Classification of tolerable/intolerable mucosal toxicity of head-and-neck radiotherapy schedules with a biomathematical model of cell dynamics

Purpose: The purpose of this study is to present a biomathematical model based on the dynamics of cell populations to predict the tolerability/intolerability of mucosal toxicity in head-and-neck radiotherapy. Methods and Materials: Our model is based on the dynamics of proliferative and functional cell populations in irradiated mucosa, and incorporates the three As: Accelerated proliferation, loss of Asymmetric proliferation, and Abortive divisions. The model consists of a set of delay differential equations, and tolerability is based on the depletion of functional cells during treatment. We calculate the sensitivity (sen) and specificity (spe) of the model in a dataset of 108 radiotherapy schedules, and compare the results with those obtained with three phenomenological classification models, two based on a biologically effective dose (BED) function describing the tolerability boundary (Fowler and Fenwick) and one based on an equivalent dose in 2 Gy fractions (EQD2) boundary (Strigari). We also perform a machine learning-like cross-validation of all the models, splitting the database in two, one for training and one for validation. Results: When fitting our model to the whole dataset, we obtain predictive values (sen + spe) up to 1.824. The predictive value of our model is very similar to that of the phenomenological models of Fowler (1.785), Fenwick (1.806), and Strigari (1.774). When performing a k = 2 cross-validation, the specificity and sensitivity in the validation dataset decrease for all models, from ˜1.82 to ˜1.55–1.63. For Fowler, the worsening is higher, down to 1.49. Conclusions: Our model has proved useful to predict the tolerability/intolerability of a dataset of 108 schedules. As the model is more mechanistic than other available models, it could prove helpful when designing unconventional dose fractionations, schedules not covered by datasets to which phenomenological models of toxicity have been fitted

A mathematical model of dynamics of cell populations in squamous epithelium after irradiation

Purpose: To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. Results: Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. Conclusions: The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to nonstandard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work

Iterative Structural and Functional Synergistic Resolution Recovery (iSFS-RR) Applied to PET-MR Images in Epilepsy

Structural Functional Synergistic Resolution Recovery (SFS-RR) is a technique that uses supplementary structural information from MR or CT to improve the spatial resolution of PET or SPECT images. This wavelet-based method may have a potential impact on the clinical decision-making of brain focal disorders such as refractory epilepsy, since it can produce images with better quantitative accuracy and enhanced detectability. In this work, a method for the iterative application of SFS-RR (iSFS-RR) was firstly developed and optimized in terms of convergence and input voxel size, and the corrected images were used for the diagnosis of 18 patients with refractory epilepsy. To this end, PET/MR images were clinically evaluated through visual inspection, atlas-based asymmetry indices (AIs) and SPM (Statistical Parametric Mapping) analysis, using uncorrected images and images corrected with SFS-RR and iSFS-RR. Our results showed that the sensitivity can be increased from 78% for uncorrected images, to 84% for SFS-RR and 94% for the proposed iSFS-RR. Thus, the proposed methodology has demonstrated the potential to improve the management of refractory epilepsy patients in the clinical routine

A Biomathematical Model of Tumor Response to Radioimmunotherapy with PDL1 and CTLA4

There is evidence of synergy between radiotherapy and immunotherapy. Radiotherapy can increase liberation of tumor antigens, causing activation of antitumor T-cells. This effect can be boosted with immunotherapy. Radioimmunotherapy has potential to increase tumor control rates. Biomathematical models of response to radioimmunotherapy may help on understanding of the mechanisms affecting response, and assist clinicians on the design of optimal treatment strategies. In this work we present a biomathematical model of tumor response to radioimmunotherapy. The model uses the linear-quadratic response of tumor cells to radiation (or variation of it), and builds on previous developments to include the radiation-induced immune effect. We have focused this study on the combined effect of radiotherapy and PDL1/CTLA4 therapies. The model can fit preclinical data of volume dynamics and control obtained with different dose fractionations and PDL1/CTLA4. A biomathematical study of optimal combination strategies suggests that a good understanding of the involved biological delays, the biokinetics of the immunotherapy drug, and the interplay between them, may be of paramount importance to design optimal radioimmunotherapy schedules. Biomathematical models like the one we present can help to interpret experimental data on the synergy between radiotherapy and immunotherapy, and to assist in the design of more effective treatments

Impact of the COVID-19 pandemic on the care of cancer patients in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer; EspanyaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer; EspañaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; SpainBackground Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. Materials and methods This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. Results Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. Conclusions This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.This work was supported by funding from the AECC, a non-profit organization, whose medical department funded the study and the medical writing (no grant number)

Efficiency improvement of a ground coupled heat pump system from energy management

The installed capacity of an air conditioning system is usually higher than the average cooling or heating demand along the year. So, most of the time, the system is working under its actual capacity. In this contribution, we study the way to improve the efficiency of a ground coupled heat pump air conditioning system by adapting its produced thermal energy to the actual thermal demand. For this purpose, an air conditioning system composed by a ground coupled heat pump and a central fan coil linked to an office located in a cooling dominated area was simulated, and a new management strategy aiming to diminish electrical consumption was developed under the basic constraint that comfort requirements are kept. This strategy takes advantage of the possibility of managing the air flow in the fan, the water mass flows in the internal and external hydraulic systems, and the set point temperature in the heat pump to achieve this objective. The electrical consumption of the system is calculated for the new management strategy and compared with the results obtained for a conventional one, resulting in estimated energy savings around 30%This work has been supported by the Spanish Government under projects "Modelado y simulacion de sistemas energeticos complejos" (2005 Ramon y Cajal program), "Modelado, simulacion y validacion experimental de la transferencia de calor en el entorno de la edificacion" (ENE2008-0059/CON). A. Sala is grateful to the financial support of grants DPI2008-06731-c02-01 (Spanish Government), and Generalitat Valenciana Prometeo/2008/088.Pardo García, N.; Montero Reguera, ÁE.; Sala Piqueras, A.; Martos Torres, J.; Urchueguía Schölzel, JF. (2011). Efficiency improvement of a ground coupled heat pump system from energy management. Applied Thermal Engineering. 31(2):391-398. https://doi.org/10.1016/j.applthermaleng.2010.09.016S39139831

Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: Outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database

Background: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. Methods: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. Results: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. Conclusions: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely

Proposing a speech to gesture translation architecture for Spanish deaf people.

This article describes an architecture for translating speech into Spanish Sign Language (SSL). The architecture proposed is made up of four modules: speech recognizer, semantic analysis, gesture sequence generation and gesture playing. For the speech recognizer and the semantic analysis modules, we use software developed by IBM and CSLR (Center for Spoken Language Research at University of Colorado), respectively. Gesture sequence generation and gesture animation are the modules on which we have focused our main effort. Gesture sequence generation uses semantic concepts (obtained from the semantic analysis) associating them with several SSL gestures. This association is carried out based on a number of generation rules. For gesture animation, we have developed an animated agent (virtual representation of a human person) and a strategy for reducing the effort in gesture animation. This strategy consists of making the system automatically generate all agent positions necessary for the gesture animation. In this process, the system uses a few main agent positions (two or three per second) and some interpolation strategies, both issues previously generated by the service developer (the person who adapts the architecture proposed in this paper to a specific domain). Related to this module, we propose a distance between agent positions and a measure of gesture complexity. This measure can be used to analyze the gesture perception versus its complexity. With the architecture proposed, we are not trying to build a domain independent translator but a system able to translate speech utterances into gesture sequences in a restricted domain: railway, flights or weather information

Phase transitions in tumor growth VI: Epithelial–Mesenchymal transition

Herewith we discuss a network model of the epithelial–mesenchymal transition (EMT) based on our previous proposed framework. The EMT appears as a “first order” phase transition process, analogous to the transitions observed in the chemical–physical field. Chiefly, EMT should be considered a transition characterized by a supercritical Andronov–Hopf bifurcation, with the emergence of limit cycle and, consequently, a cascade of saddle-foci Shilnikov's bifurcations. We eventually show that the entropy production rate is an EMT-dependent function and, as such, its formalism reminds the van der Waals equation.Fil: Guerra, A.. Universidad de La Habana; CubaFil: Rodriguez, D. J.. Universidad de La Habana; CubaFil: Montero, S.. Medical Sciences University Of Havana; CubaFil: Betancourt Mar, J. A.. Universidad de La Habana; CubaFil: Martín Pardo, Reinaldo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina. Mexican Institute Of Complex Systems. Tamaulipas; MéxicoFil: Silva Lamar, Eduardo. Universidad de La Habana; CubaFil: Bizzarri, María Julia. Universidad de La Habana; CubaFil: Cocho, G.. Universidad Nacional Autónoma de México; MéxicoFil: Mansilla, R.. Universidad Nacional Autónoma de México; MéxicoFil: Nieto Villar, José Manuel. Universidad de La Habana; Cub