Continuum-particle hybrid coupling for mass, momentum and energy transfers in unsteady fluid flow

The aim of hybrid methods in simulations is to communicate regions with disparate time and length scales. Here, a fluid described at the atomistic level within an inner region P is coupled to an outer region C described by continuum fluid dynamics. The matching of both descriptions of matter is made across an overlapping region and, in general, consists of a two-way coupling scheme (C->P and P->C) which conveys mass, momentum and energy fluxes. The contribution of the hybrid scheme hereby presented is two-fold: first it treats unsteady flows and, more importantly, it handles energy exchange between both C and P regions. The implementation of the C->P coupling is tested here using steady and unsteady flows with different rates of mass, momentum and energy exchange. In particular, relaxing flows described by linear hydrodynamics (transversal and longitudinal waves) are most enlightening as they comprise the whole set of hydrodynamic modes. Applying the hybrid coupling scheme after the onset of an initial perturbation, the cell-averaged Fourier components of the flow variables in the P region (velocity, density, internal energy, temperature and pressure) evolve in excellent agreement with the hydrodynamic trends. It is also shown that the scheme preserves the correct rate of entropy production. We discuss some general requirements on the coarse-grained length and time scales arising from both the characteristic microscopic and hydrodynamic scales.Comment: LaTex, 12 pages, 9 figure

Clinical practice guideline on the optimal radiotherapeutic management of brain metastases

BACKGROUND: An evidence-based clinical practice guideline on the optimal radiotherapeutic management of single and multiple brain metastases was developed. METHODS: A systematic review and meta-analysis was performed. The Supportive Care Guidelines Group formulated clinical recommendations based on their interpretation of the evidence. External review of the report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from Cancer Care Ontario's Practice Guidelines Coordinating Committee (PGCC). RESULTS: One hundred and nine Ontario practitioners responded to the survey (return rate 44%). Ninety-six percent of respondents agreed with the interpretation of the evidence, and 92% agreed that the report should be approved. Minor revisions were made based on feedback from external reviewers and the PGCC. The PGCC approved the final practice guideline report. CONCLUSIONS: For adult patients with a clinical and radiographic diagnosis of brain metastases (single or multiple) we conclude that, • Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis. • Postoperative whole brain radiotherapy (WBRT) should be considered to reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis. • Radiosurgery boost with WBRT may improve survival in select patients with unresectable single brain metastases. • The whole brain should be irradiated for multiple brain metastases. Standard dose-fractionation schedules are 3000 cGy in 10 fractions or 2000 cGy in 5 fractions. • Radiosensitizers are not recommended outside research studies. • In select patients, radiosurgery may be considered as boost therapy with WBRT to improve local tumour control. Radiosurgery boost may improve survival in select patients. • Chemotherapy as primary therapy or chemotherapy with WBRT remains experimental. • Supportive care is an option but there is a lack of Level 1 evidence as to which subsets of patients should be managed with supportive care alone. Qualifying statements addressing factors to consider when applying these recommendations are provided in the full report. The rigorous development, external review and approval process has resulted in a practice guideline that is strongly endorsed by Ontario practitioners

The BioDICE Taverna plugin for clustering and visualization of biological data: a workflow for molecular compounds exploration

Background: In many experimental pipelines, clustering of multidimensional biological datasets is used to detect hidden structures in unlabelled input data. Taverna is a popular workflow management system that is used to design and execute scientific workflows and aid in silico experimentation. The availability of fast unsupervised methods for clustering and visualization in the Taverna platform is important to support a data-driven scientific discovery in complex and explorative bioinformatics applications. Results: This work presents a Taverna plugin, the Biological Data Interactive Clustering Explorer (BioDICE), that performs clustering of high-dimensional biological data and provides a nonlinear, topology preserving projection for the visualization of the input data and their similarities. The core algorithm in the BioDICE plugin is Fast Learning Self Organizing Map (FLSOM), which is an improved variant of the Self Organizing Map (SOM) algorithm. The plugin generates an interactive 2D map that allows the visual exploration of multidimensional data and the identification of groups of similar objects. The effectiveness of the plugin is demonstrated on a case study related to chemical compounds. Conclusions: The number and variety of available tools and its extensibility have made Taverna a popular choice for the development of scientific data workflows. This work presents a novel plugin, BioDICE, which adds a data-driven knowledge discovery component to Taverna. BioDICE provides an effective and powerful clustering tool, which can be adopted for the explorative analysis of biological datasets

HiTSEE KNIME: a visualization tool for hit selection and analysis in high-throughput screening experiments for the KNIME platform

We present HiTSEE (High-Throughput Screening Exploration Environment), a visualization tool for the analysis of large chemical screens used to examine biochemical processes. The tool supports the investigation of structure-activity relationships (SAR analysis) and, through a flexible interaction mechanism, the navigation of large chemical spaces. Our approach is based on the projection of one or a few molecules of interest and the expansion around their neighborhood and allows for the exploration of large chemical libraries without the need to create an all encompassing overview of the whole library. We describe the requirements we collected during our collaboration with biologists and chemists, the design rationale behind the tool, and two case studies on different datasets. The described integration (HiTSEE KNIME) into the KNIME platform allows additional flexibility in adopting our approach to a wide range of different biochemical problems and enables other research groups to use HiTSEE

Neuroethics and fMRI: Mapping a Fledgling Relationship

Human functional magnetic resonance imaging (fMRI) informs the understanding of the neural basis of mental function and is a key domain of ethical enquiry. It raises questions about the practice and implications of research, and reflexively informs ethics through the empirical investigation of moral judgments. It is at the centre of debate surrounding the importance of neuroscience findings for concepts such as personhood and free will, and the extent of their practical consequences. Here, we map the landscape of fMRI and neuroethics, using citation analysis to uncover salient topics. We find that this landscape is sparsely populated: despite previous calls for debate, there are few articles that discuss both fMRI and ethical, legal, or social implications (ELSI), and even fewer direct citations between the two literatures. Recognizing that practical barriers exist to integrating ELSI discussion into the research literature, we argue nonetheless that the ethical challenges of fMRI, and controversy over its conceptual and practical implications, make this essential

The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline

Do steroids improve neurologic symptoms in patients with metastatic brain tumors compared to no treatment? If steroids are given, what dose should be used? Comparisons include: (1) steroid therapy versus none. (2) comparison of different doses of steroid therapy. Target population These recommendations apply to adults diagnosed with brain metastases. Recommendations Steroid therapy versus no steroid therapy Asymptomatic brain metastases patients without mass effect Insufficient evidence exists to make a treatment recommendation for this clinical scenario. Brain metastases patients with mild symptoms related to mass effect Level 3 Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases. It is recommended for patients who are symptomatic from metastatic disease to the brain that a starting dose of 4–8 mg/day of dexamethasone be considered. Brain metastases patients with moderate to severe symptoms related to mass effect Level 3 Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases. If patients exhibit severe symptoms consistent with increased intracranial pressure, it is recommended that higher doses such as 16 mg/day or more be considered. Choice of Steroid Level 3 If corticosteroids are given, dexamethasone is the best drug choice given the available evidence. Duration of Corticosteroid Administration Level 3 Corticosteroids, if given, should be tapered slowly over a 2 week time period, or longer in symptomatic patients, based upon an individualized treatment regimen and a full understanding of the long-term sequelae of corticosteroid therapy. Given the very limited number of studies (two) which met the eligibility criteria for the systematic review, these are the only recommendations that can be offered based on this methodology. Please see “Discussion” and “Summary” section for additional details

Telerehabilitation versus traditional centre-based pulmonary rehabilitation for people with chronic respiratory disease: protocol for a randomised controlled trial

Background: Pulmonary rehabilitation is an effective therapeutic intervention for people with chronic respiratory disease. However, fewer than 5% of eligible individuals receive pulmonary rehabilitation on an annual basis, largely due to limited availability of services and difficulties associated with travel and transport. The Rehabilitation Exercise At Home (REAcH) study is an assessor-blinded, multi-centre, randomised controlled equivalence trial designed to compare the efficacy of home-based telerehabilitation and traditional centre-based pulmonary rehabilitation in people with chronic respiratory disease. Methods: Participants will undertake an 8-week group-based pulmonary rehabilitation program of twice-weekly supervised exercise training, either in-person at a centre-based pulmonary rehabilitation program or remotely from their home via the Internet. Supervised exercise training sessions will include 30 min of aerobic exercise (cycle and/ or walking training). Individualised education and self-management training will be delivered. All participants will be prescribed a home exercise program of walking and strengthening activities. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and 12-months post intervention. The primary outcome is change in dyspnea score as measured by the Chronic Respiratory Questionnaire – dyspnea domain (CRQ-D). Secondary outcomes will evaluate the efficacy of telerehabilitation on 6- min walk distance, endurance cycle time during a constant work rate test, physical activity and quality of life. Adherence to pulmonary rehabilitation between the two models will be compared. A full economic analysis from a societal perspective will be undertaken to determine the cost-effectiveness of telerehabilitation compared to centre-based pulmonary rehabilitation. Discussion: Alternative models of pulmonary rehabilitation are required to improve both equity of access and patient-related outcomes. This trial will establish whether telerehabilitation can achieve equivalent improvement in outcomes compared to traditional centre-based pulmonary rehabilitation. If efficacious and cost-effective, the proposed telerehabilitation model is designed to be rapidly deployed into clinical practice.Narelle S. Cox, Christine F. McDonald, Jennifer A. Alison, Ajay Mahal, Richard Wootton, Catherine J. Hill, Janet Bondarenko, Heather Macdonald, Paul O’Halloran, Paolo Zanaboni, Ken Clarke, Deidre Rennick, Kaye Borgelt, Angela T. Burge, Aroub Lahham, Bruna Wageck, Hayley Crute, Pawel Czupryn, Amanda Nichols and Anne E. Hollan