Modeling the Effects of Relapse in the Transmission Dynamics of Malaria Parasites

Often regarded as “benign,” Plasmodium vivax infections lay in the shadows of the much more virulent P. falciparum infections. However, about 1.98 billion people are at risk of both parasites worldwide, stressing the need to understand the epidemiology of Plasmodium vivax, particularly under the scope of decreasing P. falciparum prevalence and ecological interactions between both species. Two epidemiological observations put the dynamics of both species into perspective: (1) ACT campaigns have had a greater impact on P. falciparum prevalence. (2) Complete clinical immunity is attained at younger ages for P. vivax, under similar infection rates. We systematically compared two mathematical models of transmission for both Plasmodium species. Simulations suggest that an ACT therapy combined with a hypnozoite killing drug would eliminate both species. However, P. vivax elimination is predicted to be unstable. Differences in age profiles of clinical malaria can be explained solely by P. vivax's ability to relapse, which accelerates the acquisition of clinical immunity and serves as an immunity boosting mechanism. P. vivax transmission can subsist in areas of low mosquito abundance and is robust to drug administration initiatives due to relapse, making it an inconvenient and cumbersome, yet less lethal alternative to P. falciparum

Cultura de segurança: tradução, adaptação cultural e validação do Safety Attitudes Questionnaire (ICU version) para a população portuguesa

Dissertação de Mestrado em Enfermagem Médico-Cirúrgica apresentada na Escola Superior de Saúde do Instituto Politécnico de Viana do CasteloA segurança do doente assume uma preocupação crescente na sociedade. Não sendo somente uma preocupação dos gestores, mobiliza os profissionais bem como o cidadão para que sejam atingidos elevados níveis de qualidade. As estratégias utilizadas vão determinar o nível da qualidade dos cuidados prestados e o futuro da organização. As unidades de cuidados intensivos são serviços altamente complexos, constituídas por equipas multidisciplinares, utilizando equipamentos de monitorização e suporte vital tecnologicamente avançados, com o objetivo de cuidar, com a máxima qualidade, o doente em estado crítico O Safety Attitudes Questionnaire, é o instrumento de recolha de dados mais utilizado em organizações que prestam cuidados de saúde, para avaliação do clima de segurança. A sua versão para cuidados intensivos permite uma melhor perceção para estes ambientes complexos. O objetivo deste estudo foi traduzir, adaptar e validar o Safety Attitudes Questionnaire – ICU version para a população portuguesa e conhecer de que forma os enfermeiros percecionam a segurança dos doentes que estão sob o seu cuidado. O processo de tradução e adaptação seguiu a metodologia cientificamente reconhecida por vários autores. A validação do instrumento foi efetuada com tratamento dos resultados obtidos após aplicação do mesmo a 120 enfermeiros a desempenhar funções em unidades de cuidados intensivos. A sua validade e fidelidade foi avaliada com recurso a tratamento estatístico dos dados recolhidos. Para a análise dos resultados foi seguida a mesma metodologia dos autores originais do instrumento, agrupando-se as perguntas por seis dimensões (trabalho em equipe, clima de segurança, satisfação profissional, reconhecimento de stress, perceções sobre a gestão e condições de trabalho) e analisados os seus resultados. O questionário Safety Attiudes Questionaire – ICU versão portuguesa demonstrou possuir boas propriedades psicométricas, sendo válido e fiável para a população portuguesa. Os profissionais reconhecem a importância das questões relativas à segurança do doente, o papel que representam e o trabalho que tem que ser desenvolvido para ser atingido um patamar cada vez mais elevado da qualidade dos cuidados prestados.A segurança do doente assume uma preocupação crescente na sociedade. Não sendo somente uma preocupação dos gestores, mobiliza os profissionais bem como o cidadão para que sejam atingidos elevados níveis de qualidade. As estratégias utilizadas vão determinar o nível da qualidade dos cuidados prestados e o futuro da organização. As unidades de cuidados intensivos são serviços altamente complexos, constituídas por equipas multidisciplinares, utilizando equipamentos de monitorização e suporte vital tecnologicamente avançados, com o objetivo de cuidar, com a máxima qualidade, o doente em estado crítico O Safety Attitudes Questionnaire, é o instrumento de recolha de dados mais utilizado em organizações que prestam cuidados de saúde, para avaliação do clima de segurança. A sua versão para cuidados intensivos permite uma melhor perceção para estes ambientes complexos. O objetivo deste estudo foi traduzir, adaptar e validar o Safety Attitudes Questionnaire – ICU version para a população portuguesa e conhecer de que forma os enfermeiros percecionam a segurança dos doentes que estão sob o seu cuidado. O processo de tradução e adaptação seguiu a metodologia cientificamente reconhecida por vários autores. A validação do instrumento foi efetuada com tratamento dos resultados obtidos após aplicação do mesmo a 120 enfermeiros a desempenhar funções em unidades de cuidados intensivos. A sua validade e fidelidade foi avaliada com recurso a tratamento estatístico dos dados recolhidos. Para a análise dos resultados foi seguida a mesma metodologia dos autores originais do instrumento, agrupando-se as perguntas por seis dimensões (trabalho em equipe, clima de segurança, satisfação profissional, reconhecimento de stress, perceções sobre a gestão e condições de trabalho) e analisados os seus resultados. O questionário Safety Attiudes Questionaire – ICU versão portuguesa demonstrou possuir boas propriedades psicométricas, sendo válido e fiável para a população portuguesa. Os profissionais reconhecem a importância das questões relativas à segurança do doente, o papel que representam e o trabalho que tem que ser desenvolvido para ser atingido um patamar cada vez mais elevado da qualidade dos cuidados prestados

brightening the future of bioanalysis

This work was fnanced by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication—i3N and by the FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the following Projects: UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO; LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB; grant PTDC/NAN-MAT/30589/2017; and fellowship SFRH/BD/132057/2017 also from MIT Portugal PhD Program (to M.J.O.). Funding also from the European Community H2020 program under grant agreement No. 716510 (ERC-2016-STG TREND), No. 640598 (ERC-StG-2014, NEWFUN), and No. 685758 (1D-Neon).A new avenue has opened up for applications of surface-enhanced Raman spectroscopy (SERS) in the biomedical field, mainly due to the striking advantages offered by SERS tags. SERS tags provide indirect identification of analytes with rich and highly specific spectral fingerprint information, high sensitivity, and outstanding multiplexing potential, making them very useful in in vitro and in vivo assays. The recent and innovative advances in nanomaterial science, novel Raman reporters, and emerging bioconjugation protocols have helped develop ultra-bright SERS tags as powerful tools for multiplex SERS-based detection and diagnosis applications. Nevertheless, to translate SERS platforms to real-world problems, some challenges, especially for clinical applications, must be addressed. This review presents the current understanding of the factors influencing the quality of SERS tags and the strategies commonly employed to improve not only spectral quality but the specificity and reproducibility of the interaction of the analyte with the target ligand. It further explores some of the most common approaches which have emerged for coupling SERS with microfluidic technologies, for biomedical applications. The importance of understanding microfluidic production and characterisation to yield excellent device quality while ensuring high throughput production are emphasised and explored, after which, the challenges and approaches developed to fulfil the potential that SERS-based microfluidics have to offer are described.publishersversionpublishe

Office paper decorated with silver nanostars-an alternative cost effective platform for trace analyte detection by SERS

FCT (Portuguese Foundation for Science and Technology) under the project DISERTOX number PTDC/CTM-NAN/2912/2014 and CENIMAT/i3N by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT under the project number POCI-01-0145-FEDER- 007688, Reference UID/CTM/50025/2013. Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO was financed by Portuguese national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). LAQV-Laboratorio associado para a Quimica Verde was partly financed by the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia), under the Partnership Agreement PT2020 through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) and Programa Operacional Regional do Norte (ON. 2), under the Quadro de Referencia Estrategico Nacional (QREN) and funded by Fundo Europeu de Desenvolvimento Regional (Feder) NORTE-01-0145-FEDER-000011. A Araujo was funded by the Portuguese Science Foundation (FCT-MCTES) through grant SFRH/BD/85587/2012. M Almeida was funded by the Portuguese Science Foundation (FCT-MCTES) through grant SFRH/BD/95983/2013 in program POCH. The authors thank the Conservation and Restoration Department, FCT/UNL and LAQV, REQUIMTE for the use of the Raman spectrometer.For analytical applications in portable sensors to be used in the point-of-need, low-cost SERS substrates using paper as a base, are an alternative. In this work, SERS substrates were produced on two different types of paper: A high porosity paper (Whatman no. 1); and a low porosity paper (commercially available office paper, Portucel Soporcel). Solutions containing spherical silver nanoparticles (AgNPs) and silver nanostars (AgNSs) were separately drop-casted on hydrophilic wells patterned on the papers. The porosity of the paper was found to play a determinant role on the AgNP and AgNS distribution along the paper fibres, with most of the nanoparticles being retained at the illuminated surface of the office paper substrate. The highest SERS enhancements were obtained for the office paper substrate, with deposited AgNSs. A limit of detection for rhodamine-6G as low as 11.4 ± 0.2 pg could be achieved, with an analytical enhancement factor of â ‰107 for this specific analyte. The well patterning technique allowed good signal uniformity (RSD of 1.7%). Besides, these SERS substrates remained stable after 5 weeks of storage (RSD of 7.3%). Paper-induced aggregation of AgNPs was found to be a viable alternative to the classical salt-induced aggregation, to obtain a highly sensitive SERS substrates.publishersversionpublishe

Percolation across households in mechanistic models of non-pharmaceutical interventions in SARS-CoV-2 disease dynamics

We thank all members of Observatório COVID-19 BR and the CoMo Consortium for the collaborative work. The authors also thank the research funding agencies: São Paulo Research Foundation (FAPESP) – Brazil (grant number: 2019/26310-2 and 2017/26770-8 to CF, 2018/24037-4 to SP, 2018/23984-0 to VS and contract number: 2016/01343-7 to RAK), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Brazil (Finance Code 001 to LSF) and the Brazilian National Council for Scientific and Technological Development (CNPq) (grant number: 315854/2020-0 to MEB, 313055/2020-3 to PIP and 311832/2017-2 to RAK). RA is funded by the Bill and Melinda Gates Foundation (OPP1193472). LW is funded by the Li Ka Shing Foundation, Hong Kong. The CoMo Consortium has support from the Oxford University COVID-19 Research Response Fund (ref: 0009280).Peer reviewedPublisher PD

Reusable and highly sensitive SERS immunoassay utilizing gold nanostars and a cellulose hydrogel-based platform

This work was funded by FEDER funds through the COMPETE 2020 Programme and National Funds through the FCT---Fun-dação para a Ciência e a Tecnologia, I. P., under the scope of the project. This work also received funding from the European Community’s H2020 program under grant agreement No. 716510 (ERC-2016-STG TREND), 640598 (ERC-StG-2014, NEWFUN), and 685758 (1D-Neon). This work was supported by the Applied Molecular Biosciences Unit – UCIBIO and Associate Laboratory for Green Chemistry – LAQV which are financed by Portugal national funds from /2016 and SFRH/BD/132057/2017 from the FCT/MCTES and MIT Portugal PhD Program (to I. C. and M. J. O., respectively). Professor César Laia (LAQV-REQUIMTE, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Portugal) is acknowledged for permitting the use of DLS equipment. Professor Ludwig Krippahl (NOVA LINCS, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Portugal) is acknowledged for developing the gel analysis application eReuss. M. J. O. acknowledges Rocío Palomares Jurado PhD for visualisation/data presentation support and continued interest in the project. M. J. O. acknowledges David Peitinho MSc for help and advice in Python script. Diego Wiechers de Carvalho BSc is acknowledged for purifying the recombinant Plasmodium falciparum histidine-rich protein 2 sample and Daniela Gomes PhD for providing SEM images. Publisher Copyright: © The Royal Society of Chemistry 2021.The development of robust and sensitive point-of-care testing platforms is necessary to improve patient care and outcomes. Surface-enhanced Raman scattering (SERS)-based immunosensors are especially suited for this purpose. Here, we present a highly sensitive and selective SERS immunoassay, demonstrating for example the detection of horseradish peroxidase (HRP), in a sandwich format. The strength of our biosensor lies in merging: (i) SERS-immunotags based on gold nanostars, allowing exceptional intense SERS from attached Raman probes, covalent attachment of anti-HRP antibodies by a simple chemical method providing exceptional antigen binding activity; (ii) the ease of preparation of the capture platform from a regenerated cellulose-based hydrogel, a transparent material, ideal for microfluidics applications, with low background fluorescence and Raman signal, particularly suited for preserving high activity of the covalently bound anti-HRP antibodies. The sandwich complexes formed were characterised by atomic force microscopy, and by scanning electron microscopy coupled with electron diffraction spectroscopy; and (iii) the robustness of the simple Classical Least Squares method for SERS data analysis, resulting in superior discrimination of SERS signals from the background and much better data fitting, compared to the commonly used peak integral method. Our SERS immunoassay greatly improves the detection limits of traditional enzyme-linked immunosorbent assay approaches, and its performance is better or comparable to those of existing SERS-based immunosensors. Our approach successfully overcomes the main challenges of application at point-of-care, including increasing reproducibility, sensitivity, and specificity, associated with an environmentally friendly and robust design. Also, the proposed design withstands several cycles of regeneration, a feature absent in paper-SERS immunoassays and this opens the way for sensitive multiplexing applications on a microfluidic platform.preprintpublishe

E-skin bimodal sensors for robotics and prosthesis using PDMS molds engraved by laser

Electronic skin (e-skin) is pursued as a key component in robotics and prosthesis to confer them sensing properties that mimic human skin. For pressure monitoring, a great emphasis on piezoresistive sensors was registered due to the simplicity of sensor design and readout mechanism. For higher sensitivity, films composing these sensors may be micro-structured, usually by expensive photolithography techniques or low-cost and low-customizable molds. Sensors commonly present different sensitivities in different pressure ranges, which should be avoided in robotics and prosthesis applications. The combination of pressure sensing and temperature is also relevant for the field and has room for improvement. This work proposes an alternative approach for film micro-structuration based on the production of highly customizable and low-cost molds through laser engraving. These bimodal e-skin piezoresistive and temperature sensors could achieve a stable sensitivity of -6.4 × 10-3 kPa-1 from 1.6 kPa to 100 kPa, with a very robust and reproducible performance over 27,500 cycles of objects grasping and releasing and an exceptionally high temperature coefficient of resistance (TCR) of 8.3%/°C. These results point toward the versatility and high benefit/cost ratio of the laser engraving technique to produce sensors with a suitable performance for robotics and functional prosthesis

Potential health and economic impacts of dexamethasone treatment for patients with COVID-19

Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries

The Impact of IPTi and IPTc Interventions on Malaria Clinical Burden – In Silico Perspectives

Background: Clinical management of malaria is a major health issue in sub-Saharan Africa. New strategies based on intermittent preventive treatment (IPT) can tackle disease burden by simultaneously reducing frequency of infections and life-threatening illness in infants (IPTi) and children (IPTc), while allowing for immunity to build up. However, concerns as to whether immunity develops efficiently in treated individuals, and whether there is a rebound effect after treatment is halted, have made it imperative to define the effects that IPTi and IPTc exert on the clinical malaria scenario. Methods and Findings: Here, we simulate several schemes of intervention under different transmission settings, while varying immunity build up assumptions. Our model predicts that infection risk and effectiveness of acquisition of clinical immunity under prophylactic effect are associated to intervention impact during treatment and follow-up periods. These effects vary across regions of different endemicity and are highly correlated with the interplay between the timing of interventions in age and the age dependent risk of acquiring an infection. However, even when significant rebound effects are predicted to occur, the overall intervention impact is positive. Conclusions: IPTi is predicted to have minimal impact on the acquisition of clinical immunity, since it does not interfere with the occurrence of mild infections, thus failing to reduce the underlying force of infection. On the contrary, IPTc has