Showing papers by "University of Cologne published in 2013"
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TL;DR: Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy.
Abstract: Background Severe pain after surgery remains a major problem, occurring in 20-40% of patients. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain therapy and develop procedure-specific, optimized pain-treatment protocols, types of surgery that may result in severe postoperative pain in everyday practice must first be identified. Methods This study considered 115,775 patients from 578 surgical wards in 105 German hospitals. A total of 70,764 patients met the inclusion criteria. On the first postoperative day, patients were asked to rate their worst pain intensity since surgery (numeric rating scale, 0-10). All surgical procedures were assigned to 529 well-defined groups. When a group contained fewer than 20 patients, the data were excluded from analysis. Finally, 50,523 patients from 179 surgical groups were compared. Results The 40 procedures with the highest pain scores (median numeric rating scale, 6-7) included 22 orthopedic/trauma procedures on the extremities. Patients reported high pain scores after many "minor" surgical procedures, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy, which ranked among the 25 procedures with highest pain intensities. A number of "major" abdominal surgeries resulted in comparatively low pain scores, often because of sufficient epidural analgesia. Conclusions Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain. To reduce the number of patients suffering from severe pain, patients undergoing so-called minor surgery should be monitored more closely, and postsurgical pain treatment needs to comply with existing procedure-specific pain-treatment recommendations.
1,060 citations
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TL;DR: A meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, and identified 29,807 SNPs for further genotyping suggests that more than 1,000 additional loci are involved in breast cancer susceptibility.
Abstract: Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility
1,048 citations
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TL;DR: Evidence from neuroimaging, psychophysiological studies, and related fields are reviewed to argue for the development of a second-person neuroscience, which will help neuroscience to really “go social” and may also be relevant for the understanding of psychiatric disorders construed as disorders of social cognition.
Abstract: In spite of the remarkable progress made in the burgeoning field of social neuroscience, the neural mechanisms that underlie social encounters are only beginning to be studied and could-paradoxically-be seen as representing the "dark matter" of social neuroscience. Recent conceptual and empirical developments consistently indicate the need for investigations that allow the study of real-time social encounters in a truly interactive manner. This suggestion is based on the premise that social cognition is fundamentally different when we are in interaction with others rather than merely observing them. In this article, we outline the theoretical conception of a second-person approach to other minds and review evidence from neuroimaging, psychophysiological studies, and related fields to argue for the development of a second-person neuroscience, which will help neuroscience to really "go social"; this may also be relevant for our understanding of psychiatric disorders construed as disorders of social cognition.
1,022 citations
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TL;DR: In this article, a framework of social media's impact on brand management is introduced, arguing that consumers are becoming pivotal authors of brand stories due to new dynamic networks of consumers and brands formed through social media and the easy sharing of brand experiences in such networks.
682 citations
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TL;DR: A positive role for mast cells in tissue inflammation is demonstrated and how this comes about with contribution from a second tissue cell, the macrophage is defined.
605 citations
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TL;DR: This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory.
Abstract: Purpose This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results. Patients and Methods HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference. Results Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who rece...
546 citations
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Max Planck Society1, National Radio Astronomy Observatory2, University of Maryland, College Park3, University of Toledo4, Ohio State University5, Princeton University6, McMaster University7, University of Massachusetts Amherst8, University of Cambridge9, University of Paris-Sud10, Stony Brook University11, Heidelberg University12, University of Hertfordshire13, ASTRON14, University of Wyoming15, Raytheon16, University of Arizona17, INAF18, Institut d'Astrophysique de Paris19, University of California, San Diego20, California Institute of Technology21, Leiden University22, Space Telescope Science Institute23, Louisiana State University24, DSM25, University of Cologne26
TL;DR: In this paper, the authors presented a large-scale spatial resolution map of the CO-to-H$2}$ conversion factor and dust-togas ratio (DGR) in 26 nearby, star-forming galaxies.
Abstract: We present ~{}kiloparsec spatial resolution maps of the CO-to-H$_{2}$ conversion factor ({$α$}$_{CO}$) and dust-to-gas ratio (DGR) in 26 nearby, star-forming galaxies. We have simultaneously solved for {$α$}$_{CO}$ and the DGR by assuming that the DGR is approximately constant on kiloparsec scales. With this assumption, we can combine maps of dust mass surface density, CO-integrated intensity, and H I column density to solve for both {$α$}$_{CO}$ and the DGR with no assumptions about their value or dependence on metallicity or other parameters. Such a study has just become possible with the availability of high-resolution far-IR maps from the Herschel key program KINGFISH, $^{12}$CO J = (2-1) maps from the IRAM 30 m large program HERACLES, and H I 21 cm line maps from THINGS. We use a fixed ratio between the (2-1) and (1-0) lines to present our {$α$}$_{CO}$ results on the more typically used $^{12}$CO J = (1-0) scale and show using literature measurements that variations in the line ratio do not affect our results. In total, we derive 782 individual solutions for {$α$}$_{CO}$ and the DGR. On average, {$α$}$_{CO}$ = 3.1 M $_{☉}$ pc$^{–2}$ (K km s$^{–1}$)$^{–1}$ for our sample with a standard deviation of 0.3 dex. Within galaxies, we observe a generally flat profile of {$α$}$_{CO}$ as a function of galactocentric radius. However, most galaxies exhibit a lower {$α$}$_{CO}$ value in the central kiloparsec{mdash}a factor of ~{}2 below the galaxy mean, on average. In some cases, the central {$α$}$_{CO}$ value can be factors of 5-10 below the standard Milky Way (MW) value of {$α$}$_{CO, MW}$ = 4.4 M $_{☉}$ pc$^{–2}$ (K km s$^{–1}$)$^{–1}$. While for {$α$}$_{CO}$ we find only weak correlations with metallicity, the DGR is well-correlated with metallicity, with an approximately linear slope. Finally, we present several recommendations for choosing an appropriate {$α$}$_{CO}$ for studies of nearby galaxies.
533 citations
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Stig E. Bojesen1, Stig E. Bojesen2, Karen A. Pooley3, Sharon E. Johnatty4 +452 more•Institutions (129)
TL;DR: Using the Illumina custom genotyping array iCOGs, SNPs at the TERT locus in breast, ovarian and BRCA1 mutation carrier cancer cases and controls and leukocyte telomere measurements are analyzed to find associations cluster into three independent peaks.
Abstract: TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
522 citations
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TL;DR: This study revealed that skyrmions vanish by a coalescence, forming elongated structures, and numerical simulations showed that changes of topology are controlled by singular magnetic point defects.
Abstract: Skyrmion crystals are regular arrangements of magnetic whirls that exist in a wide range of chiral magnets. Because of their topology, they cannot be created or destroyed by smooth rearrangements of the direction of the local magnetization. Using magnetic force microscopy, we tracked the destruction of the skyrmion lattice on the surface of a bulk crystal of Fe(1-x)Co(x)Si (x = 0.5). Our study revealed that skyrmions vanish by a coalescence, forming elongated structures. Numerical simulations showed that changes of topology are controlled by singular magnetic point defects. They can be viewed as quantized magnetic monopoles and antimonopoles, which provide sources and sinks of one flux quantum of emergent magnetic flux, respectively.
517 citations
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TL;DR: In multivariable analysis, survival for the entire study cohort was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model delineated risk groups with median survivals of 10.9–27.8 years.
Abstract: Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information (n=337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population (P<0.001). In multivariable analysis, survival for the entire study cohort (n=1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9–27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7–15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ⩾15 × 109/l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.
490 citations
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Max Planck Society1, University of Cologne2, ASTRON3, University of Melbourne4, University of Göttingen5, Vanderbilt University6, Massachusetts Institute of Technology7, University of North Carolina at Chapel Hill8, VU University Amsterdam9, Memorial Sloan Kettering Cancer Center10, University of Bonn11, University of Zurich12, University of Oslo13, Heidelberg University14, University of Jena15, Drug Abuse Resistance Education16, Praxis17, French Institute of Health and Medical Research18, University of Bologna19, University of Liverpool20, Institut Gustave Roussy21
TL;DR: Support is provided for broad implementation of genome-based diagnosis of lung cancer by demonstrating the correlation between lung tumor subtype and its predominant mutations, and the benefit of genetic testing and targeted therapy in these patients.
Abstract: We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.
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TL;DR: The Conspiracy Mentality Questionnaire (CMQ) is presented, an instrument designed to efficiently assess differences in the generic tendency to engage in conspiracist ideation within and across cultures and predicted beliefs in specific conspiracy theories over and above other individual difference measures.
Abstract: Conspiracy theories are ubiquitous when it comes to explaining political events and societal phenomena. Individuals differ not only in the degree to which they believe in specific conspiracy theories, but also in their general susceptibility to explanations based on such theories, that is, their conspiracy mentality. We present the Conspiracy Mentality Questionnaire (CMQ), an instrument designed to efficiently assess differences in the generic tendency to engage in conspiracist ideation within and across cultures. The CMQ is available in English, German, and Turkish. In four studies, we examined the CMQ’s factorial structure, reliability, measurement equivalence across cultures, and its convergent, discriminant, and predictive validity. Analyses based on a cross-cultural sample (Study 1a; N = 7,766) supported the conceptualization of conspiracy mentality as a one-dimensional construct across the three language versions of the CMQ that is stable across time (Study 1b; N = 141). Multigroup confirmatory factor analysis demonstrated cross-cultural measurement equivalence of the CMQ items. The instrument could therefore be used to examine differences in conspiracy mentality between European, North American, and Middle Eastern cultures. In Studies 2-4 (total N = 476), we report (re-)analyses of 3 datasets demonstrating the validity of the CMQ in student and working population samples in the UK and Germany. First, attesting to its convergent validity, the CMQ was highly correlated with another measure of generic conspiracy belief. Second, the CMQ showed patterns of meaningful associations with personality measures (e.g., Big Five dimensions, schizotypy), other generalized political attitudes (e.g., social dominance orientation and right-wing authoritarianism), and further individual differences (e.g., paranormal belief, lack of socio-political control). Finally, the CMQ predicted beliefs in specific conspiracy theories over and above other individual difference measures.
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Russian Academy of Sciences1, University of Cologne2, Norwegian Meteorological Institute3, Stockholm University4, University of Salento5, University of Reading6, Environment Canada7, University of Hamburg8, Free University of Berlin9, Shirshov Institute of Oceanology10, European Centre for Medium-Range Weather Forecasts11, Hokkaido University12, University of Melbourne13, Royal Netherlands Meteorological Institute14, Bjerknes Centre for Climate Research15, University of Birmingham16, University of Trás-os-Montes and Alto Douro17, University of Bern18, Embry–Riddle Aeronautical University19, ETH Zurich20, University of Lisbon21
TL;DR: In this article, the variability of results from different automated methods of detection and tracking of extratropical cyclones is assessed in order to identify uncertainties related to the choice of method.
Abstract: The variability of results from different automated methods of detection and tracking of extratropical cyclones is assessed in order to identify uncertainties related to the choice of method. Fifteen international teams applied their own algorithms to the same dataset—the period 1989–2009 of interim European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERAInterim) data. This experiment is part of the community project Intercomparison of Mid Latitude Storm Diagnostics (IMILAST; see www.proclim.ch/imilast/index.html). The spread of results for cyclone frequency, intensity, life cycle, and track location is presented to illustrate the impact of using different methods. Globally, methods agree well for geographical distribution in large oceanic regions, interannual variability of cyclone numbers, geographical patterns of strong trends, and distribution shape for many life cycle characteristics. In contrast, the largest disparities exist for the total numbers of cyclones, the detection of wea...
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California State University San Marcos1, Alfred Wegener Institute for Polar and Marine Research2, University of Alberta3, United States Department of Energy4, J. Craig Venter Institute5, Institut national de la recherche agronomique6, Ruhr University Bochum7, University of Maryland, College Park8, Monterey Bay Aquarium Research Institute9, University College London10, Centre national de la recherche scientifique11, Harvard University12, Ghent University13, Rothamsted Research14, Pierre-and-Marie-Curie University15, University of Essex16, Pontifical Catholic University of Chile17, Plymouth Marine Laboratory18, Columbia University19, Woods Hole Oceanographic Institution20, University of Cologne21, Natural History Museum22, Rutgers University23, Georgia Institute of Technology24, Moscow Institute of Physics and Technology25, University of Ostrava26, National Institutes of Health27, University of Nebraska Medical Center28, University of Southampton29, Oregon State University30, Dalhousie University31, University of Texas Health Science Center at Houston32, University of East Anglia33, University of Potsdam34, University of Bergen35, University of Washington36, University of Freiburg37, University of Marburg38, University of Los Andes39, Bigelow Laboratory For Ocean Sciences40, University of Exeter41, Oak Ridge National Laboratory42, California State University, Chico43, University of Tsukuba44
TL;DR: Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires, and reveals a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome.
Abstract: Coccolithophores have influenced the global climate for over 200 million years(1). These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems(2). They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space(3). Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean(4). Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.
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TL;DR: It is estimated that the breast cancer lifetime risks for the5% of BRCA1 carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk, and the ovarian cancer lifetime risk is 63% or higher, based on the known cancer risk-modifying loci.
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
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TL;DR: Using exome sequencing, it is inferred that loss of DGKE function results in a prothrombotic state, identifying a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treating individuals with aHUS.
Abstract: Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small-vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure. Atypical HUS (aHUS) can result from genetic or autoimmune factors that lead to pathologic complement cascade activation. Using exome sequencing, we identified recessive mutations in DGKE (encoding diacylglycerol kinase ɛ) that co-segregated with aHUS in nine unrelated kindreds, defining a distinctive Mendelian disease. Affected individuals present with aHUS before age 1 year, have persistent hypertension, hematuria and proteinuria (sometimes in the nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets and podocytes. Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C (PKC), which promotes thrombosis, and DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a prothrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treating individuals with aHUS.
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TL;DR: In this paper, the electron transfer energetics, the use of electron transfer sensitizers and mediators, as well as sacrificial reagents are discussed in the context of photochemical redox catalysis.
Abstract: Current examples of photoredox catalytic processes for CO, CN, CHal and CC bond formation are described with emphasis on the basic mechanistic scenarios. The focus is on the special aspects of photochemical redox catalysis especially on the electron transfer energetics, the use of electron transfer (ET) sensitizers and mediators as well as sacrificial reagents.
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Montserrat Garcia-Closas, Fergus J. Couch1, Sara Lindström2, Kyriaki Michailidou3 +284 more•Institutions (82)
TL;DR: SNPs at four loci were associated with ER-negative but not ER-positive breast cancer (P > 0.05), providing further evidence for distinct etiological pathways associated with invasive ER- positive and ER- negative breast cancers.
Abstract: Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
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TL;DR: It is shown that OTULin binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1, suggesting that OTulIN regulates Met1-polyUb signaling.
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TL;DR: In this article, the authors performed an unbiased spectral line survey toward Sgr B2(N) and (M), two regions where high-mass stars are formed, with the IRAM 30 m telescope in the 3 mm atmospheric transmission window.
Abstract: Context. The discovery of amino acids in meteorites fallen to Earth and the detection of glycine, the simplest of them, in samples returned from a comet to Earth strongly suggest that the chemistry of the interstellar medium is capable of producing such complex organic molecules and that they may be widespread in our Galaxy. Aims. Our goal is to investigate the degree of chemical complexity that can be reached in the interstellar medium, in particular in dense star-forming regions. Methods. We performed an unbiased, spectral line survey toward Sgr B2(N) and (M), two regions where high-mass stars are formed, with the IRAM 30 m telescope in the 3 mm atmospheric transmission window. Partial surveys at 2 and 1.3 mm were performed in parallel. The spectra were analyzed with a simple radiative transfer model that assumes local thermodynamic equilibrium but takes optical depth effects into account. Results. About 3675 and 945 spectral lines with a peak signal-to-noise ratio higher than 4 are detected at 3 mm toward Sgr B2(N) and (M), i.e. about 102 and 26 lines per GHz, respectively. This represents an increase by about a factor of two over previous surveys of Sgr B2. About 70% and 47% of the lines detected toward Sgr B2(N) and (M) are identified and assigned to 56 and 46 distinct molecules as well as to 66 and 54 less abundant isotopologues of these molecules, respectively. In addition, we report the detection of transitions from 59 and 24 catalog entries corresponding to vibrationally or torsionally excited states of some of these molecules, respectively, up to a vibration energy of 1400 cm-1 (2000 K). Excitation temperatures and column densities were derived for each species but should be used with caution. The rotation temperatures of the detected complex molecules typically range from ~50 to 200 K. Among the detected molecules, aminoacetonitrile, n- propyl cyanide, and ethyl formate were reported for the first time in space based on this survey, as were five rare isotopologues of vinyl cyanide, cyanoacetylene, and hydrogen cyanide. We also report the detection of transitions from within twelve new vibrationally or torsionally excited states of known molecules. Absorption features produced by diffuse clouds along the line of sight are detected in transitions with low rotation quantum numbers of many simple molecules and are modeled with ~30–40 velocity components with typical linewidths of ~3–5 km s-1 . Conclusions. Although the large number of unidentified lines may still allow future identification of new molecules, we expect most of these lines to belong to vibrationally or torsionally excited states or to rare isotopologues of known molecules for which spectroscopic predictions are currently missing. Significant progress in extending the inventory of complex organic molecules in Sgr B2(N) and deriving tighter constraints on their location, origin, and abundance is expected in the near future thanks to an ongoing spectral line survey at 3 mm with ALMA in its cycles 0 and 1. The present single-dish survey will serve as a solid basis for the line identification and analysis of such an interferometric survey.
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Boston Children's Hospital1, Medical University of Vienna2, University of Cologne3, University of Tübingen4, Bielefeld University5, University of Kiel6, Katholieke Universiteit Leuven7, King's College London8, Tartu University Hospital9, Helsinki University Central Hospital10, University of Helsinki11, McMaster University12, Medical University of Graz13, University College London14, University of Basel15, University of Bonn16, German Center for Neurodegenerative Diseases17
TL;DR: Results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.
Abstract: Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10(-18), Fisher's exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS (P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fisher's exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.
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TL;DR: Guided by feedback patterns observed on eBay and other platforms, laboratory experiments are run to investigate how reciprocity can be managed by changes in the way feedback information flows through the system, leading to more accurate reputation information, more trust, and more efficient trade.
Abstract: Reciprocity in feedback giving distorts the production and content of reputation information in a market, hampering trust and trade efficiency. Guided by feedback patterns observed on eBay and other platforms, we run laboratory experiments to investigate how reciprocity can be managed by changes in the way feedback information flows through the system, leading to more accurate reputation information, more trust, and more efficient trade. We discuss the implications for theory building and for managing the redesign of market trust systems.
This paper was accepted by Teck Ho, decision analysis.
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Hannover Medical School1, Charité2, University of Giessen3, Katholieke Universiteit Leuven4, University of Zurich5, University of Duisburg-Essen6, University Hospital Heidelberg7, University of Cologne8, Dresden University of Technology9, Ruhr University Bochum10, University of Hamburg11, Heidelberg University12, University of Greifswald13, Leipzig University14, Mater Misericordiae University Hospital15, Sapienza University of Rome16, VU University Medical Center17, Technische Universität München18, National Institutes of Health19
TL;DR: Compared to younger patients, elderly patients present with a balanced gender ratio and different clinical features, respond less well to medical therapy and have a higher age-adjusted mortality.
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TL;DR: In this paper, the authors proposed a new method, Prediction-Oriented Segmentation (PLSPOS), to overcome the limitations of FIMIX-PLS and other distance measure-based methods.
Abstract: A large proportion of information systems research is concerned with developing and testing models pertaining to complex cognition, behaviors, and outcomes of individuals, teams, organizations, and other social systems that are involved in the development, implementation, and utilization of information technology. Given the complexity of these social and behavioral phenomena, heterogeneity is likely to exist in the samples used in IS studies. While researchers now routinely address observed heterogeneity by introducing moderators, a priori groupings, and contextual factors in their research models, they have not examined how unobserved heterogeneity may affect their findings. We describe why unobserved heterogeneity threatens different types of validity and use simulations to demonstrate that unobserved heterogeneity biases parameter estimates, thereby leading to Type I and Type II errors. We also review different methods that can be used to uncover unobserved heterogeneity in structural equation models. While methods to uncover unobserved heterogeneity in covariance-based structural equation models (CB-SEM) are relatively advanced, the methods for partial least squares (PLS) path models are limited and have relied on an extension of mixture regression--finite mixture partial least squares (FIMIX-PLS) and distance measure-based methods--that have mismatches with some characteristics of PLS path modeling. We propose a new method--prediction-oriented segmentation (PLSPOS)--to overcome the limitations of FIMIX-PLS and other distance measure-based methods and conduct extensive simulations to evaluate the ability of PLS-POS and FIMIX-PLS to discover unobserved heterogeneity in both structural and measurement models. Our results show that both PLS-POS and FIMIX-PLS perform well in discovering unobserved heterogeneity in structural paths when the measures are reflective and that PLS-POS also performs well in discovering unobserved heterogeneity in formative measures. We propose an unobserved heterogeneity discovery (UHD) process that researchers can apply to (1) avert validity threats by uncovering unobserved heterogeneity and (2) elaborate on theory by turning unobserved heterogeneity into observed heterogeneity, thereby expanding theory through the integration of new moderator or contextual variables.
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University of Chicago1, Broad Institute2, University of Amsterdam3, Harvard University4, University of Queensland5, University of Toronto6, Vita-Salute San Raffaele University7, University of Antioquia8, Johns Hopkins University9, Yale University10, New York University11, Hofstra University12, University of Hong Kong13, University of São Paulo14, University of California, San Diego15, Université de Montréal16, University of Southern California17, University of Illinois at Chicago18, Ghent University19, University of Würzburg20, Ludwig Maximilian University of Munich21, Greifswald University Hospital22, Butler Hospital23, Shaare Zedek Medical Center24, Rutgers University25, Stellenbosch University26, Baylor College of Medicine27, University College London28, Memorial Hospital of South Bend29, University of Bonn30, University of California, San Francisco31, University of California, Irvine32, University of Utah33, National Institutes of Health34, University of California, Los Angeles35, St George's Hospital36, Federal University of São Paulo37, Wayne State University38, McGill University39, University of Cologne40, Federal University of Bahia41, VU University Amsterdam42, University of Cape Town43, Utrecht University44, Vanderbilt University45, Netherlands Institute for Neuroscience46, Erasmus University Rotterdam47, University of Michigan48, German Center for Neurodegenerative Diseases49, University of British Columbia50
TL;DR: The results indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Abstract: The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
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TL;DR: An integrative review of the existing literature on trade credit motives, order quantity decisions, credit term decisions, and settlement period decisions is provided and a detailed agenda for future research in these areas is derived.
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TL;DR: A review about the present status of experimental approaches to study low-lying electric dipole strength (often denoted as Pygmy Dipole Resonance) in stable and radioactive atomic nuclei can be found in this paper.
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TL;DR: These findings have identified mechanisms via which the COP1/SPA complex controls anthocyanin levels in Arabidopsis that may be useful for applications in biotechnology directed towards increasing anthocianin content in plants.
Abstract: Summary
Anthocyanins are natural pigments that accumulate only in light-grown and not in dark-grown Arabidopsis plants. Repression of anthocyanin accumulation in darkness requires the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) ubiquitin ligase, as cop1 and spa mutants produce anthocyanins also in the dark. Here, we show that COP1 and SPA proteins interact with the myeloblastosis (MYB) transcription factors PRODUCTION OF ANTHOCYANIN PIGMENT1 (PAP)1 and PAP2, two members of a small protein family that is required for anthocyanin accumulation and for the expression of structural genes in the anthocyanin biosynthesis pathway. The increased anthocyanin levels in cop1 mutants requires the PAP1 gene family, indicating that COP1 functions upstream of the PAP1 gene family. PAP1 and PAP2 proteins are degraded in the dark and this degradation is dependent on the proteasome and on COP1. Hence, the light requirement for anthocyanin biosynthesis results, at least in part, from the light-mediated stabilization of PAP1 and PAP2. Consistent with this conclusion, moderate overexpression of PAP1 leads to an increase in anthocyanin levels only in the light and not in darkness. Here we show that SPA genes are also required for reducing PAP1 and PAP2 transcript levels in dark-grown seedlings. Taken together, these results indicate that the COP1/SPA complex affects PAP1 and PAP2 both transcriptionally and post-translationally. Thus, our findings have identified mechanisms via which the COP1/SPA complex controls anthocyanin levels in Arabidopsis that may be useful for applications in biotechnology directed towards increasing anthocyanin content in plants.
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University of British Columbia1, Harvard University2, Broad Institute3, University of California, San Francisco4, University of Toronto5, University of Chicago6, University of Southern California7, University of Bonn8, University of Göttingen9, University of Cologne10, Greifswald University Hospital11, Vita-Salute San Raffaele University12, University of Illinois at Chicago13, Boston Children's Hospital14, University of Cape Town15, Stellenbosch University16, University of California, San Diego17, National Institutes of Health18, Hoffmann-La Roche19, Vanderbilt University20, Netherlands Institute for Neuroscience21, Ghent University22, University of Zurich23, University of Würzburg24, University of São Paulo25, Federal University of Bahia26, National Science Foundation27, VU University Amsterdam28, Johns Hopkins University29, Columbia University30, Butler Hospital31, University of California, Los Angeles32, Yale University33, University of New South Wales34, University of Iowa35, Utrecht University36, University of Milan37, University of California, Irvine38, University College London39, Johns Hopkins University School of Medicine40, University of Michigan41, University of Edinburgh42, King's College London43
TL;DR: Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio–case–control sample, a significant enrichment of methylation QTLs and frontal lobe expression quantitative trait loci (eQTLs) was observed within the top-ranked SNPs, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
Abstract: Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
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TL;DR: Translocality is used to describe socio-spatial dynamics and processes of simultaneity and identity formation that transcend boundaries, including, but also extending beyond, those of nation states.
Abstract: The employment of translocality as a research perspective is currently gaining momentum. A growing number of scholars from different research traditions concerned with the dynamics of mobility, migration and socio-spatial interconnectedness have developed conceptual approaches to the term. They usually build on insights from transnationalism while attempting to overcome some of the limitations of this long-established research perspective. As such, translocality is used to describe socio-spatial dynamics and processes of simultaneity and identity formation that transcend boundaries—including, but also extending beyond, those of nation states. In this review, we trace the emergence of the idea of translocality and summarise the characteristics that different authors associate with the term. We elucidate the underlying notions of mobility and place and sketch out fields of research where the concept has been employed. On the basis of our findings, we conclude by proposing key areas where a translocal approach has the potential to generate fruitful insights. © 2012 The Author. Geography Compass © 2012 Blackwell Publishing Ltd