep rate before damage, and the degree of vertebral bone damage, to predict creep rate of a fractured vertebra following bone damage. Mechanical testing data were obtained from 27 vertebral trabeculae samples, and 38 motion segments, from 26 human spines. These were analysed to evaluate bone damage intensity, and creep rates before and after damage, in order to estimate the model parameter, p, which represents how bone damage affects the change of creep rate after damage. Results of the model showed that p was 1.38 (R2 = 0.72, p 0.05). Further analyses revealed that p was not significantly influenced by cortical bone damage, endplate damage, disc degeneration, vertebral size, or vertebral areal bone mineral density (aBMD) (P > 0.05). The key determinant of creep deformation following vertebral compression fracture was the degree of trabecular bone damage. The proposed model could be used to identify the measures of bone damage on routine MR images that are associated with creep deformation so that a screening tool can be developed to predict progressive vertebral collapse following compression fracture

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

&lt;p&gt;Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.&lt;/p&gt; &lt;p&gt;Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.&lt;/p&gt; &lt;p&gt;Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.&lt;/p&gt; &lt;p&gt;Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.&lt;/p&gt; &lt;p&gt;Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.&lt;/p&gt; &lt;p&gt;Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.&lt;/p&gt