100 research outputs found

    Heartburn or angina? Differentiating gastrointestinal disease in primary care patients presenting with chest pain: a cross sectional diagnostic study

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    <p>Abstract</p> <p>Background</p> <p>Gastrointestinal (GI) disease is one of the leading aetiologies of chest pain in a primary care setting. The aims of the study are to describe clinical characteristics of GI disease causing chest pain and to provide criteria for clinical diagnosis.</p> <p>Methods</p> <p>We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow up information. An independent interdisciplinary reference panel reviewed clinical data of each patient and decided about the aetiology of chest pain. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out the diagnosis of GI disease and Gastroesophageal Reflux Disease (GERD).</p> <p>Results</p> <p>GI disease was diagnosed in 5.8% and GERD in 3.5% of all patients. Most patients localised the pain retrosternal (71.8% for GI disease and 83.3% for GERD). Pain worse with food intake and retrosternal pain radiation were associated positively with both GI disease and GERD; retrosternal pain localisation, vomiting, burning pain, epigastric pain and an average pain episode < 1 hour were associated positively only with GI disease. Negative associations were found for localized muscle tension (GI disease and GERD) and pain getting worse on exercise, breathing, movement and pain location on left side (only GI disease).</p> <p>Conclusions</p> <p>This study broadens the knowledge about the diagnostic accuracy of selected signs and symptoms for GI disease and GERD and provides criteria for primary care practitioners in rational diagnosis.</p

    Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

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    Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients

    Single-laser 32.5 Tbit/s Nyquist WDM transmission

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    We demonstrate 32.5 Tbit/s 16QAM Nyquist WDM transmission over a total length of 227 km of SMF-28 without optical dispersion compensation. A number of 325 optical carriers are derived from a single laser and encoded with dual-polarization 16QAM data using sinc-shaped Nyquist pulses. As we use no guard bands, the carriers have a spacing of 12.5 GHz equal to the Nyquist bandwidth of the data. We achieve a high net spectral efficiency of 6.4 bit/s/Hz using a software-defined transmitter which generates the electrical modulator drive signals in real-time.Comment: (c) 2012 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibite

    ADAM33, a New Candidate for Psoriasis Susceptibility

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    Psoriasis is a chronic skin disorder with multifactorial etiology. In a recent study, we reported results of a genome-wide scan on 46 French extended families presenting with plaque psoriasis. In addition to unambiguous linkage to the major susceptibility locus PSORS1 on Chromosome 6p21, we provided evidence for a susceptibility locus on Chromosome 20p13. To follow up this novel psoriasis susceptibility locus we used a family-based association test (FBAT) for an association scan over the 17 Mb candidate region. A total of 85 uncorrelated SNP markers located in 65 genes of the region were initially investigated in the same set of large families used for the genome wide search, which consisted of 295 nuclear families. When positive association was obtained for a SNP, candidate genes nearby were explored more in detail using a denser set of SNPs. Thus, the gene ADAM33 was found to be significantly associated with psoriasis in this family set (The best association was on a 3-SNP haplotype P = 0.00004, based on 1,000,000 permutations). This association was independent of PSORS1. ADAM33 has been previously associated with asthma, which demonstrates that immune system diseases may be controlled by common susceptibility genes with general effects on dermal inflammation and immunity. The identification of ADAM33 as a psoriasis susceptibility gene identified by positional cloning in an outbred population should provide insights into the pathogenesis and natural history of this common disease

    New evidence of factor structure and measurement invariance of the SDQ across five European nations

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    The main purpose of the present study was to test the internal structure and to study the measurement invariance of the Strength and Difficulties Questionnaire (SDQ), self-reported version, in five European countries. The sample consisted of 3012 adolescents aged between 12 and 17 years (M = 14.20; SD = 0.83). The five-factor model (with correlated errors added), and the five-factor model (with correlated errors added) with the reverse-worded items allowed to cross-load on the Prosocial subscale, displayed adequate goodness of-fit indices. Multi-group confirmatory factor analysis showed that the five-factor model had partial strong measurement invariance by countries. A total of 11 of the 25 items were non-invariant across samples. The level of internal consistency of the Total difficulties scores was .84, ranging between .69 and .78 for the SDQ subscales. The findings indicate that the SDQ's scales need to be modified in various ways for screening emotional and behavioural problems in the five European countries that were analyzed

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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