Peripheral biomarkers for first-episode psychosis-opportunities from the neuroinflammatory hypothesis of schizophrenia

Objective Schizophrenia is a disabling disorder of unknown aetiology, lacking definite diagnostic method and cure. A reliable biological marker of schizophrenia is highly demanded, for which traceable immune mediators in blood could be promising candidates. We aimed to gather the best findings of neuroinflammatory markers for first-episode psychosis (FEP). Methods We performed an extensive narrative review of online literature on inflammation-related markers found in human FEP patients only. Results Changes to cytokine levels have been increasingly reported in schizophrenia. The peripheral levels of IL-1 (or its receptor antagonist), soluble IL-2 receptor, IL-4, IL-6, IL-8, and TNF-a have been frequently reported as increased in FEP, in a suggestive continuum from high-risk stages for psychosis. Microglia and astrocytes establish the link between this immune signalling and the synthesis of noxious tryptophan catabolism products, that cause structural damage and directly hamper normal neurotransmission. Amongst these, only 3-hydroxykynurenine has been consistently described in the blood of FEP patients. Conclusion Peripheral molecules stemming from brain inflammation might provide insightful biomarkers of schizophrenia, as early as FEP or even prodromal phases, although more timeand clinically-adjusted studies are essential for their validation.This work has been conducted with the support of the Portuguese Foundation for Science and Technology

Effects of price range variation on optimal sizing and energy management performance of a hybrid fuel cell vehicle

Abstract: The usage of multi-objective cost functions (MOCFs) in sizing and energy management strategy (EMS) of fuel cell hybrid electric vehicles (FCHEVs) has expanded due to the participation of multiple technological and economic disciplines. To better understand the impact of price fluctuation on the component size and EMS of an FCHEV, this article proposed a sensitivity analysis methodology. First, a two-step optimization approach that considers hydrogen consumption, system degradation, and trip cost is used to minimize a MOCF of the Can-Am Spyder electric motorcycle simulator. Then, an effect analysis is carried out for the cost-optimal results under two driving profiles to understand the link between cost variation and system performance. These simulations indicate that each might result in different system sizes and EMS compromise. After that, an online optimization EMS based on sequential quadratic programming is used on a reduced-scale hardware-in-the-loop configuration to evaluate the simulation results with varied weights. Experimental results indicate that when an adequate size is used for each pair of weights, the EMS results in a 6% decrease in the trip cost

Nova mutação nonsense (p.Y113X) no gene do receptor do hormônio do crescimento em um paciente brasileiro com síndrome de Laron

BACKGROUND: To date, about sixty different mutations within GH receptor (GHR) gene have been described in patients with GH insensitivity syndrome (GHI). In this report, we described a novel nonsense mutation of GHR. METHODS: The patient was evaluated at the age of 6 yr, for short stature associated to clinical phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products from exons 2-10 were sequenced. RESULTS: The patient had high GH (26 µg/L), low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5 disclosed adenine duplication at nucleotide 338 of GHR coding sequence (c.338dupA) in homozygous state. CONCLUSION: We described a novel mutation that causes a truncated GHR and a loss of receptor function due to the lack of amino acids comprising the transmembrane and intracellular regions of GHR protein, leading to GHI.INTRODUÇÃO: Até o momento, aproximadamente 60 diferentes mutações envolvendo o gene do receptor do GH (GHR) foram descritas em pacientes com a síndrome de insensibilidade ao GH (GHI). Neste artigo, descrevemos uma nova mutação nonsense do GHR. MÉTODOS: O paciente foi avaliado aos 6 anos de idade para baixa estatura associada ao fenótipo clínico da GHI. Níveis de GH, IGF-1 e GHBP foram determinados. Os produtos de PCR dos éxons 2-10 foram seqüenciados. RESULTADOS: O paciente apresentou níveis elevados de GH (26 µg/L), baixos de IGF-1 (22.5 ng/ml) e indetectáveis de GHBP. O seqüenciamento do éxon 5 do GHR revelou uma duplicação da adenina no nucleotídeo 338 da sequência de codificação do GHR (c.338dupA) em homozigose. CONCLUSÃO: Descrevemos uma nova mutação que causa um GHR truncado e uma perda da função do receptor devido à perda de aminoácidos compreendendo as regiões transmembrana e intracelular do receptor, levando a GHI.Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Passive and active coupling comparison of fuel cell and supercapacitor for a three-wheel electric vehicle

The desire to reduce the power electronics related issues has turned the attentions to passive coupling of powertrain components in fuel cell hybrid electric vehicles (FCHEVs). In the passive coupling, the fuel cell (FC) stack is directly connected to an energy storage system on the DC bus as opposed to the active configuration where a DC-DC converter couples the FC stack to the DC bus. This paper compares the use of passive and active couplings in a three-wheel FCHEV to reveal their strengths and weaknesses. In this respect, a passive configuration, using a FC stack and a supercapacitor, is suggested first through formulating a sizing problem. Subsequently, the components are connected in an active configuration where an optimized fuzzy energy management strategy is used to split the power between the components. The performance of the vehicle is compared at each case in terms of capital cost and trip cost, which is composed of FC degradation and hydrogen consumption, and total cost of the system per hour. The obtained results show the superior performance of the passive configuration by 17% in terms of total hourly cost, while the active one only results in less degradation rate in the FC system. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Unlocking shore power in St. Lawrence and Great Lakes for cargo ships

Abstract This study investigates for the first time the emissions that a future shore power policy can eliminate in the St. Lawrence and Great Lakes region, providing precise evaluations with an improved bottom-up methodology. The review of cargo ship emission estimation methods showed that latest studies use a methodology that is not suited for evaluating real emissions at berth, but rather general emissions of the ships while at sea. Therefore, an improved method is proposed to determine the emissions specifically at berth with a modified bottom-up analysis that considers further geographical data, operating modes, berth-specific data, the new exclusion-area technique, and new cargo ship types. Also, the results of the proposed method applied in the St. Lawrence and Great Lakes showed that shore power policies can reduce up to an annual maximum of 227,061 t of carbon dioxide equivalent and 25 million dollars annually in external costs to society and governments

Health-wise energy management strategies in fuel cell hybrid electric vehicles: Tools to optimize performance and reduce operational costs

Abstract The primary objective of an energy management strategy (EMS) in fuel cell (FC) hybrid electric vehicles (HEVs) is twofold: to minimize hydrogen consumption and to extend the lifetime of the power sources. However, these power sources are susceptible to degradation under various operational and ambient conditions, be it from cycling or calendar aging. To achieve optimal performance, the EMS must consider variations in the power sources’ characteristics due to degradation. This article succinctly discusses the necessity of employing a health-wise EMS and the indispensable tools it requires, such as health-monitoring techniques. Subsequently, the study investigates the impact of a health-wise EMS on the total operational cost of a low-speed urban FC-HEV truck through simulations. The simulation results demonstrate that health-wise EMSs can significantly reduce fuel consumption and mitigate FC and battery degradations, resulting in a noteworthy reduction in the total operational cost

Adaptive parameter identification of a fuel cell system for health-conscious energy management applications

Since a proton exchange membrane (PEM) fuel cell (FC) has time-varying characteristics, its online characteristics estimation (voltage, power, internal resistance, etc.) is becoming a key step in designing an energy management strategy (EMS) for hybrid FC vehicles. In this respect, this paper proposes a new method based on Lyapunov adaptation law to estimate the linear and nonlinear parameters of a renowned PEMFC model in the literature. Unlike most of similar estimators, the suggested approach determines the maximum current, which is a nonlinear parameter, online while guaranteeing the system closed-loop stability. This parameter is normally assumed to be constant while it changes through time owing to degradation and operating conditions variation. This alteration makes the model imprecise while extracting some important characteristics, such as maximum power and polarization curve. Therefore, it needs to be regularly updated along with other parameters. To demonstrate the capability of the suggested method, a detailed comparison is provided with the well-known extended Kalman filter (EKF) as an attested nonlinear estimator. Moreover, to highlight the effectiveness of the nonlinearity consideration, a comparison with KF is performed where the nonlinear parameter is considered constant. The performed experiments on a 500-W PEMFC show that the proposed method can be over twice as accurate as EKF and KF concerning the estimation of maximum power and current while its runtime is nearly half of them

Multi-criteria ranking of Z-source inverter topologies for a three-wheel fuel cell hybrid electric vehicle

Abstract Replacing the regular two-stage inverters with a Z-source inverter (ZSI), based on single conversion, has come under attention in fuel cell (FC) hybrid electric vehicles (HEVs). This substitution is to decrease the circuit complexity, cost, and required space. However, fulfilling these goals highly depends on the selection of a suitable topology. This paper performs a multi-criteria ranking to deeply analyze the impact of different ZSI topologies on the performance of a recreational FC-HEV, composed of FC stack and lithium-ion capacitor bank. First, the dual-energy sources are embedded into the Z-source network (ZSN). Subsequently, the Preference Ranking Organization METHod for Enrichment Evaluation (PROMETHEE) is utilized to rank different possible ZSI topologies based on four scenarios (standard, compactness, input current ripple, and compactness versus input current ripple). This analysis indicates that each scenario can have a suitable topology with respect to its requirements. Finally, the two highest-ranked ZSI topologies according to standard scenario are implemented by signal hardware-in-the-loop (HIL) to validate the effectiveness of the performed analysis. The results indicate that the use of the ZSI topologies lead to higher average efficiencies (1.98% and 4.07%), and smaller size and volume of passive components, compared to a conventional two-stage inverter

Mode-dependent energy management of a dual-source active switched quasi-Z-source inverter for fuel cell hybrid vehicles

Abstract To prolong the fuel cell (FC) lifetime, hybridizing an FC stack with a lithium-ion capacitor (LiC) bank via a new single-stage power converter is promising in FC hybrid electric vehicles (FC-HEVs). This configuration requires efficient management of its FC hydrogen consumption under various driving conditions. Hence, this paper puts forward a mode-dependent energy management strategy (EMS) for the application of an FC-HEV, employing a high-performance active switched quasi-Z-source inverter (HP AS-qZSI) as its powertrain. Firstly, a supervised learning-based driving mode predictor is utilized to anticipate the driving modes of the FC-HEV. A four-mode fuzzy logic controller (FLC) is subsequently designed and optimized offline by an improved differential evolution (IDE) algorithm for each driving mode. Finally, hardware-in-the-loop tests are carried out to validate the performance of the proposed EMS. The experimental results analyses demonstrate the improved performance of the proposed framework, which reduces the FC hydrogen consumption and the standard deviation of the FC current by 12.67% and 21.31%, respectively, under the studied driving cycle

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Portuguese network for SARS-CoV-2 genomics (Consortium): Agostinho José S Lira, Aida M Sousa Fernandes, Alexandra Estrada, Alexandra Nunes, Alfredo Rodrigues, Ana Caldas, Ana Constança, Ana Margarida Henriques, Ana Miguel Matos, Ana Oliveira, Ana Paula Dias, Ana Pelerito, Ana Rita Couto, Anabela Vilares, António Albuquerque, Baltazar Nunes, Bruna R Gouveia, Carina de Fátima Rodrigues, Carla Feliciano, Carla Roque, Carlos Cardoso, Carlos Sousa, Cathy Paulino, Célia Rodrigues Bettencourt, Claudia C Branco, Cláudia Nunes Dos Santos, Conceição Godinho, Constantino P Caetano, Cristina Correia, Cristina Toscano, Cristina Veríssimo, Daniela Silva, Diana Patrícia Pinto da Silva, Eliana Costa, Elizabeth Pádua, Fátima Martins, Fátima Vale, Fernanda Vilarinho, Fernando Branca, Filomena Caldeira, Filomena Lacerda, Francisca Rocha, Graça Andrade, Helena Ribeiro, Helena Rodrigues, Herberto Jesus, Hugo Sousa, Idalina Ferreira, Inês Baldaque, Inês Costa, Inês Gomes, Inna Slobidnyk, Isabel Albergaria, Isabel Dias, Isabel Fernandes, Isabel Lopes de Carvalho, Ivone Água-Doce, Jácome Bruges Armas, Joana Ramos, João Carlos Sousa, João Costa, João Dias, João Rodrigues, João Sobral, Jorge Machado, Jorge Meneses, José Alves, José Vicente Constantino, Laura Brum, Leonor Silveira, Líbia Zé-Zé, Lidia Santos, Ludivina Freitas, Luís Silva, Luisa Mota-Vieira, Lurdes Lopes, Lurdes Monteiro, Márcia Faria, Margarida Farinha, Margarida Vaz, Maria Alice Pinto, Maria Ana Pessanha, Maria Beatriz Tomaz, Maria Calle Vellés, Maria da Graça Maciel de Soveral, Maria Helena Ramos, Maria Isabel Veiga, Maria João Gargate, Maria João Peres, Maria José Borrego, Maria Matos Figueiredo, Mariana Martins, Mariana Viana, Maurício Melim, Miguel Babarro Jorreto, Miguel Fevereiro, Miguel Pinheiro, Mónica Oleastro, Nair Seixas, Nelson Ventura, Nuno Verdasca, Olga Costa, Patrícia Barros, Patricia Fonseca, Patricia Miguel, Paula Bajanca-Lavado, Paula Branquinho, Paula Palminha, Paula Soares, Paula Valente, Paulo Leandro, Paulo Pereira, Pedro Cardoso, Pedro Pechirra, Pedro Ramos, Raquel Neves, Raquel Rocha, Raquel Rodrigues, Raquel Sabino, Regina Sá, Ricardo Filipe Romão Ferreira, Ricardo Rodrigues, Rita C Veloso, Rita Cordeiro, Rita Côrte-Real, Rita de Sousa, Rita Gralha, Rita Macedo, Rita Matos, Rita Rodrigues, Sandra Paulo, Sara Sousa, Sílvia Lopo, Sónia Marta Santos Magalhães, Sónia Rodrigues, Sónia Silva, Susana Ladeiro, Susana Martins, Susana Silva, Teresa Salvado, Tiago Luís, Valquíria Alves, Vera ManageiroBackground: Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods: By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARS-CoV-2 introductions and early dissemination in Portugal. Results: We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions: Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.Plain language summary: Analysing SARS-CoV-2 genetic material and how it changes over time can help us understand how the virus spreads between countries and determine the impact of control measures. In this study, we investigated SARS-CoV-2 transmission and evolution in the early stages of the COVID-19 pandemic in Portugal. In particular, we reconstructed the routes and timeliness of viral introductions into the country and assessed the relative contribution of each introduction in terms of how the epidemic evolved over time. We detected at least 277 independent introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. This study reflects an unprecedented effort in the field of the infectious diseases in Portugal, highlighting the need for systematic and geographically-representative surveillance to aid public health efforts to control the virus.This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Por tugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio