Images of psychiatry and psychiatrists

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Integrating pressure sensor control into semi-solid extrusion 3D printing to optimize medicine manufacturing

Semi-solid extrusion (SSE) is a three-dimensional printing (3DP) process that involves the extrusion of a gel or paste-like material via a syringe-based printhead to create the desired object. In pharmaceuticals, SSE 3DP has already been used to manufacture formulations for human clinical studies. To further support its clinical adoption, the use of a pressure sensor may provide information on the printability of the feedstock material in situ and under the exact printing conditions for quality control purposes. This study aimed to integrate a pressure sensor in an SSE pharmaceutical 3D printer for both material characterization and as a process analytical technology (PAT) to monitor the printing process. In this study, three materials of different consistency were tested (soft vaseline, gel-like mass and paste-like mass) under 12 different conditions, by changing flow rate, temperature, or nozzle diameter. The use of a pressure sensor allowed, for the first time, the characterization of rheological properties of the inks, which exhibited temperature-dependent, plastic and viscoelastic behaviours. Controlling critical material attributes and 3D printing process parameters may allow a quality by design (QbD) approach to facilitate a high-fidelity 3D printing process critical for the future of personalized medicine

Simultaneous fabrication of multiple tablets within seconds using tomographic volumetric 3D printing

3D printing is driving a shift in patient care away from a generalised model and towards personalised treatments. To complement fast-paced clinical environments, 3D printing technologies must provide sufficiently high throughputs for them to be feasibly implemented. Volumetric printing is an emerging 3D printing technology that affords such speeds, being capable of producing entire objects within seconds. In this study, for the first time, rotatory volumetric printing was used to simultaneously produce two torus- or cylinder-shaped paracetamol-loaded Printlets (3D printed tablets). Six resin formulations comprising paracetamol as the model drug, poly(ethylene glycol) diacrylate (PEGDA) 575 or 700 as photoreactive monomers, water and PEG 300 as non-reactive diluents, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as the photoinitiator were investigated. Two printlets were successfully printed in 12 to 32 s and exhibited sustained drug release profiles. These results support the use of rotary volumetric printing for efficient and effective manufacturing of various personalised medicines at the same time. With the speed and precision it affords, rotatory volumetric printing has the potential to become one of the most promising alternative manufacturing technologies in the pharmaceutical industry

Predicting pharmaceutical inkjet printing outcomes using machine learning

Inkjet printing has been extensively explored in recent years to produce personalised medicines due to its low cost and versatility. Pharmaceutical applications have ranged from orodispersible films to complex polydrug implants. However, the multi-factorial nature of the inkjet printing process makes formulation (e.g., composition, surface tension, and viscosity) and printing parameter optimization (e.g., nozzle diameter, peak voltage, and drop spacing) an empirical and time-consuming endeavour. Instead, given the wealth of publicly available data on pharmaceutical inkjet printing, there is potential for a predictive model for inkjet printing outcomes to be developed. In this study, machine learning (ML) models (random forest, multilayer perceptron, and support vector machine) to predict printability and drug dose were developed using a dataset of 687 formulations, consolidated from in-house and literature-mined data on inkjet-printed formulations. The optimized ML models predicted the printability of formulations with an accuracy of 97.22%, and predicted the quality of the prints with an accuracy of 97.14%. This study demonstrates that ML models can feasibly provide predictive insights to inkjet printing outcomes prior to formulation preparation, affording resource- and time-savings

O projecto INTERFRUTA II e o seu papel no desenvolvimento da fruticultura na ilha Terceira

I Congresso de Fruticultura e Viticultura. Angra do Heroísmo 17-19 Abril 2008.Trabalho de investigação desenvolvido no projecto INTERFRUTA II, financiado pelo programa INTERREG III-B (05/MAC/3.1/A4).O Projecto INTERFRUTA II é um projecto desenvolvido nas Ilhas da Madeira, Tenerife (Canárias) e Terceira (Açores) destinado a contribuir para a promoção da fruticultura e viticultura nestas três regiões insulares, procurando uma melhoria dos conhecimentos sobre as culturas de macieiras, bananeiras, castanheiros e vinha. Englobando um estudo integrado que envolve a climatologia, fenologia, pedologia, problemas fitossanitários, pragas-chave e a fauna auxiliar presente nas parcelas estudadas, distribuídas pela zona Norte e Sul da Ilha, aplicando técnicas que contribuam decisivamente para o conhecimento e procura de soluções inovadoras que conduzam ao acréscimo do rendimento dos produtores e a uma menor utilização e aplicação de pesticidas. Para atingir estes objectivos numa fase inicial realizaram-se 160 inquéritos aos produtores e foi possível a identificação, através de SIG, das áreas de produção frutícola da Ilha. Para a análise dos factores climáticos ao nível da parcela, foram instaladas estações meteorológicas de leitura automática. Na parte relativa ao estudo da fenologia e produção para além da caracterização foi avaliado o impacto da polinização na taxa de vingamento dos frutos de macieira. Dentro dos problemas fitossanitários, na identificação das pragas-chave de cada cultura foi utilizada a observação visual de órgãos predefinidos e a monitorização através de armadilhas com feromona sexual e utilizadas placas cromotrópicas com cola. Nos fungos foi utilizada a observação visual e na prospecção de vírus e fitoplasmas utilizaram-se técnicas moleculares (ELISA) e PCR. Na prospecção da fauna auxiliar foi a técnica dos batimentos (ou pancadas) e a armadilha Malaise. Foi também realizado o levantamento das plantas auxiliares de produção e feita a sua identificação. Nas pragas-chave de cada uma das culturas, centrou-se a investigação sobre as mais importantes. A mosca-do-Mediterrâneo (C. capitata Wied.) foi uma delas, onde com o objectivo da sua monitorização, recorrendo aos SIG, foi montada uma rede de armadilhas em toda a ilha. Na bananeira, centrou-se todo o trabalho no gorgulho-da-bananeira (Cosmopolites sordidus Germar) e nas tripes. No castanheiro, no bichado-da-castanha (Cydia splendana Hubner) tendo sido avaliados os prejuízos que causa e conhecida a sua curva de voo através da sua monitorização usando armadilhas com feromona sexual. Na vinha, o míldio é a doença que mais contribuiu para a diminuição da produção de uva para vinho. Nas macieiras, os principais problemas decorrem da presença de aranhiço vermelho (Panonychus ulmi Koch), traça-oriental (Cydia molesta) e bichado (Cydia pomonella L.). Para a recolha e divulgação de toda a informação foi construída uma página Web do projecto, disponível na Internet (www.interfuta.angra.uac.pt) e uma base de dados fitossanitários de diagnóstico da Macaronésia (PROFITOMAC) para a identificação de todos os problemas que afectam estas culturas nos três arquipélagos em que o projecto de desenvolve. No âmbito das actividades do projecto foram ainda realizados alguns cursos de formação de curta duração para técnicos e produtores

Poised Transcription Factories Prime Silent uPA Gene Prior to Activation

The association of poised genes with transcription factories may contribute to rapid transcriptional activation in response to stimuli and to silencing when genes are located at the interior of their chromosome territories

O contributo do projecto INTERFRUTA II para o desenvolvimento da fruticultura na ilha Terceira, Açores

13º Congresso da APDR (Associação Portuguesa para o Desenvolvimento Rural). Angra do Heroísmo, Julho de 2007.O Projecto Interfruta II é um projecto apoiado pelo programa Interreg III-B, desenvolvido nas Ilhas da Madeira, Tenerife (Canárias) e Terceira (Açores) destinado a contribuir para a promoção da fruticultura e viticultura nestas três regiões insulares, procurando uma melhoria dos conhecimentos sobre os problemas fitossanitários que afectam as macieiras, bananeiras, castanheiros e a vinha, aplicando técnicas que contribuam decisivamente para o conhecimento e procura de soluções, numa vertente de prospecção das pragas-chave, fauna auxiliar, doenças e vírus que afectam essas culturas. Destaca-se o facto de inicialmente se ter procedido à realização de 160 inquéritos aos produtores e ao levantamento e identificação, através de SIG, das áreas de produção frutícola da Ilha. Para a análise dos factores climáticos ao nível da parcela, foram instaladas nas três zonas em estudo, estações meteorológicas de leitura automática.ABSTRACT: The INTERFRUTA project is financed by the European Commission Interreg III-B Programme and was developed for the islands of Madeira, Tenerife and Terceira for the improvement of fruit and vineyard production in these three Atlantic regions. The project goal is a better knowledge of the phytossanitary problems that affect apples, bananas, chestnut and vineyards, applying methods that will contribute to solutions based on the survey of key pests, diseases and beneficial organisms. All these work began with a survey to 160 producers and those data permitted, applying GIS techniques to them to identify the Terceira island fruit and vineyard production areas. To register the climate conditions in each area studied fully automatic meteorological stations were put in each of the three studied areas

Modelling the distribution of a commercial NE-Atlantic sea cucumber, Holothuria mammata : demographic and abundance spatio-temporal patterns

Funding: This study was financed by the Operational Programme Mar2020, MAR-02.01.01-FEAMP-0052, “Newcumber – Avanços para o cultivo sustentável de pepinos do mar”. It received further financial support from Fundação para a Ciência e Tecnologia (projects UIDB/04292/2020, UIDB/00006/2020, CoastNet – PINFRA/22128/2016, AB with the Scientific Stimulus Programme – CEECIND/00095/2017 and FA with the individual research grant 2020.09563.BD). This publication was financed by Portuguese national funds through FCT – Fundação IP under project reference UIDB/04292/2020, and by the European Union’s Horizon 2020 Research and Innovation Program under grant agreement N810139: Project Portugal Twinning for Innovation and Excellence in Marine Science and Earth Observation – PORTWIMS.There is an increasing demand for sea cucumbers, for human consumption, mainly from Asian markets and, as a consequence, NE-Atlantic species are now new targets for exploitation and exportation. Holothuria mammata is one of the most valuable species in Europe. However, the lack of historical economic interest in this species in most European countries has also led to a lack of studies concerning biological and ecological aspects on wild populations and this is a major issue for stock management. This study aims to determine the temporal and spatial patterns of distribution of H. mammata, considering its abundance and demographic structure in a NE-Atlantic area, SW Portugal, as a function of environmental conditions. For that, a population from a marine protected area was followed for 1 year at 1.5-month intervals. Throughout the coastal area, six sites were selected and at each sampling campaign three random transects per site and substrate (rock and sand) in which all H. mammata individuals were counted and measured. For each site and survey several environmental parameters of interest, from the water column, the sediment and substrate cover, were also measured. Generalized Linear Models were used to model the spatial and temporal distribution of the species according to environmental conditions, to determine the species’ habitat preferences. The distribution models indicate that abiotic and biotic parameters of the water column are not the main drivers shaping the distribution of H. mammata. The species has a patchy distribution, and its habitat preferences depend on environmental stability, the presence of shelter and habitat complexity, which is more important for smaller, more vulnerable, individuals, while bigger size classes tend to venture more into less stable environments in an opportunistic fashion. The knowledge of these population traits is determinant to develop stock management measures, which are now urgent to prevent the depletion of commercial sea cucumber populations in the NE-Atlantic. Sustainable fisheries policies should be developed and start by considering to delimit fishing areas and periods, considering the species spatial and temporal distribution patterns.Publisher PDFPeer reviewe

Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

Gene expression states influence the three-dimensional conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features, which define promoter activation states or CTCF binding sites. Single cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fibre fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions