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Protecting the heart: a practical approach to account for the full extent of heart motion in radiotherapy planning
No full textPurpose: Emerging evidence suggests that the heart is more radio-sensitive than previously assumed; therefore accounting for heart motion in radiotherapy planning is becoming more critical. In this study, we determined how much heart delineations based on 3D CT, 4D average projection (AVG) and maximum intensity projection (MIP) images should be extended to represent the full extent of heart motion during 4D imaging acquisition.Materials and Methods: 3D and 4D CT scans of ten lung cancer patients treated with stereotactic ablative radiotherapy (SABR) were used. Median surfaces were derived from heart delineations of three observers on the 3D CT, AVG, MIP and 25% exhale scans. Per patient, the 25% exhale contour was propagated on every phase of the 4D scan. The union of all 4D phase delineations (U4D) represented the full extent of heart motion during imaging acquisition. Surface distances from U4D to 3D, AVG, MIP volumes were calculated. Distances in the most extreme surface points (1.5cm most superior/inferior, 10% most right/left/anterior/posterior) were used to derive margins accounting only for systematic (delineation) errors.Results: Heart delineations on the MIP were the `closest' to the full extent of motion, requiring only 2:5 mm margins. Delineations on the AVG and 3D scans required margins up to 3.4 and 7.1 mm, respectively. The largest margins were for the inferior, right and anterior aspects for the delineations on the 3D, AVG and MIP scans, respectively.Conclusion: Delineations on either 3D, AVG or MIP scans required extensions to represented the heart's full extent of motion; the MIP requiring the smallest margins. Research including daily imaging, to determine the random components for the margins, and dosimetric measurements, to determine the relevance of creating a planning organ at risk volume (PRV) of the heart, is required
Robust Stability of Barrier-Based Model Predictive Control
No full textConditions for robust input-output stability of barrier-based model predictive control of linear systems with linear and convex nonlinear (hard or soft) constraints are established through the construction of integral quadratic constraints (IQCs). The IQCs can be used to determine sufficient conditions for global closed-loop stability. In particular conditions for robust stability can be obtained in the presence of unstructured model uncertainty. IQCs with both static and dynamic multipliers are developed and appropriate convex searches for the multipliers are presented. The effectiveness of the robust stability analysis is demonstrated through an illustrative numerical example
An Efficient Floating-Point Bit-Blasting API for Verifying C Programs
No full textWe describe a new SMT bit-blasting API for floating-point programs and evaluate it using different off-the-shelf SMT solvers during the verification of several C programs. The new floating-point API is part of the SMT backend in ESBMC, a state-of-the-art bounded model checker for C and C++. For the evaluation, we compared our floatingpoint API against the native floating-point APIs in Z3 and MathSAT. We show that Boolector, when using our new oating-point API, outperforms the solvers with native support for oating-points, correctly verifying more programs in less time. Experimental results also show that our floating-point API implemented in ESBMC is on par with other state-of-the-art software verifiers. Furthermore, when verifying programs with floating-point arithmetic, our new floating-point API produced nowrong answers
Creating Gaussian Process Regression Models for Molecular Simulations Using Adaptive Sampling
No full textFFLUX is a new force field that combines the accuracy of quantum mechanics with the speed of force fields, without any link to the architecture of classical force fields. This force field is atom-focused and adopts the parameter-free topological atom from Quantum Chemical Topology (QCT). FFLUX uses Gaussian Process Regression (GPR) (aka kriging) models to make predictions of atomic properties, which in this work are atomic energies according to QCT’s Interacting Quantum Atom (IQA) approach. Here we report the adaptive sampling technique Maximum Expected Prediction Error (MEPE) to create data-compact, efficient and accurate kriging models (sub kJ mol-1 for water, ammonia, methane and methanol, and sub kcal mol-1 for N-methylacetamide (NMA)). The models cope with large molecular distortions and are ready for use in molecular simulation. A brand new press-one-button Python pipeline, called ICHOR, carries out the training
Optimal design of in-situ bioremediation system using the meshless element-free Galerkin method and particle swarm optimization
No full textNUC-1031, use of ProTide technology to circumvent gemcitabine resistance: current status in clinical trials
No full textBackground: Resistance to gemcitabine chemotherapy is common in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC) and ovarian cancers (OC), conferring poor survival. Use of ProTide technology led to the development of a ‘partially-activated’ monophosphorylated gemcitabine compound, termed NUC-1031. NUC-1031 enters cancer cells independent of the human equilibrative nucleoside transporter, does not require deoxycytidine kinase-mediated activation and resists cytidine deaminase-mediated breakdown into toxic by-products. Current findings: The phase I PRO-001 trial recruited 68 patients with advanced solid tumours; of the 49 patients that had response-evaluable disease, 5 (10%) had a partial response (PR) and 33 (67%) had stable disease (SD). Subsequently, the PRO-002 study assessed the safety and efficacy of NUC-1031 combined with carboplatin for patients with OC (n=25); preliminary data from this study reported one (4%) unconfirmed complete response (CR), 8 (35%) PRs and 13 (57%) patients with SD, the final outcome data are awaited. The ABC-08 trial for advanced BTC assessed safety and efficacy of NUC-1031 combined with cisplatin; 14 patients were recruited with a 50% objective response rate in the intention to treat population at interim analysis. ACELARATE, the phase III trial in first-line advanced PDAC comparing NUC-1031 to gemcitabine monotherapy, recruited 200 patients but has been paused for futility analysis. Conclusion: Early studies demonstrate NUC-1031 is well-tolerated with favourable pharmacokinetic profiles. NUC-1031 use in PDAC remains unclear, but encouraging results of disease control in BTC and OC has prompted phase II and III trial development. NuTide 121, is a phase III trial comparing NUC 1031-cisplatin combination to the standard of care cisplatin-gemcitabine and recruitment is ongoing. Recruiting trials and mature data from existing studies will help inform on the impact of NUC-1031 on patient survival over standard gemcitabine
Investigation of Spatial Resolution of Electrical Capacitance Tomography Based on Coupling Simulation
No full textIncluding massive neutrinos in thermal Sunyaev Zeldovich power spectrum and cluster counts analyses
No full textWhispers, Echoes, Friends and Fears: Forms and Functions of Voice Hearing in Adolescence
No full textBackground Despite the high prevalence of voice-hearing in childhood, research with adolescents aged under 16 years is scarce. Theoretical connections between clinical and developmental conceptualisations of voice-hearing are limited, resulting in missed opportunities to explore unusual sensory experiences with young people.Methods Demographic, contextual and qualitative data were collected through a web-based survey with 68 adolescents (M=14.91; SD=2.77) from Australia, Canada, Ireland, New Zealand, Spain, the United Kingdom, and United States of America. A Foucauldian-informed narrative analysis captured phenomenologically meaningful individual accounts and systemically informed narratives. Analytic layers attended specifically to the form and function of voices, including relational, protective, distressing and nuanced experiences, offering new insights into individual, systemic and cultural interpretative narratives surrounding voice hearing to inform research, policy and tailored support.Results The average self-reported age of onset of voices was 9 years, 5 months. Reciprocal relationships with pleasant voices were evidenced through the narratives and characterization of voices, while distressing voices were described without reciprocity and the voices held greater power over the young person. Positive aspects of negative voices were discussed and are illustrated with a continuum matrix reflecting interpretation and related affect.Conclusions Voice hearing is a heterogeneous and often complex relational experience for young people, with structural inequalities, relational traumas and social isolation attributed causes of voice hearing. Developing personal meaning making mitigated voice-related distress through contextualising the origin of the voices in past experiences, without attribution to mental illness. Recommendations are proposed for assessment, formulation and relational interventions that recognise the potential impact of the voice-child-other relationship upon psychosocial functioning and wellbeing
The accretion history of high-mass stars: An ArT´eMiS pilot study of Infrared Dark Clouds
No full textThe mass growth of protostars is a central element to the determination of fundamental stellar population properties such as the initial mass function. Constraining the accretion history of individual protostars is therefore an important aspect of star formation research. The goal of the study presented here is to determine whether high-mass (proto)stars gain their mass from a compact (< 0.1 pc) fixed-mass reservoir of gas, often referred to as dense cores, in which they are embedded, or whether the mass growth of high-mass stars is governed by the dynamical evolution of the parsec-scale clump that typically surrounds them. To achieve this goal, we performed a 350µm continuum mapping of 11 infrared dark clouds, along side some of their neighbouring clumps, with the ArT´eMiS camera on APEX. By identifying about 200 compact ArT´eMiS sources, and matching them with Herschel Hi-GAL 70µm sources, we have been able to produce mass vs. temperature diagrams. We compare the nature (i.e. starless or protostellar) and location of the ArT´eMiS sources in these diagrams with modelled evolutionary tracks of both core-fed and clump-fed accretion scenarios. We argue that the latter provide a better agreement with the observed distribution of high-mass star-forming cores. However, a robust and definitive conclusion on the question of the accretion history of high-mass stars requires larger number statistics