Prolonged expression of the γ-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment

The normal tissue tolerance levels to fractionated radiotherapy have been appreciated by a century of careful clinical observations and radiobiological studies in animals. During clinical fractionated radiotherapy, these normal tissue tolerance levels are respected, and severe sequelae of radiotherapy are avoided in the majority of patients. Notwithstanding, a minority of patients experience unexpectedly severe normal tissue reactions. The ability to predict which patients might form this minority would be important. We have conducted a study to develop a rapid and reliable diagnostic test to predict excessive normal tissue toxicity (NTT) in radiotherapy patients. A flow cytometric immunocytochemical assay was used to measure DNA damage in peripheral blood lymphocytes (PBL) from cancer patients exposed to 2-Gy gamma radiation. DNA damage and repair was measured by induction of cellular γ-H2AX in unirradiated and exposed cells at specific time points following exposure. In 12 cancer patients that experienced severe atypical NTT following radiotherapy, there was a failure to repair DNA double-strand breaks (DSB) as measured by γ-H2AX induction and persistence. In ten cancer patients that experienced little or no NTT and in seven normal (noncancer controls), efficient repair of DNA DSB was observed in the γ-H2AX assay. We conclude that a flow cytometric assay based on γ-H2AX induction in PBL of radiotherapy patients may represent a robust, rapid and reliable biomarker to predict NTT during radiotherapy. Further research is required with a larger patient cohort to validate this important study

Strength, Weakness, Opportunity, Threat (SWOT) Analysis of the Adaptations to Anatomical Education in the United Kingdom and Republic of Ireland in Response to the Covid‐19 Pandemic

The Covid-19 pandemic has driven the fastest changes to higher education across the globe, necessitated by social distancing measures preventing any face to face teaching. This has led to an almost immediate switch to distance learning by higher education institutions. Anatomy faces some unique challenges. Intrinsically, anatomy is a three-dimensional subject that requires a sound understanding of the relationships between structures, often achieved by the study of human cadaveric material, models and virtual resources. This study sought to identify the approaches taken in the United Kingdom and Republic of Ireland to deliver anatomical education through online means. Data were collected from 14 different universities in the United Kingdom and Republic of Ireland and compared adopting a thematic analysis approach. Once themes were generated, they were collectively brought together using a strength, weakness, opportunity, threat (SWOT) analysis. Key themes included the opportunity to develop new online resources and the chance to engage in new academic collaborations. Academics frequently mentioned the challenge that time constrains could place on the quality and effectiveness of these resources; especially as in many cases the aim of these resources is to compensate for a lack of exposure to cadaveric exposure. Comparisons of the actions taken by multiple higher education institutions reveals the ways that academics have tried to balance this demand. Discussions will facilitate decisions being made by higher education institutions regarding adapting the curriculum and assessment methods in anatomy

Automatic Goal Discovery in Subgoal Monte Carlo Tree Search

Monte Carlo Tree Search (MCTS) is a heuristic search algorithm that can play a wide range of games without requiring any domain-specific knowledge. However, MCTS tends to struggle in very complicated games due to an exponentially increasing branching factor. A promising solution for this problem is to focus the search only on a small fraction of states. Subgoal Monte Carlo Tree Search (S-MCTS) achieves this by using a predefined subgoal-predicate that detects promising states called subgoals. However, not only does this make S-MCTS domain-dependent, but also it is often difficult to define a good predicate. In this paper, we propose using quality diversity (QD) algorithms to detect subgoals in real-time. Furthermore, we show how integrating QD-algorithms into S-MCTS significantly improves its performance in the Physical Travelling Salesmen Problem without requiring any domain-specific knowledge

Magnetization reversal and local switching fields of ferromagnetic Co/Pd microtubes with radial magnetization

Three-dimensional nanomagnetism is a rapidly growing field of research covering both noncollinear spin textures and curved magnetic geometries including microtubular structures. We spatially resolve the field-induced magnetization reversal of free-standing ferromagnetic microtubes utilizing multifrequency magnetic force microscopy (MFM). The microtubes are composed of Co/Pd multilayer films with perpendicular magnetic anisotropy that translates to an anisotropy with radial easy axis upon rolling-up. Simultaneously mapping the topography and the perpendicular magnetostatic force derivative, the relation between surface angle and local magnetization configuration is evaluated for a large number of locations with slopes exceeding 45 degrees. The angle-dependence of the switching field is concurrent with the Kondorsky model, i.e., the rolled-up nanomembrane behaves like a planar magnetic film with perpendicular anisotropy and a pinning dominated magnetization reversal. Additionally, we discuss methodological challenges when detecting magnetostatic force derivatives near steep surfaces

Fundamental Aspects of the ISM Fractality

The ubiquitous clumpy state of the ISM raises a fundamental and open problem of physics, which is the correct statistical treatment of systems dominated by long range interactions. A simple solvable hierarchical model is presented which explains why systems dominated by gravity prefer to adopt a fractal dimension around 2 or less, like the cold ISM and large scale structures. This has direct relation with the general transparency, or blackness, of the Universe.Comment: 6 pages, LaTeX2e, crckapb macro, no figure, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

Spatial resolution of drug crystallisation in the skin by X-ray micro-computed tomography

Drug crystallisation in the skin is recognised as a significant problem in topical and transdermal drug delivery. Our recent investigations provided new evidence of drug crystallisation in the skin, however, confirming the precise location of crystals remains challenging. Of note, most approaches used have required disruption of the membrane by tape stripping, with crystal detection limited to the superficial skin layers. Hence, a non-destructive method for complete spatial resolution of crystallised drug in skin is still lacking. In this communication, we report the application of X-ray micro-computed tomography (microCT) to examine drug crystallisation in mammalian skin ex vivo. Permeation studies of a saturated solution of diclofenac sodium were conducted in porcine skin; subsequently, tissue samples were scanned using microCT to generate 2D and 3D maps. A layer of drug crystals was observed on the skin surface; microCT maps also confirmed the distribution of drug crystals up to a skin depth of 0.2 – 0.3 mm. MicroCT also allowed the identification of drug crystallisation as a distinct and confirmed event in the skin and as an extension from drug crystals formed on the skin. These preliminary results confirm the potential of microCT to study this important phenomenon in topical and transdermal drug delivery