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Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10–13 million people live with these conditions. Increased use of chromosome microarray assays, exome sequencing, and whole genome sequencing as first-tier testing techniques in suitable indications can shorten the diagnostic odyssey, eliminate unnecessary tests, procedures, and treatments, and lower healthcare expenditures. A selected panel of Brazilian experts in fields related to rare diseases was provided with a series of relevant questions to address before a multi-day conference. Within this conference, each narrative was discussed and edited through numerous rounds of discussion until agreement was achieved. The widespread adoption of exome sequencing and whole genome sequencing in Brazil is limited by various factors: cost and lack of funding, reimbursement, awareness and education, specialist shortages, and policy issues. To reduce the burden of rare diseases and increase early diagnosis, the Brazilian healthcare authorities/government must address the barriers to equitable access to early diagnostic methods for these conditions. Recommendations are provided, including broadening approved testing indications, increasing awareness and education efforts, increasing specialist training opportunities, and ensuring sufficient funding for genetic testing. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus was first registered in Brazil by the end of February 2020. Since then, the country counts over 150000 deaths due to COVID-19 and faces a profound social and economic crisis; there is also an ongoing health catastrophe, with the majority of hospital beds in many Brazilian cities currently occupied with COVID-19 patients. Thus, a Nonlinear Model Predictive Control (NMPC) scheme used to plan appropriate social distancing measures (and relaxations) in order to mitigate the effects of this pandemic is formulated in this paper. The strategy is designed upon an adapted data-driven Susceptible–Infected–Recovered–Deceased (SIRD) model, which includes time-varying auto-regressive immunological parameters. A novel identification procedure is proposed, composed of analytical regressions, Least-Squares optimization and auto-regressive model fits. The adapted SIRD model is validated with real data and able to adequately represent the contagion curves over large forecast horizons. The NMPC strategy is designed to generate piecewise constant quarantine guidelines, which can be reassessed (relaxed/strengthened) each week. Simulation results show that the proposed NMPC technique is able to mitigate the number of infections and progressively loosen social distancing measures. With respect to a "no-control" condition, the number of deaths could be reduced in up to 30% if the proposed NMPC coordinated health policy measures are enacted. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic (SARS-CoV-2 virus) is the global crisis of our time. The absence of mass testing and the relevant presence of asymptomatic individuals causes the available data of the COVID-19 pandemic in Brazil to be largely under-reported regarding the number of infected individuals and deaths. We develop an adapted Susceptible-Infected-Recovered (SIR) model, which explicitly incorporates the under-reporting and the response of the population to public health policies (confinement measures, widespread use of masks, etc). Large amounts of uncertainty could provide misleading predictions of the COVID-19 spread. In this paper, we discuss the role of uncertainty in these model-based predictions, which is illustrated regarding three key aspects: (i) Assuming that the number of infected individuals is under-reported, we demonstrate anticipation regarding the infection peak. Furthermore, while a model with a single class of infected individuals yields forecasts with increased peaks, a model that considers both symptomatic and asymptomatic infected individuals suggests a decrease of the peak of symptomatic cases. (ii) Considering that the actual amount of deaths is larger than what is being registered, we demonstrate an increase of the mortality rates. (iii) When we consider generally under-reported data, we demonstrate how the transmission and recovery rate model parameters change qualitatively and quantitatively. We also investigate the "the uncertainty tripod": under-reporting level in terms of cases, deaths, and the true mortality rate of the disease. We demonstrate that if two of these factors are known, the remainder can be inferred, as long as proportions are kept constant. The proposed approach allows one to determine the margins of uncertainty by assessments on the observed and true mortality rates. [ABSTRACT FROM AUTHOR]

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Copyright of Revista Subjetividades is the property of Revista Mal-estar e Subjetividade and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015–2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses. Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories. [ABSTRACT FROM AUTHOR]

Increasing pandemic influenza vaccine manufacturing capacity is considered strategic by WHO. Adjuvant use is key in this strategy in order to spare the vaccine doses and by increasing immune protection. We describe here the production and stability studies of a squalene based oil-in-water emulsion, adjuvant IB160, and the immune response of the H7N9 vaccine combined with IB160. To qualify the production of IB160 we produced 10 consistency lots of IB160 and the average results were: pH 6.4±0.05; squalene 48.8±.0.03 mg/ml; osmolality 47.6±6.9 mmol/kg; Z-average 157±2 nm, with polydispersity index (PDI) of 0.085±0.024 and endotoxin levels <0.5 EU/mL. The emulsion particle size was stable for at least six months at 25°C and 24 months at 4–8°C. Two doses of H7N9 vaccine formulated at 7.5 μg/dose or 15 μg/dose with adjuvant IB160 showed a significant increase of hemagglutination inhibition (HAI) titers in sera of immunized BALB/c mice when compared to control sera from animals immunized with the H7N9 antigens without adjuvant. Thus the antigen-sparing capacity of IB160 can potentially increase the production of the H7N9 pandemic vaccine and represents an important achievement for preparedness against pandemic influenza and a successful North (IDRI) to South (Butantan Institute) technology transfer for the production of the adjuvant emulsion IB160. [ABSTRACT FROM AUTHOR]

This article presents an analysis of the quality of advertisements for over-the-counter (OTC) drugs addressed to the medical profession, based on the new Anvisa resolution RDC 96 (17/12/2008). For this analysis, 16 volumes of the Brazilian Journal of Medicine (RBM) were collected, from August 2009 to December 2010. To investigate the quality of the adverts, we prepared a questionnaire divided into three parts. In total, 160 advertisements were found, of which 27 were related to drugs exempt from prescription, from 9 laboratories. It was observed that none of the advertisements complied fully with the new rules, as required by legislation (RDC 96/08), with violations ranging from identification of the advert to prohibitions of human figures and subjective messages. Therefore, it was concluded that there is a need to implement more effective monitoring, so as to improve the quality of the adverts, so they can be used as a reliable source of information and update by prescribers. [ABSTRACT FROM AUTHOR]

Objective: To determine the accuracy of the Timed Up and Go Test (TUGT) for screening the risk of falls among community-dwelling elderly individuals. Method: This is a prospective cohort study with a randomly by lots without reposition sample stratified by proportional partition in relation to gender involving 63 community-dwelling elderly individuals. Elderly individuals who reported having Parkinson´s disease, a history of transitory ischemic attack, stroke and with a Mini Mental State Exam lower than the expected for the education level, were on a wheelchair and that reported a single fall in the previous six months were excluded. The TUGT, a mobility test, was the measure of interested and the occurrence of falls was the outcome. The performance of basic activities of daily living (ADL) and instrumental activities of daily living (IADL) was determined through the Older American Resources and Services, and the socio-demographic and clinical data were determined through the use of additional questionnaires. Receiver Operating Characteristic Curves were used to analyze the sensitivity and specificity of the TUGT. Results: Elderly individuals who fell had greater difficulties in ADL and IADL (p<0.01) and a slower performance on the TUGT (p=0.02). No differences were found in socio-demographic and clinical characteristics between fallers and non-fallers. Considering the different sensitivity and specificity, the best predictive value for discriminating elderly individuals who fell was 12.47 seconds [(RR=3.2) 95%CI: 1.3-7.7]. Conclusions: The TUGT proved to be an accurate measure for screening the risk of falls among elderly individuals. Although different from that reported in the international literature, the 12.47 second cutoff point seems to be a better predictive value for Brazilian elderly individuals. [ABSTRACT FROM AUTHOR]

This paper formulates a Model Predictive Control (MPC) policy to mitigate the COVID-19 contagion in Brazil, designed as optimal On-Off social isolation strategy. The proposed optimization algorithm is able to determine the time and duration of social distancing policies in the country. The achieved results are based on data from the period between March and May of 2020, regarding the cumulative number of infections and deaths due to the SARS-CoV-2 virus. This dataset is assumably largely sub-notified due to the absence of mass testing in Brazil. Thus, the MPC is based on a SIR model which is identified using an uncertainty-weighted Least-Squares criterion. Furthermore, this model includes an additional dynamic variable that mimics the response of the population to the social distancing policies determined by the government, which affect the COVID-19 transmission rate. The proposed control method is set within a mixed-logical formalism, since the decision variable is forcefully binary (existence or the absence of social distance policy). A dwell-time constraint is included to avoid too frequent shifts between these two inputs. The achieved simulation results illustrate how such optimal control method would operate in practice, pointing out that no social distancing should be relaxed before mid August 2020. If relaxations are necessary, they should not be performed before this date and should be in small periods, no longer than 25 days. This paradigm would proceed roughly until January/2021. The results also indicate a possible second peak of infections, which has a forecast to the beginning of October. This peak can be reduced if the periods of days with relaxed social isolation measures are shortened. [ABSTRACT FROM AUTHOR]

• A Polynomial State-Space model for fish population dynamics in areas affected by the golden mussel. • Model identification validation for ten different species. • Discussion of real-life applicable control strategies with a Nonlinear Model Predictive Control framework. • Numerical simulations. The invasion of exotic species in aquatic environments is one of the several disturbance factors responsible for altering the dynamics of fish communities. The golden mussel Limnoperna fortunei was first recorded in the upper Uruguay river, Brazil, in 2012 and, since then, it has been needed to discuss and evaluate how this invasive species interferes with the dynamics of the ten most abundant fishes of this region. Literature lacks works that investigate how to model and control the effect of such kind of invasion. This paper proposes a polynomial-nonlinear state-space representation to model the dynamics of the these fish communities, whose parameters are identified with the use of Least Squares procedures, considering in loci collected data from 2007 to 2016. This work also evaluates quantitatively, by relying on simulation results, how the (sudden) presence of the golden mussel medelled with the aquatic life of the upper Uruguay river. The obtained model allows some ambitious automatic control objectives. Using a Nonlinear Model Predictive Control (NMPC) approach, an automatic controller is designed to determine how much and how often the golden mussel should be removed from the water in order for the most affected species to once again exhibit sustainable life conditions, in terms of its K Condition Factor and abundance. The NMPC strategy is synthesized considering performance constraints and piecewise-constant control trajectories. By relying on simulation results, this work elucidates how an automatic controller could be implemented as management policies established by environmental agencies to gradually restore the fish ecological balance of the upper Uruguay river, previously unsettled by an exotic invasor. [ABSTRACT FROM AUTHOR]

The Amazon is the largest river by discharge volume and one of the most biodiverse biomes in the world. Lately, there has been a rapid increase of the urban population in the region, which has been translated into a growing emission of organic contaminants such as polycyclic aromatic hydrocarbons (PAHs) into surface water bodies. This study provides the most comprehensive evaluation of the PAH contamination levels in surface waters of the Amazon basin. We investigated the occurrence and potential sources of 16 priority PAHs and characterised their risks for freshwater ecosystems. For this, we took 40 water samples from different sites along the Brazilian part of the Amazon River, including three major tributaries, and smaller rivers crossing the main urban areas. The results of this study show that PAHs are widespread contaminants in rivers of the Brazilian Amazon. The sum of the total concentration of the 16 priority PAHs reached values of 134 ng L−1 in the Amazon River, and 163 ng L−1 near densely populated areas. On the other hand, the total PAH concentration was generally lower in the monitored tributaries. In most samples, the contamination pattern was dominated by high molecular weight PAHs, suggesting a major contribution of pyrogenic sources, although petrogenic contamination was also present in some locations near urban areas. We assessed ecological risks posed by PAH mixtures using a hazard index. The results indicated that PAH contamination is not likely to pose direct toxic effects for Amazonian freshwater organisms, however continued monitoring is recommended near densely populated areas. [Display omitted] • The presence of 16 priority PAHs was investigated in Amazonian surface waters. • PAHs were found in all samples, with total concentrations up to 163 ng L−1. • Higher concentrations were found next to large urban areas. • In most samples, PAH contamination was of pyrogenic origin. • PAHs may not directly harm Amazonian freshwater ecosystems. [ABSTRACT FROM AUTHOR]

The use of pesticides in households and peri-urban areas of the Amazon has increased notably during the last years. Yet, the presence of these contaminants in Amazonian freshwater ecosystems remains unexplored. Here, we assessed the exposure to 18 pesticides and 5 transformation products in the Amazon River and in the urban streams of Manaus, Santarém, Macapá, and Belém (Brazil). Pesticide concentrations were analyzed by liquid and gas chromatography methods. Ecological risks were assessed following a two-tiered approach. First, hazard quotients and an overall hazard index were calculated using toxicity data for standard test species of primary producers, invertebrates, and fish. Second, the pesticides showing moderate-to-high ecological risks in the first tier were evaluated using Species Sensitivity Distributions (SSDs). Our study shows that pesticides are widespread in urban and peri-urban areas of the Brazilian Amazon. The frequency of detection was higher in urban streams than in the Amazon River, with some samples taken in Manaus, Santarém, and Belém containing up to 8 compounds. Most pesticides were measured at relatively low concentrations (ng L -1 ), except for malathion, carbendazim and the bulk concentration of chlorpyrifos, which were monitored at concentrations above 100 ng L -1 . Based on the first-tier assessment, we found moderate-to-high risks for freshwater invertebrates for malathion, chlorpyrifos, and chlorpyrifos-methyl, and moderate risks for malathion to fish. The risk assessment performed with SSDs indicated high risks of malathion and chlorpyrifos-methyl in urban areas, with up to 15% and 5% of invertebrate species potentially affected, respectively. The bulk concentrations of chlorpyrifos resulted in high risks in some urban areas (14-22% of species affected) and in areas of the main river (32-44%) impacted by agriculture. We conclude that pesticide residues may contribute to a biodiversity impact in the Amazon and should be further monitored in urban and peri-urban areas, particularly after heavy rainfall events., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)