The Topol Programme for Digital Fellowships in Healthcare is a flagship national programme for digital health aspirants in England. This programme is heavily over-subscribed with applicants, ...representing a cross section of healthcare professionals interested in a future digital health career. The aim this study was to identify motivations, priorities and experiences of these applicants.
Systematic qualitative and semi-quantitative analysis of an entire cohort of anonymised applications to the 2021 Topol Programme for Digital Fellowships in Healthcare were performed.
Two-hundred and eighty applications were received from diverse healthcare professional roles. There were limited applications from mental health or social care sectors. Most applicants reported good organisational support from their employers, but limited interaction with senior digital leaders within their organisations. Relatively limited consideration of health inequalities or engagement with industry was noted. Women were statistically significantly more likely to consider health inequality/inequity implications in their applications.
The analysis offers an insight into motivations, priorities and experiences of the next generation of digital health leaders. There is a need to link aspirants with local digital leaders and to support broader consideration of health inequalities. Supporting such needs and gaps is expected to further help meet recommendations proposed in The Topol Review and contribute to optimising the skills of the future digital health workforce.
A estrutura de espa¸co pseudo-topol´ogico ´e uma varia¸c˜ao do conceito de espa¸co topol´ogico. Surgiu como uma formaliza¸c˜ao de um quantificador de primeira ordem n˜ao defin´ıvel a partir dos ...usuais operadores existencial e universal, nomeado de o quantificador do plaus´ıvel. Posteriormente, buscou-se uma formaliza¸c˜ao no contexto l´ogico proposicional, dada num sistema dedutivo e axiom´atico, com modelo alg´ebrico. Apresentaremos estas concep¸c˜oes formais e como uma contribui¸c˜ao original, descrevemos a vers˜ao proposicional da l´ogica dos espa¸cos pseudo-topol´ogicos em tableaux.
Eric Topol, Professor of Genomics and Director of the Scripps Translational Science Unit in La Jolla, San Diego, California, seems to have the perfect job. He combines one day a week in the clinic, ...imparting 30 years of knowledge as a leading cardiologist, with his real passion--research in what he sees as the greatest revolution medicine has ever seen. By this he means smart medicine, the era of big data, bioinformatics, and consumer genomics, enthusiastically articulated in his 2015 book The Patient Will See You Now.
Here, we present the main features of human acid sphingomyelinase (ASM), its biosynthesis, processing and intracellular trafficking, its structure, its broad substrate specificity, and the proposed ...mode of action at the surface of the phospholipid substrate carrying intraendolysosomal luminal vesicles. In addition, we discuss the complex regulation of its phospholipid cleaving activity by membrane lipids and lipid-binding proteins. The majority of the literature implies that ASM hydrolyses solely sphingomyelin to generate ceramide and ignores its ability to degrade further substrates. Indeed, more than twenty different phospholipids are cleaved by ASM in vitro, including some minor but functionally important phospholipids such as the growth factor ceramide-1-phosphate and the unique lysosomal lysolipid bis(monoacylglycero)phosphate. The inherited ASM deficiency, Niemann-Pick disease type A and B, impairs mainly, but not only, cellular sphingomyelin catabolism, causing a progressive sphingomyelin accumulation, which furthermore triggers a secondary accumulation of lipids (cholesterol, glucosylceramide, GM2) by inhibiting their turnover in late endosomes and lysosomes. However, ASM appears to be involved in a variety of major cellular functions with a regulatory significance for an increasing number of metabolic disorders. The biochemical characteristics of ASM, their potential effect on cellular lipid turnover, as well as a potential impact on physiological processes will be discussed.
The central nervous system (CNS) is the major area that is affected by aging. Alzheimer’s disease (AD), Parkinson’s disease (PD), brain cancer, and stroke are the CNS diseases that will cost ...trillions of dollars for their treatment. Achievement of appropriate blood–brain barrier (BBB) penetration is often considered a significant hurdle in the CNS drug discovery process. On the other hand, BBB penetration may be a liability for many of the non-CNS drug targets, and a clear understanding of the physicochemical and structural differences between CNS and non-CNS drugs may assist both research areas. Because of the numerous and challenging issues in CNS drug discovery and the low success rates, pharmaceutical companies are beginning to deprioritize their drug discovery efforts in the CNS arena. Prompted by these challenges and to aid in the design of high-quality, efficacious CNS compounds, we analyzed the physicochemical property and the chemical structural profiles of 317 CNS and 626 non-CNS oral drugs. The conclusions derived provide an ideal property profile for lead selection and the property modification strategy during the lead optimization process. A list of substructural units that may be useful for CNS drug design was also provided here. A classification tree was also developed to differentiate between CNS drugs and non-CNS oral drugs. The combined analysis provided the following guidelines for designing high-quality CNS drugs: (i) topological molecular polar surface area of <76 Å2 (25–60 Å2), (ii) at least one (one or two, including one aliphatic amine) nitrogen, (iii) fewer than seven (two to four) linear chains outside of rings, (iv) fewer than three (zero or one) polar hydrogen atoms, (v) volume of 740–970 Å3, (vi) solvent accessible surface area of 460–580 Å2, and (vii) positive QikProp parameter CNS. The ranges within parentheses may be used during lead optimization. One violation to this proposed profile may be acceptable. The chemoinformatics approaches for graphically analyzing multiple properties efficiently are presented.
Epidemic spreading or information spreading in a network leads to a broader range of propagation due to the presence of bridge nodes, as defined by the betweenness centrality. The existing literature ...shows that computing betweenness centrality by considering connection topology is computationally expensive and less efficient. Moreover, exploiting the edge features in the network can determine how strongly the nodes are connected. This work proposes a technique to leverage connection topology and tie strength for modeling Weighted Betweenness Graph Neural Network (WBGNN) for a faster-ranking estimation. This measure is based on shortest path calculations, which take connection strength into account for determining the fastest path for contagion or information spread in the network. A variant of statistical weighted betweenness centrality, namely Stable Betweenness Centrality (C_{SB}) and the proposed GNN-based WBGNN are compared to analyze the effectiveness of the proposed model. Further, the WBGNN model is also compared with different machine learning regressors and a neural network-based model to examine the efficacy of the proposed model. The experimental outcome has revealed that the WBGNN model has achieved a 0.203 to 0.536 improvement in Kendall's \tau score, and also takes less time for node ranking estimation compared to C_{SB} and other machine learning-based regressor models.
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