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Showing papers by "University of Leicester published in 2009"


Journal ArticleDOI
TL;DR: Transfer of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol is recommended to significantly improve survival without severe disability.

2,783 citations


Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Lorenzo Galluzzi3, Stuart A. Aaronson4, John M. Abrams5, Emad S. Alnemri6, David W. Andrews7, Eric H. Baehrecke8, Nicolas G. Bazan9, Mikhail V. Blagosklonny10, Klas Blomgren11, Klas Blomgren12, Christoph Borner13, Dale E. Bredesen14, Dale E. Bredesen15, Catherine Brenner16, Maria Castedo3, Maria Castedo1, Maria Castedo2, John A. Cidlowski17, Aaron Ciechanover18, Gerald M. Cohen19, V De Laurenzi20, R De Maria21, Mohanish Deshmukh22, Brian David Dynlacht23, Wafik S. El-Deiry24, Richard A. Flavell25, Richard A. Flavell26, Simone Fulda27, Carmen Garrido28, Carmen Garrido2, Pierre Golstein16, Pierre Golstein29, Pierre Golstein2, Marie-Lise Gougeon30, Douglas R. Green, Hinrich Gronemeyer31, Hinrich Gronemeyer2, Hinrich Gronemeyer16, György Hajnóczky6, J. M. Hardwick32, Michael O. Hengartner33, Hidenori Ichijo34, Marja Jäättelä, Oliver Kepp1, Oliver Kepp2, Oliver Kepp3, Adi Kimchi35, Daniel J. Klionsky36, Richard A. Knight37, Sally Kornbluth38, Sharad Kumar, Beth Levine5, Beth Levine26, Stuart A. Lipton, Enrico Lugli17, Frank Madeo39, Walter Malorni21, Jean-Christophe Marine40, Seamus J. Martin41, Jan Paul Medema42, Patrick Mehlen16, Patrick Mehlen43, Gerry Melino44, Gerry Melino19, Ute M. Moll45, Ute M. Moll46, Eugenia Morselli3, Eugenia Morselli1, Eugenia Morselli2, Shigekazu Nagata47, Donald W. Nicholson48, Pierluigi Nicotera19, Gabriel Núñez36, Moshe Oren35, Josef M. Penninger49, Shazib Pervaiz50, Marcus E. Peter51, Mauro Piacentini44, Jochen H. M. Prehn52, Hamsa Puthalakath53, Gabriel A. Rabinovich54, Rosario Rizzuto55, Cecília M. P. Rodrigues56, David C. Rubinsztein57, Thomas Rudel58, Luca Scorrano59, Hans-Uwe Simon60, Hermann Steller61, Hermann Steller26, J. Tschopp62, Yoshihide Tsujimoto63, Peter Vandenabeele64, Ilio Vitale3, Ilio Vitale1, Ilio Vitale2, Karen H. Vousden65, Richard J. Youle17, Junying Yuan66, Boris Zhivotovsky67, Guido Kroemer1, Guido Kroemer2, Guido Kroemer3 
University of Paris-Sud1, French Institute of Health and Medical Research2, Institut Gustave Roussy3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, Boston Children's Hospital11, University of Gothenburg12, University of Freiburg13, University of California, San Francisco14, Buck Institute for Research on Aging15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, University of Göttingen45, Stony Brook University46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells

2,218 citations


Journal ArticleDOI
TL;DR: Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

1,710 citations


Journal ArticleDOI
TL;DR: New definitions for asthma control, severity, and exacerbations are developed, based on current treatment principles and clinical and research relevance, to provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.
Abstract: Background: The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.Purpose: The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.Methods: A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.Results: The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge ...

1,642 citations


Journal ArticleDOI
TL;DR: A homogeneous X-rays analysis of all 318 gamma-ray bursts detected by the X-ray telescope (XRT) on the Swift satellite up to 2008 July 23 is presented; this represents the largest sample ofX-ray GRB data published to date.
Abstract: We present a homogeneous X-ray analysis of all 318 gamma-ray bursts detected by the X-ray telescope (XRT) on the Swift satellite up to 2008 July 23; this represents the largest sample of X-ray GRB data published to date. In Sections 2-3, we detail the methods which the Swift-XRT team has developed to produce the enhanced positions, light curves, hardness ratios and spectra presented in this paper. Software using these methods continues to create such products for all new GRBs observed by the Swift-XRT. We also detail web-based tools allowing users to create these products for any object observed by the XRT, not just GRBs. In Sections 4-6, we present the results of our analysis of GRBs, including probability distribution functions of the temporal and spectral properties of the sample. We demonstrate evidence for a consistent underlying behaviour which can produce a range of light-curve morphologies, and attempt to interpret this behaviour in the framework of external forward shock emission. We find several difficulties, in particular that reconciliation of our data with the forward shock model requires energy injection to continue for days to weeks.

1,613 citations


Journal ArticleDOI
TL;DR: The objective of this study is to quantify the risk of developing dementia in those with mild cognitive impairment (MCI) and to establish a biomarker for dementia in these patients.
Abstract: Objective: To quantify the risk of developing dementia in those with mild cognitive impairment (MCI). Method: Meta-analysis of inception cohort studies. Results: Forty-one robust cohort studies were identified. To avoid heterogeneity clinical studies, population studies and clinical trials were analysed separately. Using Mayo defined MCI at baseline and adjusting for sample size, the cumulative proportion who progressed to dementia, to Alzheimer’s disease (AD) and to vascular dementia (VaD) was 39.2%, 33.6% and 6.2%, respectively in specialist settings and 21.9%, 28.9% and 5.2%, respectively in population studies. The adjusted annual conversion rate (ACR) from Mayo defined MCI to dementia, AD and VaD was 9.6%, 8.1% and 1.9%, respectively in specialist clinical settings and 4.9%, 6.8% and 1.6% in community studies. Figures from non-Mayo defined MCI and clinical trials are also reported. Conclusion: The ACR is approximately 5–10% and most people with MCI will not progress to dementia even after 10 years of follow-up.

1,249 citations


Journal ArticleDOI
TL;DR: In this paper, the association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2(P = 1 × 10-23), FGF5 (P=1 × 10 -21), SH2B3(P= 3 × 10−18), MTHFR(MTHFR), c10orf107(P), ZNF652(ZNF652), PLCD3 (P,P = 5 × 10 −9),
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

1,205 citations


Journal ArticleDOI
TL;DR: In this paper, the authors explored how pre-registration engagement with a university Facebook network influenced students' postregistration social networks and found that Facebook was part of the social glue that helped students settle into university life.
Abstract: Whilst recent studies suggest that over 95% of British undergraduate students are regularly using social networking sites, we still know very little about how this phenomenon impacts on the student experience and, in particular, how it influences students’ social integration into university life. This paper explores how pre‐registration engagement with a university Facebook network influences students’ post‐registration social networks. Research was conducted with first year undergraduates at a British university using an online survey. Students reported that they specifically joined Facebook pre‐registration as a means of making new friends at university, as well as keeping in touch with friends and family at home. The survey data also illustrate that once at university, Facebook was part of the ‘social glue’ that helped students settle into university life. However, care must be taken not to over‐privilege Facebook: it is clearly only one aspect of students’ more general social networking practices and ...

1,184 citations


Proceedings ArticleDOI
04 Apr 2009
TL;DR: The draft ISO definition on UX seems to be in line with the survey findings, although the issues of experiencing anticipated use and the object of UX will require further explication.
Abstract: Despite the growing interest in user experience (UX), it has been hard to gain a common agreement on the nature and scope of UX. In this paper, we report a survey that gathered the views on UX of 275 researchers and practitioners from academia and industry. Most respondents agree that UX is dynamic, context-dependent, and subjective. With respect to the more controversial issues, the authors propose to delineate UX as something individual (instead of social) that emerges from interacting with a product, system, service or an object. The draft ISO definition on UX seems to be in line with the survey findings, although the issues of experiencing anticipated use and the object of UX will require further explication. The outcome of this survey lays ground for understanding, scoping, and defining the concept of user experience.

1,100 citations


Journal ArticleDOI
Sekar Kathiresan1, Benjamin F. Voight1, Shaun Purcell2, Kiran Musunuru1, Diego Ardissino, Pier Mannuccio Mannucci3, Sonia S. Anand4, James C. Engert5, Nilesh J. Samani6, Heribert Schunkert7, Jeanette Erdmann7, Muredach P. Reilly8, Daniel J. Rader8, Thomas M. Morgan9, John A. Spertus10, Monika Stoll11, Domenico Girelli12, Pascal P. McKeown13, Christopher Patterson13, David S. Siscovick14, Christopher J. O'Donnell15, Roberto Elosua, Leena Peltonen16, Veikko Salomaa17, Stephen M. Schwartz14, Olle Melander18, David Altshuler1, Pier Angelica Merlini, Carlo Berzuini19, Luisa Bernardinelli19, Flora Peyvandi3, Marco Tubaro, Patrizia Celli, Maurizio Ferrario, Raffaela Fetiveau, Nicola Marziliano, Giorgio Casari20, Michele Galli, Flavio Ribichini12, Marco Rossi, Francesco Bernardi21, Pietro Zonzin, Alberto Piazza22, Jean Yee14, Yechiel Friedlander23, Jaume Marrugat, Gavin Lucas, Isaac Subirana, Joan Sala24, Rafael Ramos, James B. Meigs1, Gordon H. Williams1, David M. Nathan1, Calum A. MacRae1, Aki S. Havulinna17, Göran Berglund18, Joel N. Hirschhorn1, Rosanna Asselta, Stefano Duga, Marta Spreafico25, Mark J. Daly1, James Nemesh2, Joshua M. Korn1, Steven A. McCarroll1, Aarti Surti2, Candace Guiducci2, Lauren Gianniny2, Daniel B. Mirel2, Melissa Parkin2, Noël P. Burtt2, Stacey Gabriel2, John R. Thompson6, Peter S. Braund6, Benjamin J. Wright6, Anthony J. Balmforth26, Stephen G. Ball26, Alistair S. Hall26, Patrick Linsel-Nitschke7, Wolfgang Lieb7, Andreas Ziegler7, Inke R. König7, Christian Hengstenberg27, Marcus Fischer27, Klaus Stark27, Anika Grosshennig7, Michael Preuss7, H-Erich Wichmann28, Stefan Schreiber29, Willem H. Ouwehand19, Panos Deloukas30, Michael Scholz, François Cambien31, Mingyao Li8, Zhen Chen8, Robert L. Wilensky8, William H. Matthai8, Atif Qasim8, Hakon Hakonarson8, Joe Devaney32, Mary-Susan Burnett32, Augusto D. Pichard32, Kenneth M. Kent32, Lowell F. Satler32, Joseph M. Lindsay32, Ron Waksman32, Stephen E. Epstein32, Thomas Scheffold, Klaus Berger11, Andreas Huge11, Nicola Martinelli12, Oliviero Olivieri12, Roberto Corrocher12, Hilma Holm33, Gudmar Thorleifsson33, Unnur Thorsteinsdottir34, Kari Stefansson34, Ron Do5, Changchun Xie4, David S. Siscovick14 
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk

1,092 citations


Journal ArticleDOI
TL;DR: In this article, the authors provide a more direct test of the gender roles hypothesis by analyzing community epidemiological data collected from respondents surveyed in 15 countries as part of the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative.
Abstract: Epidemiological surveys have consistently documented significantly higher rates of anxiety and mood disorders among women than men1, 2 and significantly higher rates of externalizing and substance use disorders among men than women.3–5 Although a number of biological, psychosocial, and biopsychosocial hypotheses have been proposed to account for these patterns,6–8 evidence that gender differences in depression9, 10 and substance use11–13 have narrowed in a number of countries has led to a special interest in the “gender roles” hypothesis. The latter asserts that gender differences in the prevalence of mental disorders are due to differences in the typical stressors, coping resources, and opportunity structures for expressing psychological distress made available differentially to women and men in different countries at different points in history.14, 15 Consistent with this hypothesis, evidence of decreasing gender differences in depression and substance use has been found largely in countries where the roles of women have improved in terms of opportunities for employment, access to birth control, and other indicators of increasing gender role equality, while trend studies in countries where gender roles have been more static11, 16 or over periods of historical time when gender role changes have been small17 have failed to document a reduction in gender differences in depression or substance use. Most research aimed at investigating the gender roles hypothesis has focused on individual-level variation in roles in a single country at a single point in time.18–20 This approach is limited in three ways. First, selection bias into roles due to pre-existing mental illness (e.g., women with agoraphobia having a higher probability than other women of becoming homemakers rather than seeking employment outside the home) confounds attempts to evaluate the causal effects of gender roles. Second, gender differences are largely confined to differences in lifetime risk, with much less evidence for gender differences in recent prevalence among lifetime cases.21 This means that investigation of the determinants of gender difference should focus on lifetime first onset rather than on the recent prevalence that has been the focus of most studies. Third, as the gender roles hypothesis is a hypothesis about the effects of social context, a rigorous test of the hypothesis requires an analysis of societal-level time-space variation rather than analysis of the individual-level variation that has been the focus of most studies. A small number of cross-national comparative studies have examined spatial variation in gender differences in depression22 and alcohol abuse13 at a point in time or, more rarely, at two points in time.11 Although these studies raised the possibility that gender roles might be associated with variation in the magnitude of gender differences in these outcomes, they were unable to test this hypothesis due to the small number of cross-sectional country-level observations included in the analyses. The current report provides a more direct test of the gender roles hypothesis by analyzing community epidemiological data collected from respondents surveyed in 15 countries as part of the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative.21 Previous cross-national comparisons of gender differences in mental illness focused on cross-sectional differences. We, in comparison, use retrospective reports obtained in the WMH surveys about lifetime occurrence and age-of-onset of mental disorders in different birth cohorts to study time-space variation in lifetime risk. Specifically, we examine both variation across cohorts within a single country (i.e., temporal variation) and variation across countries within a single cohort (i.e., special variation) in lifetime risk of mental disorders as a function of time-space variation in the traditionality of gender roles. Lifetime risk is the focus rather than recent prevalence even though accuracy of reporting is doubtlessly better for recent episodes than lifetime occurrence in order to address the fact that gender differences in lifetime risk are much more robust than gender differences in current prevalence among lifetime cases

Journal ArticleDOI
TL;DR: In this paper, the authors classify orogens into retreating and advancing types, based on their kinematic framework and resulting geological character, including the supra-subduction zone forearc, magmatic arc and back-arc components.
Abstract: Accretionary orogens form at intraoceanic and continental margin convergent plate boundaries. They include the supra-subduction zone forearc, magmatic arc and back-arc components. Accretionary orogens can be grouped into retreating and advancing types, based on their kinematic framework and resulting geological character. Retreating orogens (e.g. modern western Pacific) are undergoing long-term extension in response to the site of subduction of the lower plate retreating with respect to the overriding plate and are characterized by back-arc basins. Advancing orogens (e.g. Andes) develop in an environment in which the overriding plate is advancing towards the downgoing plate, resulting in the development of foreland fold and thrust belts and crustal thickening. Cratonization of accretionary orogens occurs during continuing plate convergence and requires transient coupling across the plate boundary with strain concentrated in zones of mechanical and thermal weakening such as the magmatic arc and back-arc region. Potential driving mechanisms for coupling include accretion of buoyant lithosphere (terrane accretion), flat-slab subduction, and rapid absolute upper plate motion overriding the downgoing plate. Accretionary orogens have been active throughout Earth history, extending back until at least 3.2 Ga, and potentially earlier, and provide an important constraint on the initiation of horizontal motion of lithospheric plates on Earth. They have been responsible for major growth of the continental lithosphere through the addition of juvenile magmatic products but are also major sites of consumption and reworking of continental crust through time, through sediment subduction and subduction erosion. It is probable that the rates of crustal growth and destruction are roughly equal, implying that net growth since the Archaean is effectively zero.

Journal ArticleDOI
TL;DR: All aspects of BioMart are described from a user's perspective and it is demonstrated how it can be used to solve real biological use cases such as SNP selection for candidate gene screening or annotation of microarray results.
Abstract: Biologists need to perform complex queries, often across a variety of databases. Typically, each data resource provides an advanced query interface, each of which must be learnt by the biologist before they can begin to query them. Frequently, more than one data source is required and for high-throughput analysis, cutting and pasting results between websites is certainly very time consuming. Therefore, many groups rely on local bioinformatics support to process queries by accessing the resource's programmatic interfaces if they exist. This is not an efficient solution in terms of cost and time. Instead, it would be better if the biologist only had to learn one generic interface. BioMart provides such a solution.

Journal ArticleDOI
TL;DR: In this paper, the authors presented the late Paleozoic to early Mesozoic accretionary tectonics of two key areas, North Xinjiang in the west and Inner Mongolia in the east, together with neighboring Mongolia, based on structural geology, geochemical, geochronological, and paleomagnetic data.
Abstract: The Altaids is one of the largest accretionary orogenic collages in the world with the highest rate of Phanerozoic continental growth and significant metallogenic importance. It is widely accepted that subduction-related orogenesis of the Altaids started in the late Precambrian and gradually migrated southward (present coordinates). However, it is uncertain when and how the building of the Altaids was finally completed. Based on structural geology, geochemical, geochronological, and paleomagnetic data, this paper presents late Paleozoic to early Mesozoic accretionary tectonics of two key areas, North Xinjiang in the west and Inner Mongolia in the east, together with neighboring Mongolia. The late Paleozoic tectonics of North Xinjiang and adjacent areas were characterized by continuous southward accretion along the wide southern active margin of Siberia and its final amalgamation with the passive margin of Tarim, which may have lasted to the end-Permian to early/mid-Triassic. In contrast, in Inner Mongolia and adjacent areas two wide accretionary wedges developed along the southern active margin of Siberia and the northern active margin of the North China craton, which may have lasted to the mid-Triassic. The final products of the long-lived accretionary processes in the southern Altaids include late Paleozoic to Permian arcs, late Paleozoic to mid-Triassic accretionary wedges composed of radiolarian cherts, pillow lavas, and ophiolitic fragments, and high-pressure/ultrahigh-pressure metamorphic rocks. Permian Alaskan-type zoned mafic-ultramafic complexes intruded along some major faults of the Tien Shan. We define a new Tarim suture zone immediately north of the Tarim craton that is probably now buried below the Tien Shan as a result of northward subduction of the Tarim block in the Cenozoic. The docking of the Tarim and North China cratons against the southern active margin of Siberia in the end-Permian to mid-Triassic resulted in the final closure of the Paleoasian Ocean and terminated the accretionary orogenesis of the southern Altaids in this part of Central Asia. This complex geodynamic evolution led to formation of giant metal deposits in Central Asia and to substantial continental growth.

Journal ArticleDOI
TL;DR: A review of the extant research on youth life satisfaction is provided in this paper, which details how life satisfaction among youth relates to various other important emotional, social, and behavioural constructs.
Abstract: A central construct within the positive psychology literature is life satisfaction. Whereas adult life satisfaction has been studied extensively, the life satisfaction of children and adolescents has only received attention more recently. This article provides a review of the extant research on youth life satisfaction. Empirical studies (n = 141) on life satisfaction among youth are reviewed. The review details how life satisfaction among youth relates to various other important emotional, social, and behavioural constructs. Evidenced by the review are the conditions that foster positive life satisfaction and the implications of positive life satisfaction among youth. Future directions in life satisfaction research among youth are briefly discussed.

Journal ArticleDOI
TL;DR: A review of the state of scientific understanding in relation to global and regional air quality is outlined in this article, in terms of emissions, processing and transport of trace gases and aerosols.

Journal ArticleDOI
TL;DR: In this article, the effects of albuminuria and reduced estimated GFR (eGFR) on the risk for cardiovascular and renal events among individuals with type 2 diabetes were investigated. But, there was no evidence of an interaction between the effect of higher eGFR and lower UACR.
Abstract: There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

Journal ArticleDOI
TL;DR: This article showed that the marginal effects of trade openness are negatively related to the degree of financial openness, indicating that relatively closed economies stand to benefit most from opening up their trade and/or capital accounts.

Journal ArticleDOI
20 Nov 2009
TL;DR: GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer and the meta-analysis of published studies showed a significant survival benefit in favor of GEM- CAP.
Abstract: Purpose Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP). Patients and Methods Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted. Results Between May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity. Conclusion On the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

Journal ArticleDOI
29 Oct 2009-Nature
TL;DR: In this paper, the authors reported that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang.
Abstract: Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars(1), and some are bright enough that they should be observable out to redshifts of z > 20 using current technology(2-4). Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy(5). Here we report that GRB 090423 lies at a redshift of z approximate to 8.2, implying that massive stars were being produced and dying as GRBs similar to 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Journal ArticleDOI
03 Sep 2009-Nature
TL;DR: A panorama of galaxy structure of the Andromeda galaxy (M31) is reported, which directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.
Abstract: In hierarchical cosmological models, galaxies grow in mass through the continual accretion of smaller ones. The tidal disruption of these systems is expected to result in loosely bound stars surrounding the galaxy, at distances that reach 10-100 times the radius of the central disk. The number, luminosity and morphology of the relics of this process provide significant clues to galaxy formation history, but obtaining a comprehensive survey of these components is difficult because of their intrinsic faintness and vast extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We detect stars and coherent structures that are almost certainly remnants of dwarf galaxies destroyed by the tidal field of M31. An improved census of their surviving counterparts implies that three-quarters of M31's satellites brighter than M(v) = -6 await discovery. The brightest companion, Triangulum (M33), is surrounded by a stellar structure that provides persuasive evidence for a recent encounter with M31. This panorama of galaxy structure directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.

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TL;DR: To further understand how the brain processes information, it is important to shift from a single-neuron, multiple-trial framework to multiple-NEuron, single-trial methodologies.
Abstract: To a large extent, progress in neuroscience has been driven by the study of single-cell responses averaged over several repetitions of stimuli or behaviours. However,the brain typically makes decisions based on single events by evaluating the activity of large neuronal populations. Therefore, to further understand how the brain processes information, it is important to shift from a single-neuron, multiple-trial framework to multiple-neuron, single-trial methodologies. Two related approaches--decoding and information theory--can be used to extract single-trial information from the activity of neuronal populations. Such population analysis can give us more information about how neurons encode stimulus features than traditional single-cell studies.

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Cecilia M. Lindgren1, Iris M. Heid2, Joshua C. Randall1, Claudia Lamina3  +152 moreInstitutions (36)
TL;DR: By focusing on anthropometric measures of central obesity and fat distribution, a meta-analysis of 16 genome-wide association studies informative for adult waist circumference and waist–hip ratio identified three loci implicated in the regulation of human adiposity.
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

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TL;DR: Transport data is presented and an adjusted Walden plot that makes explicit allowance for differences in ion sizes is shown to be an improvement to this approach for the series of ionic liquids described, confirming the validity of the adjustedwalden plot approach.
Abstract: Ionic liquids are liquids comprised totally of ions However, not all of the ions present appear to be available to participate in conduction processes, to a degree that is dependent on the nature of the ionic liquid and its structure There is much interest in quantifying and understanding this ‘degree of ionicity’ phenomenon In this paper we present transport data for a range of ionic liquids and evaluate the data firstly in terms of the Walden plot as an approximate and readily accessible approach to estimating ionicity An adjusted Walden plot that makes explicit allowance for differences in ion sizes is shown to be an improvement to this approach for the series of ionic liquids described In some cases, where diffusion measurements are possible, it is feasible to directly quantify ionicity via the Nernst–Einstein equation, confirming the validity of the adjusted Walden plot approach Some of the ionic liquids studied exhibit ionicity values very close to ideal; this is discussed in terms of a model of a highly associated liquid in which the ion correlations have similar impact on both the diffusive and conductive motions Ionicity, as defined, is thus a useful measure of adherence to the Nernst–Einstein equation, but is not necessarily a measure of ion availability in the chemical sense

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TL;DR: A new command is introduced, stpm2, that extends the methodology of Royston and Parmar's flexible parametric survival models and enables simple quantification of differences between any two covariate patterns through calculation of time-dependent hazard ratios, hazard differences, and survival differences.
Abstract: Royston and Parmar (2002, Statistics in Medicine 21: 2175–2197) developed a class of flexible parametric survival models that were programmed in Stata with the stpm command (Royston, 2001, Stata Jo...

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TL;DR: It is demonstrated that high temperature-induced architectural adaptations are mediated through the bHLH transcriptional regulator PHYTOCHROME INTERACTING FACTOR 4 (PIF4), and it is concluded that PIF4 is an important component of plant high temperature signaling and integrates multiple environmental cues during plant development.

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TL;DR: A review of the state of the art in understanding the processes involved in the exchange of trace gases and aerosols between the earth's surface and the atmosphere can be found in this article.

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TL;DR: The 2XMM catalogue as mentioned in this paper is the largest ever made at X-ray wavelengths, containing 246 897 detections drawn from 3491 public XMM-Newton observations over a 7-year interval, which relate to 191 870 unique sources.
Abstract: Aims. Pointed observations with XMM-Newton provide the basis for creating catalogues of X-ray sources detected serendipitously in each field. This paper describes the creation and characteristics of the 2XMM catalogue. Methods. The 2XMM catalogue has been compiled from a new processing of the XMM-Newton EPIC camera data. The main features of the processing pipeline are described in detail. Results. The catalogue, the largest ever made at X-ray wavelengths, contains 246 897 detections drawn from 3491 public XMM-Newton observations over a 7-year interval, which relate to 191 870 unique sources. The catalogue fields cover a sky area of more than 500 deg(2). The non-overlapping sky area is similar to 360 deg(2) (similar to 1% of the sky) as many regions of the sky are observed more than once by XMM-Newton. The catalogue probes a large sky area at the flux limit where the bulk of the objects that contribute to the X-ray background lie and provides a major resource for generating large, well-defined X-ray selected source samples, studying the X-ray source population and identifying rare object types. The main characteristics of the catalogue are presented, including its photometric and astrometric properties

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TL;DR: Proton-transfer reaction mass spectrometry (PTR-MS) is a technique developed almost exclusively for the detection of gaseous organic compounds in air, which has both natural and anthropogenic sources.
Abstract: Proton-transfer reaction mass spectrometry (PTR-MS) is a technique developed almost exclusively for the detection of gaseous organic compounds in air. Volatile organic compounds (VOCs) in air have both natural and anthropogenic sources. Natural sources include the emission of organic gases by living objects, both plants and animals. A well-known example, which is discussed later in this review, is the emission of a variety of gaseous organic compounds in the breath of animals, which are released from both the digestive system and the lungs. Plants are major sources of organic gases, as is the decay of dead animal and plant matter. Subsequent photochemistry can add further compounds to the mixture. Consequently, even without contributions from humans, ambient air from the Earth’s atmosphere would consist of a complex mixture of VOCs.

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TL;DR: A comprehensive review of 196 studies which employ operational research (O.R.) and artificial intelligence (A.I.) techniques in the assessment of bank performance, including numerous applications of data envelopment analysis, which is the most widely applied O.R. technique in the field.
Abstract: This paper presents a comprehensive review of 179 studies which employ operational research (O.R.) and Artificial Intelligence (A.I.) techniques in the assessment of bank performance. We first discuss numerous applications of data envelopment analysis which is the most widely applied O.R. technique in the field. Then we discuss applications of other techniques such as neural networks, support vector machines, and multicriteria decision aid that have also been used in recent years, in bank failure prediction studies and the assessment of bank creditworthiness and underperformance.