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HEPfit is a flexible open-source tool which, given the Standard Model or any of its extensions, allows to (i) fit the model parameters to a given set of experimental observables; (ii) obtain predictions for observables. HEPfit can be used either in Monte Carlo mode, to perform a Bayesian Markov Chain Monte Carlo analysis of a given model, or as a library, to obtain predictions of observables for a given point in the parameter space of the model, allowing HEPfit to be used in any statistical framework. In the present version, around a thousand observables have been implemented in the Standard Model and in several new physics scenarios. In this paper, we describe the general structure of the code as well as models and observables implemented in the current release.

Extensive stage Small-Cell Lung Cancer (ES-SCLC) is the most lethal lung cancer, and the addition of immunotherapy conferred a slight survival benefit for patients. Extensive molecular profiling of patients treated with chemotherapy (CT) or chemotherapy plus immunotherapy (CT+IO) would be able to identify molecular factors associated with patients' survival. In this retrospective study, 99 ES-SCLC patients were considered. Of the 79 includible patients, 42 received CT (median age 71 y/o, I-IIIQ: 65-76), and 37 received CT+IO (median age 71 y/o, I-IIIQ 66-75). The FoundationOne CDx assay was performed on patients' tumor tissues. The most mutated genes were (99%), (78%), (23%) and (20%), with no significant differences between the treatment groups. As a continuous variable, Tumor Mutation Burden (TMB) had an effect on patients' progression-free survival (PFS) by type of treatment (HR 1.81 (95%, CI: 0.99-3.31) and HR 0.84 (95%, CI: 0.56-1.26) for patients treated with CT and CT+IO, respectively). TMB was also computed and dichotomized using two different cut-offs: considering cut-offs of 10 mut/Mb and >16 mut/Mb, 45 patients (57%) and 68 patients (86.1%) had a low TMB, respectively. A high TMB (cut-off 10 mut/Mb) predicted worse PFS in patients treated with CT ( =0.046); even though not statistically significant, a high TMB (cut-off 16 mut/Mb) predicted a better survival in patients treated with CT+IO. Moreover, at univariate analysis, mutations were associated with better prognosis in the overall case series (HR = 0.51, 95% CI: 0.28-0.94), and overall survival (HR = 0.52, 95% CI: 0.28-0.97). In ES-SCLC, TMB is associated with worse survival in patients treated with CT alone, and with better survival in patients treated with CT+IO, whether considered as a continuous or a dichotomized variable, at different cut-offs. Alterations in epigenetic factors are also associated to better patient prognosis.

HEPfit is a flexible open-source tool which, given the Standard Model or any of its extensions, allows to (i) fit the model parameters to a given set of experimental observables; (ii) obtain predictions for observables. HEPfit can be used either in Monte Carlo mode, to perform a Bayesian Markov Chain Monte Carlo analysis of a given model, or as a library, to obtain predictions of observables for a given point in the parameter space of the model, allowing HEPfit to be used in any statistical framework. In the present version, around a thousand observables have been implemented in the Standard Model and in several new physics scenarios. In this paper, we describe the general structure of the code as well as models and observables implemented in the current release.

The authors use the mathematical tool of Maccone's lognormal distribution to further factor the Drake equation, which calculates the number of advanced civilizations in the galaxy, from the seven original levels of the Drake equation to 49 levels of overall analysis. The Maccone approach, in fact, supported by the central limit theorem, becomes more reliable the more levels are introduced. The resulting study necessarily draws upon an array of disciplines ranging from astronomy, chemistry and geology to biology, palaeontology and futurology. The final result calculates the number of planetary systems suitable for life in its various stages of development: those which have probably hosted life in the past and those which still host it at its various evolutionary levels. The final evolutionary level is the so-called galactic civilization (often called ETC, or extraterrestrial civilizations). The number of resulting galactic civilizations is divided between static civilizations, which do not move around the galaxy and whose Kardašëv rating is still low (<1.4), of which we find three examples (we ourselves plus, perhaps, two others), and potentially dynamic civilizations, which move around the galaxy and have a sufficiently high Kardašëv rating (≥1.4), of which we find 2000.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens, increasing tumor elimination efficiency. In recent years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate in patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable for use as mathematical models. In this work, we develop a three-population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities are considered uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reducing and optimizing the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such an in silico laboratory is an easy-to-run open-source simulator, built on a Shiny R-based platform called CARTmath. It contains the results of this manuscript as examples and documentation. The developed model together with the CARTmath platform have potential use in assessing different CAR-T cell immunotherapy protocols and its associated efficacy, becoming an accessory for in silico trials.

In this study, irradiation of the internal mammary and medial supraclavicular nodes plus whole breast or thoracic-wall radiation therapy in women with localized breast cancer was linked to increased disease-free survival but only a marginal gain in overall survival. The first filter stations for the lymphatic drainage of the breast are the axillary and internal mammary lymph nodes. 1 Surgical studies have shown that the incidence of metastatic involvement of the internal mammary nodes varies between 4% and 9% in patients with axillary node–negative breast cancer and between 16% and 65% in patients with axillary node–positive breast cancer. 2 – 4 As a consequence, surgical dissection of the internal mammary nodes was attempted but abandoned in the 1970s, since no improvement in survival was observed. 4 , 5 Elective irradiation of the regional nodes remained widely used until the late 1980s, when it became . . .

The H.E.S.S. collaboration recently reported a new analysis of the gamma-ray diffuse emission from a “semi-annulus” region of 1.4 × 10−4 steradiants around Sagittarius A*. The gamma-ray spectral energy distribution measured from this region suggests the presence of interacting cosmic rays at PeV energies. This analysis adds a important piece to the previous measurements obtained with Fermi-LAT, H.E.S.S. and VERITAS telescopes in this particular region of the Central Molecular Zone. Here we describe this diffuse gamma-ray emission observed around the galactic center within a comprensive model implying a cosmic-ray population with a harder spectrum in the central part of the galaxy respect to the standard scenarios. With this phenomenological model we obtain the expected diffuse gamma-ray and neutrino components for this target rich region considering the energy range from GeV to PeV. While for the gamma-ray expectations we compare the results with the data of the mentioned experiments, for the expected neutrino spectra we consider the possibility to observe the signal with Cherenkov telescopes.

Conventional cosmic ray propagation models face problems reproducing the diffuse 7-ray spectrum measured by Fermi-LAT over the entire sky. Those models also fail to smoothly connect Fermi-LAT results with data above the TeV as those taken by Milagro in the inner Galactic plane. In this contribution we show that a representative model adopting a spatial dependent rigidity scaling of the diffusion coefficient can reproduce all those experimental results without spoiling the consistency with local cosmic-ray measurements. We use the same model to compute the diffuse neutrino emission of the Galaxy and compare it with IceCube and ANTARES results.

Several independent analyzes of Fermi-LAT results found evidences of an excess of γ -ray diffuse emission along the inner Galactic plane and of a related spatial dependence of the cosmic ray (CR) proton spectral index. These features are not accounted for by conventional models of CR transport. We show that a phenomenological model accounting for those results in terms of spatial dependent CR transport also reproduces the γ -ray excess found by Milagro at 15 TeV in the inner Galactic plane and by H.E.S.S. in the Galactic center. We then use that model to compute the neutrino emission along the Galactic plane finding that is significantly larger than expected on the basis of conventional models. This emission is compatible with ANTARES upper limits and may soon be detected by IceCube or, more likely, by Km3NeT.

A 76-year-old woman presented with symptoms suggestive of acute sinusitis. Previously, her breast carcinoma was treated with right lumpectomy, adjuvant chemotherapy and breast radiotherapy. She remained free from recurrence for the following 8 years. After initial treatment with antibiotics, the local symptom worsened with exophthalmos, eye blindness and development of an ulceration of the hard palate. MRI showed irregular enhancement of the nasal cavity extended to the maxillary sinus and ethmoidal lamina and concomitant infiltration of the orbit and skull base. A biopsy of the palatal ulcer showed a poorly differentiated adenocarcinoma and was compared with the histology of the primary breast tumour and it was concluded for the same morphology. After discussion at the multidisciplinary team, a specific chemotherapy has been activated with an initial local response. Further surgical resection was not thought appropriate and the patient has subsequently undergone palliative radiotherapy to the right paranasal lesions to improve local disease control.