Algorithm and performance of a clinical IMRT beam-angle optimization system

This paper describes the algorithm and examines the performance of an IMRT beam-angle optimization (BAO) system. In this algorithm successive sets of beam angles are selected from a set of predefined directions using a fast simulated annealing (FSA) algorithm. An IMRT beam-profile optimization is performed on each generated set of beams. The IMRT optimization is accelerated by using a fast dose calculation method that utilizes a precomputed dose kernel. A compact kernel is constructed for each of the predefined beams prior to starting the FSA algorithm. The IMRT optimizations during the BAO are then performed using these kernels in a fast dose calculation engine. This technique allows the IMRT optimization to be performed more than two orders of magnitude faster than a similar optimization that uses a convolution dose calculation engine.Comment: Final version that appeared in Phys. Med. Biol. 48 (2003) 3191-3212. Original EPS figures have been converted to PNG files due to size limi

Dynamics of a hyperbolic system that applies at the onset of the oscillatory instability

A real hyperbolic system is considered that applies near the onset of the oscillatory instability in large spatial domains. The validity of that system requires that some intermediate scales (large compared with the basic wavelength of the unstable modes but small compared with the size of the system) remain inhibited; that condition is analysed in some detail. The dynamics associated with the hyperbolic system is fully analysed to conclude that it is very simple if the coefficient of the cross-nonlinearity is such that , while the system exhibits increasing complexity (including period-doubling sequences, quasiperiodic transitions, crises) as the bifurcation parameter grows if ; if then the system behaves subcritically. Our results are seen to compare well, both qualitatively and quantitatively, with the experimentally obtained ones for the oscillatory instability of straight rolls in pure Rayleigh - Bénard convection

The role of serological testing in the SARS-CoV-2 outbreak

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies

Teachers' views of their primary school classrooms

This article presents the views of 222 head teachers and classroom-based teachers about their experiences and perceptions of 193 specific classroom environments from 29 primary schools in 3 different areas in England, UK. One-to-one interviews were carried out focusing on teachers’ perceptions about their classrooms throughout the year. It was found that teachers’ views of their overall comfort were fairly high, despite widespread problems with overheating, stuffiness, glare and noise. Surprisingly, schools built in 1950s had the least negative feelings, while those since the 1990s to date had the highest. The teachers appear to be aware of the ‘hard’ aspects of the physical environment, but less conscious of the impact of ‘softer’ aspects, especially those with impact on the level of stimulation created

Beyond the performance gap: reclaiming building appraisal through archival research

Current debates about building performance evaluation often emphasise the ‘performance gap’ between how buildings perform in practice and how performance was envisaged during the design stage. While such debates continue to be dominated by energy considerations, increasing attention is directed towards the subjective experiences of building users in terms of thermal comfort and wellbeing. The latter trends are undoubtedly to be welcomed, but buildings continue to be conceptualised as fixed physical objects rather than entities that are enacted in practice. With the aim of challenging current assumptions, research is described which sought to reclaim the concept of building appraisal as practised by the pioneering architectural practice DEGW. The concept of building appraisal differs from current notions of building performance evaluation in that the point of departure was not the supposedly fixed entity of the building, but the essential fluidity of the occupying organisation and their aspirations in terms of space. Empirical data is derived from archival sources and through extensive interaction with the DEGW diaspora, many of whom remain active at the leading edge of international practice. It is concluded that the continued fixation with the ‘performance gap’ reinforces long-since discredited assumptions of environmental determinism

Bright spots: seeds of a good Anthropocene

The scale, rate, and intensity of humans’ environmental impact has engendered broad discussion about how to find plausible pathways of development that hold the most promise for fostering a better future in the Anthropocene. However, the dominance of dystopian visions of irreversible environmental degradation and societal collapse, along with overly optimistic utopias and business‐as‐usual scenarios that lack insight and innovation, frustrate progress. Here, we present a novel approach to thinking about the future that builds on experiences drawn from a diversity of practices, worldviews, values, and regions that could accelerate the adoption of pathways to transformative change (change that goes beyond incremental improvements). Using an analysis of 100 initiatives, or “seeds of a good Anthropocene”, we find that emphasizing hopeful elements of existing practice offers the opportunity to: (1) understand the values and features that constitute a good Anthropocene, (2) determine the processes that lead to the emergence and growth of initiatives that fundamentally change human–environmental relationships, and (3) generate creative, bottom‐up scenarios that feature well‐articulated pathways toward a more positive future

Next-generation, personalised, model-based critical care medicine : a state-of-the art review of in silico virtual patient models, methods, and cohorts, and how to validation them

© 2018 The Author(s). Critical care, like many healthcare areas, is under a dual assault from significantly increasing demographic and economic pressures. Intensive care unit (ICU) patients are highly variable in response to treatment, and increasingly aging populations mean ICUs are under increasing demand and their cohorts are increasingly ill. Equally, patient expectations are growing, while the economic ability to deliver care to all is declining. Better, more productive care is thus the big challenge. One means to that end is personalised care designed to manage the significant inter- and intra-patient variability that makes the ICU patient difficult. Thus, moving from current "one size fits all" protocolised care to adaptive, model-based "one method fits all" personalised care could deliver the required step change in the quality, and simultaneously the productivity and cost, of care. Computer models of human physiology are a unique tool to personalise care, as they can couple clinical data with mathematical methods to create subject-specific models and virtual patients to design new, personalised and more optimal protocols, as well as to guide care in real-time. They rely on identifying time varying patient-specific parameters in the model that capture inter- and intra-patient variability, the difference between patients and the evolution of patient condition. Properly validated, virtual patients represent the real patients, and can be used in silico to test different protocols or interventions, or in real-time to guide care. Hence, the underlying models and methods create the foundation for next generation care, as well as a tool for safely and rapidly developing personalised treatment protocols over large virtual cohorts using virtual trials. This review examines the models and methods used to create virtual patients. Specifically, it presents the models types and structures used and the data required. It then covers how to validate the resulting virtual patients and trials, and how these virtual trials can help design and optimise clinical trial. Links between these models and higher order, more complex physiome models are also discussed. In each section, it explores the progress reported up to date, especially on core ICU therapies in glycemic, circulatory and mechanical ventilation management, where high cost and frequency of occurrence provide a significant opportunity for model-based methods to have measurable clinical and economic impact. The outcomes are readily generalised to other areas of medical care

Infusion fluids contain harmful glucose degradation products

PURPOSE: Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients' blood. METHODS: The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. RESULTS: All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. CONCLUSIONS: These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients