Improved Ad26 vaccine stability by mitigating interaction of viral particles with glass surfaces

Long term vaccine stability at refrigerated temperatures (2-8°C and ambient) is critical to ensure a global reach of the vaccine using a standardized supply chain. During Ad26 clinical vaccine development, some instability at 2-8°C was observed which triggered a root cause investigation. There was a risk that the target shelf life of at least 2 years at 2-8°C would not be met. The root cause was identified as adsorption of viral particles (vp’s) to the glass surface. This phenomenon is in particular observed upon inversion of the vial at 2-8°C due to the additional loss of vp’s to unexposed glass surface. Various innovative analytical tools were applied including spectroscopic kinetic monitoring of the loss of the vp’s directly inside the 2R glass vials. This was enabled by creating custom 3D printed accessories to fit the equipment. Models were created that allowed further predictions on the amount of vp’s adsorbed, dependent on volume, titer and vial type. Additional orthogonal analytical methods were applied to confirm the results, such as visualizing adsorbed material by dyes (staining) on the glass walls (Figure 1) as well as determining the vp content using VPqPCR and CZE. Please click Download on the upper right corner to see the full abstract

Descripçao funebre das Exequias que a Inquisiçao de Goa dedicou à memoria do Eminent.mo e Rever.mo Senhor Nuno da Cunha de Ataide, ... com a Oraçao funebre que nas mesmas Exequias recitou ... Fr. Joao do Pilar ... e Elogio do mesmo Em.mo e R.mo Sen.or ... por Romualdo Glohysio Freire, ...

Biblioteca Emil van der Vekene. - No consta en Van der Vekene I, II, III. #617

Displacer-type liquid level sensor with liquid density auto-compensation

In the classic displacer-type liquid level measuring method, liquid level is calculated via the buoyancy force exerted by the liquid on a displacer. This technology has high linearity, precision, accuracy, ease of installation and low cost. Nonetheless, displacer level sensors have significant sensitivity to variations in liquid density, which hinder its use in industrial applications that such quantity is not held constant. In this paper a novel displacer-type liquid level sensor is presented and analyzed. The innovation of the new sensor consists of adding another displacer and thus calculating the new measured value by the quotient of the buoyancy forces of both displacers. Therefore, the new measurement is ideally insensitive to the variations in liquid density. A prototype was built and prototype results presented high linearity, being able to mitigate the sensitivity to the liquid density, increasing accuracy in the measurements

a nationwide retrospective cohort study in mainland Portugal

Introduction There is growing concern about the aggressiveness of cancer care at the end of life (ACCEoL), defined as overly aggressive treatments that compromise the quality of life at its end. Recognising the most affected patients is a cornerstone to improve oncology care. Our aim is to identify factors associated with ACCEoL for patients with cancer dying in hospitals. Methods All adult patients with cancer who died in public hospitals in mainland Portugal (January 2010 to December 2015), identified from the hospital morbidity database. This database provided individual clinical and demographic data. We obtained hospital and region-level variables from a survey and National Statistics. The primary outcome is a composite ACCEoL measure of 16 indicators. We used multilevel random effects logistic regression modelling (p14 days in the hospital (43%, 42-43) and surgery (28%, 28-28) in the last 30 days. Older age (p<0·001), breast cancer (OR 0·83; 95% CI 0·76 to 0·91), and metastatic disease (0·54; 95% CI 0·50 to 0·58) were negatively associated with ACCEoL. In contrast, higher Deyo-Charlson Comorbidity Index (p<0·001), gastrointestinal and haematological malignancies (p<0·001), and death at cancer centre (1·31; 95% CI 1·01 to 1·72) or hospital with medical oncology department (1·29; 95% CI 1·02 to 1·63) were positively associated with ACCEoL. There was no association between hospital palliative care services at the hospital of death and ACCEoL. Conclusion Clinical factors related to a better understanding of disease course are associated with ACCEoL reduction. Patients with more comorbidities and gastrointestinal malignancies might represent groups with complex needs, and haematological patients may be at increased risk because of unpredictable prognosis. Improvement of hospital palliative care services could help reduce ACCEoL, particularly in cancer centres and hospitals with medical oncology department, as those services are usually under-resourced, thus reaching few.publishersversionpublishe

Trans-sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes

In experimental Trypanosoma cruzi infections, severe thymic atrophy leads to release of activated CD4+CD8+ double-positive (DP) T cells to the periphery. In humans, activated DP T cells are found in the blood in association with severe cardiac forms of human chronic Chagas disease. The mechanisms underlying the premature thymocyte release during the chagasic thymic atrophy remain elusive. We tested whether the migratory properties of intrathymic thymocytes are modulated by the parasite trans-sialidase (TS). We found that TS affected the dynamics of thymocytes undergoing intrathymic maturation, and these changes were accompanied by an increase in the number of recent DP thymic emigrants in the peripheral lymphoid organs. We demonstrated that increased percentages of blood DP T cell subsets were associated with augmented antibody titers against TS in chagasic patients with chronic cardiomyopathy. In vitro studies showed that TS was able to activate the MAPK pathway and actin filament mobilization in thymocytes. These effects were correlated with its ability to modulate the adhesion of thymocytes to thymic epithelial cells and their migration toward extracellular matrix. These findings point to effects of TS that could influence the escape of immature thymocytes in Chagas disease.Fil: Nardy, Ana Flávia F.R.. Universidade Federal do Rio de Janeiro; BrasilFil: Silva Filho, Joao Luiz da. Universidade Federal do Rio de Janeiro; BrasilFil: Perez, Ana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Meis, Juliana de. Instituto Oswaldo Cruz; BrasilFil: Farias de Oliveira, Désio Aurélio. Instituto Oswaldo Cruz; BrasilFil: Penha, Luciana. Universidade Federal do Rio de Janeiro; BrasilFil: Oliveira, Isadora de Araújo. Universidade Federal do Rio de Janeiro; BrasilFil: Dias, Wagner B.. Universidade Federal do Rio de Janeiro; BrasilFil: Todeschini, Adriane. Universidade Federal do Rio de Janeiro; BrasilFil: Freire de Lima, Célio Geraldo. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Caruso Neves, Celso. Universidade Federal do Rio de Janeiro; BrasilFil: Pinheiro, Ana Acácia. Universidade Federal do Rio de Janeiro; BrasilFil: Takiya, Christina Maeda. Universidade Federal do Rio de Janeiro; BrasilFil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Savino, Wilson. Instituto Oswaldo Cruz; BrasilFil: Morrot, Alexandre. Universidade Federal do Rio de Janeiro; Brasi

Feeding in advanced dementia: consensus report from the Portuguese Society of Internal Medicine and Portuguese Enteral and Parenteral Nutrition Society

A demência é uma síndrome neurológica de agravamento progressivo, sem cura, cuja prevalência tem vindo a aumentar devido ao envelhecimento da população. Existe um grande desconhecimento entre profissionais de saúde e cuidadores relativamente à melhor abordagem da alimentação nos doentes com demência avançada. Dado não existirem recomendações nacionais acerca deste tema, foi elaborado um documento de consenso da Sociedade Portuguesa de Medicina Interna e da Associação Portuguesa de Nutrição Entérica e Parentérica que explicita as orientações existentes relativas à abordagem dos problemas alimentares nos doentes com demência avançada. A demência avançada é uma condição terminal em que deve ser privilegiado o conforto do doente, frequentemente acamado, incapaz de comunicar verbalmente e com dificuldade na alimentação. Nesta população, a literatura atual não recomenda o uso de alimentação por sonda (nasogástrica, nasojejunal, gastrostomia percutânea ou jejunostomia percutânea), que está associada a maior risco de infeção, maior utilização de meios de contenção e desenvolvimento de úlceras de decúbito. Como alternativa, recomenda-se a alimentação por via oral de acordo com a tolerância e vontade do doente (alimentação de conforto). Do ponto de vista ético e legal, é legítimo não proceder à artificialização da alimentação na fase terminal da demência caso este procedimento seja contrário aos valores da pessoa e não se objetivem benefícios. Esta decisão deve ser tomada após discussão multidisciplinar incluindo o doente (se possível), representante legal, cuidadores, família e equipa de profissionais de saúde envolvidos, elaborando um plano individual de cuidados que permita a tomada de decisões no melhor interesse do doente.ABSTRACT - Dementia is a progressive neurological syndrome without cure whose prevalence is increasing due to population aging. There is a lack of knowledge among healthcare professionals and caregivers regarding the best feeding approach in patients with advanced dementia. As there are no national recommendations on this subject, a consensus report from the Portuguese Society of Internal Medicine and the Portuguese Enteral and Parental Nutrition Society was made, clarifying existing guidelines regarding the approach of eating difficulties in these patients. Advanced dementia is a terminal condition where patient comfort should be the goal. These patients are usually bedbound, have limited ability to communicate verbally and have difficulty eating. In this population, current literature does not support tube feeding (nasogastric tube, nasojejunal tube, percutaneous gastrostomy or percutaneous jejunostomy feeding), which is associated with higher rates of infection, greater use of chemical and physical restraints and development of pressure ulcers. As an alternative, careful hand feeding should be offered (comfort feeding). From an ethical and legal standpoint, it is acceptable not to use tube feeding in the terminal phase of dementia if it is against patient values and offers no benefits. This decision should be made using a multidisciplinary approach including the patient (if possible), legal representative, caregivers, family and healthcare professionals, in order to establish an individual care plan allowing decision making in the patient’s best interest.info:eu-repo/semantics/publishedVersio

Ensino remoto emergencial na Medicina: aspectos positivos e negativos no ensino e na aprendizagem em tempos de pandemia

Resumo: Introdução: O ensino remoto surgiu como ferramenta emergencial no processo de educação superior durante a pandemia da Covid-19. Nesse cenário, amplia-se a possibilidade de ensinar e aprender por meio das tecnologias da informação e comunicação (TIC) nos cursos de Medicina. Objetivo: Este estudo teve como objetivo realizar uma revisão integrativa que esclareça os principais aspectos positivos e negativos encontrados no exercício do ensino médico, nessas condições atípicas. Método: A busca dos artigos se deu nas seguintes bases: Biblioteca Virtual em Saúde (BVS), Embase, Education Resources Information Center (ERIC), Medline (via PubMed), Scopus e Web of Science. Resultado: Ao final dos processos de triagem e seleção, incluíram-se 69 artigos, dos quais foram extraídas informações quanto às características dos aspectos positivos e negativos de cada experiência de ensino remoto médico ofertado nesse período pandêmico. Entre os principais aspectos positivos, destacam-se a avaliação positiva do componente curricular pelos estudantes, a maior autonomia do aluno, a maior participação e comunicação entre os alunos, e a ausência de déficit de aprendizado. Entre os principais pontos negativos, observam-se a suspensão das aulas práticas, as complicações decorrentes do uso das tecnologias (conectividade, capacitação e organização) e a ausência de contato social. Conclusão: Observa-se que a autonomia e a autodisciplina discentes são fatores cruciais para o aproveitamento pleno de abordagem de aprendizagem remotamente, e talvez o aluno presencial clássico não estivesse preparado para tal mudança brusca. Ainda, percebe-se que, pela urgência de implantação dessa nova forma de aprendizagem, o ensino remoto não tenha tido tempo e maturidade o suficiente para que fosse aperfeiçoado ao ponto de ser considerado uma estratégia de educação médica aplicável em longo prazo. O ensino remoto foi crucial para que a formação de novos médicos não fosse descontinuada por um período de tempo tão extenso. Porém, o ensino remoto precisa ser reavaliado e aperfeiçoado como estratégia pedagógica que utiliza TIC para o ensino médico

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO