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Showing papers by "Utrecht University published in 2013"


Journal ArticleDOI
TL;DR: This review focuses on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
Abstract: Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.

6,141 citations


Journal ArticleDOI
TL;DR: This new handbook has a better balance between whole-plant traits, leaf traits, root and stem traits and regenerative traits, and puts particular emphasis on traits important for predicting species’ effects on key ecosystem properties.
Abstract: Plant functional traits are the features (morphological, physiological, phenological) that represent ecological strategies and determine how plants respond to environmental factors, affect other trophic levels and influence ecosystem properties. Variation in plant functional traits, and trait syndromes, has proven useful for tackling many important ecological questions at a range of scales, giving rise to a demand for standardised ways to measure ecologically meaningful plant traits. This line of research has been among the most fruitful avenues for understanding ecological and evolutionary patterns and processes. It also has the potential both to build a predictive set of local, regional and global relationships between plants and environment and to quantify a wide range of natural and human-driven processes, including changes in biodiversity, the impacts of species invasions, alterations in biogeochemical processes and vegetation–atmosphere interactions. The importance of these topics dictates the urgent need for more and better data, and increases the value of standardised protocols for quantifying trait variation of different species, in particular for traits with power to predict plant- and ecosystem-level processes, and for traits that can be measured relatively easily. Updated and expanded from the widely used previous version, this handbook retains the focus on clearly presented, widely applicable, step-by-step recipes, with a minimum of text on theory, and not only includes updated methods for the traits previously covered, but also introduces many new protocols for further traits. This new handbook has a better balance between whole-plant traits, leaf traits, root and stem traits and regenerative traits, and puts particular emphasis on traits important for predicting species’ effects on key ecosystem properties. We hope this new handbook becomes a standard companion in local and global efforts to learn about the responses and impacts of different plant species with respect to environmental changes in the present, past and future.

2,744 citations


Journal ArticleDOI
01 Sep 2013-Episodes
TL;DR: The International Commission on Stratigraphy (ICS) has a long tradition of producing international charts that communicate higher-order divisions of geological time and actual knowledge on the absolute numerical ages of their boundaries as mentioned in this paper.
Abstract: The International Commission on Stratigraphy (ICS) has a long tradition of producing international charts that communicate higher-order divisions of geological time and actual knowledge on the absolute numerical ages of their boundaries. The primary objective of ICS is to define precisely a global standard set of time-correlative units (Systems, Series, and Stages) for stratigraphic successions worldwide. These units are, in turn, the basis for the Periods, Epochs and Ages of the Geological Time Scale. Setting an international global standard is fundamental for expressing geological knowledge. It is also of considerable pragmatic importance as it provides the framework through which regional-scale higher-resolution divisions can be linked, equated and collated. This is a status update on the International Chronostratigraphic Chart and the ICS website www.stratigraphy.org.

2,164 citations


Journal ArticleDOI
S. Hong Lee1, Stephan Ripke2, Stephan Ripke3, Benjamin M. Neale3  +402 moreInstitutions (124)
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

2,058 citations


Journal ArticleDOI
TL;DR: The need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results is emphasized, and it is recognized that continual development and evaluation of techniques will be necessary as new knowledge is amassed.
Abstract: The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments. Keywords: extracellular vesicle; exosome; microvesicle; standardization; isolation (Published: 27 May 2013) Citation: Journal of Extracellular Vesicles 2013, 2 : 20360 - http://dx.doi.org/10.3402/jev.v2i0.20360

1,840 citations


Journal ArticleDOI
TL;DR: Combining data from numerous empirical and computational studies, network approaches strongly suggest that brain hubs play important roles in information integration underpinning numerous aspects of complex cognitive function.

1,760 citations


Journal ArticleDOI
14 Mar 2013-Nature
TL;DR: Dipeptidyl peptidase 4 (DPP4; also known as CD26) is identified as a functional receptor for hCoV-EMC and will contribute critically to the understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
Abstract: Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.

1,743 citations


Journal ArticleDOI
TL;DR: These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections.
Abstract: Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

1,733 citations


Journal ArticleDOI
TL;DR: The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenoust-PA alone.
Abstract: BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0 percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.)

1,702 citations


Journal ArticleDOI
TL;DR: In this paper, the authors construct decadal budgets for methane sources and sinks between 1980 and 2010, using a combination of atmospheric measurements and results from chemical transport models, ecosystem models, climate chemistry models and inventories of anthropogenic emissions.
Abstract: Methane is an important greenhouse gas, responsible for about 20% of the warming induced by long-lived greenhouse gases since pre-industrial times. By reacting with hydroxyl radicals, methane reduces the oxidizing capacity of the atmosphere and generates ozone in the troposphere. Although most sources and sinks of methane have been identified, their relative contributions to atmospheric methane levels are highly uncertain. As such, the factors responsible for the observed stabilization of atmospheric methane levels in the early 2000s, and the renewed rise after 2006, remain unclear. Here, we construct decadal budgets for methane sources and sinks between 1980 and 2010, using a combination of atmospheric measurements and results from chemical transport models, ecosystem models, climate chemistry models and inventories of anthropogenic emissions. The resultant budgets suggest that data-driven approaches and ecosystem models overestimate total natural emissions. We build three contrasting emission scenarios-which differ in fossil fuel and microbial emissions-to explain the decadal variability in atmospheric methane levels detected, here and in previous studies, since 1985. Although uncertainties in emission trends do not allow definitive conclusions to be drawn, we show that the observed stabilization of methane levels between 1999 and 2006 can potentially be explained by decreasing-to-stable fossil fuel emissions, combined with stable-to-increasing microbial emissions. We show that a rise in natural wetland emissions and fossil fuel emissions probably accounts for the renewed increase in global methane levels after 2006, although the relative contribution of these two sources remains uncertain. © 2013 Macmillan Publishers Limited.

1,668 citations


Journal ArticleDOI
TL;DR: In this paper, the authors critically review recent research assessing the impacts of climate on ground water through natural and human-induced processes as well as through groundwater-driven feedbacks on the climate system, and highlight the possible opportunities and challenges of using and sustaining groundwater resources in climate adaptation strategies.
Abstract: As the world's largest distributed store of fresh water, ground water plays a central part in sustaining ecosystems and enabling human adaptation to climate variability and change. The strategic importance of ground water for global water and food security will probably intensify under climate change as more frequent and intense climate extremes (droughts and floods) increase variability in precipitation, soil moisture and surface water. Here we critically review recent research assessing the impacts of climate on ground water through natural and human-induced processes as well as through groundwater-driven feedbacks on the climate system. Furthermore, we examine the possible opportunities and challenges of using and sustaining groundwater resources in climate adaptation strategies, and highlight the lack of groundwater observations, which, at present, limits our understanding of the dynamic relationship between ground water and climate.

Journal ArticleDOI
TL;DR: In subjects with lower education and obese subjects a larger effect estimate for mortality related to fine PM was found, though the evidence for differences related to education has been weakened in more recent studies.
Abstract: Current day concentrations of ambient air pollution have been associated with a range of adverse health effects, particularly mortality and morbidity due to cardiovascular and respiratory diseases. In this review, we summarize the evidence from epidemiological studies on long-term exposure to fine and coarse particles, nitrogen dioxide (NO2) and elemental carbon on mortality from all-causes, cardiovascular disease and respiratory disease. We also summarize the findings on potentially susceptible subgroups across studies. We identified studies through a search in the databases Medline and Scopus and previous reviews until January 2013 and performed a meta-analysis if more than five studies were available for the same exposure metric.

Journal ArticleDOI
TL;DR: This review focuses on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions.
Abstract: With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering - the combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue - is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three-dimensional tissue-like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell-laden hydrogels are commonly used in biofabrication and are termed "bioinks". Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three-dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically-relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico-chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a "printable" hydrogel that supports cell adhesion, migration, and differentiation will significantly advance this exciting and promising approach for tissue engineering.

Journal ArticleDOI
TL;DR: The contaminant repository for affinity purification (the CRAPome) is presented and its use for scoring protein-protein interactions is described and aggregating negative controls from multiple AP-MS studies can increase coverage and improve the characterization of background associated with a given experimental protocol.
Abstract: Affinity purification coupled with mass spectrometry (AP-MS) is a widely used approach for the identification of protein-protein interactions. However, for any given protein of interest, determining which of the identified polypeptides represent bona fide interactors versus those that are background contaminants (for example, proteins that interact with the solid-phase support, affinity reagent or epitope tag) is a challenging task. The standard approach is to identify nonspecific interactions using one or more negative-control purifications, but many small-scale AP-MS studies do not capture a complete, accurate background protein set when available controls are limited. Fortunately, negative controls are largely bait independent. Hence, aggregating negative controls from multiple AP-MS studies can increase coverage and improve the characterization of background associated with a given experimental protocol. Here we present the contaminant repository for affinity purification (the CRAPome) and describe its use for scoring protein-protein interactions. The repository (currently available for Homo sapiens and Saccharomyces cerevisiae) and computational tools are freely accessible at http://www.crapome.org/.

Journal ArticleDOI
TL;DR: In the ocean, the lifetime of Nr is less well known but seems to be longer than in terrestrial ecosystems and may represent an important long-term source of N2O that will respond very slowly to control measures on the sources of NR from which it is produced.
Abstract: Global nitrogen fixation contributes 413 Tg of reactive nitrogen (Nr) to terrestrial and marine ecosystems annually of which anthropogenic activities are responsible for half, 210 Tg N. The majority of the transformations of anthropogenic Nr are on land (240 Tg N yr−1) within soils and vegetation where reduced Nr contributes most of the input through the use of fertilizer nitrogen in agriculture. Leakages from the use of fertilizer Nr contribute to nitrate (NO3−) in drainage waters from agricultural land and emissions of trace Nr compounds to the atmosphere. Emissions, mainly of ammonia (NH3) from land together with combustion related emissions of nitrogen oxides (NOx), contribute 100 Tg N yr−1 to the atmosphere, which are transported between countries and processed within the atmosphere, generating secondary pollutants, including ozone and other photochemical oxidants and aerosols, especially ammonium nitrate (NH4NO3) and ammonium sulfate (NH4)2SO4. Leaching and riverine transport of NO3 contribute 40–70 Tg N yr−1 to coastal waters and the open ocean, which together with the 30 Tg input to oceans from atmospheric deposition combine with marine biological nitrogen fixation (140 Tg N yr−1) to double the ocean processing of Nr. Some of the marine Nr is buried in sediments, the remainder being denitrified back to the atmosphere as N2 or N2O. The marine processing is of a similar magnitude to that in terrestrial soils and vegetation, but has a larger fraction of natural origin. The lifetime of Nr in the atmosphere, with the exception of N2O, is only a few weeks, while in terrestrial ecosystems, with the exception of peatlands (where it can be 102–103 years), the lifetime is a few decades. In the ocean, the lifetime of Nr is less well known but seems to be longer than in terrestrial ecosystems and may represent an important long-term source of N2O that will respond very slowly to control measures on the sources of Nr from which it is produced.

Journal ArticleDOI
TL;DR: The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 and PM2·5, and no association between lungcancer and nitrogen oxides concentration or traffic intensity on the nearest street.
Abstract: Summary Background Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. Methods This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Eff ects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffi c indicators. We used Cox regression models with adjustment for potential confounders for cohort-specifi c analyses and random eff ects models for meta-analyses. Findings The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically signifi cant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03–1·45] per 10 μg/m³). For PM2·5 the HR was 1·18 (0·96–1·46) per 5 μg/m³. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10–2·08) and 1·55 (1·05–2·29), respectively. An increase in road traffi c of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99–1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95–1·07] per 20 μg/m³) or traffi c intensity on the nearest street (HR 1·00 [0·97–1·04] per 5000 vehicles per day).

Journal ArticleDOI
TL;DR: The CRISPR/Cas9 genome editing system is used to correct the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients and the corrected allele is expressed and fully functional as measured in clonally expanded organoids.

Journal ArticleDOI
TL;DR: In this article, the authors used meta-analytic techniques to investigate whether serious games are more effective in terms of learning and more motivating than conventional instruction methods (learning: k = 77, N 5,547; motivation:k = 31, N 2,216).
Abstract: It is assumed that serious games influences learning in 2 ways, by changing cognitive processes and by affecting motivation. However, until now research has shown little evidence for these assumptions. We used meta-analytic techniques to investigate whether serious games are more effective in terms of learning and more motivating than conventional instruction methods (learning: k = 77, N 5,547; motivation: k = 31, N 2,216). Consistent with our hypotheses, serious games were found to be more effective in terms of learning (d= 0.29, p .05) than conventional instruction methods. Additional moderator analyses on the learning effects revealed that learners in serious games learned more, relative to those taught with conventional instruction methods, when the game was supplemented with other instruction methods, when multiple training sessions were involved, and when players worked in groups.

Journal ArticleDOI
14 Feb 2013-Nature
TL;DR: Findings indicate that previous observations concerning Lgr5+ stem cells in actively self-renewing tissues can also be extended to damage-induced stem Cells in a tissue with a low rate of spontaneous proliferation.
Abstract: The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A three-dimensional culture system allows long-term clonal expansion of single Lgr5(+) stem cells into transplantable organoids (budding cysts) that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist RSPO1, the recently discovered ligand of LGR5. Here we show that Lgr5-lacZ is not expressed in healthy adult liver, however, small Lgr5-LacZ(+) cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signalling. As shown by mouse lineage tracing using a new Lgr5-IRES-creERT2 knock-in allele, damage-induced Lgr5(+) cells generate hepatocytes and bile ducts in vivo. Single Lgr5(+) cells from damaged mouse liver can be clonally expanded as organoids in Rspo1-based culture medium over several months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into Fah(-/-) mice. These findings indicate that previous observations concerning Lgr5(+) stem cells in actively self-renewing tissues can also be extended to damage-induced stem cells in a tissue with a low rate of spontaneous proliferation.

Journal ArticleDOI
TL;DR: The 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext
Abstract: 1. INTRODUCTION1.1 PrinciplesThe 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext

Journal ArticleDOI
17 May 2013-Science
TL;DR: It is found that glaciers in the Arctic, Canada, Alaska, coastal Greenland, the southern Andes, and high-mountain Asia contribute approximately as much melt water as the ice sheets themselves: 260 billion tons per year between 2003 and 2009, accounting for about 30% of the observed sea-level rise during that period.
Abstract: Glaciers distinct from the Greenland and Antarctic Ice Sheets are losing large amounts of water to the world's oceans. However, estimates of their contribution to sea level rise disagree. We provide a consensus estimate by standardizing existing, and creating new, mass-budget estimates from satellite gravimetry and altimetry and from local glaciological records. In many regions, local measurements are more negative than satellite-based estimates. All regions lost mass during 2003-2009, with the largest losses from Arctic Canada, Alaska, coastal Greenland, the southern Andes, and high-mountain Asia, but there was little loss from glaciers in Antarctica. Over this period, the global mass budget was -259 ± 28 gigatons per year, equivalent to the combined loss from both ice sheets and accounting for 29 ± 13% of the observed sea level rise.

Journal ArticleDOI
TL;DR: Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy.
Abstract: Background Severe pain after surgery remains a major problem, occurring in 20-40% of patients. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain therapy and develop procedure-specific, optimized pain-treatment protocols, types of surgery that may result in severe postoperative pain in everyday practice must first be identified. Methods This study considered 115,775 patients from 578 surgical wards in 105 German hospitals. A total of 70,764 patients met the inclusion criteria. On the first postoperative day, patients were asked to rate their worst pain intensity since surgery (numeric rating scale, 0-10). All surgical procedures were assigned to 529 well-defined groups. When a group contained fewer than 20 patients, the data were excluded from analysis. Finally, 50,523 patients from 179 surgical groups were compared. Results The 40 procedures with the highest pain scores (median numeric rating scale, 6-7) included 22 orthopedic/trauma procedures on the extremities. Patients reported high pain scores after many "minor" surgical procedures, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy, which ranked among the 25 procedures with highest pain intensities. A number of "major" abdominal surgeries resulted in comparatively low pain scores, often because of sufficient epidural analgesia. Conclusions Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain. To reduce the number of patients suffering from severe pain, patients undergoing so-called minor surgery should be monitored more closely, and postsurgical pain treatment needs to comply with existing procedure-specific pain-treatment recommendations.

Journal ArticleDOI
TL;DR: During the summer of 2012, in Jeddah, Saudi Arabia, a hitherto unknown coronavirus was isolated from the sputum of a patient with acute pneumonia and renal failure and was provisionally called human coronav virus Erasmus Medical Center (EMC).
Abstract: During the summer of 2012, in Jeddah, Saudi Arabia, a hitherto unknown coronavirus (CoV) was isolated from the sputum of a patient with acute pneumonia and renal failure ([1][1], [2][2]). The isolate was provisionally called human coronavirus Erasmus Medical Center (EMC) ([3][3]). Shortly thereafter

Journal ArticleDOI
TL;DR: A meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, and identified 29,807 SNPs for further genotyping suggests that more than 1,000 additional loci are involved in breast cancer susceptibility.
Abstract: Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility

Journal ArticleDOI
TL;DR: Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work.
Abstract: The objective was to develop evidence -based recommendations and a research and educational agenda for the non-pharmacological management of hip and knee osteoarthritis (OA). The multidisciplinary task force comprised 21 experts: nurses, occupational therapists, physiotherapists, rheumatologists, orthopaedic surgeons, general practitioner, psychologist, dietician, clinical epidemiologist and patient representatives. After a preliminary literature review, a first task force meeting and five Delphi rounds, provisional recommendations were formulated in order to perform a systematic review. A literature search of Medline and eight other databases was performed up to February 2012. Evidence was graded in categories I-IV and agreement with the recommendations was determined through scores from 0 (total disagreement) to 10 (total agreement). Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work. The average level of agreement ranged between 8.0 and 9.1. The proposed research agenda included an overall need for more research into non-pharmacological interventions for hip OA, moderators to optimise individualised treatment, healthy lifestyle with economic evaluation and long-term follow-up, and the prevention and reduction of work disability. Proposed educational activities included the required skills to teach, initiate and establish lifestyle changes. The 11 recommendations provide guidance on the delivery of non-pharmacological interventions to people with hip or knee OA. More research and educational activities are needed, particularly in the area of lifestyle changes.

Journal ArticleDOI
23 Aug 2013-Science
TL;DR: The reconstitution of ARSA activity in the cerebrospinal fluid and the arrested progression of neurodegenerative disease in the three treated patients demonstrate that the transplanted cells, or their progeny, can seed the nervous system and deliver therapeutic levels of active enzyme.
Abstract: Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within a few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. The disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.

Journal ArticleDOI
Hans ter Steege1, Hans ter Steege2, Nigel C. A. Pitman3, Daniel Sabatier4, Christopher Baraloto5, Rafael de Paiva Salomão6, Juan Ernesto Guevara7, Oliver L. Phillips8, Carolina V. Castilho9, William E. Magnusson10, Jean-François Molino4, Abel Monteagudo, Percy Núñez Vargas11, Juan Carlos Montero10, Ted R. Feldpausch12, Ted R. Feldpausch8, Eurídice N. Honorio Coronado8, Timothy J. Killeen13, Bonifacio Mostacedo14, Rodolfo Vasquez, Rafael L. Assis10, Rafael L. Assis15, John Terborgh3, Florian Wittmann16, Ana Andrade10, William F. Laurance17, Susan G. Laurance17, Beatriz Schwantes Marimon18, Ben Hur Marimon18, Ima Célia Guimarães Vieira6, Iêda Leão do Amaral10, Roel J. W. Brienen8, Hernán Castellanos, Dairon Cárdenas López, Joost F. Duivenvoorden19, Hugo Mogollón20, Francisca Dionízia de Almeida Matos10, Nállarett Dávila21, Roosevelt García-Villacorta22, Pablo Roberto Stevenson Diaz23, Flávia R. C. Costa10, Thaise Emilio10, Carolina Levis10, Juliana Schietti10, Priscila Souza10, Alfonso Alonso24, Francisco Dallmeier24, Álvaro Javier Duque Montoya25, Maria Teresa Fernandez Piedade10, Alejandro Araujo-Murakami, Luzmila Arroyo, Rogério Gribel, Paul V. A. Fine7, Carlos A. Peres26, Marisol Toledo14, A C Gerardo Aymard, Timothy R. Baker8, Carlos Cerón27, Julien Engel28, Terry W. Henkel29, Paul J. M. Maas2, Pascal Petronelli, Juliana Stropp, Charles E. Zartman10, Doug Daly30, David A. Neill, Marcos Silveira31, Marcos Ríos Paredes, Jérôme Chave32, Diogenes de Andrade Lima Filho10, Peter M. Jørgensen33, Alfredo F. Fuentes33, Jochen Schöngart16, Fernando Cornejo Valverde34, Anthony Di Fiore35, E. M. Jimenez25, Maria Cristina Peñuela Mora25, Juan Fernando Phillips, Gonzalo Rivas36, Tinde van Andel2, Patricio von Hildebrand, Bruce Hoffman2, Egleé L. Zent37, Yadvinder Malhi38, Adriana Prieto25, Agustín Rudas25, Ademir R. Ruschell9, Natalino Silva39, Vincent A. Vos, Stanford Zent37, Alexandre Adalardo de Oliveira40, Angela Cano Schutz23, Therany Gonzales34, Marcelo Trindade Nascimento41, Hirma Ramírez-Angulo23, Rodrigo Sierra, Milton Tirado, Maria Natalia Umaña Medina23, Geertje M. F. van der Heijden42, Geertje M. F. van der Heijden43, César I.A. Vela11, Emilio Vilanova Torre23, Corine Vriesendorp, Ophelia Wang44, Kenneth R. Young35, Cláudia Baider40, Henrik Balslev45, Cid Ferreira10, Italo Mesones7, Armando Torres-Lezama23, Ligia Estela Urrego Giraldo25, Roderick Zagt46, Miguel Alexiades47, Lionel Hernández, Isau Huamantupa-Chuquimaco, William Milliken48, Walter Palacios Cuenca, Daniela Pauletto, Elvis H. Valderrama Sandoval49, Elvis H. Valderrama Sandoval50, Luis Valenzuela Gamarra, Kyle G. Dexter22, Kenneth J. Feeley51, Kenneth J. Feeley52, Gabriela Lopez-Gonzalez8, Miles R. Silman53 
Utrecht University1, Naturalis2, Duke University3, Institut de recherche pour le développement4, Institut national de la recherche agronomique5, Museu Paraense Emílio Goeldi6, University of California, Berkeley7, University of Leeds8, Empresa Brasileira de Pesquisa Agropecuária9, National Institute of Amazonian Research10, National University of Saint Anthony the Abbot in Cuzco11, University of Exeter12, World Wide Fund for Nature13, Universidad Autónoma Gabriel René Moreno14, Norwegian University of Life Sciences15, Max Planck Society16, James Cook University17, Universidade do Estado de Mato Grosso18, University of Amsterdam19, Silver Spring Networks20, State University of Campinas21, University of Edinburgh22, University of Los Andes23, Smithsonian Conservation Biology Institute24, National University of Colombia25, University of East Anglia26, Central University of Ecuador27, Centre national de la recherche scientifique28, Humboldt State University29, New York Botanical Garden30, Universidade Federal do Acre31, Paul Sabatier University32, Missouri Botanical Garden33, Amazon.com34, University of Texas at Austin35, University of Florida36, Venezuelan Institute for Scientific Research37, Environmental Change Institute38, Federal Rural University of Amazonia39, University of São Paulo40, State University of Norte Fluminense41, University of Wisconsin–Milwaukee42, Smithsonian Tropical Research Institute43, Northern Arizona University44, Aarhus University45, Tropenbos International46, University of Kent47, Royal Botanic Gardens48, University of Missouri–St. Louis49, Universidad Nacional de la Amazonía Peruana50, Florida International University51, Fairchild Tropical Botanic Garden52, Wake Forest University53
18 Oct 2013-Science
TL;DR: The finding that Amazonia is dominated by just 227 tree species implies that most biogeochemical cycling in the world’s largest tropical forest is performed by a tiny sliver of its diversity.
Abstract: The vast extent of the Amazon Basin has historically restricted the study of its tree communities to the local and regional scales. Here, we provide empirical data on the commonness, rarity, and richness of lowland tree species across the entire Amazon Basin and Guiana Shield (Amazonia), collected in 1170 tree plots in all major forest types. Extrapolations suggest that Amazonia harbors roughly 16,000 tree species, of which just 227 (1.4%) account for half of all trees. Most of these are habitat specialists and only dominant in one or two regions of the basin. We discuss some implications of the finding that a small group of species—less diverse than the North American tree flora—accounts for half of the world’s most diverse tree community.


Journal ArticleDOI
TL;DR: In this article, collective flow, its anisotropies, and its event-to-event fluctuations in relativistic heavy-ion collisions, as well as the extraction of the specific shear viscosity of quark-gluon plasma from collective flow data collected in heavy ion collision experiments at RHIC and the LHC are reviewed.
Abstract: We review collective flow, its anisotropies, and its event-to-event fluctuations in relativistic heavy-ion collisions, as well as the extraction of the specific shear viscosity of quark–gluon plasma from collective flow data collected in heavy-ion collision experiments at RHIC and the LHC. We emphasize the similarities between the Big Bang of our universe and the Little Bangs created in heavy-ion collisions.

Journal ArticleDOI
TL;DR: More robust estimates of the proportion of affected voxels, the number of fiber orientations within each WM voxel, and the impact on tensor‐derived analyses are provided, using large, high‐quality diffusion‐weighted data sets, with reconstruction parameters optimized specifically for this task.
Abstract: It has long been recognized that the diffusion tensor model is inappropriate to characterize complex fiber architecture, causing tensor-derived measures such as the primary eigenvector and fractional anisotropy to be unreliable or misleading in these regions. There is however still debate about the impact of this problem in practice. A recent study using a Bayesian automatic relevance detection (ARD) multicompartment model suggested that a third of white matter (WM) voxels contain crossing fibers, a value that, whilst already significant, is likely to be an underestimate. The aim of this study is to provide more robust estimates of the proportion of affected voxels, the number of fiber orientations within each WM voxel, and the impact on tensor-derived analyses, using large, high-quality diffusion-weighted data sets, with reconstruction parameters optimized specifically for this task. Two reconstruction algorithms were used: constrained spherical deconvolution (CSD), and the ARD method used in the previous study. We estimate the proportion of WM voxels containing crossing fibers to be ∼90% (using CSD) and 63% (using ARD). Both these values are much higher than previously reported, strongly suggesting that the diffusion tensor model is inadequate in the vast majority of WM regions. This has serious implications for downstream processing applications that depend on this model, particularly tractography, and the interpretation of anisotropy and radial/axial diffusivity measures.