Reduced genomic tumor heterogeneity after neoadjuvat chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

Neoadjuvant chemo(radio)therapy followed by surgery is the standard of care for patients with locally advanced resectable esophageal adenocarcinoma (EAC). There is increasing evidence that drug resistance might be related to genomic heterogeneity. We investigated whether genomic tumor heterogeneity is different after cytotoxic chemotherapy and is associated with EAC patient survival. We used arrayCGH and a quantitative assessment of the whole genome DNA copy number aberration patterns (‘DNA copy number entropy’) to establish the level of genomic tumor heterogeneity in 80 EAC treated with neoadjuvant chemotherapy followed by surgery (CS group) or surgery alone (S group). The association between DNA copy number entropy, clinicopathological variables and survival was investigated. DNA copy number entropy was reduced after chemotherapy, even if there was no morphological evidence of response to therapy (p<0.001). Low DNA copy number entropy was associated with improved survival in the CS group (p=0.011) but not in the S group (p=0.396). Our results suggest that cytotoxic chemotherapy reduces DNA copy number entropy, which might be a more sensitive tumor response marker than changes in the morphological tumor phenotype. The use of DNA copy number entropy in clinical practice will require validation of our results in a prospective study

Combining EGM2008 and SRTM/DTM2006.0 residual terrain model data to improve quasigeoid computations in mountainous areas devoid of gravity data

A global geopotential model, like EGM2008, is not capable of representing the high-frequency components of Earth?s gravity field. This is known as the omission error. In mountainous terrain, omission errors in EGM2008, even when expanded to degree 2,190, may reach amplitudes of10cm and more for height anomalies. The present paper proposes the utilisation of high-resolution residual terrain model (RTM) data for computing estimates of the omission error in rugged terrain. RTM elevations may be constructed as the difference between the SRTM (Shuttle Radar Topography Mission) elevation model and the DTM2006.0 spherical harmonic topographic expansion. Numerical tests, carried out in the German Alps with a precise gravimetric quasigeoid model (GCG05) and GPS/levelling data as references, demonstrate that RTM-based omission error estimatesimprove EGM2008 height anomaly differences by 10cm in many cases. The comparisons of EGM2008-only height anomalies and the GCG05 model showed 3.7 cm standard deviation after a bias-fit. Applying RTM omission error estimates to EGM2008 reduces the standard deviation to 1.9 cm which equates to a significant improvement rate of 47%. Using GPS/levelling data strongly corroborates thesefindings with an improvement rate of 49%. The proposed RTM approach may be of practical value to improve quasigeoid determination in mountainous areas without sufficient regional gravity data coverage, e.g., in parts of Asia, South America or Africa. As a further application, RTMomission error estimates will allow refined validation of global gravity field models like EGM2008 from GPS/levelling data

Structure Preserving Port-Hamiltonian Model Reduction of Electrical Circuits

This paper discusses model reduction of electrical circuits based on a port-Hamiltonian representation. It is shown that by the use of the Kalman decomposition an uncontrollable and/or unobservable port-Hamiltonian system is reduced to a controllable/observable system that inherits the port-Hamiltonian structure. Energy and co-energy variable representations for port-Hamiltonian systems are defined and the reduction procedures are used for both representations. These exact reduction procedures motivate two approximate reduction procedures that are structure preserving for general port-Hamiltonian systems, one reduction procedure is called the effort-constraint reduction methods. The other procedure is structure preserving under a given condition. A numerical example illustrating the model reduction of a ladder network as a port-Hamiltonian system is considered

Clinical judgment and decision-making in wound assessment and management: is experience enough?

Item not available in this repository.The assessment and management of wounds forms a large proportion of community nurses' workload, often requiring judgment and decision-making in complex, challenging and uncertain circumstances. The processes through which nurses form judgments and make decisions within this context are reviewed in this article against existing theories on these subjects. There is variability in wound assessment and management practice which may be attributed to uncertainties within the context, a lack of knowledge in appropriate treatment choices and the inability to correctly value the importance of the clinical information presented. Nurses may be required to draw on intuition to guide their judgments and decision-making by association with experience and expertise. In addition, a step-by-step analytical approach underpinned by an evidence base may be required to ensure accuracy in practice. Developing an understanding of the different theories of judgment and decision-making may facilitate nurses' abilities to reflect on their own decision tasks, thereby enhancing the care provided.https://doi.org/10.12968/bjcn.2015.20.Sup3.S2120pubpubSup.