L-NAME causes antinociception by stimulation of the arginine-NO-cGMP pathway.

NG-nitro-L-arginine methyl ester (L-NAME) has been used extensively as a paradigmatic inhibitor of NO synthase and has been shown to cause antinociception in several experimental models. We describe here how L-NAME produced a dose-dependent antinociceptive effect when injected intraperitoneally in the mouse after acetic acid induced writhings, or intraplantarly in the rat paw pressure hyperalgesia induced by carrageenin or prostaglandin E2. In contrast another NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), had no significant effect per se but inhibited L-NAME systemic induced antinociception in mice and local induced antinociception in the rat paw hyperalgesia test. D-NAME had no antinociceptive effect upon carrageenin-induced hyperalgesia. Pretreatment of the paws with two inhibitors of guanylate cyclase, methylene blue (MB) and 1H-:[1,2,4]-oxadiazolo-:[4,3-a] quinoxalin-1-one (ODQ) abolished the antinociceptive effect of L-NAME. L-Arginine and the cGMP phosphodiesterase inhibitor, MY 5445 significantly enhanced the L-NAME antinociceptive effect. The central antinociceptive effect of L-NAME was blocked by co-administration of L-NMMA, ODQ and MB. The present series of experiments shows that L-NAME, but not L-NMMA, has an antinociceptive effect. It can be suggested that L-NAME causes the antinociceptive effect by stimulation of the arginine/ NO/ cGMP pathway, since the antinociceptive effect of L-NAME can be antagonized by L-NMMA and abolished by the guanylate cyclase inhibitors (MB and ODQ). In addition, the NO synthase substrate, L-arginine and the cGMP phosphodiesterase inhibitor, MY5445 were seen to potentiate the effects of L-NAME. Thus, L-NAME used alone, has limitations as a specific inhibitor of the arginine-NO-cGMP pathway and may therefore be a poor pharmacological tool for use in characterising participation in pathophysiological processes

Multiscale Partition of Unity

We introduce a new Partition of Unity Method for the numerical homogenization of elliptic partial differential equations with arbitrarily rough coefficients. We do not restrict to a particular ansatz space or the existence of a finite element mesh. The method modifies a given partition of unity such that optimal convergence is achieved independent of oscillation or discontinuities of the diffusion coefficient. The modification is based on an orthogonal decomposition of the solution space while preserving the partition of unity property. This precomputation involves the solution of independent problems on local subdomains of selectable size. We deduce quantitative error estimates for the method that account for the chosen amount of localization. Numerical experiments illustrate the high approximation properties even for 'cheap' parameter choices.Comment: Proceedings for Seventh International Workshop on Meshfree Methods for Partial Differential Equations, 18 pages, 3 figure

Why does it take so long? The reasons behind tuberculosis treatment delay in Portugal

Introduction Delayed diagnosis and treatment of tuberculosis contributes to the spread of the disease. In this study, we aimed to determine the patient and healthcare system delay among tuberculosis patients in Portugal and identify associated factors at individual and contextual level. Methods We analysed all TB cases notified in Portugal between 2010 and 2014 using data from the national surveillance system. Patient and healthcare system delay were computed, log-transformed, and used as outcomes. Adjusted generalized linear models were fitted to identify sociodemographic, contextual and clinical determinants. Results The study included 6838 patients. The median of patient and healthcare system were 33 and 17 days, respectively. Adjusted regression models revealed that higher patient delay occurred in foreign patients (exponentiated beta: 1.177, 95%CI 1.091–1.270) and those addicted to alcohol (1.169, 1.072–1.276) and drugs (1.153, 1.027–1.295). Higher healthcare system delay was observed among patients with extra-pulmonary TB (2.067, 1.885–2.268) and pulmonary comorbidities – lung cancer (2.391, 1.656–3.452), sarcoidosis (3.316, 1.370–8.022) and COPD (1.295, 1.059–1.584) – and in patients residing further from a healthcare service (1.040, 1.018–1.062). Conclusion We found that various individual and contextual factors affect the time delay in tuberculosis treatment. Our findings indicate that some strategies, such as facilitating the access to healthcare services among foreign patients and patients with addictions and increasing the awareness towards TB among healthcare professionals, may result in better TB control.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the EPIUnit – Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013)

Optimal life insurance purchase, consumption and investment on a financial market with multi-dimensional diffusive terms

We introduce an extension to Merton’s famous continuous time model of optimal consumption and investment, in the spirit of previous works by Pliska and Ye, to allow for a wage earner to have a random lifetime and to use a portion of the income to purchase life insurance in order to provide for his estate, while investing his savings in a financial market comprised of one risk-free security and an arbitrary number of risky securities driven by multidimensional Brownian motion. We then provide a detailed analysis of the optimal consumption, investment, and insurance purchase strategies for the wage earner whose goal is to maximize the expected utility obtained from his family consumption, from the size of the estate in the event of premature death, and from the size of the estate at the time of retirement. We use dynamic programming methods to obtain explicit solutions for the case of discounted constant relative risk aversion utility functions and describe new analytical results which are presented together with the corresponding economic interpretations.We thank the Calouste Gulbenkian Foundation, PRODYN-ESF, POCTI and POSI by FCT and Ministerio da Ciencia, Tecnologia e Ensino Superior, CEMAPRE, LIAAD-INESC Porto LA, Centro de Matematica da Universidade do Minho and Centro de Matematica da Universidade do Porto for their financial support. D. Pinheiro's research was supported by FCT - Fundacao para a Ciencia e Tecnologia program 'Ciencia 2007' and project 'Randomness in Deterministic Dynamical Systems and Applications' (PTDC/MAT/105448/2008). I. Duarte's research was supported by FCT - Fundacao para a Ciencia e Tecnologia grant with reference SFRH/BD/33502/2008

Development of new vocational training modules on sustainable buildings maintenance and refurbishment

This article presents the methodology and main results obtained in Spain within the FORMAR project, a European-funded project under the Leonardo Da Vinci scheme (Lifelong Learning Programme), whose main goal is to jointly develop training resources and modules to improve the skills on sustainability issues of buildings maintenance and refurbishment workers, in three different European countries: Spain, Portugal (Project Coordinator) and France. The Units of Short-term Training (UST) developed within this project are focused on the VET of carpenters, painters, bricklayers, building technicians and installers of solar panels, and a transversal unit containing basic concepts on sustainable construction and nearly Zero Energy Buildings (n-ZEB) is also developed. In parallel, clients’ guides for the aforementioned professionals are also implemented to improve the information provided to clients and owners in order to support the procurement decisions regarding building products and materials. Therefore, the project provides an opportunity to exchange experiences between organizations of these three European countries, as the UST will be developed simultaneously in each of them, exploring opportunities for training, guidance and exchange of experience. Even though the UST will have a common structure and contents, they will be slightly different in each country to adapt them to the different specific training needs and regulations of Spain, Portugal and France. This paper details, as a case study, the development process of the UST for carpenters and building technicians in Spain, including the analysis of needs and existing training materials, the main contents developed and the evaluation and testing process of the UST, which involves the active participation of several stakeholders of this sector as well as a classroom testing to obtain the students’ feedback

Tobacco rattle virus and its associated vector trichodorid nematodes in Portugal

Tobacco rattle virus (TRV, genus Tobravirus), transmitted by trichodorid nematodes, occurs as a wide range of serologically distinguishable strains that cause diseases in various economically important crops. The virus and its associated vector nematodes occur world-wide, being particularly prevalent in Europe and North America. In Portugal, an investigation is being conducted to identify TRV strains occurring in association with their natural vector species. The project has focused on potato growing areas in northern and central Portugal, with soil sampling biased in favour of areas where TRV-like symptoms have been reported. Nematodes were extracted from soil and phenotypically identified. TRV was recovered from nematodes in virus transmission studies, and identification confirmed using sap transmission tests, a leaf squash method with EM, ELISA, ISEM, and RT-PCR. Trichodorids were recovered frequently from potato fields, and the species identified were: Trichodorus lusitanicus, T. primitivus, Paratrichodorus anemones, P. hispanus, P. minor, P. pachydermus, also three new undescribed species and an unidentified Paratrichodorus species. TRV occurred in 4 of 58 (7%) soil samples in association with trichodorids: one in the North and the others in the centre of the country. Molecular characterisation of the TRV isolates and their associated vector trichodorids is presently in process

Peptide Receptor Radionuclide Therapy with 177 Lu-DOTA-TATE As a Promising Treatment of Malignant Insulinoma: a Series of Case Reports and Literature Review

Introduction: Insulinomas are a rare type of pancreatic neuroendocrine tumours characterized by insulin hypersecretion. They are considered malignant when metastases are present. Traditional therapies often promote only temporarily symptomatic relief and may be associated with severe adverse effects. There is scarce experience in treating malignant insulinomas with peptide receptors radionuclide therapy (PRRNT). Patients and methods: We describe PRRNT results in four patients with inoperable malignant insulinomas with poorly controllable hypoglycaemia. All patients received therapy with 177Lu-DOTA-TATE after conventional therapies failed in controlling disease progression and symptoms. The activity administered per cycle was 4.8-7.4 GBq. The interval between cycles was 10-16 weeks. Haematology, liver and kidney function tests were performed before treatment initiation and 5 and 10 weeks after each cycle. Results: Patient 1 presented significant clinical benefit for 13 months after PRRNT, with imaging improvement. Patient 2 obtained reduction of the number and severity of hypoglycaemic episodes during 15 months after therapy. Patient 3 is asymptomatic since PRRNT first cycle performed 23 months ago and revealed significant imaging improvement. Patient 4 had resolution of hypoglycaemia only 3 days after PRRNT first cycle and today, 16 months after therapy, the disease seems to be in remission and the patient maintains euglycaemic state. PRRNT was well tolerated, with only hematologic grade 2 toxicity in patient 1 and mild kidney toxicity in patient 3. Conclusions: After the start of 177Lu-DOTA-TATE all patients achieved hypoglycaemia symptomatic control and had evident improvement of their quality of life. Three patients showed imagiological improvement suggesting reduced tumour load.info:eu-repo/semantics/publishedVersio

Inverse Low Gain Avalanche Detectors (iLGADs) for precise tracking and timing applications

Low Gain Avalanche Detector (LGAD) is the baseline sensing technology of the recently proposed Minimum Ionizing Particle (MIP) end-cap timing detectors (MTD) at the Atlas and CMS experiments. The current MTD sensor is designed as a multi-pad matrix detector delivering a poor position resolution, due to the relatively large pad area, around 1 $mm^2$; and a good timing resolution, around 20-30 ps. Besides, in his current technological incarnation, the timing resolution of the MTD LGAD sensors is severely degraded once the MIP particle hits the inter-pad region since the signal amplification is missing for this region. This limitation is named as the LGAD fill-factor problem. To overcome the fill factor problem and the poor position resolution of the MTD LGAD sensors, a p-in-p LGAD (iLGAD) was introduced. Contrary to the conventional LGAD, the iLGAD has a non-segmented deep p-well (the multiplication layer). Therefore, iLGADs should ideally present a constant gain value over all the sensitive region of the device without gain drops between the signal collecting electrodes; in other words, iLGADs should have a 100${\%}$ fill-factor by design. In this paper, tracking and timing performance of the first iLGAD prototypes is presented.Comment: Conference Proceedings of VCI2019, 15th Vienna Conference of Instrumentation, February 18-22, 2019, Vienna, Austri