506 research outputs found

    Heavy-light decay topologies as a new strategy to discover a heavy gluon

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    We study the collider phenomenology of the lightest Kaluza-Klein excitation of the gluon, G*, in theories with a warped extra dimension. We do so by means of a two-site effective lagrangian which includes only the lowest-lying spin-1 and spin-1/2 resonances. We point out the importance of the decays of G* to one SM plus one heavy fermion, that were overlooked in the previous literature. It turns out that, when kinematically allowed, such heavy-light decays are powerful channels for discovering the G*. In particular, we present a parton-level Montecarlo analysis of the final state Wtb that follows from the decay of G* to one SM top or bottom quark plus its heavy partner. We find that at \sqrt{s} = 7 TeV and with 10 fb^{-1} of integrated luminosity, the LHC can discover a KK gluon with mass in the range M_{G*} = (1.8 - 2.2) TeV if its coupling to a pair of light quarks is g_{G*qqbar} = (0.2-0.5) g_3. The same process is also competitive for the discovery of the top and bottom partners as well. We find, for example, that the LHC at \sqrt{s} = 7 TeV can discover a 1 TeV KK bottom quark with an integrated luminosity of (5.3 - 0.61) fb^{-1} for g_{G*qqbar} = (0.2-0.5) g_3.Comment: 36 pages, 13 figures. v2: a few typos corrected, comments added, version published in JHE

    Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis

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    INTRODUCTION: Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis. METHODS: This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls. RESULTS: Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-alpha/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-alpha and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45). CONCLUSIONS: The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis

    Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients

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    Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers

    A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa

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    Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis

    Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

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    <p>Abstract</p> <p>Background</p> <p>Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like <it>env </it>gene sequences.</p> <p>Results</p> <p>The MMTV-like <it>env </it>gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number <ext-link ext-link-id="AY161347" ext-link-type="gen">AY161347</ext-link>. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the <it>env </it>sequences exhibited disruption of the reading frame due to mutations.</p> <p>Conclusion</p> <p>In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.</p

    Phenomenology of Non-Custodial Warped Models

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    We study the effect of bulk fermions on electroweak precision observables in a recently proposed model with warped extra dimensions and no custodial symmetry. We find that the top-quark mass, together with the corrections to the Zbb vertex and the one-loop contribution to the T parameter, which is finite, impose important constraints that single out a well defined region of parameter space. New massive vector bosons can be as light as 1.5 TeV and have large couplings to the t_R quark, and suppressed couplings to the t_L, b_L and lighter quarks. We discuss the implications for searches of models with warped extra dimensions at the LHC.Comment: Most relevant one-loop contributions to EWP observables included, physics results partially changed. References added. 29 pages, 14 Figure

    The Discrete Composite Higgs Model

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    We describe a concrete, predictive incarnation of the general paradigm of a composite Higgs boson, which provides a valid alternative to the standard holographic models in five space-time dimensions. Differently from the latter, our model is four-dimensional and simple enough to be implemented in an event generator for collider studies. The model is inspired by dimensional deconstruction and hence it retains useful features of the five-dimensional scenario, in particular, the Higgs potential is finite and calculable. Therefore our setup, in spite of being simple, provides a complete description of the composite Higgs physics. After constructing the model we present a first analysis of its phenomenology, focusing on the structure of the Higgs potential, on the constraints from the EWPT and on the spectrum of the new particles.Comment: 42 pages, 10 figures; v2: minor changes and references added; v3: version published in JHE

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Source water, phenology and growth of two tropical dry forest tree species growing on shallow karst soils

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    Seasonally dry tropical forests are dominated by deciduous and evergreen tree species with a wide range of leaf phenology. We hypothesized that Piscidia piscipula is able to extend leaf senescence until later in the dry season due to deeper and more reliable water sources than Gymnopodium floribundum, which loses leaves earlier in the dry season. Physiological performance was assessed as timing of leaf production and loss, growth, leaf water potential, depth of water uptake determined by stable isotopes, and leaf stable isotopic composition of carbon (δ¹³C) and oxygen (δ¹⁸O). P. piscipula took water primarily from shallow sources, whereas G. floribundum took water from shallow and deep sources. The greatest variation in water sources occurred during the onset of the dry season, when G. floribundum was shedding old leaves and growing new leaves, but P. piscipula maintained its leaves from the previous wet season. P. piscipula showed greater relative growth rate, greater leaf expansion rates, and more negative predawn and midday water potentials than G. floribundum. P. piscipula also exhibited greater leaf organic δ¹³C and lower δ¹⁸O values, indicating that the decrease in photosynthetic carbon isotope discrimination was associated with greater stomatal conductance and greater photosynthesis. Our results indicate that the contrasting early and late dry season leaf loss phenology of these two species is not simply determined by rooting depth, but rather a more complicated suite of characteristics based on opportunistic use of dynamic water sources, maximizing carbon gain, and maintenance of water potential during the dry season
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