The ethical matrix as a method for involving people living with disease and the wider public (PPI) in near-term artificial intelligence research.

INTRODUCTION: The rapid pace of research in the field of Artificial Intelligence in medicine has associated risks for near-term AI. Ethical considerations of the use of AI in medicine remain a subject of much debate. Concurrently, the Involvement of People living with disease and the Public (PPI) in research is becoming mandatory in the EU and UK. The goal of this research was to elucidate the important values for our relevant stakeholders: People with MS, Radiologists, neurologists, Registered Healthcare Practitioners and Computer Scientists concerning AI in radiology and synthesize these in an ethical matrix. METHODS: An ethical matrix workshop co-designed with a patient expert. The workshop yielded a survey which was disseminated to the professional societies of the relevant stakeholders. Quantitative data were analysed using the Pingouin 0.53 python package. Qualitative data were examined with word frequency analysis and analysed for themes with grounded theory with a patient expert. RESULTS: 184 participants were recruited, (54, 60, 17, 12, 41 respectively). There were significant (p < 0.00001) differences in age, gender and ethnicity between groups. Key themes emerging from our results were the importance fast and accurate results, explanations over model performance and the significance of maintaining personal connections and choice. These themes were used to construct the ethical matrix. CONCLUSION: The ethical matrix is a useful tool for PPI and stakeholder engagement with particular advantages for near-term AI in the pandemic era. IMPLICATIONS FOR PRACTICE: We have produced an ethical matrix that allows for the inclusion of stakeholder opinion in medical AI research design.

Visualizing genomic data: The mixing perspective.

We report on a novel way to visualize genomic data. By considering genome coding sequences, cds, as sets of the N=61 non-stop codons, one obtains a partition of the total number of codons in each cds. Partitions exhibit a statistical property known as mixing character which characterizes how mixed the partition is. Mixing characters have been shown mathematically to exhibit a partial order known as majorization (Ruch, 1975). In previous work (Seitz and Kirwan, 2022) we developed an approach that combined mixing and entropy that is visualized as a scatter plot. If we consider all 1,121,505 partitions of 61 codons, this produces a plot we call the theoretical mixing space, TGMS. A normalization procedure is developed here and applied to real genomic data to produce the genome mixing signature, GMS. Example GMS's of 19 species, including Homo sapiens, are shown and discussed.

Mixed-Up-Ness or Entropy?

Mixed-up-ness can be traced to unpublished notes by Josiah Gibbs. Subsequently, the concept was developed independently, and under somewhat different names, by other investigators. The central idea of mixed-up-ness is that systems states can be organized in a hierarchy by their degree of mixed-up-ness. In its purest form, the organizing principle is independent of thermodynamic and statistical mechanics principles, nor does it imply irreversibility. Yet, Gibbs and subsequent investigators kept entropy as the essential concept in determining system evolution, thus retaining the notion that systems evolve from states of perfect "order" to states of total "disorder". Nevertheless, increasing mixed-up-ness is consistent with increasing entropy; however, there is no unique one-to-one connection between the two. We illustrate the notion of mixed-up-ness with an application to the permutation function of integer partitions and then formalize the notion of mixed-up-ness as a fundamental hierarchal principle, the law of mixed-up-ness (LOM), for non-thermodynamic systems.

Ocean convergence and the dispersion of flotsam.

Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s-1 and 0.01 ms-1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material.

[Congenital rubella syndrome in infants treated at a pediatrics hospital]. / Síndrome de rubéola congénita en lactantes atendidos en un hospital pediátrico.

UNLABELLED: Congenital rubella syndrome (CRS) has been considered an uncommon problem in Mexico. OBJECTIVE: To analyze and describe clinical features of CRS cases in infants from a pediatric hospital in Mexico City during an 8 year period. DESIGN: retrospective study. Patients younger than 18 months of age with a positive serologic test for IgG and IgM rubella antibodies were included. Antibodies were measured by an immunoenzymatic microparticles assay. RESULTS: Fifty-six cases were identified, 42 complete clinical records were available for review. Of these, 23 (54.7%) were female and 19 (45.3%) male. Median for age was five months. A total of 9/42 mothers (21%) had history of rash during pregnancy. IgM antibodies were detected in 15 infants and IgG in 27. Major manifestations were ocular (74%), neurologic (66%), and congenital heart disease (67%). Congenital cataracts were detected in 69%, in 52% hepatomegaly, in 43% jaundice, in 40% anemia, in 48% thrombocytopenia, and hearing loss 19%. CONCLUSION: Five confirmed cases with CRS per year in one hospital indicate a high frequency. Only a small percentage of women had a history of rash during pregnancy. CRS must be investigated in infants with ocular, neurologic, and congenital heart diseases.

Inhibitory properties of the regulatory domains of human protein kinase Calpha and mouse protein kinase Cepsilon.

Two fusion proteins in which the regulatory domains of human protein kinase Calpha (Ralpha; amino acids 1-270) or mouse protein kinase Cepsilon (Repsilon; amino acids 1-385) were linked in frame with glutathione S-transferase (GST) were examined for their abilities to inhibit the catalytic activities of protein kinase Calpha (PKCalpha) and other protein kinases in vitro. Both GST-Ralpha and GST-Repsilon but not GST itself potently inhibited the activities of lipid-activated rat brain PKCalpha. In contrast, the fusion proteins had little or no inhibitory effect on the activities of the Ser/Thr protein kinases cAMP-dependent protein kinase, cGMP-dependent protein kinase, casein kinase II, myosin light chain kinase, and mitogen activated protein kinase or on the src Tyr kinase. GST-Ralpha and GST-Repsilon, on a molar basis, were 100-200-fold more potent inhibitors of PKCalpha activity than was the pseudosubstrate peptide PKC19-36. In addition, a GST-Ralpha fusion protein in which the first 32 amino acids of Ralpha were deleted (including the pseudosubstrate sequence from amino acids 19-31) was an effective competitive inhibitor of PKCalpha activity. The three GST-R fusion proteins also inhibited protamine-activated PKCalpha and proteolytically activated PKCalpha (PKM), two lipid-independent forms of PKCalpha; however, the IC50 values for inhibition were 1 order of magnitude greater than the IC50 values obtained in the presence of lipid. These results suggest that part of the inhibitory effect of the GST-R fusion proteins on lipid-activated PKCalpha may have resulted from sequestration of lipid activators. Nonetheless, as evidenced by their abilities to inhibit the lipid-independent forms of the enzyme, the GST-R fusion proteins also inhibited PKCalpha catalytic activity through direct interactions. These data indicate that the R domains of PKCalpha and PKCepsilon are specific inhibitors of protein kinase Calpha activity and suggest that regions of the R domain outside the pseudosubstrate sequence contribute to autoinhibition of the enzyme.

Tradeoff of semantic relatedness and degree of overlearning: differential effects on metamemory and on long-term retention.

We investigated people's recall and recognition of, and Judgments of Learning (JOLs) and Feelings of Knowing (FOKs) about: (a) pairs of related words that were learned to a criterion of two correct recalls (criterion-learned/related) versus (b) pairs of unrelated words that were learned to a criterion of eight correct recalls (overlearned/unrelated). Recall, FOK on unrecalled targets, and recognition were tested at either (between-subjects variable) two or six weeks after learning. In Experiment 1, subjects JOLs were greater in magnitude for criterion-learned/related items than for overlearned/unrelated items, and they predicted that recall would be the same after a 2-week retention interval as after a 6-week retention interval (between-subjects prediction). In contrast, however, subsequent recall was greater on the 2-week retention test than on the 6-week retention test and was greater for the overlearned/unrelated items than for the criterion-learned/related items; also, subjects' FOKs (and recognition performance) were greater in magnitude for the overlearned/unrelated items than for the criterion-learned/related items. Experiment 2 revealed that the overweighting of the importance of relatedness disappears from JOLs when those JOLs occur one day after the acquisition session. These findings imply that the information tracked by metacognitive monitoring judgments is different for JOLs than for FOKs, with the JOLs (relative to FOKs) based more on semantic relatedness and less on the degree of learning during acquisition. Also, subjects' JOLs are not particularly good at accurately forecasting their eventual level of recall on long-term retention tests that occur several weeks after acquisition.

Molecular strategies for the dominant inhibition of protein kinase C.

The regulatory (R) domain of PKC alpha fused to glutathione-S-transferase (GST-R alpha) competitively inhibited PKC activity associated with extracts of Y1 mouse adrenocortical tumor cells and the activities of several specific PKC isozymes. GST-R alpha did not inhibit the activities of cAMP-dependent protein kinase, cGMP-dependent protein kinase or calmodulin-dependent myosin light chain kinase. GST-R alpha inhibited PKC activities 20 times more potently than did a synthetic peptide corresponding to the pseudosubstrate sequence of PKC alpha. In intact yeast cells, the R domain prevented PKC beta-1-induced inhibition of growth and cytokinesis. These results indicate that the R domain of PKC alpha acts as a specific, dominant inhibitor of PKC activity, and suggest that the PKC alpha R domain may provide a useful genetic tool to assess the roles of PKC in various signal transduction processes.