A Generalised RBF Finite Difference Approach to Solve Nonlinear Heat Conduction Problems on Unstructured Datasets

Radial Basis Functions have traditionally been used to provide a continuous interpolation of scattered data sets. However, this interpolation also allows for the reconstruction of partial derivatives throughout the solution field, which can then be used to drive the solution of a partial differential equation. Since the interpolation takes place on a scattered dataset with no local connectivity, the solution is essentially meshless. RBF-based methods have been successfully used to solve a wide variety of PDEs in this fashion. Such full-domain RBF methods are highly flexible and can exhibit spectral convergence rates Madych & Nelson (1990). However, in their traditional implementation the fully-populated matrix systems which are produced lead to computational complexities of at least order-N2 with datasets of size N. In addition, they suffer fromincreasingly poor numerical conditioning as the size of the dataset grows, and also with increasingly flat interpolating functions. This is a consequence of ill-conditioning in the determination of RBF weighting coefficients (as demonstrated in Driscoll & Fornberg (2002)), and is described by Robert Schaback Schaback (1995) as the uncertainty relation; better conditioning is associated with worse accuracy, and worse conditioning is associated with improved accuracy. Many techniques have been developed to reduce the effect of the uncertainty relation in the traditional RBF formulation, such as RBF-specific preconditioners Baxter (2002); Beatson et al. (1999); Brown (2005); Ling & Kansa (2005), or adaptive selection of data centres Ling et al. (2006); Ling & Schaback (2004). However, at present the only reliable methods of controlling numerical ill-conditioning and computational cost as problem size increases are domain decomposition Hernandez Rosales & Power (2007); Wong et al. (1999); Zhang (2007); Zhou et al. (2003), or the use of locally supported basis functions Fasshauer (1999); Schaback (1997); Wendland (1995); Wu (1995). In this work the domain decomposition principle is applied, forming a large number of heavily overlapping systems that cover the solution domain. A small RBF collocation system is formed around each global data centre, with each collocation system used to approximate the governing PDE at its centrepoint, in terms of the solution value at surrounding collocation points. This leads to a sparse global linear system which may be solved using a variety of standard solvers. In this way, the proposed formulation emulates a finite difference method, with the RBF collocation systems replacing the polynomial interpolation functions used in traditional finite difference methods. However, unlike such polynomial functions RBF collocation is well suited to scattered data, and the method may be applied to both structured and unstructured datasets without modification. The method is applied here to solve the nonlinear heat conduction equation. In order to reduce the nonlinearity in the governing equation the Kirchhoff integral transformation is applied, and the transformed equation is solved using a Picard iterative process. The application of the Kirchhoff transform necessitates that the thermal property functions be transformed to Kirchhoff space also. If the thermal properties are a known and integrable function of temperature then the transformation may be performed analytically. Otherwise, an integration-interpolation procedure can be performed using 1D radial basis functions, as described in Stevens & Power (2010). In recent years a number of local RBF collocation techniques have been proposed, and applied a wide variety of problems (for example; Divo & Kassab (2007); Lee et al. (2003); Sarler & Vertnik (2006); Wright & Fornberg (2006)). A more comprehensive review of such methods is given in Stevens et al. (2009). Unlike most local RBF collocation methods that are used in the literature, the technique described here utilises the Hermitian RBF collocation formulation (see section 2 for more details), and allows both the PDE-boundary and PDE-governing operators to be included within in the local collocation systems. This inclusion of the governing PDE within the basis functions is shown in Stevens et al. (2009) to significantly improve the accuracy and stability of solutions obtained for linear transport problems. Additionally, the incorporation of information about the convective velocity field into the basis functionswas shown to have a stabilising effect, similar to traditional upwinding methods but without the requirement to alter the stencil configuration based on the local convective field. The standard approach to the solution of linear and nonlinear heat conduction problems is the use of finite difference and finite volume methods with simple polynomial interpolants Bejan (1993); Holman (2002); Kreith & Bohn (2000). Due to the dominance of diffusion in most cases, central differencing techniques are commonly used to compute the heat fluxes. However, limiter methods (such as the unconditionally stable TVD schemes) may be used for nonlinear heat conduction problems where the effective convection term, which results from the non-zero variation of thermal conductivity with temperature, can be expected to approach the magnitude of the diffusive term (see, for example, Shen & Han (2002)). Full-domain RBF methods have also been examined for use with nonlinear heat conduction problems (see Chantasiriwan (2007)), however such methods are restricted to small dataset sizes, due to the computational cost and numerical conditioning experienced by full-domain RBF techniques on large datasets. The present work demonstrates how local RBF collocation may be used as an alternative to traditional finite difference and finite volume methods, for nonlinear heat conduction problems. The described method retains freedom from a volumetric mesh, while allowing solution over unstructured datasets. A central stencil configuration is used in each case, and the solution is stabilised via the inclusion of the governing and boundary PDEs within the local collocation systems (\u201cimplicit upwinding\u201d), rather than by adjusting the stencil configuration based on the local solution field (\u201ctraditional upwinding\u201d). The method is validated using a transient numerical example with a known analytical solution (see section 4), and the ability of the formulation to handle strongly nonlinear problems is demonstrated in the solution of a food freezing problem (see section 5)

Earth conductivity structures and their effects on geomagnetic induction in pipelines

Anomalous, large pipe-to-soil potentials (PSP) have been observed along a natural gas pipeline in eastern Ontario, Canada, where there is a major geological contact between the highly resistive rocks of the Precambrian Shield to the west and the more conductive Paleozoic sediments to the east. This study tested the hypothesis that large variations of PSP are related to lateral changes of Earth conductivity under the pipeline. Concurrent and co-located PSP and magnetotelluric (MT) geophysical data were acquired in the study area. Results from the MT survey were used to model PSP variations based on distributed-source transmission line theory, using a spatially-variant surface geoelectric field. Different models were built to investigate the impact of different subsurface features. Good agreement between modelled and observed PSP was reached when impedance peaks related to major changes of subsurface geological conditions were included. The large PSP could therefore be attributed to the presence of resistive intrusive bodies in the upper crust and/or boundaries between tectonic terranes. This study demonstrated that combined PSP-MT investigations are a useful tool in the identification of potential hazards caused by geomagnetically induced currents in pipelines

Melflufen in relapsed/refractory multiple myeloma refractory to prior alkylators:A subgroup analysis from the OCEAN study

Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS), but not overall survival (OS), versus pomalidomide plus dexamethasone in relapsed/refractory multiple myeloma in the OCEAN study. Time to progression (TTP) &lt;36 months after a prior autologous stem cell transplantation (ASCT) was a negative prognostic factor for OS with melflufen. This post hoc exploratory analysis evaluated patients refractory to prior alkylators (e.g., cyclophosphamide and melphalan) in OCEAN. In 153 patients refractory to prior alkylators (melflufen, n = 78; pomalidomide, n = 75), the melflufen and pomalidomide arms had similar median PFS (5.6 months [95% CI, 4.2–8.3] vs. 4.7 months [95% CI, 3.1–7.3]; hazard ratio [HR], 0.92 [95% CI, 0.63–1.33]) and OS (23.4 months [95% CI, 14.4–31.7] vs. 20.0 months [95% CI, 12.0–28.7]; HR, 0.92 [95% CI, 0.62–1.38]). Among alkylator-refractory patients with a TTP ≥ 36 months after a prior ASCT or no prior ASCT (melflufen, n = 54; pomalidomide, n = 53), the observed median PFS and OS were longer in the melflufen arm than the pomalidomide arm. The safety profile of melflufen was consistent with previous reports. These results suggest that melflufen is safe and effective in patients with alkylator-refractory disease, suggesting differentiated activity from other alkylators.</p

Relevamiento y análisis previos a la instalación de un sistema piloto fotovoltaico conectado a red en el Poder Judicial de Salta como aporte al uso racional de energía y a la promoción de la energía solar

Se relatan las mediciones y relevamientos preliminares a la instalación de un SFVCR - en el marco del Proyecto IRESUD - en la Escuela de la Magistratura del Poder Judicial de Salta que pretende contribuir a la producción distribuida de energía limpia. La innovación es acompañada por un proceso de relevamiento del consumo de energía y de los hábitos de uso por parte de los agentes que diariamente desarrollan su tarea en ese edificio público mediante la aplicación de una encuesta. La caracterización del consumo de energía eléctrica estimado muestra unos 2,6kW destinados a iluminación, 10,15kW a alimentar equipos de oficina (incluyendo equipos de informática) y 40,80kW a climatización. Se realiza una caracterización preliminar de dos de los módulos fotovoltaicos y se estima la energía a ser producida anualmente. Se analiza la inclinación de los paneles a ser ubicados en la fachada Norte y se discute el aporte que el SFVCR hace al consumo de electricidad de la EM. Se detectan problemas en el uso de la energía eléctrica destinada a la climatización de las oficinas del ala Este debido a la incidencia de radiación  solar directa y  a un  uso  inadecuado  de las aberturas mientras funcionan  equipos de aire acondicionado. Se proponen algunas medidas de uso racional de la energía y se discute su integración con el novedoso sistema de co-generación para contribuir, desde dos vertientes- la generación de electricidad a partir de la energía solar en el punto de consumo - y el uso racional de la energía a una mejora en el abastecimiento eléctrico urbano.Measurements and preliminary survey to the installation of a SFVCR in the School of the Magistrature of the Judicial Power of Salta are related. It is pretending electrical energy generation and contributing to the distributed production of clean energy. The innovation is accompanied by a process of surveying about the consumption of energy and of the habits of use by part of the agents that daily develop his task in this public building by means of the application of a survey. The characterization of the consumption of electrical energy estimated shows about 2,6kW destined to illumination, 10,15kW to feed office equipment (including computers) and 40,80kW to air condition. A sample of two of the photovoltaic modules is preliminary characterized and the energy to be produced annually estimated. It was analyzed the inclination of the panels to be situated in the north front and discussed the contribution that the SFVCR does to the consumption of electricity of the SM. Problems in the use of the electrical energy destined to the air conditioning of the offices are detected due to the incidence of direct solar radiation on the East and to the unsuitable use of the openings when the air conditioning equipment were working. Some measures of rational use of the energy are proposed and his integration discussed with the new system of co-generation. There are a dobble contribution: the generation of electricity from the solar energy in the point of consumption and the rational use of the energy to improve the urban electrical supply.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Melflufen for relapsed and refractory multiple myeloma

Introduction: The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with new mechanisms of action could be beneficial. Melphalan flufenamide (melflufen) has demonstrated encouraging activity in patients with relapsed and refractory multiple myeloma. Areas covered: This review provides an overview of the mechanism of action of melflufen, a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly delivers alkylating agents into tumor cells. It reviews key Phase I and II clinical trial data for melflufen in combination with dexamethasone as well as in triplet combinations with daratumumab or bortezomib. The safety profile of melflufen, which is characterized primarily by clinically manageable hematologic adverse events, is described. Expert opinion: Melflufen has potential to fill a gap in the myeloma treatment landscape by providing a new mechanism of action with clinically meaningful efficacy and a favorable safety profile in patients refractory to multiple novel agents

Cardiovascular adverse events in modern myeloma therapy - incidence and risks. A review from European Myeloma Network (EMN) and Italian Society of Arterial Hypertension (SIIA)

Cardiovascular disease in myeloma patients may derive from factors unrelated to the disease (age, diabetes, dyslipidemia, obesity, prior cardiovascular diseases), related to the disease (cardiac AL-amyloidosis, hyperviscosity, high-output failure, arteriovenous shunting, anemia, renal dysfunction) and linked to antimyeloma treatment (anthracyclines, corticosteroids, alkylating agents, immunomodulatory drugs, proteasome inhibitors). An accurate knowledge of cardiovascular events, effective dose reductions, prevention and management of early and late cardiovascular side effects of chemotherapeutic agents are essential in current clinical practice. Myeloma experts are obliged to carefully balance drugs' efficacy and toxicity for each individual patient. This review summarizes current data and novel insights on cardiovascular adverse events of today's antimyeloma treatment, focusing on carfilzomib, which is the starting point to develop consensus recommendations on preventing and managing cardiovascular side effects in myeloma patients

Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN)

Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked hete rogeneity. Many new and highly effective drugs have been introduced in the last few years, and resu lts from clinical trials are promising. Besides the availability of novel agents, a careful evaluation of elderly patients showed to be a key factor for the success of therapy. A geriatric assessment is a valid strategy to better stratify patients. In particular, different scores are available today to appropriately assess elderly patients and define their fitness/frailty status. The choice of treatm ent – transplantation, triplets, doublets, or reduced- dose therapies including novel agents – should depend on the patient’s fitness status (fit, intermediate-fit or frail). Second-generation no vel agents have also been evaluated as salvage therapy in the elderly, and these new agents certai nly represent a further step forward in the treatment armamentarium for elderly patients with multiple myeloma

Contemporary use of devices in chronic heart failure in the Netherlands

Aims: Despite previous surveys regarding device implantation rates in heart failure (HF), insight into the real-world management with devices is scarce. Therefore, we investigated device implantation rates in HF with reduced left ventricular ejection fraction (LVEF) in 34 Dutch centres. Methods and results: A cross-sectional outpatient registry was conducted in 6666 patients with LVEF < 50% and with information about device implantation available [74 (66–81) years of age; 64% male]. Patients were classified into conventional pacemakers (PM, n = 562), implantable cardioverter defibrillato

Inhibitory receptor expression on memory CD8 T cells following Ad vector immunization

T cells are an important component of immune responses, and their function is influenced by their expression of inhibitory receptors. Immunization with alternative serotype adenovirus (Ad) vectors induces highly functional T cell responses with lower programmed cell death 1 (PD-1) expression and increased boostability relative to Ad5 vectors. However, a detailed phenotypic characterization of other inhibitory receptors is lacking, and it is unknown whether Ad5-induced CD8 T cells eventually recover function with time. In this report, we measure the expression of various inhibitory receptors and memory markers during early and late time points following vaccination with Ad5 and alternative serotype Ad vectors. CD8 T cells induced by Ad5 exhibited increased expression of the inhibitory receptor Tim-3 and showed decreased central memory differentiation as compared with alternative serotype Ad vectors, even a year following immunization. Moreover, relative to Ad5-primed mice, Ad26-primed mice exhibited substantially improved recall of SIV Gag-specific CD8 T cell responses following heterologous boosting with MVA or Ad35 vectors. We also demonstrate that low doses of Ad5 priming resulted in more boostable immune responses with lower PD-1 expression as compared to high Ad5 doses, suggesting a role for vector dose in influencing immune dysfunction following Ad5 vaccination. These data suggest that Ad5 vectors induce a long-term pattern of immune exhaustion that can be partly overcome by lowering vector dose and modulating inhibitory signals