Application of Quality by Design in a Commercialized Lyophilized Vaccine

The pharmaceutical industry has being implementing regulatory practices to assure that consumers obtain products with quality, safety, and efficacy. The use of Quality by Design (QbD) for products on development has increased though the years to avoid issues related to quality parameters and has been suggested by Regulatory Agencies to standardize globally the documentation for the registration of new products. Although the concepts of QbD gain importance, it is still not a widespread practice to existing systems and products already on the market. This work aims to propose a case study with a vaccine using QbD concepts on the lyophilization unit operation production step to provide robustness and increase efficiency, leading to a lyophilization cycle time reduction. To this end, a reverse way of the use of QbD principles were applied based on historical batches database, down scale experiments, and finally in industrial scale to establish new boundaries in the lyophilization cycle. Experimental batches samples were analyzed through accelerated and real time stability study. At the end, this case became a possibility to establish new ranges to lyophilization process predicting risks and assure robustness to this production step with the maintenance of quality and safety of vaccine

NDVI e EVI Aplicados à Análise da Dinâmica Temporal da Cobertura Vegetal e Usos da Terra da Bacia do Córrego Padre Inácio-Mato Grosso, Brasil

O objetivo deste estudo é aplicar os índices de vegetação Normalized Difference Vegetation Index (NDVI) e Enhanced Vegetation Index (EVI) para análise da dinâmica temporal da cobertura vegetal e dos usos da terra da Bacia Hidrográfica do Córrego Padre Inácio, no Estado de Mato Grosso. O estudo é desenvolvido na perspectiva de que os dados e informações geradas contribuam para a conservação ambiental do bioma Pantanal, a qual a bacia é contribuinte hídrica. Para tal, foram gerados os dados de cobertura vegetal e dos usos da terra, para o ano de 2016; extração dos dados de NDVI e EVI para o período de 16 anos; verificação a campo para correções e validação; cálculos das curvas médias das classes para cada índice e confecção dos perfis médios. Quatro classes de cobertura vegetal e usos da terra foram identificadas na bacia: Agricultura na Região de Savana (Ac.S); Floresta Estacional Semidecidual Aluvial (Fa); Pastagem plantada na Região de Savana (Ap.S) e Savana Arborizada com Presença de Savana Florestada (Sa+Sd). A Ap.S ocupou áreas originalmente de Fa e Sa+Sd, sendo que as práticas de manejo contribuíram para a aceleração da degradação na bacia, fato evidenciado pelo baixo índice de biomassa. Atualmente a Ac.S (cana-de-açúcar, majoritariamente) tem se expandido, ocupando as áreas de Ap.S degradadas. A baixa densidade da vegetação nativa no entorno dos cursos hídricos sinaliza o descumprimento das normas do Código Florestal. Dessa maneira, é urgente a adoção de práticas de manejo conservacionistas e recuperação das Áreas de Preservação Permanentes dos cursos hídricos, caso contrário, as práticas agropecuárias desenvolvidas na bacia se tornarão inviáveis, provocando o surgimento e a intensificação de problemas ambientais

AMBIENTE DE ENSINO-APRENDIZAGEM NA FORMAÇÃO INICIAL UNIVERSITÁRIA DE EDUCAÇÃO FÍSICA

The objective was to analyze the perceptions of university students of Physical Education, at different levels of progression in the course, about the teaching-learning environment in the initial formation. A total of 273 students (bachelor n=150; pre-service teachers n=123) of the Physical Education, from a public university in Santa Catarina state, Brazil, responded to the adapted version of the Initial Formation Perceived Environment Assessment Questionnaire in Physical Education. The Chi-square test was used to analyze the associations between the level of student progression in the courses and their perceptions about the initial training environment. The results indicated the predominant use of classes/practical experiences and written theoretical assessments as teaching-learning strategies, especially in the early stages. The infrequent observation experiences, and learning through practice or observation was the role assumed, especially evidenced in the final semesters. Although students perceived their level of participation as being mostly active, they indicated that professors are primarily responsible for making decisions. We concluded that the initial formation in Physical Education in the investigated university needs to reconsider certain teaching-learning practices to increase student involvement and responsibility for the training process itself. Objetivou-se, neste estudo, analisar as percepções de estudantes universitários de Educação Física em distintos níveis de progressão no curso, sobre o ambiente de ensino-aprendizagem na formação inicial. Participaram 273 estudantes (Bacharelado n=150; Licenciatura n=123) do curso de licenciatura em Educação Física de uma universidade pública de Santa Catarina, Brasil, os quais responderam à versão adaptada do Questionário de Avaliação do Ambiente Percebido da Formação Inicial em Educação Física. O teste Qui-quadrado foi utilizado para analisar as associações entre o nível de progressão discente nos cursos e suas percepções sobre o ambiente de formação inicial. Os resultados indicaram a predominância de aulas/vivências práticas e de avaliações teóricas escritas, especialmente nas fases iniciais. As experiências poucos frequentes de observação, e o aprendizado pela prática ou por observação foi o papel assumido, especialmente evidenciados nos semestres finais. Apesar de os estudantes terem se percebido ativos quanto ao seu nível de participação, indicaram que os professores são os principais responsáveis por tomar as decisões. Conclui-se que a formação inicial em Educação Física necessita reconfigurar determinadas práticas de ensino-aprendizagem para aumentar o envolvimento e a responsabilidade discentes pelo próprio processo formativo

PADRÕES DE DESMATAMENTO NOS BIOMAS AMAZÔNIA, CERRADO E PANTANAL NA BACIA HIDROGRÁFICA DO ALTO PARAGUAI, MATO GROSSO - BRASIL

The objective of this study is to analyze the spatial dynamics of vegetation cover and land use and the rate of deforestation in the Upper Paraguay River Basin, located in the Brazilian state of Mato Grosso, so that the information can contribute to the development of territorial planning strategies aimed at environmental conservation. Analyses of the dynamics of changes in vegetation cover and land use and deforestation rates were carried out through procedures carried out via geoprocessing (cutting, reclassification, resizing and quantification) of the annual mapping data (1985-2020) generated by the Annual Mapping Project of Land Cover and Use in Brazil (MapBiomas). In the investigated hydrographic unit, the Natural Vegetation Areas decreased by 19.82%, while the Agricultural Anthropogenic Areas increased by 76.74%. In the basin, the average deforestation rate was 1.57%/year, while in the Amazon, Cerrado and Pantanal biomes in the basin it was 4.09%/year, 1.58%/year and 0.75%/year, respectively. In the Pantanal, the average deforestation rate went from 0.77%/year to 0.88%/year from the initial five-year period (1986-1990) to the end (2016-2020), while in the same period there was a reduction in the Amazon (5.12%/year to 2.22%/year) and in the Cerrado (1.68%/year to 1.21%/year). It can be seen that deforestation occurs heterogeneously in the basin with greater intensity in the biomes located in the plateau region (Amazon and Cerrado), where anthropogenic areas have surpassed areas of natural vegetation. Although the average rate of deforestation is low in the Pantanal, compared to the other biomes, a recent upward trend (2016-2020) in the average was observed.El objetivo de este estudio es analizar la dinámica espacial de la cobertura vegetal y el uso del suelo y la tasa de deforestación en la Cuenca del Río Alto Paraguay, ubicada en el estado brasileño de Mato Grosso, de manera que la información pueda contribuir al desarrollo de estrategias de planificación territorial orientadas a la conservación ambiental. Los análisis de la dinámica de los cambios en la cobertura vegetal y en las tasas de uso y deforestación del suelo se realizaron a través de procedimientos realizados a través del geoprocesamiento (corte, reclasificación, redimensionamiento y cuantificación) de los datos de mapeo anual (1985-2020) generados por el Proyecto Anual de Mapeo de Cobertura y Uso del Suelo en Brasil (MapBiomas). En la unidad hidrográfica investigada, las Áreas de Vegetación Natural disminuyeron en 19.82%, mientras que las Áreas Antropogénicas Agrícolas aumentaron en 76.74%. En la cuenca, la tasa promedio de deforestación fue de 1,57%/año, mientras que en los biomas Amazonia, Cerrado y Pantanal de la cuenca fue de 4,09%/año, 1,58%/año y 0,75%/año, respectivamente. En el Pantanal, la tasa promedio de deforestación pasó de 0,77%/año a 0,88%/año desde el quinquenio inicial (1986-1990) hasta el final (2016-2020), mientras que en el mismo período hubo una reducción en la Amazonia (5,12%/año a 2,22%/año) y en el Cerrado (1,68%/año a 1,21%/año). Se puede observar que la deforestación ocurre de manera heterogénea en la cuenca, con mayor intensidad en los biomas ubicados en la región de la meseta (Amazonas y Cerrado), donde las áreas antropogénicas han superado las áreas de vegetación natural. Aunque la tasa promedio de deforestación es baja en el Pantanal, en comparación con los otros biomas, se observó una tendencia al alza reciente (2016-2020) en el promedio.O objetivo deste estudo é analisar a dinâmica espacial da cobertura vegetal e uso da terra e a taxa de desmatamento na Bacia Hidrográfica do Alto Paraguai, localizada no estado brasileiro de Mato Grosso, visando que as informações possam contribuir no desenvolvimento de estratégias de planejamento territorial voltadas à conservação ambiental. Foram realizadas análises da dinâmica de mudanças da cobertura vegetal e uso da terra e das taxas de desmatamento por meio de procedimentos efetuados via geoprocessamento (recorte, reclassificação, redimensionamento e quantificação) dos dados anuais de mapeamentos (1985-2020) gerados pelo Projeto de Mapeamento Anual da Cobertura e Uso do Solo no Brasil (MapBiomas). Na unidade hidrográfica investigada as Áreas de Vegetação Natural sofreram redução de 19,82%, ao passo que as Áreas Antrópicas Agrícolas aumentaram 76,74%. Na bacia a taxa média de desmatamento foi de 1,57%/ano, enquanto que nos biomas Amazônia, Cerrado e Pantanal na bacia foi de 4,09%/ano, 1,58%/ano e 0,75%/ano, respectivamente. No Pantanal a taxa média de desmatamento foi de 0,77%/ano para 0,88%/ano do quinquênio inicial (1986-1990) para o final (2016-2020), enquanto no mesmo período houve redução na Amazônia (5,12%/ano para 2,22%/ano) e no Cerrado (1,68%/ano para 1,21%/ano). Constata-se que na bacia o desmatamento ocorre de forma heterogênea, com maior intensidade nos biomas localizados na região de planalto (Amazônia e Cerrado), onde as áreas antrópicas superaram as áreas de vegetação natural. Embora a taxa média de desmatamento seja baixa no Pantanal, comparado aos demais biomas, foi observada uma tendência de aumento recente (2016-2020) na médi

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis"

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration