183 research outputs found
Recent Advances in Graph Partitioning
We survey recent trends in practical algorithms for balanced graph
partitioning together with applications and future research directions
Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis
Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs).
Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature.
Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece.
Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases
Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells
Abstract
Background
Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.
Methods
We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we integrated network and gene set enrichment analyses of BAL cell transcriptional profiles.
Results
Sarcoidosis patients were either non-smokers or former smokers, all had lung involvement and only two were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1500 differentially expressed genes. Several previously described immune mediators, such as interferon gamma, were upregulated in the sarcoidosis subjects. Using an integrative computational approach we constructed a modular network of over 80 gene sets that were highly enriched in patients with sarcoidosis. Many of these pathways mapped to inflammatory and immune-related processes including adaptive immunity, T-cell signaling, graft vs. host disease, interleukin 12, 23 and 17 signaling. Additionally, we uncovered a close association between the proteasome machinery and adaptive immunity, highlighting a potentially important and targetable relationship in the pathobiology of sarcoidosis.
Conclusions
BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional programs involved in immunity and proteasomal processes. Our findings add to the growing evidence implicating alveolar resident immune effector cells in the pathogenesis of sarcoidosis and identify specific pathways whose activation may modulate disease progression
EQ-5D in Central and Eastern Europe : 2000-2015
Objective: Cost per quality-adjusted life year data are required for reimbursement decisions in many Central and Eastern European (CEE) countries. EQ-5D is by far the most commonly used instrument to generate utility values in CEE. This study aims to systematically review the literature on EQ-5D from eight CEE countries. Methods: An electronic database search was performed up to July 1, 2015 to identify original EQ-5D studies from the countries of interest. We analysed the use of EQ-5D with respect to clinical areas, methodological rigor, population norms and value sets. Results: We identified 143 studies providing 152 country-specific results with a total sample size of 81,619: Austria (n=11), Bulgaria (n=6), Czech Republic (n=18), Hungary (n=47), Poland (n=51), Romania (n=2), Slovakia (n=3) and Slovenia (n=14). Cardiovascular (20%), neurologic (16%), musculoskeletal (15%) and endocrine/nutritional/metabolic diseases (14%) were the most frequently studied clinical areas. Overall 112 (78%) of the studies reported EQ VAS results and 86 (60%) EQ-5D index scores, of which 27 (31%) did not specify the applied tariff. Hungary, Poland and Slovenia have population norms. Poland and Slovenia also have a national value set. Conclusions: Increasing use of EQ-5D is observed throughout CEE. The spread of health technology assessment activities in countries seems to be reflected in the number of EQ-5D studies. However, improvement in informed use and methodological quality of reporting is needed. In jurisdictions where no national value set is available, in order to ensure comparability we recommend to apply the most frequently used UK tariff. Regional collaboration between CEE countries should be strengthened
Thermal and electrostatic tuning of surface phonon-polaritons in LaAlO<sub>3</sub>/SrTiO<sub>3</sub> heterostructures
Phonon polaritons are promising for infrared applications due to a strong light-matter coupling and subwavelength energy confinement they offer. Yet, the spectral narrowness of the phonon bands and difficulty to tune the phonon polariton properties hinder further progress in this field. SrTiO3 – a prototype perovskite oxide - has recently attracted attention due to two prominent far-infrared phonon polaritons bands, albeit without any tuning reported so far. Here we show, using cryogenic infrared near-field microscopy, that long-propagating surface phonon polaritons are present both in bare SrTiO3 and in LaAlO3/SrTiO3 heterostructures hosting a two-dimensional electron gas. The presence of the two-dimensional electron gas increases dramatically the thermal variation of the upper limit of the surface phonon polariton band due to temperature dependent polaronic screening of the surface charge carriers. Furthermore, we demonstrate a tunability of the upper surface phonon polariton frequency in LaAlO3/SrTiO3 via electrostatic gating. Our results suggest that oxide interfaces are a new platform bridging unconventional electronics and long-wavelength nanophotonics.</p
Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling
Background: Anaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed. Objective: We sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis. Methods: Bulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken. Results: 1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling. Conclusion: Our study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis
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Author Correction: Highly confined epsilon-near-zero and surface phonon polaritons in SrTiO3 membranes
Correction to: Nature Communicationshttps://doi.org/10.1038/s41467-024-47917-x, published online 04 June 2024 In this article the grant number #200020_201096 relating to the Swiss National Science Foundation was omitted. The original article has been corrected
Highly confined epsilon-near-zero- and surface-phonon polaritons in SrTiO3 membranes
Recent theoretical studies have suggested that transition metal perovskite
oxide membranes can enable surface phonon polaritons in the infrared range with
low loss and much stronger subwavelength confinement than bulk crystals. Such
modes, however, have not been experimentally observed so far. Here, using a
combination of far-field Fourier-transform infrared (FTIR) spectroscopy and
near-field synchrotron infrared nanospectroscopy (SINS) imaging, we study the
phonon-polaritons in a 100 nm thick freestanding crystalline membrane of SrTiO3
transferred on metallic and dielectric substrates. We observe a
symmetric-antisymmetric mode splitting giving rise to epsilon-near-zero and
Berreman modes as well as highly confined (by a factor of 10) propagating
phonon polaritons, both of which result from the deep-subwavelength thickness
of the membranes. Theoretical modeling based on the analytical finite-dipole
model and numerical finite-difference methods fully corroborate the
experimental results. Our work reveals the potential of oxide membranes as a
promising platform for infrared photonics and polaritonics
Endoplasmic reticulum Ca2+-homeostasis is altered in small and non-small cell lung cancer cell lines
<p>Abstract</p> <p>Background</p> <p>Knowledge of differences in the cellular physiology of malignant and non-malignant cells is a prerequisite for the development of cancer treatments that effectively kill cancer without damaging normal cells. Calcium is a ubiquitous signal molecule that is involved in the control of proliferation and apoptosis. We aimed to investigate if the endoplasmic reticulum (ER) Ca<sup>2+</sup>-homeostasis is different in lung cancer and normal human bronchial epithelial (NHBE) cells.</p> <p>Methods</p> <p>The intracellular Ca<sup>2+</sup>-signaling was investigated using fluorescence microscopy and the expression of Ca<sup>2+</sup>-regulating proteins was assessed using Western Blot analysis.</p> <p>Results</p> <p>In a Small Cell Lung Cancer (H1339) and an Adeno Carcinoma Lung Cancer (HCC) cell line but not in a Squamous Cell Lung Cancer (EPLC) and a Large Cell Lung Cancer (LCLC) cell line the ER Ca<sup>2+</sup>-content was reduced compared to NHBE. The reduced Ca<sup>2+</sup>-content correlated with a reduced expression of SERCA 2 pumping calcium into the ER, an increased expression of IP<sub>3</sub>R releasing calcium from the ER, and a reduced expression of calreticulin buffering calcium within the ER. Lowering the ER Ca<sup>2+</sup>-content with CPA led to increased proliferation NHBE and lung cancer cells.</p> <p>Conclusion</p> <p>The significant differences in Ca<sup>2+</sup>-homeostasis between lung cancer and NHBE cells could represent a new target for cancer treatments.</p
Free breathing contrast-enhanced time-resolved magnetic resonance angiography in pediatric and adult congenital heart disease
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