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Purpose A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer. Methods This systematic review evaluated the literature on predictive models for estimating a patient’s risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review. Conclusions All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents. Implications for Cancer Survivors Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.

The assembly of the vessel wall from its cellular and extracellular matrix components is a critical process in the development and maturation of the cardiovascular system. However, fundamental questions concerning the origin of vessel wall cells and the mechanisms that regulate their development and differentiation remain unanswered. The initial step of vessel wall morphogenesis is formation of a primary vascular network, comprised of nascent endothelial cell tubes, via the processes of vasculogenesis and angiogenesis. Subsequently, primordial vascular smooth muscle cells (VSMCs) are recruited to the endothelium to form a multilayered vessel wall. During the course of development and maturation, the VSMC plays diverse roles: it is a biosynthetic, proliferative, and contractile component of the vessel wall. Although the field of vascular development has blossomed in the past decade, the molecules and mechanisms that regulate this developmental pathway are not well defined. The focus of this review is on those facets of VSMC development important for transforming a nascent endothelial tube into a multilayered structure. We discuss the primordial VSMC with particular attention to its purported origins, the components of the extracellular milieu that contribute to its development, and the contribution of embryonic hemodynamics to vessel wall assembly.

A bstract The very low radioactive background of the Borexino detector, its large size, and the well proved capability to detect both low energy electron neutrinos and antineutrinos make an ideal case for the study of short distance neutrino oscillations with artificial sources at Gran Sasso. This paper describes the possible layouts of 51 Cr ( ν e ) and 144 Ce- 144 Pr source experiments in Borexino and shows the expected sensitivity to eV mass sterile neutrinos for three possible different phases of the experiment. Expected results on neutrino magnetic moment, electroweak mixing angle, and couplings to axial and vector currents are shown too.

Borexino is a 280-ton liquid scintillator detector located at the Laboratori Nazionali del Gran Sasso (LNGS), Italy and is one of the two detectors that has measured geoneutrinos so far. The unprecedented radio-purity of the scintillator, the shielding with highly purified water, and the placement of the detector at 3800 m w.e. depth have resulted in very low background levels, making Borexino an excellent apparatus for geoneutrino measurements. This article will summarize the recent geoneutrino analysis and results with Borexino, from the period December 2007 to April 2019. The updated statistics and the optimized analysis techniques such as an increased fiducial volume and sophisticated cosmogenic vetoes, have led to more than a two-fold increase in exposure when compared to the previous measurement in 2015, resulting in a significant improvement in the precision. In addition, Borexino has also been able to reject the null hypothesis of the mantle geoneutrino signal with 99% C.L., for the first time, by exploiting the extensive knowledge of the crust surrounding the detector. This article will also include other geological interpretations of the obtained results such as the calculation of the radiogenic heat and the comparison of the results to various predictions. Additionally, upper limits for a hypothetical georeactor that might be present at different locations inside the Earth will also be discussed.

About 99 per cent of solar energy is produced through sequences of nuclear reactions that convert hydrogen into helium, starting from the fusion of two protons (the pp chain). The neutrinos emitted by five of these reactions represent a unique probe of the Sun’s internal working and, at the same time, offer an intense natural neutrino beam for fundamental physics. Here we report a complete study of the pp chain. We measure the neutrino–electron elastic-scattering rates for neutrinos produced by four reactions of the chain: the initial proton–proton fusion, the electron-capture decay of beryllium-7, the three-body proton–electron–proton (pep) fusion, here measured with the highest precision so far achieved, and the boron-8 beta decay, measured with the lowest energy threshold. We also set a limit on the neutrino flux produced by the ³ He–proton fusion (hep). These measurements provide a direct determination of the relative intensity of the two primary terminations of the pp chain (pp-I and pp-II) and an indication that the temperature profile in the Sun is more compatible with solar models that assume high surface metallicity. We also determine the survival probability of solar electron neutrinos at different energies, thus probing simultaneously and with high precision the neutrino flavour-conversion paradigm, both in vacuum and in matter-dominated regimes.

Extensions of nuclear physics to the strange sector are reviewed, covering data and models of Lambda and other hypernuclei, multi-strange matter, and anti-kaon bound states and condensation. Past achievements are highlighted, present unresolved problems discussed, and future directions outlined.

Borexino is a 280-ton liquid scintillator detector located at the Laboratori Nazionali del Gran Sasso (LNGS), Italy and is one of the two detectors that has measured geoneutrinos so far. The unprecedented radio-purity of the scintillator, the shielding with highly purified water, and the placement of the detector at a 3800 m w.e. depth have resulted in very low background levels and have made Borexino an excellent apparatus for geoneutrino measurements. The analysis techniques of the latest geoneutrino results with Borexino were presented using the data obtained from December 2007 to April 2019, corresponding to an exposure of (1.12 ± 0.05) × 10 32 protons × yr. Enhanced analysis techniques, such as an increased fiducial volume, improved veto for cosmogenic backgrounds, extended energy and coincidence time windows, as well as a more efficient α/β particle discrimination have been adopted in this measurement. The updated statistics and these elaborate resulted in a geoneutrino signal of 47.0 − 7.7 + 8.4 ( stat ) − 1.9 + 2.4 ( sys ) TNU with − 17.2 + 18.3 % total precision.

Borexino is a 280-ton liquid scintillator detector located at the Laboratori Nazionali del Gran Sasso (LNGS), Italy and is one of the two detectors that has measured geoneutrinos so far. The unprecedented radio-purity of the scintillator, the shielding with highly purified water, and the placement of the detector at a 3800 m w.e. depth have resulted in very low background levels and has made Borexino an excellent apparatus for geoneutrino measurements. The new update of the Borexino geoneutrino measurement, using the data obtained from December 2007 to April 2019, has been presented. Enhanced analysis techniques, adopted in this measurement, have been also presented (poster presentation #39 by S. Kumaran). The updated statistics and the new elaborate analysis have led to more than a factor two increase in exposure ((1.12 ± 0.05) × 10 32 protons × yr) when compared to the latest Borexino result from 2015. The resulting geoneutrino signal of 47.0 − 7.7 + 8.4 ( stat ) − 1.9 + 2.4 ( sys ) TNU has − 17.2 + 18.3 % total precision. The geological interpretations of this measurement have been discussed. In particular, the 99% C.L. observation of the mantle signal by exploiting the relatively well-known lithospheric contribution, the estimation of the radiogenic heat, as well as the comparison of these results to the predictions based on different geological models. The upper limits on the power of a hypothetical georeactor that might be present at different locations inside the Earth have been set.

The Borexino liquid scintillator neutrino observatory has a unique capability to perform high-precision solar neutrino observations thanks to its exceptional radiopurity and good energy resolution (5% at 1 MeV). A comprehensive study of the pp-chain neutrinos was presented that includes the direct measurements of 7 Be, pp and pep neutrino fluxes with the highest precision ever achieved (down to 2.8% in the 7 Be component), the 8 B with the lowest energy threshold, the best limit on CNO neutrinos and the first Borexino limit on hep neutrinos. These results are important to validate the MSW-LMA oscillation paradigm across the full solar energy range and to exclude possible Non-Standard neutrino Interactions (NSIs). In particular the effects of neutrino-flavor-diagonal Neutral-Current (NC) interactions that modify the v e e and v τ e couplings while preserving their chiral and flavor structures, have been investigated. At detection, the shape of the electron-recoil spectrum is affected by changes in the v e e and v τ e couplings, quantified by the parameters ε e L / R and ε τ L / R . New bounds to all four parameters were obtained, quite stringent compared to the global ones. In particular, the best constraint to-date on ε e L was achieved. A comprehensive summary of all the recent results on solar neutrinos from Borexino is reported in the present paper.

A spectral fitter based on the graphics processor unit (GPU) has been developed for Borexino solar neutrino analysis. It is able to shorten the fitting time to a superior level compared to the CPU fitting procedure. In Borexino solar neutrino spectral analysis, fitting usually requires around one hour to converge since it includes time-consuming convolutions in order to account for the detector response and pile-up effects. Moreover, the convergence time increases to more than two days when including extra computations for the discrimination of 11C and external γs. In sharp contrast, with the GPU-based fitter it takes less than 10 seconds and less than four minutes, respectively. This fitter is developed utilizing the GooFit project with customized likelihoods, pdfs and infrastructures supporting certain analysis methods. In this proceeding the design of the package, developed features and the comparison with the original CPU fitter are presented.