Incorporating a radiative hydrodynamics scheme in the numerical-relativity code BAM

To study binary neutron star systems and to interpret observational data such as gravitational-wave and kilonova signals, one needs an accurate description of the processes that take place during the final stages of the coalescence, e.g., through numerical-relativity simulations. In this work, we present an updated version of the numerical-relativity code BAM in order to incorporate nuclear-theory based Equations of State and a simple description of neutrino interactions through a Neutrino Leakage Scheme. Different test simulations, for stars undergoing a neutrino-induced gravitational collapse and for binary neutron stars systems, validate our new implementation. For the binary neutron stars systems, we show that we can evolve stably and accurately distinct microphysical models employing the different equations of state: SFHo, DD2, and the hyperonic BHB$\Lambda \phi$. Overall, our test simulations have good agreement with those reported in the literature

Numerical Simulations of Dark Matter Admixed Neutron Star Binaries

Multi-messenger observations of compact binary mergers provide a new way to constrain the nature of dark matter that may accumulate in and around neutron stars. In this article, we extend the infrastructure of our numerical-relativity code BAM to enable the simulation of neutron stars that contain an additional mirror dark matter component. We perform single star tests to verify our code and the first binary neutron star simulations of this kind. We find that the presence of dark matter reduces the lifetime of the merger remnant and favors a prompt collapse to a black hole. Furthermore, we find differences in the merger time for systems with the same total mass and mass ratio, but different amounts of dark matter. Finally, we find that electromagnetic signals produced by the merger of binary neutron stars admixed with dark matter are very unlikely to be as bright as their dark matter free counterparts. Given the increasing sensitivity of multi-messenger facilities, our analysis gives a new perspective on how to probe the presence of dark matter

Back and Forth: Reverse Phase Transitions in Numerical Relativity Simulations

Multi-messenger observations of binary neutron star mergers provide a uniqueopportunity to constrain the dense-matter equation of state. Although it isknown from quantum chromodynamics that hadronic matter will undergo a phasetransition to exotic forms of matter, e.g., quark matter, the onset density ofsuch a phase transition cannot be computed from first principles. Hence, itremains an open question if such phase transitions occur inside isolatedneutron stars or during binary neutron star mergers, or if they appear at evenhigher densities that are not realized in the Cosmos. In this article, weperform numerical-relativity simulations of neutron-star mergers andinvestigate scenarios in which the onset density of such a phase transition isexceeded in at least one inspiralling binary component. Our simulations revealthat shortly before the merger it is possible that such stars undergo a"reverse phase transition", i.e., densities decrease and the quark core insidethe star disappears leaving a purely hadronic star at merger. After the merger,when densities increase once more, the phase transition occurs again and leads,in the cases considered in this work, to a rapid formation of a black hole. Wecompute the gravitational-wave signal and the mass ejection for our simulationsof such scenarios and find clear signatures that are related to the postmergerphase transition, e.g., smaller ejecta masses due to the softening of theequation of state through the quark core formation. Unfortunately, we do notfind measurable imprints of the reverse phase transition.<br

Production and release of antimicrobial and immune defense proteins by mammary epithelial cells following Streptococcus uberis infection of sheep

Investigating the innate immune response mediators released in milk has manifold implications, spanning from elucidation of the role played by mammary epithelial cells (MECs) in fighting microbial infections to the discovery of novel diagnostic markers for monitoring udder health in dairy animals. Here, we investigated the mammary gland response following a two-step experimental infection of lactating sheep with the mastitis-associated bacterium Streptococcus uberis. The establishment of infection was confirmed both clinically and by molecular methods, including PCR and fluorescent in situ hybridization of mammary tissues. Proteomic investigation of the milk fat globule (MFG), a complex vesicle released by lactating MECs, enabled detection of enrichment of several proteins involved in inflammation, chemotaxis of immune cells, and antimicrobial defense, including cathelicidins and calprotectin (S100A8/S100A9), in infected animals, suggesting the consistent involvement of MECs in the innate immune response to pathogens. The ability of MECs to produce and release antimicrobial and immune defense proteins was then demonstrated by immunohistochemistry and confocal immunomicroscopy of cathelicidin and the calprotectin subunit S100A9 on mammary tissues. The time course of their release in milk was also assessed by Western immunoblotting along the course of the experimental infection, revealing the rapid increase of these proteins in the MFG fraction in response to the presence of bacteria. Our results support an active role of MECs in the innate immune response of the mammary gland and provide new potential for the development of novel and more sensitive tools for monitoring mastitis in dairy animals

Immunological and Molecular Correlates of Disease Recurrence after Liver Resection for Hepatocellular Carcinoma

The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in particular CD4 and CD8+ memory subsets within TIL was predictive of better overall survival (OS) and time to recurrence (TTR). Increased programmed death ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells were associated with shorter OS and TTR, respectively. By combined evaluation of infiltrating cell subsets along with mRNA profiling of immune and tumor related genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells as well as PDL1 expression as the best predictors of clinical outcome. HCC infiltrate is characterized by the expression of molecules with negative regulatory function that may favor tumor recurrence and poor survival

Os retratos de Maria Isabel e Maria Francisca de Bragança, de Nicolas-Antoine Taunay

Nicolas-Antoine Taunay, French landscape painter, produced also several portraits during his stay at the Rio de Janeiro Court. In this city, in 1816, he paints the queen Carlota Joaquina and all her daughters. In this group, two portraits have a very special way: the paintings still today catalogued as Maria Francisca and Maria Teresa, but probably being Maria Isabel and Maria Francisca de Assis - princesses that, in this year, left Brazil to marry the Spanish King Fernando VII, and his brother Carlos Maria Isidro de Bourbon. In this article, beyond to describe these portraits (and analyse the identities of the portrayed princesses), I analyse their functions in the Court society and the mains artists of this gender in Europe. I will discuss, as well, the hypothesis about the Taunay choices. In this sense, I will analyse the possible circulation of the typologies of portrait between Italy, Portugal, Spain and France, understanding these productions by Taunay and the functions occupied by these portraits in the political relations between Brazil and Europe.Nicolas-Antoine Taunay, pintor de paisagens francês, também realizou alguns retratos durante sua estadia na corte do Rio de Janeiro. Nessa cidade, em 1816, ele pinta a rainha Carlota Joaquina e todas as suas filhas. Nesse conjunto, dois retratos sobressaem-se de modo especial: os hoje ainda inventariados como de Maria Francisca e de Maria Teresa, mas que provavelmente são o de Maria Isabel e o de Maria Francisca de Assis - princesas que, nesse ano, deixavam o Brasil para casar-se, respectivamente, com Fernando VII, o rei espanhol, e com seu irmão Carlos Isidro de Bourbon. Neste artigo, além de descrevermos os retratos (e analisarmos a questão da identidade das princesas retratadas), abordamos suas funções na sociedade das cortes e os principais artistas do gênero na Europa. Discutimos, também, as hipóteses que permeiam as escolhas de Taunay para sua execução. Nesse sentido, tratamos da possível circulação de tipologias entre Itália, Portugal, Espanha e França, buscando entender a forma como Taunay os realizou e as funções que doravante tais retratos ocupariam nas relações entre o Brasil e a Europa.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective