Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases

Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies

BACKGROUND: Primary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal. METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective. RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years. CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.info:eu-repo/semantics/publishedVersio

Continuous dynamic monitoring of bridges: different perspectives of application

This paper makes a brief characterisation of some aspects related with the extensive research activity of the Laboratory of Vibrations and Structural Monitoring (ViBest) of the Faculty of Engineering of the University of Porto (FEUP) in the field of Continuous Dynamic Monitoring of Bridges and Special Structures, selecting four examples where large high quality databases have been created since 2007, namely Infante D. Henrique bridge, Pedro e Ines footbride, FEUP Campus stress-ribbon footbridge and Trezoi railway bridge

Do individual factors matter? : A survey of scientists’ patenting in Portuguese public research organisations

This paper addresses scientists’ behaviour regarding the patenting of knowledge produced in universities and other public sector research organisations (PSROs). Recent years have witnessed a rapid growth in patenting and licensing activities by PSROs. We argue that the whole process depends to a certain extent on scientists’ willingness to disclose their inventions. Given this assumption, we conduct research into individual behaviour in order to understand scientists’ views concerning the patenting of their research results. Data from a questionnaire survey of Portuguese researchers from nine PSROs in life sciences and biotechnology is presented and analysed and complemented with in-depth interviews. The results reveal that overall the scientists surveyed show a low propensity to become involved in patenting and licensing activities, despite the fact that the majority had no “ethical” objections to the disclosure of their inventions and the commercial exploitation of these. Perceptions about the impacts of these activities on certain fundamental aspects of knowledge production and dissemination are however divergent. This may account for the low participation levels. Furthermore, most scientists perceived the personal benefits deriving from this type of activity to be low. Similarly, the majority also believed that there are many difficulties associated with the patenting process and that they receive limited support from their organisations, which lack the proper competences and structures to assist with patenting and licensing.info:eu-repo/semantics/publishedVersio

Accounting for Sources of Information in Trade Fairs: Evidence from Portuguese Exhibitors

Trade fairs are important sources of information for decision making in marketing management. Currently, trade fairs are places where participants share useful data and information, while creating relationships between customers (visitors) and suppliers (exhibitors). However, only a limited number of studies have focused on the identification of the sources of information that exhibitors can provide for marketing managers at trade fairs. This study examines the importance of the different types of information resources that can be delivered by exhibitors to managers in order to transfer information about product and market trends. Based on the data from a survey of 172 Portuguese executives from different industries, the theoretical hypotheses are tested, using CFA (Confirmatory Factor Analysis). Consistent with our hypotheses, the results show that Direct Marketing techniques, such as face-to-face contacts and product/service demonstrations, are often used by exhibitors. Information in digital formats and demonstration in digital equipment (Digital Marketing) are also used in trade fairs to display information to potential customers. Additionally, the organization of parallel events (Event Marketing) during a trade fair supplements the package of activities developed by exhibitors to transmit and capture information for their companies. These results provide certain support for the importance of trade fairs in view of being a rich source of market information about not only new technological developments of products, but also major strengths and weaknesses of competitors, and future market trends, among other types of information needed for the marketing planning.info:eu-repo/semantics/publishedVersio

Carrier depletion and grain misorientations on individual grain boundaries of polycrystalline si thin films

Structural and microelectrical properties of grain boundaries (GBs) in polycrystalline Si thin films were investigated by electron backscattering diffraction (EBSD) and scanning capacitance microscopy (SCM). The SCM measurements revealed highly nonuniform carrier depletions among the GBs, indicating the variety of electrical properties due to the specific GB structures. The EBSD measurement showed that the films are weakly [001]-oriented with small fractions of grains in the [111] and [110] orientations. Comparison of the SCM and EBSD measurements taken on the same film area led to the following observations: (1) Σ3 GBs do not exhibit carrier depletions and thus do not have charged deep levels; (2) Some Σ9 GBs exhibit carrier depletions and some do not, indicating that the intrinsic Σ9 GBs do not have charged deep levels and the carrier depletions are due to impurity gettering at the GBs; (3) No significant relationship between the carrier depletion behavior and the grain misorientationwas found so far on the GBs with random misorientations; (4) The carrier depletion behavior does not depend only on the grain misorientation but also on the facet where the GB is taken. ©2009 IEEE.published_or_final_versionThe 34th IEEE Conference on Photovoltaic Specialists (PVSC 2009), Philadelphia, PA., 7-12 June 2009. In Conference Record, 2009, p. 000471-00047

A Comparison between the Presence and Absence of Regulation in the Spanish Electricity Market

There is an important gap in the literature on the promotion of competition in electricity markets in what pertains to the analysis of two different streams: the absence and presence of regulation. Accordingly, the main objective of this study is to analyze the interactions among market power indexes, marginal costs, and bidding strategies in the two mentioned scenarios, for comparative purposes. The methodology used is based on panel cointegration methods. The results point to the significant inclusion of different bidding strategies in the retail market: (i) fuel prices exercise a differential impact on the power plants’ marginal costs, (ii) the marginal costs have a significantly positive effect on quantity sold and on net quantity, and (iii) the market power measures under regulation have a significantly positive long-term impact on the quantity sold and a negative impact on net quantity supplied in wholesale market. Although there is some literature on this issue, the main novelty of this article is the discussion of the regulatory implications that could have been adopted in order to control and mitigate the market power, to encourage new investments in new technologies, and to recover sunk costs with the transition to a competitive market

HIV: neuropsychiatric aspects of infection and therapy

Desde o seu reconhecimento na década de 80, a infecção por VIH atingiu já 65 milhões de pessoas, em todo o mundo. A presença do vírus no SNC acontece na maioria dos doentes afectados, sendo cada vez mais identificadas perturbações neuropsiquiátricas associadas à infecção e/ou ao tratamento com ARV. Este artigo pretende rever sumariamente a neuropatogénese e as alterações neuropsiquiátricas associadas à infecção VIH e ao tratamento com TARV, bem como a sua abordagem terapêutica