Planeamento de rotas dinâmicas para a prestação de cuidados respiratórios domiciliários

Trabalho de projeto de mestrado, Matemática Aplicada à Economia e Gestão, Universidade de Lisboa, Faculdade de Ciências, 2022A prestação de cuidados de saúde no domicílio é um serviço cada vez mais relevante e exigente, que cresceu muito nos últimos anos devido à evolução tecnológica e à atual crise pandémica. Na prestação deste serviço estão envolvidos vários agentes que concentram os seus esforços no bem-estar e qualidade de vida dos seus pacientes com tratamentos prescritos. Existe, no entanto, um agente que, devido à função que desempenha junto dos pacientes, desenvolve uma relação de proximidade e intimidade que se revela ser um critério relevante na análise da qualidade e valor dos serviços prestados. Este agente é constituído pelas empresas especializadas com equipas de técnicos que se deslocam até ao domicílio dos pacientes que necessitam dos vários tipos de serviços disponíveis. O caso em estudo é baseado em dados reais de uma empresa que presta serviços de cuidados respiratórios domiciliários. No início do dia existem serviços que já se encontram agendados nas rotas dos técnicos disponíveis. Este planeamento é realizado no dia anterior sendo assegurada disponibilidade para que possam ser inseridos novos pedidos que chegam ao longo do dia. A empresa deve satisfazer em tempo útil cada novo pedido, minimizando o número total de horas de trabalho. Trata-se de um problema de rotas dinâmico.Para encontrar soluções admissíveis para o problema foram desenvolvidos e implementados dois algoritmos em Python. No primeiro, partindo-se do conjunto inicial das rotas planeadas, à medida que vão surgindo novos pedidos ao longo do dia, aplica-se a heurística de inserção de menor custo com o objetivo de integrar os novos pedidos nessas rotas. O segundo, com o objetivo de melhorar a solução obtida pela heurística de menor custo de inserção, consiste em aplicar uma heurística 2-optimal sempre que inserido um novo pedido numa rota. Os testes computacionais são realizados considerando dois cenários que variam na distribuição temporal da chegada de novos pedidos ao longo do dia e um cenário em que se consideram dois turnos de trabalho no horário laboral dos técnicos. É realizada uma análise dos resultados obtidos em termos percentuais comparando as soluções dos diferentes cenários com a solução obtida considerando os dados reais fornecidos pela empresa.Home healthcare is an increasingly relevant and demanding service, which has grown in recent years due to technological developments and the current pandemic crisis. In the provision of this service, several agents are involved, who focus their efforts on the well-being and quality of life of their patients with prescribed treatments.There is, however, one agent who, due to the role he plays with the patients, develops a relationship of proximity and intimacy that proves to be a relevant criterion in the analysis of the quality and value of the services provided. This agent is made up of specialized companies with teams of technicians who travel to the patient’s homes who need the various types of services available. The case under study is based on real data from a company that provides home respiratory care services. At the beginning of the day there are services that have already been scheduled on the available technicians’ routes. This planning is done the day before, and availability is ensured to attend new requests that come up during the day. The company must satisfy each new request on time, minimizing the total number of working hours. This problem is classified as a dynamic routing problem. To find feasible solutions to the problem two algorithms were developed and implemented in Python. In the first one, starting from the initial set of planned routes, the cheapest insertion heuristic is applied as new requests arise throughout the day, with the objective of integrating the new requests into those routes. The second one, with the goal of improving the solution obtained by the cheapest insertion heuristic, consists in applying a 2-optimal heuristic whenever a new request is inserted in a route. The computational tests are performed considering two scenarios that vary in the temporal distribution of the arrival of new requests throughout the day and a third scenario in which two shifts are considered. An analysis of the results obtained in percentage terms is performed comparing the solutions of the different scenarios with the solution obtained considering the actual data provided by the company

Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation

Funding PPBI—Portuguese Platform of BioImaging, POCI-01-0145-FEDER-022122; FCT—Fundação para a Ciência e Tecnologia, UID/Multi/00709/2013, SFRH/ BD/137440/2018 (MMP), IF/00178/2015/CP1300/CT0001 (RF); FCT—L’Oréal— UNESCO Portugal for Women in Science (RF).Background: The brain vasculature plays a pivotal role in the inflammatory process by modulating the interaction between blood cells and the neurovascular unit. Argonaute-2 (Ago2) has been suggested as essential for endothelial survival but its role in the brain vasculature or in the endothelial–glial crosstalk has not been addressed. Thus, our aim was to clarify the significance of Ago2 in the inflammatory responses elicited by these cell types. Methods: Mouse primary cultures of brain endothelial cells, astrocytes and microglia were used to evaluate cellular responses to the modulation of Ago2. Exposure of microglia to endothelial cell-conditioned media was used to assess the potential for in vivo studies. Adult mice were injected intraperitoneally with lipopolysaccharide (LPS) (2 mg/kg) followed by three daily intraperitoneal injections of Ago2 (0.4 nM) to assess markers of endothelial disruption, glial reactivity and neuronal function. Results: Herein, we demonstrated that LPS activation disturbed the integrity of adherens junctions and downregulated Ago2 in primary brain endothelial cells. Exogenous treatment recovered intracellular Ago2 above control levels and recuperated vascular endothelial-cadherin expression, while downregulating LPS-induced nitric oxide release. Primary astrocytes did not show a significant change in Ago2 levels or response to the modulation of the Ago2 system, although endogenous Ago2 was shown to be critical in the maintenance of tumor necrosis factor-α basal levels. LPS-activated primary microglia overexpressed Ago2, and Ago2 silencing contained the inflammatory response to some extent, preventing interleukin-6 and nitric oxide release. Moreover, the secretome of Ago2-modulated brain endothelial cells had a protective effect over microglia. The intraperitoneal injection of LPS impaired blood–brain barrier and neuronal function, while triggering inflammation, and the subsequent systemic administration of Ago2 reduced or normalized endothelial, glial and neuronal markers of LPS damage. This outcome likely resulted from the direct action of Ago2 over the brain endothelium, which reestablished glial and neuronal function. Conclusions: Ago2 could be regarded as a putative therapeutic agent, or target, in the recuperation of the neurovascular unit in inflammatory conditions.publishersversionpublishe

From Expression Pattern to Dopaminergic Survival

Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by “Programa Operacional do Centro, Centro 2020” through the funding of the ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01–0145-FEDER-000013), and by the following national funds: Foundation for Science and Technology (doctoral grant SFRH/BD/121822/2016), UBI-Santander/Totta (BID/ICI-FCS/CICS/Santander Universidades-UBI/2017) and the PPBI-Portuguese Platform of BioImaging: POCI-01–0145-FEDER-022122. Publisher Copyright: © 2023, The Author(s).C-terminal binding proteins (CtBP) are transcriptional co-repressors regulating gene expression. CtBP promote neuronal survival through repression of pro-apoptotic genes, and may represent relevant targets for neurodegenerative disorders, such as Parkinson’s disease (PD). Nevertheless, evidence of the role of CtBP1 and CtBP2 in neurodegeneration are scarce. Herein, we showed that CtBP1 and CtBP2 are expressed in neurons, dopaminergic neurons, astrocytes, and microglia in the substantia nigra (SN) and striatum of adult mice. Old mice showed a lower expression of CtBP1 in the SN and higher expression of CtPB2 in the SN and striatum compared with adult mice. In vivo models for PD (paraquat, MPTP, 6-OHDA) showed increased expression of CtBP1 in the SN and striatum while CtBP2 expression was increased in the striatum of paraquat-treated rats only. Moreover, an increased expression of both CtBP was found in a dopaminergic cell line (N27) exposed to 6-OHDA. In the 6-OHDA PD model, we found a dual effect using an unspecific ligand of CtBP, the 4-methylthio 2-oxobutyric acid (MTOB): higher concentrations (e.g. 2500 µM, 1000 µM) inhibited dopaminergic survival, while at 250 μM it counteracted cell death. In vitro, this latter protective role was absent after the siRNA silencing of CtBP1 or CtBP2. Altogether, this is the first report exploring the cellular and regional expression pattern of CtBP in the nigrostriatal pathway and the neuroprotective role in PD toxin-based models. CtBP could counteract dopaminergic cell death in the 6-OHDA PD model and, therefore, CtBP function and therapeutic potential in PD should be further explored.publishersversionepub_ahead_of_prin

Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells

KRAS and BRAF mutations are frequent in colorectal carcinoma (CRC) and have the potential to activate proliferation and survival through MAPK/ERK and/or PI3K signalling pathways. Because diet is one of the most important determinants of CRC incidence and progression, we studied the effects of the dietary phytochemicals quercetin (Q), luteolin (L) and ursolic acid (UA) on cell proliferation and apoptosis in two human CRC derived cell lines, HCT15 and CO115, harboring KRAS and BRAF activating mutations, respectively. In KRAS mutated HCT15 cells, Q and L significantly decreased ERK phosphorylation, whereas in BRAF mutated CO115 cells the three compounds decreased Akt phosphorylation but had no effect on phospho-ERK. Our findings show that these natural compounds have antiproliferative and proapoptotic effects and simultaneously seem to act on KRAS and PI3K but not on BRAF. These results shed light on the molecular mechanisms of action of Q, L and UA and emphasize the potential of dietary choices for the control of CRC progression.This work was supported by the Foundation for Science and Technology, Portugal, by the research Grant POCI/AGR/62040/2004. CPRX and CFL were supported by the Foundation for Science and Technology, Portugal, through the Grants SFRH/BD/ 27524/2006 and SFRH/BPD/26316/2006, respectively

AVALIAÇÃO IN VITRO DO FATOR DE PROTEÇÃO SOLAR A PARTIR DE FOTOPROTETORES MANIPULADOS CONTENDO AGENTES ATIVOS ANTIENVELHECIMENTO

Questões críticas foram levantadas envolvendo interações potenciais entre os componentes do filtro solar e os componentes de agentes ativos antienvelhecimento (AA). O objetivo foi avaliar fotoprotetores contendo diferentes agentes AA, com ou sem fragrância, que foram submetidos à uma análise macroscópica, centrifugação, determinação de pH e o fator de proteção solar (FPS) in vitro. Todas as preparações apresentaram estabilidade física. No entanto, as formulações contendo Deanol® apresentaram o pH significativamente mais baixo do que os outros fotoprotetores, independentemente da fragrância, indicando que a estabilidade destas formulações pode ser menor. Quanto à variação do FPS in vitro não foi encontrada diferença significativa após a adição do agente de AA em fotoprotetores. No entanto, os filtros solares contendo Enteline® apresentaram o FPS significativamente maior nas formulações sem fragrância. Em conclusão, as preparações estudadas apresentaram estabilidade física e o intervalo de estabilidade apresentado do pH em conformidade com a necessidade de filtros solares contendo compostos Longevicell®, Enteline® ou Iris Iso® como os agentes AA. No entanto, as formulações contendo Deanol® devem ser ajustadas para a o intervalo de pH (6,0-7,0), independentemente da fragrância. Além disso, a fragrância usada em fotoprotetores Enteline® avaliados neste trabalho pode diminuir significativamente o FPS na preparação e devem ser evitados a fim de garantir a segurança e eficácia dos protetores solares associadas aos agentes AA

Entre consumos suntuários e comuns: a posse de objetos exóticos entre alguns habitantes do Porto (séculos XVI – XVII)

O estudo da documentação referente aos doadores da Misericórdia do Porto entre os séculos XVI e XVII, através dos objetos exóticos patentes nos respectivos testamentos e inven- tários – estes últimos provenientes de uma área que se estende de Macau ao Brasil –, permite discernir uma panóplia de objetos que mudaram a cultura material dos portuenses em contato com os territórios da expansão portuguesa. Um levantamento sistemático permitiu já rastrear, até o ano de 1699, 257 doadores, dos quais se apresentarão aqui apenas alguns, referentes a benfeitores que, não obstante possuírem bens móveis nesse âmbito, não são dados como tendo estado nos territórios de expansão transoceânica. Argumentar-se-á que essa circulação de objetos não foi exclusiva das elites nobiliárquicas, nem dos grandes centros urbanos, pelo que a sua difusão atingiu maiores proporções do que aquelas que a historiografia tem admitido até agora. A cidade em observação neste estudo – o Porto dos séculos XVI e XVII – estava longe de ser das maiores da Europa nesse período, quer em dimensão territorial, quer em efetivos populacionais, embora se situasse numa região de demografia pujante, que canalizou os seus excedentes desde cedo para a emigração interna e externa – o Entre Douro e Minho. Como teremos ocasião de verificar, fidalgos e nobres possuíam bens exóticos, mas estes encontravam-se também entre mercadores e até artesãos mais desafogados. Por outro lado, nem todos os objetos provenientes dos espaços da expansão transoceânica devem ser conotados com bens de luxo.The study of the sources referring to the donors of the Misericórdia of the city of Porto during the sixteenth and seventeenth centuries has revealed the presence of numerous exotic objects in their last wills and inventories. A survey has traced 257 donors until 1699, some of them having died in an area that extends from Macao to Brazil. Only a small number of cases shall be presented here, pertaining to benefactors who, in spite of owning objects of transoceanic origin, seem to have remained in mainland Portugal. It shall be argued that the circulation of objects has not been exclusive either to the elites of the nobility or to the large urban centres, their diffusion having been on a larger scale than what has been admitted until now. The city under scrutiny in this study – Porto during the sixteenth and seventeenth centuries – was not one of the bigger cities in this period, either in what respects to size or population, although it was located in an area of flourishing demography, that channelled its surplus population early on to internal and external emigration. Fidalgos and noblemen owned exotic goods, but these were to be found among merchants and even well-to-do artisans. On the other hand, not all objects originating from the areas of transoceanic expansion should be considered as luxury goods.info:eu-repo/semantics/publishedVersio

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis