Data mining in HIV-AIDS surveillance system: application to portuguese data

The Human Immunodeficiency Virus (HIV) is an infectious agent that attacks the immune system cells. Without a strong immune system, the body becomes very susceptible to serious life threatening opportunistic diseases. In spite of the great progresses on medication and prevention over the last years, HIV infection continues to be a major global public health issue, having claimed more than 36 million lives over the last 35 years since the recognition of the disease. Monitoring, through registries, of HIV-AIDS cases is vital to assess general health care needs and to support long-term health-policy control planning. Surveillance systems are therefore established in almost all developed countries. Typically, this is a complex system depending on several stakeholders, such as health care providers, the general population and laboratories, which challenges an efficient and effective reporting of diagnosed cases. One issue that often arises is the administrative delay in reports of diagnosed cases. This paper aims to identify the main factors influencing reporting delays of HIV-AIDS cases within the portuguese surveillance system. The used methodologies included multilayer artificial neural networks (MLP), naive bayesian classifiers (NB), support vector machines (SVM) and the k-nearest neighbor algorithm (KNN). The highest classification accuracy, precision and recall were obtained for MLP and the results suggested homogeneous administrative and clinical practices within the reporting process. Guidelines for reductions of the delays should therefore be developed nationwise and transversally to all stakeholders.- A. Rita Gaio was partially supported by CMUP (UID/MAT/00144/2013), which is funded by FCT (Portugal) with national (MEC) and European structural funds (FEDER), under the partnership agreement PT2020. Luis Paulo Reis was partially by the European Regional Development Fund through the programme COMPETE by FCT (Portugal) in the scope of the project PEst - UID/ CEC/00027/2015 Luis Paulo Reis and Brigida Monica Faria were partially funded by QVida+: Estimacao Continua de Qualidade de Vida para Auxilio Eficaz a Decisao Clinica, NORTE-01-0247-FEDER-003446, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas

BACKGROUND: Malignant gliomas are the most prevalent type of primary brain tumours but the therapeutic armamentarium for these tumours is limited. Platelet-derived growth factor (PDGF) signalling has been shown to be a key regulator of glioma development. Clinical trials evaluating the efficacy of anti-PDGFRA therapies on gliomas are ongoing. In this study, we intended to analyse the expression of PDGFA and its receptor PDGFRA, as well as the underlying genetic (mutations and amplification) mechanisms driving their expression in a large series of human gliomas. METHODS: PDGFA and PDGFRA expression was evaluated by immunohistochemistry in a series of 160 gliomas of distinct World Health Organization (WHO) malignancy grade. PDGFRA-activating gene mutations (exons 12, 18 and 23) were assessed in a subset of 86 cases by PCR-single-strand conformational polymorphism (PCR-SSCP), followed by direct sequencing. PDGFRA gene amplification analysis was performed in 57 cases by quantitative real-time PCR (QPCR) and further validated in a subset of cases by chromogenic in situ hybridisation (CISH) and microarray-based comparative genomic hybridisation (aCGH). RESULTS: PDGFA and PDGFRA expression was found in 81.2% (130 out of 160) and 29.6% (48 out of 160) of gliomas, respectively. Its expression was significantly correlated with histological type of the tumours; however, no significant association between the expression of the ligand and its receptor was observed. The absence of PDGFA expression was significantly associated with the age of patients and with poor prognosis. Although PDGFRA gene-activating mutations were not found, PDGFRA gene amplification was observed in 21.1% (12 out of 57) of gliomas. No association was found between the presence of PDGFRA gene amplification and expression, excepting for grade II diffuse astrocytomas. CONCLUSION: The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas

Fatal drug poisonings in a Swedish general population

ABSTRACT: BACKGROUND: Pharmaceutical drug poisonings have previously been reported using single sources of information, either hospital data or forensic data, which might not reveal the true incidence. We therefore aimed to estimate the incidence of suspected fatal drug poisonings, defined as poisonings by pharmaceutical agents, by using all relevant case records from various sources in a Swedish population. METHODS: Every seventh randomly selected deceased in three counties in southeastern Sweden during a one-year period was identified in the Cause of Death Register. Relevant case records (death certificates, files from hospitals and/or primary care centres and medico-legal files) were reviewed for all study subjects. RESULTS: Of 1574 deceased study subjects, 12 cases were classified as pharmaceutical drug poisonings according to the death certificates and 10 according to the medico-legal files. When reviewing all available data sources, 9 subjects (0.57%; 95% confidence interval: 0.20-0.94%) were classified as drug poisonings, corresponding to an incidence of 6.5 (95% confidence interval: 2.3-10.7) per 100 000 person-years in the general population. The drug groups most often implicated were benzodiazepines (33%), antihistamines (33%) and analgesics (22%). CONCLUSIONS: Fatal drug poisonings is a relatively common cause of death in Sweden. By using multiple sources of information when investigating the proportion of fatal poisonings in a population, more accurate estimates may be obtained.Original Publication:Anna Jonsson, Olav Spigset, Micaela Tjäderborn, Henrik Druid and Staffan Hägg, Fatal drug poisonings in a Swedish general population., 2009, BMC clinical pharmacology, (9), 7, 1-5.http://dx.doi.org/10.1186/1472-6904-9-7Licensee: BioMed Centralhttp://www.biomedcentral.com

Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

<p>Abstract</p> <p>Background</p> <p>Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen <it>Leishmania </it>has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of <it>Leishmania</it>-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease.</p> <p>Methods</p> <p>We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of <it>Leishmania </it>using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of <it>Leishmania </it>uptake on LPS-induced cytokine expression with uptake of inert latex beads.</p> <p>Results</p> <p>Whilst <it>Leishmania </it>uptake alone did not induce significant levels of any cytokine analysed in this study, <it>Leishmania </it>uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, <it>L. amazonensis </it>was generally more suppressive than <it>L. major</it>. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during <it>Leishmania </it>uptake, in a parasite-specific manner.</p> <p>Conclusions</p> <p>During uptake by macrophages, <it>Leishmania </it>evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, <it>Leishmania </it>suppresses certain proinflammatory cytokine responses in a parasite-specific manner, however it augments the production of other proinflammatory cytokines. Our findings highlight the complexity of inflammatory cytokine signalling regulation in the context of the macrophage and <it>Leishmania </it>interaction and confirm the utility of the <it>Leishmania</it>/macrophage infection model as an experimental system for further studies of inflammatory regulation. Such studies may advance the development of therapies against inflammatory disease.</p

Granulomatous Reactivation during the Course of a Leprosy Infection: Reaction or Relapse

Leprosy is a serious infectious disease whose treatment still poses some challenges. Patients are usually treated with a combination of antimicrobial drugs called multidrug therapy. Although this treatment is effective against Mycobacterium leprae, the bacillus that causes leprosy, patients may develop severe inflammatory reactions during treatment. These reactions may be either attributed to an improvement in the immunological reactivity of the patient along with the treatment, or to relapse of the disease due to the proliferation of remaining bacilli. In certain patients these two conditions may be difficult to differentiate. The present study addresses the histopathology picture of and the M. leprae bacilli in sequential biopsies taken from lesions of patients who presented such reactions aiming to improve the differentiation of the two conditions. This is important because these reactions are one of the major causes of the disabilities of the patients with leprosy, and should be treated early and appropriately. Our results show that the histopathology picture alone is not sufficient, and that bacilli's counting is necessary