KRAS early testing. Consensus initiative and cost-effectiveness evaluation for metastatic colorectal patients in an italian setting

KRAS testing is relevant for the choice of the most appropriate first-line therapy of metastatic colorectal cancer (CRC). Strategies for preventing unequal access to the test should be implemented, but their relevance in the practice is related to economic sustainability. The study adopted the Delphi technique to reach a consensus on several topics. Issues related to execution of KRAS testing were identified by an expert's board and proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The emerging proposal was evaluated by decision analyses models employed by technology assessment agencies in order to assess cost-effectiveness. Alternative therapeutic strategies included most commonly used chemotherapy regimens alone or in combination with cetuximab or bevacizumab. The survey indicated that time interval for obtaining KRAS test should not exceed 15 days, 10 days being an optimal interval. To assure the access to proper treatment, a useful strategy should be to anticipate the test after radical resection in patients at high risk of relapse. Early KRAS testing in high risk CRC patients generates incremental cost-effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY) gained. In extensive sensitivity analyses ICER's were always below 15,000 Euro per QALY gained, far within the threshold of 60,000 Euro/QALY gained accepted by regulatory institutions in Italy. In metastatic CRC a time interval higher than 15 days for result of KRAS testing limits access to therapeutic choices. Anticipating KRAS testing before the onset of metastatic disease in patients at high risk does not affect the sustainability and cost-effectiveness profile of cetuximab in first-line mCRC. Early KRAS testing may prevent this inequality in high-risk patients, whether they develop metastases, and is a cost-effective strategy. Based on these results, present joined recommendations of Italian societies of Oncology and Pathology should be updated including early KRAS testing

Recording from two neurons: second order stimulus reconstruction from spike trains and population coding

We study the reconstruction of visual stimuli from spike trains, recording simultaneously from the two H1 neurons located in the lobula plate of the fly Chrysomya megacephala. The fly views two types of stimuli, corresponding to rotational and translational displacements. If the reconstructed stimulus is to be represented by a Volterra series and correlations between spikes are to be taken into account, first order expansions are insufficient and we have to go to second order, at least. In this case higher order correlation functions have to be manipulated, whose size may become prohibitively large. We therefore develop a Gaussian-like representation for fourth order correlation functions, which works exceedingly well in the case of the fly. The reconstructions using this Gaussian-like representation are very similar to the reconstructions using the experimental correlation functions. The overall contribution to rotational stimulus reconstruction of the second order kernels - measured by a chi-squared averaged over the whole experiment - is only about 8% of the first order contribution. Yet if we introduce an instant-dependent chi-square to measure the contribution of second order kernels at special events, we observe an up to 100% improvement. As may be expected, for translational stimuli the reconstructions are rather poor. The Gaussian-like representation could be a valuable aid in population coding with large number of neurons

Quantum Cosmology in Scalar-Tensor Theories With Non Minimal Coupling

Quantization in the minisuperspace of non minimal scalar-tensor theories leads to a partial differential equation which is non separable. Through a conformal transformation we can recast the Wheeler-DeWitt equation in an integrable form, which corresponds to the minimal coupling case, whose general solution is known. Performing the inverse conformal transformation in the solution so found, we can construct the corresponding one in the original frame. This procedure can also be employed with the bohmian trajectories. In this way, we can study the classical limit of some solutions of this quantum model. While the classical limit of these solutions occurs for small scale factors in the Einstein's frame, it happens for small values of the scalar field non minimally coupled to gravity in the Jordan's frame, which includes large scale factors.Comment: latex, 18 page

Diagnóstico, planejamento ecológico e análise da adubação verde nos agroecossistemas de São Carlos, SP.

bitstream/CNPDIA/9822/1/CiT04_96.pd

ICEPY4D: A PYTHON TOOLKIT FOR ADVANCED MULTI-EPOCH GLACIER MONITORING WITH DEEP-LEARNING PHOTOGRAMMETRY

Glacier monitoring plays a crucial role in understanding the impacts of climate change on these dynamic natural systems. One or more time-lapse cameras are often employed to acquire short-term observations of glacier flow dynamics. However, the lack of multi-camera photogrammetric software packages for multi-temporal 3D scene reconstruction, especially in case of wide camera baselines, hinders the application of Structure-from-Motion techniques to these scenarios. To address this, we present ICEpy4D, a novel Python toolkit designed for 4D monitoring of alpine glaciers using low-cost time-lapse cameras and state-of-the-art computer vision techniques. ICEpy4D leverages deep-learning-based matching algorithms to solve 3D reconstruction with wide camera baselines, making it well-suited for challenging scenarios encountered in mountainous regions. The toolkit offers comprehensive functionalities for multi-epoch monitoring, enabling short-term glacier 3D reconstruction and extraction of relevant information from time-series point clouds, such as volume variations and glacier retreat. In a pilot study on the Belvedere Glacier northern snout (Italian Alps), ICEpy4D estimated glacier volume loss of 63 × 103 m3 of ice and ∼17.5m of retreat. Results showcased the toolkit’s potential for analyzing a glacier ice cliff, with prospects for application to other glaciers with varying characteristics. ICEpy4D is actively being developed as an open-source project at github.com/labmgf-polimi/icepy4d/, promoting ease of extension and customization