Evolution number of litigation cases and expenditure with monoclonal antibodies (MoAbs) (Bevacizumab, Cetuximab and Panitumumab) and tirosine kinase inhibitor (Regorafenib) for the treatment of cancer in Minas Gerais-Brazil : A preliminary analysis from 2009 to 2016

Introduction: The last decade was marked by the widespread use of molecular biological agents in combination with 5-FU / oxaliplatin or irinotecan-containing regimens in the treatment of cancer. Such biological medicines have significantly increased the costs of oncological treatment, leading to concerns about the future sustainability of drug policy and, as a consequence, health systems with universal access to health care. In the case of Brazil, the tree MoAbs BEVACIZUMAB(BEVA), CETUXIMAB(CETUX), PANITUMUMAB(PANIT) and one tirosin kinase inhibitor REGORAFENIB(REGORA) compared in this study can only be used by the patient when there is a litigation against the State, since they are not incorporated into the Single System of Health-SUS. Objectives: To evaluate the evolution number of litigation cases and expenditure with monoclonal antibodies(MoAbs) (Bevacizumab, Cetuximab and Panitumumab) and tirosin kinase inhibitor (Regorafenib) for the treatment of cancer in Minas Gerais-Brazil. Method: Retrospective descriptive study whose judicial information was extracted from the database of the Minas Gerais State Secretariat - SES-MG. The judicial actions were filed against the State of Minas Gerais for Cancer treatment and refer to the period from January 2009 to December 2016. The study was cut from the judicialized MoAbs (BEVA, CETUX, PANIT) and tirosin kinase inhibitor (REGORA) for the treatment of Colorectal Cancer (CCR). The cost of the treatments was calculated based on the prices of the Câmara de Regulação do Mercado de Medicamentos (CMED) ANVISA, taking into account the official dollar exchange rate of the Central Bank on January 31, 2018 and there is no adjustment for inflation. Results and discussion: Preliminary results showed that in the period between 2009 and 2016, 1024 lawsuits were filed against the State of Minas Gerais for cancer treatment, making 766 for BEVA, 206 for CETUX, 35 for PANIT and 17 for REGORA . The total cost obtained considering a 6-month overall survival for each patient was $ 22,260,536. In Brazil, the growing number of litigation and drug costs (BEVA, CETUX, PANIT and REGORA) per year is worrying, considering the increase of 5.100% for judicial actions and 1899% for treatment costs in the period 2009 to 2016 (TABLE 1). Conclusion: The exponential increase in lawsuits against the State of Minas Gerais demonstrates the growing pressure on the resources available to attend a reduced number of patients, who are available to judicialize treatments outside universal health coverage, which is already guaranteed right by the Brazilian constitution

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

Evaluation of an Antimicrobial L-Amino Acid Oxidase and Peptide Derivatives from Bothropoides mattogrosensis Pitviper Venom

Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms

The formation of Jupiter’s diluted core by a giant impact

The Juno mission has provided an accurate determination of Jupiter's gravitational field, which has been used to obtain information about the planet's composition and internal structure. Several models of Jupiter's structure that fit the probe's data suggest that the planet has a diluted core, with a total heavy-element mass ranging from ten to a few tens of Earth masses (~5-15 % of the Jovian mass), and that heavy elements (elements other than H and He) are distributed within a region extending to nearly half of Jupiter's radius. Planet-formation models indicate that most heavy elements are accreted during the early stages of a planet's formation to create a relatively compact core and that almost no solids are accreted during subsequent runaway gas accretion. Jupiter's diluted core, combined with its possible high heavy-element enrichment, thus challenges standard planet-formation theory. A possible explanation is erosion of the initially compact heavy-element core, but the efficiency of such erosion is uncertain and depends on both the immiscibility of heavy materials in metallic hydrogen and on convective mixing as the planet evolves. Another mechanism that can explain this structure is planetesimal enrichment and vaporization during the formation process, although relevant models typically cannot produce an extended diluted core. Here we show that a sufficiently energetic head-on collision (giant impact) between a large planetary embryo and the proto-Jupiter could have shattered its primordial compact core and mixed the heavy elements with the inner envelope. Models of such a scenario lead to an internal structure that is consistent with a diluted core, persisting over billions of years. We suggest that collisions were common in the young Solar system and that a similar event may have also occurred for Saturn, contributing to the structural differences between Jupiter and Saturn.Comment: Published, author's versio

Formation of Terrestrial Planets

The past decade has seen major progress in our understanding of terrestrial planet formation. Yet key questions remain. In this review we first address the growth of 100 km-scale planetesimals as a consequence of dust coagulation and concentration, with current models favoring the streaming instability. Planetesimals grow into Mars-sized (or larger) planetary embryos by a combination of pebble- and planetesimal accretion. Models for the final assembly of the inner Solar System must match constraints related to the terrestrial planets and asteroids including their orbital and compositional distributions and inferred growth timescales. Two current models -- the Grand-Tack and low-mass (or empty) primordial asteroid belt scenarios -- can each match the empirical constraints but both have key uncertainties that require further study. We present formation models for close-in super-Earths -- the closest current analogs to our own terrestrial planets despite their very different formation histories -- and for terrestrial exoplanets in gas giant systems. We explain why super-Earth systems cannot form in-situ but rather may be the result of inward gas-driven migration followed by the disruption of compact resonant chains. The Solar System is unlikely to have harbored an early system of super-Earths; rather, Jupiter's early formation may have blocked the ice giants' inward migration. Finally, we present a chain of events that may explain why our Solar System looks different than more than 99\% of exoplanet systems