Showing papers by "Radboud University Nijmegen published in 2018"
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
TL;DR: In this paper, the cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies were presented, with good consistency with the standard spatially-flat 6-parameter CDM cosmology having a power-law spectrum of adiabatic scalar perturbations from polarization, temperature, and lensing separately and in combination.
Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies. We find good consistency with the standard spatially-flat 6-parameter $\Lambda$CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted "base $\Lambda$CDM" in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density $\Omega_c h^2 = 0.120\pm 0.001$, baryon density $\Omega_b h^2 = 0.0224\pm 0.0001$, scalar spectral index $n_s = 0.965\pm 0.004$, and optical depth $\tau = 0.054\pm 0.007$ (in this abstract we quote $68\,\%$ confidence regions on measured parameters and $95\,\%$ on upper limits). The angular acoustic scale is measured to $0.03\,\%$ precision, with $100\theta_*=1.0411\pm 0.0003$. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-$\Lambda$CDM cosmology, the inferred late-Universe parameters are: Hubble constant $H_0 = (67.4\pm 0.5)$km/s/Mpc; matter density parameter $\Omega_m = 0.315\pm 0.007$; and matter fluctuation amplitude $\sigma_8 = 0.811\pm 0.006$. We find no compelling evidence for extensions to the base-$\Lambda$CDM model. Combining with BAO we constrain the effective extra relativistic degrees of freedom to be $N_{\rm eff} = 2.99\pm 0.17$, and the neutrino mass is tightly constrained to $\sum m_
u< 0.12$eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base -$\Lambda$CDM at over $2\,\sigma$, which pulls some parameters that affect the lensing amplitude away from the base-$\Lambda$CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. (Abridged)
3,077 citations
Northeastern University1, Tufts Medical Center2, McGill University3, Johns Hopkins University4, Utrecht University5, Vanderbilt University Medical Center6, Brigham and Women's Hospital7, New York University8, McMaster University9, Ohio State University10, Radboud University Nijmegen11, London Health Sciences Centre12, University of Western Ontario13, University of Montpellier14, RMIT University15, University of Poitiers16, Maine Medical Center17, University of Washington18, University of Chicago19, Intermountain Healthcare20, Deakin University21, Johns Hopkins University School of Medicine22, Yale University23, University of Grenoble24, University of California, San Francisco25, Monash University26, Case Western Reserve University27, New York Medical College28, University of Toronto29, Stanford University30
TL;DR: Substantial agreement was found among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults.
Abstract: Objective:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.Design:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups g
1,935 citations
TL;DR: This analysis expands upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars.
Abstract: On 17 August 2017, the LIGO and Virgo observatories made the first direct detection of gravitational waves from the coalescence of a neutron star binary system. The detection of this gravitational-wave signal, GW170817, offers a novel opportunity to directly probe the properties of matter at the extreme conditions found in the interior of these stars. The initial, minimal-assumption analysis of the LIGO and Virgo data placed constraints on the tidal effects of the coalescing bodies, which were then translated to constraints on neutron star radii. Here, we expand upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars. Our analysis employs two methods: the use of equation-of-state-insensitive relations between various macroscopic properties of the neutron stars and the use of an efficient parametrization of the defining function pðρÞ of the equation of state itself. From the LIGO and Virgo data alone and the first method, we measure the two neutron star radii as R1 ¼ 10.8 þ2.0 −1.7 km for the heavier star and R2 ¼ 10.7 þ2.1 −1.5 km for the lighter star at the 90% credible level. If we additionally require that the equation of state supports neutron stars with masses larger than 1.97 M⊙ as required from electromagnetic observations and employ the equation-of-state parametrization, we further constrain R1 ¼ 11.9 þ1.4 −1.4 km and R2 ¼ 11.9 þ1.4 −1.4 km at the 90% credible level. Finally, we obtain constraints on pðρÞ at supranuclear densities, with pressure at twice nuclear saturation density measured at 3.5 þ2.7 −1.7 × 1034 dyn cm−2 at the 90% level.
1,595 citations
Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan1, Brendan Bulik-Sullivan2 +717 more•Institutions (270)
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
1,357 citations
TL;DR: In this article, a detailed review of the state of the art and future perspectives of Li-ion batteries with emphasis on this potential is presented, with a focus on electric vehicles.
Abstract: Lithium-ion batteries play an important role in the life quality of modern society as the dominant technology for use in portable electronic devices such as mobile phones, tablets and laptops. Beyond this application lithium-ion batteries are the preferred option for the emerging electric vehicle sector, while still underexploited in power supply systems, especially in combination with photovoltaics and wind power. As a technological component, lithium-ion batteries present huge global potential towards energy sustainability and substantial reductions in carbon emissions. A detailed review is presented herein on the state of the art and future perspectives of Li-ion batteries with emphasis on this potential.
1,353 citations
French Institute of Health and Medical Research1, Paris Descartes University2, Pierre-and-Marie-Curie University3, Mayo Clinic4, Providence Portland Medical Center5, University of Bern6, University Hospital of Bern7, Radboud University Nijmegen8, University of Erlangen-Nuremberg9, Université catholique de Louvain10, University Health Network11, University of Toronto12, Memorial Sloan Kettering Cancer Center13, Karolinska Institutet14, First Faculty of Medicine, Charles University in Prague15, Humanitas University16, Keio University17, Yamaguchi University18, Kindai University19, Sapporo Medical University20, Kurume University21, Xi'an Jiaotong University22, Qatar Airways23, Oregon Health & Science University24
TL;DR: The immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer and supports the implementation of the consensus Immunoscore as a new component of a TNM-Immune classification of cancer.
1,326 citations
University of Milan1, Instituto Português de Oncologia Francisco Gentil2, Curie Institute3, Leiden University Medical Center4, Vienna General Hospital5, University College London6, Leiden University7, Institut Jules Bordet8, Netherlands Cancer Institute9, Turku University Hospital10, University of Oxford11, University of Mannheim12, Ludwig Maximilian University of Munich13, Helsinki University Central Hospital14, The Royal Marsden NHS Foundation Trust15, Institute of Cancer Research16, University Medical Center Groningen17, Radboud University Nijmegen18, Institut Gustave Roussy19, Tel Aviv Sourasky Medical Center20, University Hospital of Lausanne21, University of Bologna22, University of Turin23, Weston Park Hospital24, Aarhus University Hospital25, Katholieke Universiteit Leuven26, Erasmus University Rotterdam27, Oslo University Hospital28, University College Hospital29, Claude Bernard University Lyon 130
1,150 citations
TL;DR: Although the inflammatory properties of the IL‐1 family dominate in innate immunity, IL‐2 family member can play a role in acquired immunity and this overview is a condensed update.
Abstract: The interleukin-1 (IL-1) family of cytokines and receptors is unique in immunology because the IL-1 family and Toll-like receptor (TLR) families share similar functions. More than any other cytokine family, the IL-1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T- and B-cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL-1 receptor and TLR family contains the cytoplasmic Toll-IL-1-Receptor (TIR) domain. The 50 amino acid TIR domains are highly homologous with the Toll protein in Drosophila. The TIR domain is nearly the same and present in each TLR and each IL-1 receptor family. Whereas IL-1 family cytokine members trigger innate inflammation via IL-1 family of receptors, TLRs trigger inflammation via bacteria, microbial products, viruses, nucleic acids, and damage-associated molecular patterns (DAMPs). In fact, IL-1 family member IL-1a and IL-33 also function as DAMPs. Although the inflammatory properties of the IL-1 family dominate in innate immunity, IL-1 family member can play a role in acquired immunity. This overview is a condensed update of the IL-1 family of cytokines and receptors.
981 citations
TL;DR: Among patients with stage III epithelial ovarian cancer, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in longer recurrence‐free survival and overall survival than surgery alone and did not result in higher rates of side effects.
Abstract: Background Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer. Methods In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measu...
928 citations
Hacettepe University1, Boston Children's Hospital2, Katholieke Universiteit Leuven3, University of Bologna4, Radboud University Nijmegen5, University of Aberdeen6, European Respiratory Society7, Claude Bernard University Lyon 18, Cardiff University9, University Hospital of Lausanne10, University of Queensland11, Ghent University12, University of Paris13, Istituto Giannina Gaslini14, Post Graduate Institute of Medical Education and Research15, Carlos III Health Institute16, National and Kapodistrian University of Athens17, University of Rennes18, University Hospital Heidelberg19, University College London20, Goethe University Frankfurt21, Catholic University of the Sacred Heart22, McGill University23
TL;DR: Treatment duration for aspergillosis is strongly recommended based on clinical improvement, degree of immunosuppression and response on imaging, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended.
TL;DR: In this article, the authors present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves.
Abstract: We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg2 requires at least three detectors of sensitivity within a factor of ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.
TL;DR: BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain, with a key role for IL-1β as a mediator of trained immunity responses.
VU University Medical Center1, Hannover Medical School2, University of Birmingham3, University of Rome Tor Vergata4, King's College London5, Cardiff University6, National Institutes of Health7, University of Texas MD Anderson Cancer Center8, Radboud University Nijmegen9, University of Oxford10, Fred Hutchinson Cancer Research Center11, University of Washington12, NewYork–Presbyterian Hospital13
TL;DR: The objective of this work was to identify key clinical and scientific issues in the measurement and application of MRD in AML, to achieve consensus on these issues, and to provide guidelines for the current and future use of MRd in clinical practice.
Goethe University Frankfurt1, University of Maryland, College Park2, University of Guelph3, Duke University4, Swedish University of Agricultural Sciences5, Radboud University Nijmegen6, Federal University of Mato Grosso do Sul7, University of Alberta8, Royal Veterinary College9, Wildlife Conservation Society10, Mississippi State University11, Sao Paulo State University12, Michigan Department of Natural Resources13, University of California, Davis14, Aarhus University15, Max Planck Society16, University of Potsdam17, Middle Tennessee State University18, Mammal Research Institute19, Edmund Mach Foundation20, Harvard University21, Smithsonian Conservation Biology Institute22, University of Évora23, University of Montpellier24, Parks Victoria25, Monash University26, Ohio State University27, Fiji National University28, University of Massachusetts Amherst29, United States Geological Survey30, Save the Elephants31, University of Oxford32, German Primate Center33, Technische Universität München34, Institute of Ecosystem Studies35, University of British Columbia36, University of Zurich37, University of Wyoming38, University of Washington39, University of Montana40, University of Freiburg41, Bavarian Forest National Park42, University of Toulouse43, University of Veterinary Medicine Vienna44, University College Cork45, North Carolina State University46, North Carolina Museum of Natural Sciences47, Karatina University48, University of Lethbridge49, Lamont–Doherty Earth Observatory50, University of Valencia51, Stony Brook University52, International Union for Conservation of Nature and Natural Resources53, University of Alicante54, Empresa Brasileira de Pesquisa Agropecuária55, University of Glasgow56, New York University57, University of Oslo58, Hebrew University of Jerusalem59, Norwegian University of Science and Technology60, Field Museum of Natural History61, University of Grenoble62, University of Bayreuth63, University of New South Wales64, Pennsylvania Game Commission65, Princeton University66, University of Konstanz67, University of Haifa68, Polish Academy of Sciences69, Instituto Superior de Agronomia70, University of Lisbon71, University of Porto72, University of California, Santa Cruz73, University of Pretoria74, Colorado State University75
TL;DR: Using a unique GPS-tracking database of 803 individuals across 57 species, it is found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in area with a low human footprint.
Abstract: Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.
University of Cambridge1, University of Barcelona2, INAF3, University of Edinburgh4, Instituto Politécnico Nacional5, Rutherford Appleton Laboratory6, University of Leicester7, Leiden University8, Centre national de la recherche scientifique9, University of Geneva10, Radboud University Nijmegen11, University of Warsaw12
TL;DR: In this paper, the authors describe the photometric content of the second data release of the Gaia project (Gaia DR2) and its validation along with the quality of the data.
Abstract: Aims. We describe the photometric content of the second data release of the Gaia project (Gaia DR2) and its validation along with the quality of the data.Methods. The validation was mainly carried out using an internal analysis of the photometry. External comparisons were also made, but were limited by the precision and systematics that may be present in the external catalogues used.Results. In addition to the photometric quality assessment, we present the best estimates of the three photometric passbands. Various colour-colour transformations are also derived to enable the users to convert between the Gaia and commonly used passbands.Conclusions. The internal analysis of the data shows that the photometric calibrations can reach a precision as low as 2 mmag on individual CCD measurements. Other tests show that systematic effects are present in the data at the 10 mmag level.
Catholic University of the Sacred Heart1, Memorial Sloan Kettering Cancer Center2, International Agency for Research on Cancer3, University Health Network4, University of Lausanne5, Centre Hospitalier Universitaire de Grenoble6, Utrecht University7, Charité8, University of Texas MD Anderson Cancer Center9, Technische Universität München10, Belfast Health and Social Care Trust11, University of Zurich12, University of Nottingham13, Beatson West of Scotland Cancer Centre14, Tohoku University15, University of Verona16, Institut Gustave Roussy17, University of Bologna18, Radboud University Nijmegen19
TL;DR: This work believes this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.
TL;DR: Genes for colibactin and Bacteroides fragilis toxin, encoding secreted oncotoxins, were highly enriched in FAP patients’ colonic mucosa compared to healthy individuals, suggesting an unexpected link between early neoplasia of the colon and tumorigenic bacteria.
Abstract: Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life We identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis Genes for colibactin ( clbB ) and Bacteroides fragilis toxin ( bft ), encoding secreted oncotoxins, were highly enriched in FAP patients’ colonic mucosa compared to healthy individuals Tumor-prone mice cocolonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria
University of Massachusetts Medical School1, University Hospital Bonn2, University of Bonn3, Ludwig Maximilian University of Munich4, Broad Institute5, Radboud University Nijmegen6, University Medical Center Groningen7, Texas A&M University8, Harvard University9, Norwegian University of Science and Technology10, German Center for Neurodegenerative Diseases11
TL;DR: NLRP3 mediates trained immunity following WD and could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases.
TL;DR: The world is facing a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches, and additional factors, including increasing longevity, declining smoking rates, and increasing industrialization could raise the burden to over 17 million.
Abstract: Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.
TL;DR: The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice, suggesting modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity.
TL;DR: In this paper, the authors describe the processing of the Gaia DR2 data, and describe the criteria used to select the sample published in Gaia DR 2, and explore the data set to assess its quality.
Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
TL;DR: In this paper, the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way is demonstrated. But the accuracy of the errors, statistical and systematic, are relatively well understood.
Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.
University of Southern California1, Oslo University Hospital2, University of Oslo3, University of Pittsburgh4, Oxford Health NHS Foundation Trust5, University of Cape Town6, University of Texas Health Science Center at Houston7, Heidelberg University8, Neuroscience Research Australia9, Karolinska Institutet10, King's College London11, City University London12, University of Münster13, Icahn School of Medicine at Mount Sinai14, University of Barcelona15, Brown University16, French Institute of Health and Medical Research17, University of Pennsylvania18, Utrecht University19, University of Göttingen20, University of Amsterdam21, Hartford Hospital22, Yale University23, National University of Ireland, Galway24, University of São Paulo25, University of Edinburgh26, University of California, Los Angeles27, West Los Angeles College28, University of California, Irvine29, Medical College of Wisconsin30, McGovern Institute for Brain Research31, Radboud University Nijmegen32, Northumberland, Tyne and Wear NHS Foundation Trust33, National Institutes of Health34, University of California, San Diego35, Dresden University of Technology36, University of Adelaide37, Semel Institute for Neuroscience and Human Behavior38, Pasteur Institute39, University of Birmingham40, VU University Medical Center41, University of Cincinnati Academic Health Center42, University of New South Wales43, Poznan University of Medical Sciences44, Dalhousie University45, Karolinska University Hospital46, University of Gothenburg47, University of Exeter48, Janssen Pharmaceutica49, Cardiff University50
TL;DR: The largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of bipolar disorder patients is performed, revealing previously undetected associations and providing an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Abstract: Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
TL;DR: Recent advances in the understanding of the neural sources and targets of expectations in perception are reviewed and Bayesian theories of perception that prescribe how an agent should integrate prior knowledge and sensory information are discussed.
TL;DR: The Parkinson disease community should follow the efforts of the HIV community as detailed in David France’s book How to Survive a Plague, allowing millions of individuals around the world to live long, healthy lives.
Abstract: Pandemics are usually equated with infectious diseases such as Zika, influenza, and HIV. However, an imminent noninfectious pandemic, Parkinson disease (PD), requires immediate action. Neurological disorders are now the leading cause of disability in the world.1 Among these neurological disorders, the fastest growing is PD, whose growth is surpassing that of Alzheimer disease.1 From 1990 to 2015, the prevalence of, and thus disability and deaths owing to, PD more than doubled.1 The Global Burden of Disease Study estimates that 6.2 million individuals currently have PD. Because the incidence of PD increases sharply with age and because the world’s population is aging, the number of individuals affected is poised for exponential growth (Figure). Conservatively applying worldwide prevalence data from a 2014 meta-analysis2 to projections of the world’s future population,3 the number of people with PD will double from 6.9 million in 2015 to 14.2 million in 2040. Applying this same growth rate to the lower estimate by the Global Burden of Disease study (6.2 million in 2015) projects to a staggering 12.9 million affected by 2040. All these estimates likely understate the true prevalence of PD. The future burden will probably be higher owing to underreporting (record-based studies miss many who have not been diagnosed), declining smoking rates (smoking is associated with a 50% decreased risk of PD), and increasing longevity. Regardless of the exact numbers, if PD were an infectious condition, it would rightly be called a pandemic.4 To address this pandemic, the PD community should follow the efforts of the HIV community as detailed in David France’s book How to Survive a Plague.5 In just 15 years, the affected community took what was initially an unknown and rapidly fatal illness and transformed it into one that was highly treatable, allowing millions of individuals around the world to live long, healthy lives. France outlines at least 4 efforts that should be applied to PD.
Georgia Institute of Technology1, Leipzig University2, Johns Hopkins University3, University of Cambridge4, University of Tartu5, Ontario Institute for Cancer Research6, University of Washington7, VU University Amsterdam8, University of Chicago9, Greifswald University Hospital10, University of Bristol11, Erasmus University Rotterdam12, University of Exeter13, University of Lausanne14, University of Geneva15, Swiss Institute of Bioinformatics16, University of Helsinki17, Weizmann Institute of Science18, Agency for Science, Technology and Research19, University of Queensland20, Leiden University Medical Center21, University of Liège22, University of Oxford23, University of Tampere24, Stanford University25, Turku University Hospital26, Maastricht University Medical Centre27, Karolinska Institutet28, Radboud University Nijmegen29, Utrecht University30, European Bioinformatics Institute31
TL;DR: It is observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting the ability to use cis- eZTLs to pinpoint causal genes within susceptibility loci.
Abstract: While many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear. To identify these effects, we performed cis- and trans-expression quantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium. We observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to use cis-eQTLs to pinpoint causal genes within susceptibility loci. In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology. We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.
Richard A. Klein1, Michelangelo Vianello2, Fred Hasselman3, Byron G. Adams4 +187 more•Institutions (118)
TL;DR: This paper conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings, and found that very little heterogeneity was attributable to the order in which the tasks were performed or whether the task were administered in lab versus online.
Abstract: We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely high-powered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.
TL;DR: A comprehensive overview of the clinical characteristics of RP specific to genetically defined patient subsets is provided, including a unique atlas with color fundus photographs of most RP subtypes, and the relevant considerations with respect to differential diagnoses are discussed.
TL;DR: Evidence is emerging regarding gene-environment interactions, particularly for tobacco and occupational exposures, and standardisation of reporting may help improve epidemiologic evaluation of risk.