Some properties of the dissipative model of strain-gradient plasticity

A theoretical and computational investigation is carried out of a dissipative model of rate-independent strain-gradient plasticity and its regularization. It is shown that the flow relation, when expressed in terms of the Cauchy stress, is necessarily global. The most convenient approach to formulating the flow relation is through the use of a dissipation function. It is shown, however, that the task of obtaining the dual version, in the form of a normality relation, is a complex one. A numerical investigation casts further light on the response using the dissipative theory in situations of non-proportional loading. The elastic gap, a feature reported in recent investigations, is observed in situations in which passivation has been imposed. It is shown computationally that the gap may be regarded as an efficient path between a load-deformation response corresponding to micro-free boundary conditions, and that corresponding to micro-hard boundary conditions, in which plastic strains are set equal to zero.Comment: 26 pages, 10 figure

Parsec-scale magnetic fields in Arp 220

We present the first very-long-baseline interferometry (VLBI) detections of Zeeman splitting in another galaxy. We used Arecibo Observatory, the Green Bank Telescope, and the Very Long Baseline Array to perform dual-polarization observations of OH maser lines in the merging galaxy Arp 220. We measured magnetic fields of $\sim$1-5 mG associated with three roughly parsec-sized clouds in the nuclear regions of Arp 220. Our measured magnetic fields have comparable strengths and the same direction as features at the same velocity identified in previous Zeeman observations with Arecibo alone. The agreement between single dish and VLBI results provides critical validation of previous Zeeman splitting observations of OH megamasers that used a single large dish. The measured magnetic field strengths indicate that magnetic energy densities are comparable to gravitational energy in OH maser clouds. We also compare our total intensity results to previously published VLBI observations of OH megamasers in Arp 220. We find evidence for changes in both structure and amplitude of the OH maser lines that are most easily explained by variability intrinsic to the masing region, rather than variability produced by interstellar scintillation. Our results demonstrate the potential for using high-sensitivity VLBI to study magnetic fields on small spatial scales in extragalactic systems.Comment: 9 pages, accepted to MNRA

A 0535+26: Back in business

In May/June 2005, after 10 years of inactivity, the Be/X-ray binary system A 0535+26 underwent a major X-ray outburst. In this paper data are presented from 10 years of optical, IR and X-ray monitoring showing the behaviour of the system during the quiescent epoch and the lead up to the new outburst. The results show the system going through a period when the Be star in the system had a minimal circumstellar disk and then a dramatic disk recovery leading, presumably, to the latest flare up of X-ray emission. The data are interpreted in terms of the state of the disk and its interaction with the neutron star companion.Comment: Accepted for publication in MNRA

Computational and theoretical aspects of a grain-boundary model at finite deformations

A model to describe the role of grain boundaries in the overall response of a polycrystalline material at small length scales subject to finite deformations is presented. Three alternative thermodynamically consistent plastic flow relations on the grain boundary are derived and compared using a series of numerical experiments. The numerical model is obtained by approximating the governing relations using the finite element method. In addition, the infinitesimal and finite deformation theories are compared, and the limitations of the former made clear

Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas.

PurposeGlioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies.Methods and materialsA number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration.ResultsVarious immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials.ConclusionsThis review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response

Variation in compulsory psychiatric inpatient admission in England:a cross-sectional, multilevel analysis

Background: Rates of compulsory admission have increased in England in recent decades, and this trend is accelerating. Studying variation in rates between people and places can help identify modifiable causes. Objectives: To quantify and model variances in the rate of compulsory admission in England at different spatial levels and to assess the extent to which this was explained by characteristics of people and places. Design: Cross-sectional analysis using multilevel statistical modelling. Setting: England, including 98% of Census lower layer super output areas (LSOAs), 95% of primary care trusts (PCTs), 93% of general practices and all 69 NHS providers of specialist mental health services. Participants: 1,287,730 patients. Main outcome measure: The study outcome was compulsory admission, defined as time spent in an inpatient mental illness bed subject to the Mental Health Act (2007) in 2010/11. We excluded patients detained under sections applying to emergency assessment only (including those in places of safety), guardianship or supervision of community treatment. The control group comprised all other users of specialist mental health services during the same period. Data sources: The Mental Health Minimum Data Set (MHMDS). Data on explanatory variables, characterising each of the spatial levels in the data set, were obtained from a wide range of sources, and were linked using MHMDS identifiers. Results: A total of 3.5% of patients had at least one compulsory admission in 2010/11. Of (unexplained) variance in the null model, 84.5% occurred between individuals. Statistically significant variance occurred between LSOAs [6.7%, 95% confidence interval (CI) 6.2% to 7.2%] and provider trusts (6.9%, 95% CI 4.3% to 9.5%). Variances at these higher levels remained statistically significant even after adjusting for a large number of explanatory variables, which together explained only 10.2% of variance in the study outcome. The number of provider trusts whose observed rate of compulsory admission differed from the model average to a statistically significant extent fell from 45 in the null model to 20 in the fully adjusted model. We found statistically significant associations between compulsory admission and age, gender, ethnicity, local area deprivation and ethnic density. There was a small but statistically significant association between (higher) bed occupancy and compulsory admission, but this was subsequently confounded by other covariates. Adjusting for PCT investment in mental health services did not improve model fit in the fully adjusted models. Conclusions: This was the largest study of compulsory admissions in England. While 85% of the variance in this outcome occurred between individuals, statistically significant variance (around 7% each) occurred between places (LSOAs) and provider trusts. This higher-level variance in compulsory admission remained largely unchanged even after adjusting for a large number of explanatory variables. We were constrained by data available to us, and therefore our results must be interpreted with caution. We were also unable to consider many hypotheses suggested by the service users, carers and professionals who we consulted. There is an imperative to develop and evaluate interventions to reduce compulsory admission rates. This requires further research to extend our understanding of the reasons why these rates remain so high. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Parameterisation of sediment geochemistry for simulating water quality responses to long-term catchment and climate changes in polymictic, eutrophic Lake Rotorua, New Zealand

Numerical models of aquatic ecosystems that couple physics and biogeochemistry are valuable tools in aquatic ecosystem research. These models provide opportunities to test theories and to inform environmental management. In this study, we used the dynamic, process-based hydrodynamic-ecological model DYRESM-CAEDYM to simulate key ecosystem processes of Lake Rotorua, New Zealand, for six 8-year periods between 1920 and 2100 in order to evaluate the potential effects of future changes in land use and climate. Longterm variations in external boundary conditions (e.g. inflows) to the lake ecosystem are incorporated by varying the relevant input files in the DYRESMCAEDYM model. However, quantification of internal lake processes, specifically those at the sediment-water interface, presents a major challenge for long-term simulations. The sediment model within CAEDYM is ‘static’, with assumed constant sediment composition and a relatively simplistic process representation for nutrient and oxygen fluxes between sediment and water. Specifically, the model regulates sediment phosphate and ammonium release according to concentrations of oxidising species (i.e. oxygen and nitrate), and temperature in the overlying water layer. Sediment oxygen demand is controlled by dissolved oxygen concentrations and temperature in the water layer overlying the sediments. We used a ‘trial and error’ approach to estimate parameters for calibrating and validating the model, and regression modelling to infer the parameters beyond the calibration/validation simulation period (2001–2009). We observed a significant relationship in historic monitoring data between the external nitrogen load to the lake and its hypolimnetic oxygen demand as well as the bottom-sediment nitrogen concentrations. This relationship was used to hindcast and forecast model parameters for sediment nutrient release and oxygen demand in the six model simulation periods. The inclusion of a dynamic response of sediment nutrient release and oxygen demand parameters to changes in external nutrient loads enabled a more conceptually concise simulation of water quality for the simulations. This model is currently being used by regional environmental management authorities for developing an Action Plan for the restoration of Lake Rotorua

Constructing applicative functors

Applicative functors define an interface to computation that is more general, and correspondingly weaker, than that of monads. First used in parser libraries, they are now seeing a wide range of applications. This paper sets out to explore the space of non-monadic applicative functors useful in programming. We work with a generalization, lax monoidal functors, and consider several methods of constructing useful functors of this type, just as transformers are used to construct computational monads. For example, coends, familiar to functional programmers as existential types, yield a range of useful applicative functors, including left Kan extensions. Other constructions are final fixed points, a limited sum construction, and a generalization of the semi-direct product of monoids. Implementations in Haskell are included where possible