Linear and shared objects in concurrent programming

Tese de mestrado, Engenharia Informática (Engenharia de Software), Universidade de Lisboa, Faculdade de Ciências, 2010Although mainstream object-oriented languages, like Java, are currently able to detect and prevent many programming errors by static type-checking, common usage-related errors are not captured and signaled to programmers. In general, no (formal) support is available in these languages for ensuring that an object is used according to the protocol which the programmer had in mind when describing the behavior of a class. The file reader protocol is a simple but clarifying example: first a file must be opened, then it can be read multiple times (though not beyond the end-of-file), and finally it must be closed. As client code is not checked for protocol conformance, trying to read the file without first opening it, or when it is closed, are simple disregards caught only by runtime exceptions, assuming the language is equipped with built-in support to handle errors and exceptional events. The MOOL programming language presented in this work is an attempt to formalize object usage and access. It consists in a simple class-based object-oriented language that includes standard primitives found in most object-oriented language formalisms. Additionally, the language offers constructs that can be attached at class definitions for specifying (1) the available methods based on an object state, and (2) how methods may be called in that state – by a single client, in which case we say that the object has a linear status, or without restrictions, in which case we say it has a shared one. We refer to this abstract view that defines an object state and status the class usage type. We formalize the language syntax, the operational semantics, and a type system that enforces by static typing that methods are called only when available, and by a single client if so specified in the class usage type. We illustrate the language capabilities by encoding in MOOL the protocols of two well-known examples: the file reader and the auction system. We have built a prototype compiler to implement our ideas, and its architecture is also described. Finally, we anticipate some of the related topics which we are interested in pursuing in future work

Adding dependent types to class-based mutable objects

Tese de doutoramento, Informática (Ciência da Computação), Universidade de Lisboa, Faculdade de Ciências, 2018In this thesis, we present an imperative object-oriented language featuring a dependent type system designed to support class-based programming and inheritance. The system brings classes and dependent types into play so as to enable types (classes) to be refined by value parameters (indices) drawn from some constraint domain. This combination allows statically checking interesting properties of imperative programs that are impossible to check in conventional static type systems for objects. From a pragmatic point of view, this work opens the possibility to combine the scalability and modularity of object orientation with the safety provided by dependent types in the form of index refinements. These may be used to provide additional guarantees about the fields of objects, and to prevent, for example, a method call that could leave an object in a state that would violate the class invariant. One key feature is that the programmer is not required to prove equations between indices issued by types, but instead the typechecker depends on external constraint solving. From a theoretic perspective, our fundamental contribution is to formulate a system that unifies the three very different features: dependent types, mutable objects and class-based inheritance with subtyping. Our approach includes universal and existential types, as well as union types. Subtyping is induced by inheritance and quantifier instantiation. Moreover, dependent types require the system to track type varying objects, a feature missing from standard type systems in which the type is constant throughout the object’s lifetime. To ensure that an object is used correctly, aliasing is handled via a linear type discipline that enforces unique references to type varying objects. The system is decidable, provided indices are drawn from some decidable theory, and proved sound via subject reduction and progress. We also formulate a typechecking algorithm that gives a precise account of quantifier instantiation in a bidirectional style, combining type synthesis with checking. We prove that our algorithm is sound and complete. By way of example, we implement insertion and deletion for binary search trees in an imperative style, and come up with types that ensure the binary search tree invariant. To attest the relevance of the language proposed, we provide a fully functional prototype where this and other examples can be typechecked, compiled and run. The prototype can be found at http://rss.di.fc.ul.pt/tools/dol/

Violência no trabalho dos enfermeiros no serviço de urgência

Dissertação de Mestrado em Enfermagem Médico-Cirúrgica apresentada na Escola Superior de Saúde do Instituto Politécnico de Viana do CasteloOs trabalhadores da área da saúde são dos que maior risco apresentam de sofrer incidentes violentos no trabalho, especialmente os que laboram em áreas como a psiquiatria e a urgência. A falta de medidas de segurança, o contacto físico próximo e a preocupação dos doentes com o estado de saúde predispõem os enfermeiros a sofrerem violência. Este estudo refere-se à violência no trabalho dos enfermeiros nos serviços de urgência médico-cirúrgicos da região norte de Portugal. Trata-se de um estudo de metodologia qualitativa, do tipo exploratório-descritivo e observacional. Com ele pretendemos compreender o fenómeno da violência no trabalho a que os enfermeiros dos serviços de urgência estão expostos. Foram analisados doze relatos de enfermeiros vítimas de violência no local de trabalho, através da técnica de análise de conteúdo. Dos doze participantes, nove são do género feminino e três do género masculino, variando as suas idades entre os 28 e os 58 anos e com uma média de 14 anos de experiência profissional em serviço de urgência. Os dados sugerem que a violência no trabalho dos enfermeiros é uma realidade frequente, ocorrendo independentemente da idade, experiência profissional, caraterísticas pessoais ou profissionais. Verificaram-se agressões psicológicas (6) e físicas (6) em igual proporção e o principal agressor foi o próprio doente, principalmente sob o comportamento de estalos, murros ou insultos. A maioria das vítimas referiu ter sofrido após a agressão consequências psicológicas, com impacto tanto na vida profissional como na pessoal. As consequências psicológicas da agressão identificadas foram perturbação, stress, desgaste emocional, insegurança, receio de agressão física, ansiedade, angústia, tristeza, medo, impaciência, receio pela segurança e nervosismo. A maioria dos participantes referiu porta automática, maior privacidade na triagem (local onde se verificaram mais agressões) e policiamento como possíveis medidas para diminuir a violência. O apoio prestado pela Instituição às vítimas nos casos de agressão foi considerado como insatisfatório e cinco vítimas notificaram a violência de que foram alvo. Conclui-se ser urgente a adoção de medidas para o combate deste problema e a prevenção só será possível através do comprometimento conjunto entre sociedade, Instituições de Saúde, gestores e profissionais de saúde envolvidos, responsabilizando os utentes pelos seus atos e incentivando os profissionais a notificar a violência sofrida. É um dever das Instituições promoverem um ambiente de trabalho seguro para os seus profissionais. Esperamos que este estudo seja mais um contributo para a segurança no trabalho deste grupo profissional no exercício das suas funções nos serviços de urgência, melhorando a satisfação no trabalho e a qualidade dos cuidados prestados ao doente crítico/família.The healthcare workers are those who have higher risk of suffering violent incidents at work, especially those who work in areas such as psychiatry and emergency. The lack of security measures, the close physical contact and the patient’s concern for the health predispose nurses to suffer violence. This study refers to violence at work of nurses in the medical-surgical emergency services in the northern region of Portugal. It is a qualitative methodology study, exploratory-descriptive and observational. With it we aim to understand the phenomenon of violence at work that nurses of the emergency services are exposed. Twelve reports of nurses who were victims of violence were analyzed in the workplace, through the content analysis technique. Of the twelve participants, nine are female and three are male, varying their ages between 28 and 58 years and with an average of 14 years of professional experience in emergency department. The data suggest that violence at work of the nurses is a common reality, occurring regardless of age, professional experience, personal or professional characteristics. There were psychological aggression (6) and physical (6) in the same proportion and the main aggressor was the patient himself, mainly under the popping behavior, punches and insults. The consequences after the aggression that most of the victims said were the psychological consequences that impact both professional and personal life. The psychological consequences of the aggression identified were the disturbance, stress, emotional stress, insecurity, fear of physical aggression, anxiety, anguish, sadness, fear, impatience, fear for the safety and nervousness. Most participants said that automatic door, greater privacy screening (where there have been more attacks) and policing as possible measures to reduce violence. The support provided by the Institution for victims in cases of aggression was considered unsatisfactory and five victims reported the suffered violence. We conclude that it’s urgent to adopt measures to combat this problem and the prevention can only be achieved through the commitment set between society, Health Institutions, health managers and professionals involved by giving users responsibility for their actions and encouraging professionals to report the suffered violence. It is a duty of the Institutions to promote a safe working environment for its employees. We hope this study will be a further contribution to safety at work of this professional group in the performance of their duties in emergency services, enhancing job satisfaction and quality of care to the critically ill patient/family

Chronic stress targets adult neurogenesis preferentially in the suprapyramidal blade of the rat dorsal dentate gyrus

First Online: 29 August 2017The continuous generation of new neurons and glial cells in the adult hippocampal dentate gyrus (DG) represents an important form of adult neuroplasticity, involved in normal brain function and behavior but also associated with the etiopathogenesis and treatment of psychiatric disorders. Despite the large number of studies addressing cell genesis along the septotemporal axis, data on the anatomical gradients of cytogenesis along the DG transverse axis is scarce, especially after exposure to stress. As such, in this study we characterized both basal proliferation and survival of adult-born neural cells along the transverse axis of the rat dorsal DG, and after stress exposure. In basal conditions, both proliferating cells and newborn neurons and glial cells were preferentially located at the subgranular zone and suprapyramidal blade. Exposure to chronic stress induced an overall decrease in the generation of adult-born neural cells and, more specifically, produced a regional-specific decrease in the survival of adult-born neurons at the suprapyramidal blade. No particular region-specific alterations were observed on surviving adult-born glial cells. This work reveals, for the first time, a distinct survival profile of adult-born neural cells, neurons and glial cells, among the transverse axis of the DG, in both basal and stress conditions. Our results unveil that adult-born neurons are preferentially located in the suprapyramidal blade and suggest a regional-specific impact of chronic stress in this blade with potential repercussions for its functional significance.NDA, PP, AMP, ARMS, MM and LP received fellowships from the Portuguese Foundation for Science and Technology (FCT). This work was funded by FCT (IF/01079/2014). This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038.info:eu-repo/semantics/publishedVersio

DIABETIC FOOT: THE DIAGNOSTIC POWER OF THE RADIOLOGICAL IMAGING

pé diabético é uma complicação da Diabetes Mellitus (DM) responsável por 1250 amputações (705 minor e 545 major) em 2015 em Portugal1,2. É uma consequência da vasculopatia, imunopatia e neuropatia3,4, sendo esta última o mecanismo mais importante da Neuroartropatia de Charcot (NC)5. Ainda com a fisiopatologia exata por definir, defendem-se atualmente duas correntes — a neurotraumática e a neurovascular — ou mesmo uma terceira que combina ambas as teorias. Apesar do diagnóstico permanecer primariamente clínico, particularmente nos estadios iniciais da doença, é importante distingui-la de patologias com a mesma sintomatologia4. A radiografia convencional deverá ser o método de imagem inicial na avaliação do pé diabético. Realizando incidências em ambos os pés, preferencialmente em três projeções, podem-se comparar alterações subtis e identificar 25% dos pacientes que acabam por desenvolver alterações similares no pé contralateral3,4,7. Numa fase inicial a radiografia convencional poderá ser normal, sendo o achado mais precoce a desmineralização focal8,9. Uma vez que 50% do osso precisa de ser perdido para que se detete radiologicamente, demorando este processo entre 1 a 2semanas, realça-se a importância da repetição periódica deste exame de imagem. Eichenholtz classificou a progressão radiográfica da NC em três estadios: fragmentação/dissolução (Estadio I), coalescência (Estadio II) e reconstrução (Estadio III)5,. Na fase crónica crónica estável, este método de imagem é igualmente importante no follow-up, podendo sumariar-se a evolução pela regra dos “6 D’s”: Dense subchondral bones; Degeneration; Destruction; Deformity; Debris, Dislocation. Os achados radiológicos da forma severa da NC são patognomónicos. Deste modo, pretende-se relacionar os dados imagiológicos da radiografia simples do pé com a clínica e a fisiopatologia da entidade “Pé Diabético”, tendo como mote a descrição de um caso clínico.info:eu-repo/semantics/acceptedVersio

PÉ DIABÉTICO: O PODER DIAGNÓSTICO DA RADIOGRAFIA CONVENCIONAL

Introdução: O pé diabético é uma complicação da Diabetes Mellitus (DM) responsável por 250 amputações em 2015 em Portugal1,2. É uma consequência da vasculopatia, imunopatia e neuropatia3,4, sendo esta última o mecanismo mais importante da Neuroartropatia de Charcot (NC)5. A radiografia convencional permite uma primeira abordagem imagiológica, identificando os “6 D’s”: Dense subchondral bones; Degeneration; Destruction; Deformity; Debris, Dislocation6,7. Deste modo, pretende-se relacionar os dados imagiológicos da radiografia simples do pé com a clínica e a fisiopatologia da entidade “Pé Diabético”, tendo como mote a descrição de um caso clínico. Caso clínico: Homem de 59 anos, com antecedentes de DM tipo 2 e amputação transmetatársica à direita recorreu ao Serviço de Urgência por dor, eritema e edema no pé e terço inferior da perna direita e úlcera plantar com exsudato purulento. Apresentava pulsos femorais e poplíteos. Pulsos distais ausentes. Foi internado para antibioterapia, descarga total, cuidados de penso e avaliação analítica, radiológica e multidisciplinar. Apesar do controlo da infeção associada foi impossível o realinhamento do pé e restituição das relações dos ossos pela grande destruição óssea. O doente foi submetido a amputação abaixo do joelho. Comentários: Na radiografia de perfil observou-se perda dos arcos plantares longitudinais medial e lateral e calcificação (encurtamento) do tendão de Aquiles (Figura 1, nº1), com aumento da pressão na face plantar que, associada à neuropatia sensitiva, contribuíram para a formação de úlcera, como observado neste caso8,9. A úlcera traduz-se neste exame do pé pela radio-lucência identificada na zona média plantar, patognomónica de Neuroartropatia de Charcot. (Figura 1, número 2)10. Verificou-se destruição óssea - fragmentos ósseos (Figura 1, nº3) com fratura da tuberosidade do calcâneo e colapso sub-astragalino (Figura 1, nº4). A localização desta fratura é das menos frequentemente observadas na Neuroartropatia de Charcot11. A neuropatia sensitiva permite submeter o pé a extremos de stress com consequentes fraturas indolores. A neuropatia autonómica, a abertura de “shunts” arteriovenosos e a hipervascularização óssea, acarretam osteopenia (Figura 1, nº5) e diminuição da resistência à fratura11,12. Observou-se edema (Figura 1, nº6) e enfisema subcutâneo (Figura 1, nº7), tradutor da presença de agentes microbiológicos anaeróbios, geralmente identificados em 90% das culturas13. Constatou-se calcificação da artéria tibial posterior (Figura 1, nº8), tipicamente uma mediocalcinose de Monckeberg, que está associada a elevada taxa de amputação e de mortalidade. Esta alteração vascular aumenta o grau de dificuldade técnica e compromete o prognóstico da revascularização11,14,15.  Conclusões: Apesar da grande variedade de técnicas imagiológicas, o custo-efetividade na deteção das principais alterações patológicas tornam a radiografia convencional a primeira linha de diagnóstico do pé diabético16

Remdesivir and corticosteroids in the treatment of hospitalized COVID-19 patients

okCoronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7-12.8; 14.9-17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.publishersversionpublishe

Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure

Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field.ARMS: ELC, NDA, PP, AMP, JSC, MM, AJR, JFO, and L.P. received fellowships from the Portuguese Foundation for Science and Technology (FCT) (IF/00328/2015 to J.F.O.; 2020.02855.CEECIND to LP). This work was funded by FCT (IF/01079/2014, PTDC/MED-NEU/31417/2017 Grant to JFO), BIAL Foundation Grants (037/18 to J.F.O. and 427/14 to L.P.), “la Caixa” Foundation Health Research Grant (LCF/PR/HR21/52410024) and Nature Research Award for Driving Global Impact—2019 Brain Sciences (to L.P.). This was also co-funded by the Life and Health Sciences Research Institute (ICVS), and by FEDER, through the Competitiveness Internationalization Operational Program (POCI), and by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020. Moreover, this work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020; “la Caixa” Foundation (ID 100010434 to A.J.R.), under the agreement LCF/PR/HR20/52400020; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 101003187 to A.J.R.)

a preliminary report

© European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES: Since the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pressure to minimise its impact on public health has led to the implementation of different therapeutic strategies, the efficacy of which for the treatment of coronavirus disease 2019 (COVID-19) was unknown at the time. Remdesivir (REM) was granted its first conditional marketing authorisation in the EU in June 2020. The European Medicines Agency (EMA) and local health authorities all across the EU have since strongly recommended the implementation of pharmacovigilance activities aimed at further evaluating the safety of this new drug. The objective of this study was to evaluate adverse drug reactions (ADRs) attributed to either REM or hydroxychloroquine (HCQ) in patients hospitalised for COVID-19 in Centro Hospitalar de Lisboa Ocidental, a Portuguese hospital centre based in Lisbon. We present the preliminary results reporting plausible adverse effects of either HCQ or REM. METHODS: An observational cohort study was carried out between 16 March and 15 August 2020. Participants were divided into two cohorts: those prescribed an HCQ regimen, and those prescribed REM. Suspected ADRs were identified using an active monitoring model and reported to the Portuguese Pharmacovigilance System through its online notification tool. The ADR cumulative incidence was compared between the two cohorts. RESULTS: The study included 149 patients, of whom 101 were treated with HCQ and the remaining 48 with REM. The baseline characteristics were similar between the two cohorts. A total of 102 ADRs were identified during the study period, with a greater incidence in the HCQ cohort compared with the REM cohort (47.5% vs 12.5%; p<0.001). Causality was assessed in 81 ADRs, all of which were considered possible. CONCLUSIONS: Real-world data are crucial to further establish the safety profile for REM. HCQ is no longer recommended for the treatment of COVID-19.publishersversionpublishe

Molecular and physiological basis of Saccharomyces cerevisiae tolerance to adverse lignocellulose-based process conditions

Lignocellulose-based biorefineries have been gaining increasing attention to substitute current petroleum-based refineries. Biomass processing requires a pretreatment step to break lignocellulosic biomass recalcitrant structure, which results in the release of a broad range of microbial inhibitors, mainly weak acids, furans, and phenolic compounds. Saccharomyces cerevisiae is the most commonly used organism for ethanol production; however, it can be severely distressed by these lignocellulose-derived inhibitors, in addition to other challenging conditions, such as pentose sugar utilization and the high temperatures required for an efficient simultaneous saccharification and fermentation step. Therefore, a better understanding of the yeast response and adaptation towards the presence of these multiple stresses is of crucial importance to design strategies to improve yeast robustness and bioconversion capacity from lignocellulosic biomass. This review includes an overview of the main inhibitors derived from diverse raw material resultants from different biomass pretreatments, and describes the main mechanisms of yeast response to their presence, as well as to the presence of stresses imposed by xylose utilization and high-temperature conditions, with a special emphasis on the synergistic effect of multiple inhibitors/stressors. Furthermore, successful cases of tolerance improvement of S. cerevisiae are highlighted, in particular those associated with other process-related physiologically relevant conditions. Decoding the overall yeast response mechanisms will pave the way for the integrated development of sustainable yeast cell--based biorefineries.This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the strategic funding of UID/BIO/04469/2013 unit, MIT Portugal Program (Ph.D. grant PD/BD/128247/ 2016 to Joana T. Cunha), Ph.D. grant SFRH/BD/130739/2017 to Carlos E. Costa, COMPETE 2020 (POCI-01-0145-FEDER-006684), BioTecNorte operation (NORTE-01-0145-FEDER-000004), YeasTempTation (ERA-IB-2-6/0001/2014), and MultiBiorefinery project (POCI-01-0145-FEDER-016403). Funding by the Institute for Bioengineering and Biosciences (IBB) from FCT (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (Project N. 007317) was also receiveinfo:eu-repo/semantics/publishedVersio