A tall space with a small bottom

We introduce a general method of constructing locally compact scattered spaces from certain families of sets and then, with the help of this method, we prove that if kappa(<kappa) = kappa then there is such a space of height kappa(+) with only kappa many isolated points. This implies that there is a locally compact scattered space of height omega(2) with omega(1) isolated points in ZFC, solving an old problem of the first author

The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles.

The magnetic moment and anisotropy of magnetite nanoparticles can be optimised by doping with transition metal cations, enabling their properties to be tuned for different biomedical applications. In this study, we assessed the suitability of bacterially synthesized zinc- and cobalt-doped magnetite nanoparticles for biomedical applications. To do this we measured cellular viability and activity in primary human bone marrow-derived mesenchymal stem cells and human osteosarcoma-derived cells. Using AC susceptibility we studied doping induced changes in the magnetic response of the nanoparticles both as stable aqueous suspensions and when associated with cells. Our findings show that the magnetic response of the particles was altered after cellular interaction with a reduction in their mobility. In particular, the strongest AC susceptibility signal measured in vitro was from cells containing high-moment zinc-doped particles, whilst no signal was observed in cells containing the high-anisotropy cobalt-doped particles. For both particle types we found that the moderate dopant levels required for optimum magnetic properties did not alter their cytotoxicity or affect osteogenic differentiation of the stem cells. Thus, despite the known cytotoxicity of cobalt and zinc ions, these results suggest that iron oxide nanoparticles can be doped to sufficiently tailor their magnetic properties without compromising cellular biocompatibility

An Integrated Literature Review of Time-on-Task Effects With a Pragmatic Framework for Understanding and Improving Decision-Making in Multidisciplinary Oncology Team Meetings

Multidisciplinary oncology team meetings (MDMs) or tumor boards, like other MDMs in healthcare, facilitate the incorporation of diverse clinical expertise into treatment planning for patients. Decision-making (DM) in relation to treatment planning in MDMs is carried out repeatedly until all patients put forward for discussion have been reviewed. Despite continuing financial pressure and staff shortages, the workload of cancer MDMs, and therefore meeting duration continue to increase (up to 5 h) with patients often receiving less than 2 min of team input. This begs the question as to whether the current set-up is conducive to achieve optimal DM, which these multi-specialty teams were set out to achieve in the first place. Much of what it is known, however, about the effects of prolonged cognitive activity comes from various subfields of science, leaving a gap in applied knowledge relating to complex healthcare environments. The objective of this review was thus to synthesize theory, evidence and clinical practice in order to bring the current understanding of prolonged, repeated DM into the context of cancer MDMs. We explore how and why time spent on a task affects performance in such settings, and what strategies can be employed by cancer teams to counteract negative effects and improve quality and safety. In the process, we propose a pragmatic framework of repeated DM that encompasses the strength, the process and the cost-benefit models of self-control as applied to real-world contexts of cancer MDMs. We also highlight promising research avenues for closing the research-to-practice gap. Theoretical and empirical evidence reviewed in this paper suggests that over prolonged time spent on a task, repeated DM is cognitively taxing, leading to performance detriments. This deterioration is associated with various cognitive-behavioral pitfalls, including decreased attentional capacity and reduced ability to effectively evaluate choices, as well as less analytical DM and increased reliance on heuristics. As a short to medium term improvement for ensuring safety, consistently high quality of care for all patients, and the clinician wellbeing, future research and interventions in cancer MDMs should address time-on-task effects with a combination of evidence-based cognitive strategies. We propose in this review multiple measures that range from food intake, short breaks, rewards, and mental exercises. As a long term imperative, however, capacity within cancer services needs to be reviewed as well as how best to plan workforce development and service delivery models to achieve population coverage whilst maintaining safety and quality of care. Hence the performance detriments that arise in healthcare workers as a result of the intensity (time spent on a task) and complexity of the workload require not only more research, but also wider regulatory focus and recognition

ASO Author Reflections: The Pursuit of Digitalised Quality Improvement Assessment Tools for Cancer Multidisciplinary Teams

Funder: King's Health Partners; doi: http://dx.doi.org/10.13039/501100002102Funder: Guy's and St Thomas’ CharityFunder: Maudsley Charity; doi: http://dx.doi.org/10.13039/10001217

A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals.

Synapses are often far from the soma and independently cope with proteopathic stress induced by intense neuronal activity. However, how presynaptic compartments turn over proteins is poorly understood. We show that the synapse-enriched protein EndophilinA, thus far studied for its role in endocytosis, induces macroautophagy at presynaptic terminals. We find that EndophilinA executes this unexpected function at least partly independent of its role in synaptic vesicle endocytosis. EndophilinA-induced macroautophagy is activated when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in animals where EndophilinA cannot be phosphorylated. EndophilinA-phosphorylation promotes the formation of highly curved membranes, and reconstitution experiments show these curved membranes serve as docking stations for autophagic factors, including Atg3. Functionally, deregulation of the EndophilinA phosphorylation state accelerates activity-induced neurodegeneration. Given that EndophilinA is connected to at least three Parkinson's disease genes (LRRK2, Parkin and Synaptojanin), dysfunction of EndophilinA-dependent synaptic macroautophagy may be common in this disorder

The Collins-Roscoe mechanism and D-spaces

We prove that if a space X is well ordered $(\alpha A)$, or linearly semi-stratifiable, or elastic then X is a D-space

The anatomy of clinical decision-making in multidisciplinary cancer meetings:A cross-sectional observational study of teams in a natural context

In the UK, treatment recommendations for patients with cancer are routinely made by multidisciplinary teams in weekly meetings. However, their performance is variable.The aim of this study was to explore the underlying structure of multidisciplinary decision-making process, and examine how it relates to team ability to reach a decision.This is a cross-sectional observational study consisting of 1045 patient reviews across 4 multidisciplinary cancer teams from teaching and community hospitals in London, UK, from 2010 to 2014. Meetings were chaired by surgeons.We used a validated observational instrument (Metric for the Observation of Decision-making in Cancer Multidisciplinary Meetings) consisting of 13 items to assess the decision-making process of each patient discussion. Rated on a 5-point scale, the items measured quality of presented patient information, and contributions to review by individual disciplines. A dichotomous outcome (yes/no) measured team ability to reach a decision. Ratings were submitted to Exploratory Factor Analysis and regression analysis.The exploratory factor analysis produced 4 factors, labeled "Holistic and Clinical inputs" (patient views, psychosocial aspects, patient history, comorbidities, oncologists', nurses', and surgeons' inputs), "Radiology" (radiology results, radiologists' inputs), "Pathology" (pathology results, pathologists' inputs), and "Meeting Management" (meeting chairs' and coordinators' inputs). A negative cross-loading was observed from surgeons' input on the fourth factor with a follow-up analysis showing negative correlation (r = -0.19, P &lt; 0.001). In logistic regression, all 4 factors predicted team ability to reach a decision (P &lt; 0.001).Hawthorne effect is the main limitation of the study.The decision-making process in cancer meetings is driven by 4 underlying factors representing the complete patient profile and contributions to case review by all core disciplines. Evidence of dual-task interference was observed in relation to the meeting chairs' input and their corresponding surgical input into case reviews.</p