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Showing papers by "University of Zurich published in 2009"


Journal ArticleDOI
TL;DR: This 5-year evaluation provides strong evidence that the classification of complications is valid and applicable worldwide in many fields of surgery, and subjective, inaccurate, or confusing terms such as “minor or major” should be removed from the surgical literature.
Abstract: Background and Aims:The lack of consensus on how to define and grade adverse postoperative events has greatly hampered the evaluation of surgical procedures. A new classification of complications, initiated in 1992, was updated 5 years ago. It is based on the type of therapy needed to correct the co

7,537 citations


Journal ArticleDOI
TL;DR: A series of improvements to the spectroscopic reductions are described, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.
Abstract: This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11,663 deg^2 of imaging data, with most of the ~2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry on a 120° long, 2°.5 wide stripe along the celestial equator in the Southern Galactic Cap, with some regions covered by as many as 90 individual imaging runs. We include a co-addition of the best of these data, going roughly 2 mag fainter than the main survey over 250 deg^2. The survey has completed spectroscopy over 9380 deg^2; the spectroscopy is now complete over a large contiguous area of the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog, reducing the rms statistical errors at the bright end to 45 milliarcseconds per coordinate. We further quantify a systematic error in bright galaxy photometry due to poor sky determination; this problem is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.

5,665 citations


Journal ArticleDOI
29 Jan 2009-Nature
TL;DR: An initial analysis of the ∼730-megabase Sorghum bicolor (L.) Moench genome is presented, placing ∼98% of genes in their chromosomal context using whole-genome shotgun sequence validated by genetic, physical and syntenic information.
Abstract: Sorghum, an African grass related to sugar cane and maize, is grown for food, feed, fibre and fuel. We present an initial analysis of the approximately 730-megabase Sorghum bicolor (L.) Moench genome, placing approximately 98% of genes in their chromosomal context using whole-genome shotgun sequence validated by genetic, physical and syntenic information. Genetic recombination is largely confined to about one-third of the sorghum genome with gene order and density similar to those of rice. Retrotransposon accumulation in recombinationally recalcitrant heterochromatin explains the approximately 75% larger genome size of sorghum compared with rice. Although gene and repetitive DNA distributions have been preserved since palaeopolyploidization approximately 70 million years ago, most duplicated gene sets lost one member before the sorghum-rice divergence. Concerted evolution makes one duplicated chromosomal segment appear to be only a few million years old. About 24% of genes are grass-specific and 7% are sorghum-specific. Recent gene and microRNA duplications may contribute to sorghum's drought tolerance.

2,809 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 Castedo2, Maria Castedo1, 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 Gronemeyer16, Hinrich Gronemeyer2, György Hajnóczky6, J. M. Hardwick32, Michael O. Hengartner33, Hidenori Ichijo34, Marja Jäättelä, Oliver Kepp3, Oliver Kepp2, Oliver Kepp1, Adi Kimchi35, Daniel J. Klionsky36, Richard A. Knight37, Sally Kornbluth38, Sharad Kumar, Beth Levine5, Beth Levine25, Stuart A. Lipton, Enrico Lugli17, Frank Madeo39, Walter Malorni21, Jean-Christophe Marine40, Seamus J. Martin41, Jan Paul Medema42, Patrick Mehlen43, Patrick Mehlen16, Gerry Melino19, Gerry Melino44, Ute M. Moll45, Ute M. Moll46, Eugenia Morselli1, Eugenia Morselli2, Eugenia Morselli3, 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 Steller25, Hermann Steller61, J. Tschopp62, Yoshihide Tsujimoto63, Peter Vandenabeele64, Ilio Vitale3, Ilio Vitale2, Ilio Vitale1, Karen H. Vousden65, Richard J. Youle17, Junying Yuan66, Boris Zhivotovsky67, Guido Kroemer3, Guido Kroemer2, Guido Kroemer1 
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, University of Gothenburg11, Boston Children's Hospital12, University of Freiburg13, Buck Institute for Research on Aging14, University of California, San Francisco15, 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, Howard Hughes Medical Institute25, Yale University26, 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: The familiar pick-a-point approach and the much less familiar Johnson-Neyman technique for probing interactions in linear models are described and macros for SPSS and SAS are introduced to simplify the computations and facilitate the probing of interactions in ordinary least squares and logistic regression.
Abstract: Researchers often hypothesize moderated effects, in which the effect of an independent variable on an outcome variable depends on the value of a moderator variable. Such an effect reveals itself statistically as an interaction between the independent and moderator variables in a model of the outcome variable. When an interaction is found, it is important to probe the interaction, for theories and hypotheses often predict not just interaction but a specific pattern of effects of the focal independent variable as a function of the moderator. This article describes the familiar pick-a-point approach and the much less familiar Johnson-Neyman technique for probing interactions in linear models and introduces macros for SPSS and SAS to simplify the computations and facilitate the probing of interactions in ordinary least squares and logistic regression. A script version of the SPSS macro is also available for users who prefer a point-and-click user interface rather than command syntax.

2,204 citations


Journal ArticleDOI
TL;DR: Sherpa as mentioned in this paper is a general-purpose tool for the simulation of particle collisions at high-energy colliders and contains a very flexible tree-level matrix-element generator for the calculation of hard scattering processes within the Standard Model and various new physics models.
Abstract: In this paper the current release of the Monte Carlo event generator Sherpa, version 1.1, is presented. Sherpa is a general-purpose tool for the simulation of particle collisions at high-energy colliders. It contains a very flexible tree-level matrix-element generator for the calculation of hard scattering processes within the Standard Model and various new physics models. The emission of additional QCD partons off the initial and final states is described through a parton-shower model. To consistently combine multi-parton matrix elements with the QCD parton cascades the approach of Catani, Krauss, Kuhn and Webber is employed. A simple model of multiple interactions is used to account for underlying events in hadron-hadron collisions. The fragmentation of partons into primary hadrons is described using a phenomenological cluster-hadronisation model. A comprehensive library for simulating tau-lepton and hadron decays is provided. Where available form-factor models and matrix elements are used, allowing for the inclusion of spin correlations; effects of virtual and real QED corrections are included using the approach of Yennie, Frautschi and Suura.

2,099 citations


Journal ArticleDOI
TL;DR: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonf fatal myocardial infarction, or nonfatal stroke.
Abstract: BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not bee ...

1,789 citations


Journal ArticleDOI
22 Jan 2009-Nature
TL;DR: ‘stream-fed galaxies’ are reported, formed from steady, narrow, cold gas streams that penetrate the shock-heated media of massive dark matter haloes and keep the rotating disk configuration intact, although turbulent and broken into giant star-forming clumps that merge into a central spheroid.
Abstract: Massive galaxies in the young Universe, ten billion years ago, formed stars at surprising intensities. Although this is commonly attributed to violent mergers, the properties of many of these galaxies are incompatible with such events, showing gas-rich, clumpy, extended rotating disks not dominated by spheroids Cosmological simulations and clustering theory are used to explore how these galaxies acquired their gas. Here we report that they are 'stream-fed galaxies', formed from steady, narrow, cold gas streams that penetrate the shock-heated media of massive dark matter haloes8, 9. A comparison with the observed abundance of star-forming galaxies implies that most of the input gas must rapidly convert to stars. One-third of the stream mass is in gas clumps leading to mergers of mass ratio greater than 1:10, and the rest is in smoother flows. With a merger duty cycle of 0.1, three-quarters of the galaxies forming stars at a given rate are fed by smooth streams. The rarer, submillimetre galaxies that form stars even more intensely2, 12, 13 are largely merger-induced starbursts. Unlike destructive mergers, the streams are likely to keep the rotating disk configuration intact, although turbulent and broken into giant star-forming clumps that merge into a central spheroid4, 10, 11. This stream-driven scenario for the formation of discs and spheroids is an alternative to the merger picture

1,713 citations


Journal ArticleDOI
27 Aug 2009-Nature
TL;DR: The results reveal a spin-momentum locked Dirac cone carrying a non-trivial Berry’s phase that is nearly 100 per cent spin-polarized, which exhibits a tunable topological fermion density in the vicinity of the Kramers point and can be driven to the long-sought topological spin transport regime.
Abstract: Helical Dirac fermions—charge carriers that behave as massless relativistic particles with an intrinsic angular momentum (spin) locked to its translational momentum—are proposed to be the key to realizing fundamentally new phenomena in condensed matter physics. Prominent examples include the anomalous quantization of magneto-electric coupling, half-fermion states that are their own antiparticle, and charge fractionalization in a Bose– Einstein condensate, all of which are not possible with conventional Dirac fermions of the graphene variety. Helical Dirac fermions have so far remained elusive owing to the lack of necessary spin-sensitive measurements and because such fermions are forbidden to exist in conventional materials harbouring relativistic electrons, such as graphene or bismuth. It has recently been proposed that helical Dirac fermions may exist at the edges of certain types of topologically ordered insulators—materials with a bulk insulating gap of spin–orbit origin and surface states protected against scattering by time-reversal symmetry—and that their peculiar properties may be accessed provided the insulator is tuned into the so-called topological transport regime. However, helical Dirac fermions have not been observed in existing topological insulators. Here we report the realization and characterization of a tunable topological insulator in a bismuthbased class of material by combining spin-imaging and momentum-resolved spectroscopies, bulk charge compensation, Hall transport measurements and surface quantum control. Our results reveal a spin-momentum locked Dirac cone carrying a nontrivial Berry’s phase that is nearly 100 per cent spin-polarized, which exhibits a tunable topological fermion density in the vicinity of the Kramers point and can be driven to the long-sought topological spin transport regime. The observed topological nodal state is shown to be protected even up to 300 K. Our demonstration of room-temperature topological order and non-trivial spintexture in stoichiometric Bi_2Se_3.M_x (M_x indicates surface doping or gating control) paves the way for future graphene-like studies of topological insulators, and applications of the observed spinpolarized edge channels in spintronic and computing technologies possibly at room temperature.

1,685 citations


Journal ArticleDOI
TL;DR: In this article, the authors characterize dynamic tax policies that achieve sustainable growth or maximize intertemporal welfare, as a function of the degree of substitutability between clean and dirty inputs, environmental and resource stocks, and cross-country technological spillovers.
Abstract: This paper introduces endogenous and directed technical change in a growth model with environmental constraints and limited resources. A unique final good is produced by combining inputs from two sectors. One of these sectors uses "dirty" machines and thus creates environmental degradation. Research can be directed to improving the technology of machines in either sector. We characterize dynamic tax policies that achieve sustainable growth or maximize intertemporal welfare, as a function of the degree of substitutability between clean and dirty inputs, environmental and resource stocks, and cross-country technological spillovers. We show that: (i) in the case where the inputs are sufficiently substitutable, sustainable long-run growth can be achieved with temporary taxation of dirty innovation and production; (ii) optimal policy involves both "carbon taxes" and research subsidies, so that excessive use of carbon taxes is avoided; (iii) delay in intervention is costly: the sooner and the stronger is the policy response, the shorter is the slow growth transition phase; (iv) the use of an exhaustible resource in dirty input production helps the switch to clean innovation under laissez-faire when the two inputs are substitutes. Under reasonable parameter values (corresponding to those used in existing models with exogenous technology) and with sufficient substitutability between inputs, it is optimal to redirect technical change towards clean technologies immediately and optimal environmental regulation need not reduce long-run growth. We also show that in a two-country extension, even though optimal environmental policy involves global policy coordination, when the two inputs are sufficiently substitutable environmental regulation only in the North may be sufficient to avoid a global disaster.

1,669 citations


Journal ArticleDOI
TL;DR: An in‐depth and critical discussion of the findings of recent studies showing that empathy is a highly flexible phenomenon, and that vicarious responses are malleable with respect to a number of factors.
Abstract: The phenomenon of empathy entails the ability to share the affective experiences of others. In recent years social neuroscience made considerable progress in revealing the mechanisms that enable a person to feel what another is feeling. The present review provides an in-depth and critical discussion of these findings. Consistent evidence shows that sharing the emotions of others is associated with activation in neural structures that are also active during the first-hand experience of that emotion. Part of the neural activation shared between self- and other-related experiences seems to be rather automatically activated. However, recent studies also show that empathy is a highly flexible phenomenon, and that vicarious responses are malleable with respect to a number of factors--such as contextual appraisal, the interpersonal relationship between empathizer and other, or the perspective adopted during observation of the other. Future investigations are needed to provide more detailed insights into these factors and their neural underpinnings. Questions such as whether individual differences in empathy can be explained by stable personality traits, whether we can train ourselves to be more empathic, and how empathy relates to prosocial behavior are of utmost relevance for both science and society.

Journal ArticleDOI
TL;DR: Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable.
Abstract: BACKGROUND Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 μg per liter or between 100 and 299 μg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. RESULTS Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable. (ClinicalTrials.gov number, NCT00520780.)

Journal ArticleDOI
TL;DR: A seminal view on recent advances in techniques for hyperspectral image processing, focusing on the design of techniques able to deal with the high-dimensional nature of the data, and to integrate the spa- tial and spectral information.

Journal ArticleDOI
TL;DR: The psychometric validity of criteria for prolonged grief disorder (PGD) is tested to enhance the detection and care of bereaved individuals at heightened risk of persistent distress and dysfunction.
Abstract: Background: Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction. Methods and Findings: A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12– 24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment. Conclusions: The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. Please see later in the article for the Editors’ Summary.

MonographDOI
01 Jan 2009
TL;DR: This paper aims to unify MD and electronic structure by using the plane wave basis set and beyond to go beyond standard ab initio molecular dynamics.
Abstract: Ab initio molecular dynamics revolutionized the field of realistic computer simulation of complex molecular systems and processes, including chemical reactions, by unifying molecular dynamics and electronic structure theory. This book provides the first coherent presentation of this rapidly growing field, covering a vast range of methods and their applications, from basic theory to advanced methods. This fascinating text for graduate students and researchers contains systematic derivations of various ab initio molecular dynamics techniques in order that readers can understand and assess the merits and drawbacks of commonly used methods. It also discusses the special features of the widely-used Car-Parrinello approach, correcting various misconceptions currently found in research literature. The book also contains pseudo-code and program layout for typical plane wave electronic structure codes, allowing newcomers to the field to understand commonly-used program packages, and enabling developers to improve and add new features in their code. • Discusses the Car-Parrinello approach and its special features helping to correct various misconceptions currently found in research literature • Allows readers to understand widely used program packages and to improve their own programs by featuring pseudo-code and program layout • Enables readers to assess the pros and cons of commonly used ab initio simulation methods by including systematic derivations of ab initio molecular dynamics schemes

Journal ArticleDOI
01 Oct 2009-BMJ
TL;DR: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D.
Abstract: Objective To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals. Data sources We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D 3 (1α-hydroxycalciferol) or 1,25-dihydroxyvitamin D 3 (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion. Results Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D 3 concentration (25(OH)D concentration: v ≥60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94). Conclusions Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

Journal ArticleDOI
TL;DR: This review describes sAA as an emerging biomarker for stress and provides an overview of the current literature on stress-related alterations in sAA, and critically discusses how sAA might reflect changes in the autonomic nervous system.

Journal ArticleDOI
TL;DR: A unifying model in which insula cortex supports different levels of representation of current and predictive states allowing for error-based learning of both feeling states and uncertainty is proposed.

Journal ArticleDOI
06 Mar 2009-Science
TL;DR: It is shown that the LR34 protein resembles adenosine triphosphate–binding cassette transporters of the pleiotropic drug resistance subfamily, which functions in the adult plant and stimulates senescence-like processes in the flag leaf tips and edges.
Abstract: Agricultural crops benefit from resistance to pathogens that endures over years and generations of both pest and crop. Durable disease resistance, which may be partial or complete, can be controlled by several genes. Some of the most devastating fungal pathogens in wheat are leaf rust, stripe rust, and powdery mildew. The wheat gene Lr34 has supported resistance to these pathogens for more than 50 years. Lr34 is now shared by wheat cultivars around the world. Here, we show that the LR34 protein resembles adenosine triphosphate-binding cassette transporters of the pleiotropic drug resistance subfamily. Alleles of Lr34 conferring resistance or susceptibility differ by three genetic polymorphisms. The Lr34 gene, which functions in the adult plant, stimulates senescence-like processes in the flag leaf tips and edges.

Journal ArticleDOI
TL;DR: An inverse association of IDH1 and IDH2 mutations of the R132C type are strongly associated with astrocytoma, while IDH 2 mutations predominantly occur in oligodendroglial tumors.
Abstract: Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.

Posted Content
TL;DR: In this article, a growth model that is consistent with salient features of the Chinese growth experience since 1992 is presented, which includes high output growth, sustained returns on capital investments, extensive reallocation within the manufacturing sector, falling labor share and accumulation of a large foreign surplus.
Abstract: This paper constructs a growth model that is consistent with salient features of the Chinese growth experience since 1992: high output growth, sustained returns on capital investments, extensive reallocation within the manufacturing sector, falling labor share and accumulation of a large foreign surplus. The theory makes only minimal deviations from a neoclassical growth model. Its building blocks are financial imperfections and reallocation among firms with heterogeneous productivity. Some firms use more productive technologies than others, but low-productivity firms survive because of better access to credit markets. Due to the financial imperfections, high-productivity firms - which are run by entrepreneurs - must be financed out of internal savings. If these savings are sufficiently large, the high-productivity sector outgrows the low-productivity sector, and attracts an increasing employment share. During the transition, low wage growth sustains the return to capital. The downsizing of the financially integrated sector forces a growing share of domestic savings to be invested in foreign assets, generating a foreign surplus. We test some auxiliary implications of the theory and find robust empirical support.

Journal ArticleDOI
01 May 2009-Science
TL;DR: Using experimental grassland plant communities, it is found that addition of light to the grassland understory prevented the loss of biodiversity caused by eutrophication, and there was no detectable role for competition for soil resources in diversity loss.
Abstract: Human activities have increased the availability of nutrients in terrestrial and aquatic ecosystems. In grasslands, this eutrophication causes loss of plant species diversity, but the mechanism of this loss has been difficult to determine. Using experimental grassland plant communities, we found that addition of light to the grassland understory prevented the loss of biodiversity caused by eutrophication. There was no detectable role for competition for soil resources in diversity loss. Thus, competition for light is a major mechanism of plant diversity loss after eutrophication and explains the particular threat of eutrophication to plant diversity. Our conclusions have implications for grassland management and conservation policy and underscore the need to control nutrient enrichment if plant diversity is to be preserved.

Journal ArticleDOI
TL;DR: NBR1 (neighbor of BRCA1 gene 1) is an autophagy receptor containing LC3- and ubiquitin (Ub)-binding domains and it is proposed that NBR1 and p62 act as receptors for selective autophagosomal degradation of ubiquitinated targets.

Journal ArticleDOI
11 Dec 2009-Science
TL;DR: An analytical solution to the master equation shows that amyloid growth kinetics is often limited by the fragmentation rate rather than by the rate of primary nucleation, and reveals the existence of generic scaling laws that provide mechanistic information in contexts ranging from in vitro amyloids growth to the in vivo development of mammalian prion diseases.
Abstract: We present an analytical treatment of a set of coupled kinetic equations that governs the self-assembly of filamentous molecular structures. Application to the case of protein aggregation demonstrates that the kinetics of amyloid growth can often be dominated by secondary rather than by primary nucleation events. Our results further reveal a range of general features of the growth kinetics of fragmenting filamentous structures, including the existence of generic scaling laws that provide mechanistic information in contexts ranging from in vitro amyloid growth to the in vivo development of mammalian prion diseases.

Journal ArticleDOI
13 Feb 2009-Science
TL;DR: Using Mott polarimetry, it is demonstrated that topological quantum numbers are completely determined from spin texture–imaging measurements and the origin of its topological order and unusual chiral properties are identified.
Abstract: A topologically ordered material is characterized by a rare quantum organization of electrons that evades the conventional spontaneously broken symmetry–based classification of condensed matter. Exotic spin-transport phenomena, such as the dissipationless quantum spin Hall effect, have been speculated to originate from a topological order whose identification requires a spin-sensitive measurement, which does not exist to this date in any system. Using Mott polarimetry, we probed the spin degrees of freedom and demonstrated that topological quantum numbers are completely determined from spin texture–imaging measurements. Applying this method to Sb and Bi1–xSbx, we identified the origin of its topological order and unusual chiral properties. These results taken together constitute the first observation of surface electrons collectively carrying a topological quantum Berry's phase and definite spin chirality, which are the key electronic properties component for realizing topological quantum computing bits with intrinsic spin Hall–like topological phenomena.

Journal ArticleDOI
TL;DR: A total of 130 IDH1 mutations were detected in 321 gliomas of various histological types and biological behaviors, and all were located at amino acid residue 132.
Abstract: IDH1 encodes isocitrate dehydrogenase 1, which participates in the citric acid cycle and was recently reported to be mutated in 12% of glioblastomas. We assessed IDH1 mutations in 321 gliomas of various histological types and biological behaviors. A total of 130 IDH1 mutations was detected, and all were located at amino acid residue 132. Of these, 91% were G→A mutations (Arg→His). IDH1 mutations were frequent in low-grade diffuse astrocytomas (88%) and in secondary glioblastomas that developed through progression from low-grade diffuse or anaplastic astrocytoma (82%). Similarly, high frequencies of IDH1 mutations were found in oligodendrogliomas (79%) and oligoastrocytomas (94%). Analyses of multiple biopsies from the same patient (51 cases) showed that there were no cases in which an IDH1 mutation occurred after the acquisition of either a TP53 mutation or loss of 1p/19q, suggesting that IDH1 mutations are very early events in gliomagenesis and may affect a common glial precursor cell population. IDH1 mutations were co-present with TP53 mutations in 63% of low-grade diffuse astrocytomas and with loss of heterozygosity 1p/19q in 64% of oligodendrogliomas; they were rare in pilocytic astrocytomas (10%) and primary glioblastomas (5%) and absent in ependymomas. The frequent presence of IDH1 mutations in secondary glioblastomas and their near-complete absence in primary glioblastomas reinforce the concept that despite their histological similarities, these subtypes are genetically and clinically distinct entities.

Journal ArticleDOI
01 Dec 2009-Science
TL;DR: The results from the completed Cryogenic Dark Matter Search (CDMS II) experiment, which searched for dark matter in the form of weakly interacting massive particles (WIMP), cannot be interpreted with confidence as evidence for WIMP interactions, but neither event can be ruled out as representing signal.
Abstract: We report results from a blind analysis of the final data taken with the Cryogenic Dark Matter Search experiment (CDMS II) at the Soudan Underground Laboratory, Minnesota, USA. A total raw exposure of 612 kg-days was analyzed for this work. We observed two events in the signal region; based on our background estimate, the probability of observing two or more background events is 23%. These data set an upper limit on the Weakly Interacting Massive Particle (WIMP)-nucleon elastic-scattering spin-independent cross-section of 7.0 x 10{sup -44} cm{sup 2} for a WIMP of mass 70 GeV/c{sup 2} at the 90% confidence level. Combining this result with all previous CDMS II data gives an upper limit on the WIMP-nucleon spin-independent cross-section of 3.8 x 10{sup -44} cm{sup 2} for a WIMP of mass 70 GeV/c{sup 2}. We also exclude new parameter space in recently proposed inelastic dark matter models.

Journal ArticleDOI
TL;DR: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
Abstract: Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Journal ArticleDOI
TL;DR: It is directly shown that Bi2Te3 is a large spin-orbit-induced indirect bulk band gap semiconductor whose surface is characterized by a single topological spin-Dirac cone, and it is demonstrated that the dynamics of spin- Dirac fermions can be controlled through systematic Mn doping.
Abstract: We show that the strongly spin-orbit coupled materials Bi_2Te_3 and Sb_2Te_3 and their derivatives belong to the Z_2 topological-insulator class. Using a combination of first-principles theoretical calculations and photoemission spectroscopy, we directly show that Bi_2Te_3 is a large spin-orbit-induced indirect bulk band gap (δ∼150 meV) semiconductor whose surface is characterized by a single topological spin-Dirac cone. The electronic structure of self-doped Sb_2Te_3 exhibits similar Z_2 topological properties. We demonstrate that the dynamics of spin-Dirac fermions can be controlled through systematic Mn doping, making these materials classes potentially suitable for topological device applications.

Journal ArticleDOI
TL;DR: Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.
Abstract: Results: The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n=33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n=31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in communitydwelling individuals (�29%) and institutionalized older individuals (�15%), and its effect was independent of additional calcium supplementation. Conclusion: Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.