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Sökning: WFRF:(McGuire E)

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2.
  • 2017
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Tidskriftsartikel (refereegranskat)
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3.
  • Adrian-Martinez, S., et al. (författare)
  • A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
  • 2013
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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4.
  • Aasi, J., et al. (författare)
  • The characterization of Virgo data and its impact on gravitational-wave searches
  • 2012
  • Ingår i: Classical and Quantum Gravity. - : IOP Publishing. - 1361-6382 .- 0264-9381. ; 29:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Between 2007 and 2010 Virgo collected data in coincidence with the LIGO and GEO gravitational-wave (GW) detectors. These data have been searched for GWs emitted by cataclysmic phenomena in the universe, by non-axisymmetric rotating neutron stars or from a stochastic background in the frequency band of the detectors. The sensitivity of GW searches is limited by noise produced by the detector or its environment. It is therefore crucial to characterize the various noise sources in a GW detector. This paper reviews the Virgo detector noise sources, noise propagation, and conversion mechanisms which were identified in the three first Virgo observing runs. In many cases, these investigations allowed us to mitigate noise sources in the detector, or to selectively flag noise events and discard them from the data. We present examples from the joint LIGO-GEO-Virgo GW searches to show how well noise transients and narrow spectral lines have been identified and excluded from the Virgo data. We also discuss how detector characterization can improve the astrophysical reach of GW searches.
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5.
  • Abadie, J., et al. (författare)
  • All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration less than or similar to 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc(3) for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range similar to 5 x 10(-22) Hz(-1/2) to similar to 1 x 10(-20) Hz(-1/2). The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.
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6.
  • Abadie, J., et al. (författare)
  • Search for Gravitational Waves Associated with Gamma-Ray Bursts during LIGO Science Run 6 and Virgo Science Runs 2 and 3
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X. ; 760:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a search for gravitational waves associated with 154 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments in 2009-2010, during the sixth LIGO science run and the second and third Virgo science runs. We perform two distinct searches: a modeled search for coalescences of either two neutron stars or a neutron star and black hole, and a search for generic, unmodeled gravitational-wave bursts. We find no evidence for gravitational-wave counterparts, either with any individual GRB in this sample or with the population as a whole. For all GRBs we place lower bounds on the distance to the progenitor, under the optimistic assumption of a gravitational-wave emission energy of 10(-2) M-circle dot c(2) at 150 Hz, with a median limit of 17 Mpc. For short-hard GRBs we place exclusion distances on binary neutron star and neutron-star-black-hole progenitors, using astrophysically motivated priors on the source parameters, with median values of 16 Mpc and 28 Mpc, respectively. These distance limits, while significantly larger than for a search that is not aided by GRB satellite observations, are not large enough to expect a coincidence with a GRB. However, projecting these exclusions to the sensitivities of Advanced LIGO and Virgo, which should begin operation in 2015, we find that the detection of gravitational waves associated with GRBs will become quite possible.
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7.
  • Aasi, J., et al. (författare)
  • Einstein@Home all-sky search for periodic gravitational waves in LIGO S5 data
  • 2013
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:4
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents results of an all-sky search for periodic gravitational waves in the frequency range [50, 1190] Hz and with frequency derivative range of similar to[-20, 1.1] x 10(-10) Hz s(-1) for the fifth LIGO science run (S5). The search uses a noncoherent Hough-transform method to combine the information from coherent searches on time scales of about one day. Because these searches are very computationally intensive, they have been carried out with the Einstein@Home volunteer distributed computing project. Postprocessing identifies eight candidate signals; deeper follow-up studies rule them out. Hence, since no gravitational wave signals have been found, we report upper limits on the intrinsic gravitational wave strain amplitude h(0). For example, in the 0.5 Hz-wide band at 152.5 Hz, we can exclude the presence of signals with h(0) greater than 7.6 x 10(-25) at a 90% confidence level. This search is about a factor 3 more sensitive than the previous Einstein@Home search of early S5 LIGO data.
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8.
  • Aasi, J., et al. (författare)
  • Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network
  • 2013
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 88:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.
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9.
  • Aasi, J., et al. (författare)
  • Search for gravitational waves from binary black hole inspiral, merger, and ringdown in LIGO-Virgo data from 2009-2010
  • 2013
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a search for gravitational waves from the inspiral, merger and ringdown of binary black holes (BBH) with total mass between 25 and 100 solar masses, in data taken at the LIGO and Virgo observatories between July 7, 2009 and October 20, 2010. The maximum sensitive distance of the detectors over this period for a (20, 20)M-circle dot coalescence was 300 Mpc. No gravitational wave signals were found. We thus report upper limits on the astrophysical coalescence rates of BBH as a function of the component masses for nonspinning components, and also evaluate the dependence of the search sensitivity on component spins aligned with the orbital angular momentum. We find an upper limit at 90% confidence on the coalescence rate of BBH with nonspinning components of mass between 19 and 28M(circle dot) of 3:3 x 10(-7) mergers Mpc(-3) yr(-1).
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10.
  • Abadie, J., et al. (författare)
  • First low-latency LIGO plus Virgo search for binary inspirals and their electromagnetic counterparts
  • 2012
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The detection and measurement of gravitational-waves from coalescing neutron-star binary systems is an important science goal for ground-based gravitational-wave detectors. In addition to emitting gravitational-waves at frequencies that span the most sensitive bands of the LIGO and Virgo detectors, these sources are also amongst the most likely to produce an electromagnetic counterpart to the gravitational-wave emission. A joint detection of the gravitational-wave and electromagnetic signals would provide a powerful new probe for astronomy. Methods. During the period between September 19 and October 20, 2010, the first low-latency search for gravitational-waves from binary inspirals in LIGO and Virgo data was conducted. The resulting triggers were sent to electromagnetic observatories for followup. We describe the generation and processing of the low-latency gravitational-wave triggers. The results of the electromagnetic image analysis will be described elsewhere. Results. Over the course of the science run, three gravitational-wave triggers passed all of the low-latency selection cuts. Of these, one was followed up by several of our observational partners. Analysis of the gravitational-wave data leads to an estimated false alarm rate of once every 6.4 days, falling far short of the requirement for a detection based solely on gravitational-wave data.
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11.
  • Abadie, J., et al. (författare)
  • Search for gravitational waves from intermediate mass binary black holes
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a weakly modeled burst search for gravitational waves from mergers of nonspinning intermediate mass black holes in the total mass range 100-450 M-circle dot and with the component mass ratios between 1: and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the intermediate mass black holes mergers as a function of the component masses. In the most efficiently detected bin centered on 88 + 88 M-circle dot, for nonspinning sources, the rate density upper limit is 0.13 per Mpc(3) per Myr at the 90% confidence level.
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12.
  • Abadie, J., et al. (författare)
  • Upper limits on a stochastic gravitational-wave background using LIGO and Virgo interferometers at 600-1000 Hz
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A stochastic background of gravitational waves is expected to arise from a superposition of many incoherent sources of gravitational waves, of either cosmological or astrophysical origin. This background is a target for the current generation of ground-based detectors. In this article we present the first joint search for a stochastic background using data from the LIGO and Virgo interferometers. In a frequency band of 600-1000 Hz, we obtained a 95% upper limit on the amplitude of Omega(GW)(f) = Omega(3)(f/900 Hz)(3), of Omega(3) < 0.32, assuming a value of the Hubble parameter of h(100) = 0.71. These new limits are a factor of seven better than the previous best in this frequency band.
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13.
  • Evans, P. A., et al. (författare)
  • Swift Follow-up Observations of Candidate Gravitational-wave Transient Events
  • 2012
  • Ingår i: The Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 203:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors (within less than 10 minutes) and their candidate sky locations were observed by the Swift observatory (within 12 hr). Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge." With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime, multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.
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14.
  • Abadie, J., et al. (författare)
  • Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts
  • 2012
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec. 17, 2009 to Jan. 8, 2010 and Sep. 2 to Oct. 20, 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with similar to 50% or better probability with a few pointings of wide-field telescopes.
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  • Abadie, J., et al. (författare)
  • Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:8
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.
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17.
  • Abadie, J., et al. (författare)
  • All-sky search for periodic gravitational waves in the full S5 LIGO data
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on an all-sky search for periodic gravitational waves in the frequency band 50-800 Hz and with the frequency time derivative in the range of 0 through -6 x 10(-9) Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. After recent improvements in the search program that yielded a 10x increase in computational efficiency, we have searched in two years of data collected during LIGO's fifth science run and have obtained the most sensitive all-sky upper limits on gravitational-wave strain to date. Near 150 Hz our upper limit on worst-case linearly polarized strain amplitude h(0) is 1 x 10(-24), while at the high end of our frequency range we achieve a worst-case upper limit of 3.8 x 10(-24) for all polarizations and sky locations. These results constitute a factor of 2 improvement upon previously published data. A new detection pipeline utilizing a loosely coherent algorithm was able to follow up weaker outliers, increasing the volume of space where signals can be detected by a factor of 10, but has not revealed any gravitational-wave signals. The pipeline has been tested for robustness with respect to deviations from the model of an isolated neutron star, such as caused by a low-mass or long-period binary companion.
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18.
  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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22.
  • Botvinik-Nezer, Rotem, et al. (författare)
  • Variability in the analysis of a single neuroimaging dataset by many teams
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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23.
  • Ederle, Joerg, et al. (författare)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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25.
  • Kobel, M., et al. (författare)
  • p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
  • 2023
  • Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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28.
  • Chown, Ryan, et al. (författare)
  • PDRs4All: IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 µm. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. These high-quality data allow for an unprecedentedly detailed view of AIBs. Aims. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR (i.e. the three H2 dissociation fronts), the atomic PDR, and the H II region. Methods. We used JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extracted five template spectra to represent the morphology and environment of the Orion Bar PDR. We investigated and characterised the AIBs in these template spectra. We describe the variations among them here. Results. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. The Orion Bar spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 µm with well-defined profiles. In addition, the spectra display a wealth of weaker features and sub-components. The widths of many AIBs show clear and systematic variations, being narrowest in the atomic PDR template, but showing a clear broadening in the H II region template while the broadest bands are found in the three dissociation front templates. In addition, the relative strengths of AIB (sub-)components vary among the template spectra as well. All AIB profiles are characteristic of class A sources as designated by Peeters (2022, A&A, 390, 1089), except for the 11.2 µm AIB profile deep in the molecular zone, which belongs to class B11.2. Furthermore, the observations show that the sub-components that contribute to the 5.75, 7.7, and 11.2 µm AIBs become much weaker in the PDR surface layers. We attribute this to the presence of small, more labile carriers in the deeper PDR layers that are photolysed away in the harsh radiation field near the surface. The 3.3/11.2 AIB intensity ratio decreases by about 40% between the dissociation fronts and the H II region, indicating a shift in the polycyclic aromatic hydrocarbon (PAH) size distribution to larger PAHs in the PDR surface layers, also likely due to the effects of photochemistry. The observed broadening of the bands in the molecular PDR is consistent with an enhanced importance of smaller PAHs since smaller PAHs attain a higher internal excitation energy at a fixed photon energy. Conclusions. Spectral-imaging observations of the Orion Bar using JWST yield key insights into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 µm AIB emission from class B11.2 in the molecular PDR to class A11.2 in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a “weeding out” of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called ‘grandPAHs’.
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29.
  • Habart, Emilie, et al. (författare)
  • PDRs4All II. JWST’s NIR and MIR imaging view of the Orion Nebula
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The James Webb Space Telescope (JWST) has captured the most detailed and sharpest infrared (IR) images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). Aims. We investigate the fundamental interaction of far-ultraviolet (FUV) photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Methods. We utilized NIRCam and MIRI to obtain sub-arcsecond images over ∼150′′ and 42′′ in key gas phase lines (e.g., Pa α, Br α, [FeII] 1.64 µm, H2 1–0 S(1) 2.12 µm, 0–0 S(9) 4.69 µm), aromatic and aliphatic infrared bands (aromatic infrared bands at 3.3–3.4 µm, 7.7, and 11.3 µm), dust emission, and scattered light. Their emission are powerful tracers of the IF and DF, FUV radiation field and density distribution. Using NIRSpec observations the fractional contributions of lines, AIBs, and continuum emission to our NIRCam images were estimated. A very good agreement is found for the distribution and intensity of lines and AIBs between the NIRCam and NIRSpec observations. Results. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of ∼0.1–1′′ (∼0.0002–0.002 pc or ∼40–400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. The spatial distribution of the AIBs reveals that the PDR edge is steep and is followed by an extensive warm atomic layer up to the DF with multiple ridges. A complex, structured, and folded H0/H2 DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar as our observations show that a 3D “terraced” geometry is required to explain the JWST observations. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate. Conclusions. This study offers an unprecedented dataset to benchmark and transform PDR physico-chemical and dynamical models for the JWST era. A fundamental step forward in our understanding of the interaction of FUV photons with molecular clouds and the role of FUV irradiation along the star formation sequence is provided.
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30.
  • Hollestelle, Antoinette, et al. (författare)
  • No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
  • 2016
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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31.
  • Natali, S. M., et al. (författare)
  • Large loss of CO2 in winter observed across the northern permafrost region
  • 2019
  • Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 9:11, s. 852-857
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent warming in the Arctic, which has been amplified during the winter(1-3), greatly enhances microbial decomposition of soil organic matter and subsequent release of carbon dioxide (CO2)(4). However, the amount of CO2 released in winter is not known and has not been well represented by ecosystem models or empirically based estimates(5,6). Here we synthesize regional in situ observations of CO2 flux from Arctic and boreal soils to assess current and future winter carbon losses from the northern permafrost domain. We estimate a contemporary loss of 1,662 TgC per year from the permafrost region during the winter season (October-April). This loss is greater than the average growing season carbon uptake for this region estimated from process models (-1,032 TgC per year). Extending model predictions to warmer conditions up to 2100 indicates that winter CO2 emissions will increase 17% under a moderate mitigation scenario-Representative Concentration Pathway 4.5-and 41% under business-as-usual emissions scenario-Representative Concentration Pathway 8.5. Our results provide a baseline for winter CO2 emissions from northern terrestrial regions and indicate that enhanced soil CO2 loss due to winter warming may offset growing season carbon uptake under future climatic conditions.
  •  
32.
  • Peeters, Els, et al. (författare)
  • PDRs4All: III. JWST's NIR spectroscopic view of the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. JWST has taken the sharpest and most sensitive infrared (IR) spectral imaging observations ever of the Orion Bar photodis-sociation region (PDR), which is part of the nearest massive star-forming region the Orion Nebula, and often considered to be the 'prototypical'strongly illuminated PDR. Aims. We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the H II region to the atomic PDR -crossing the ionisation front (IF) -, and the subsequent transition to the molecular PDR -crossing the dissociation front (DF). Given the prevalence of PDRs in the interstellar medium and their dominant contribution to IR radiation, understanding the response of the PDR gas to far-ultraviolet (FUV) photons and the associated physical and chemical processes is fundamental to our understanding of star and planet formation and for the interpretation of any unresolved PDR as seen by JWST. Methods. We used high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science programme. We constructed a 3″ × 25″ spatio-spectral mosaic covering 0.97-5.27 μm at a spectral resolution R of ~2700 and an angular resolution of 0.075″-0.173″. To study the properties of key regions captured in this mosaic, we extracted five template spectra in apertures centred on the three H2 dissociation fronts, the atomic PDR, and the H II region. This wealth of detailed spatial-spectral information was analysed in terms of variations in the physical conditions-incident UV field, density, and temperature -of the PDR gas. Results. The NIRSpec data reveal a forest of lines including, but not limited to, He I, H I, and C I recombination lines; ionic lines (e.g. Fe III and Fe II); O I and N I fluorescence lines; aromatic infrared bands (AIBs, including aromatic CH, aliphatic CH, and their CD counterparts); pure rotational and ro-vibrational lines from H2; and ro-vibrational lines from HD, CO, and CH+, with most of them having been detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. In addition, we observed numerous smaller-scale structures whose typical size decreases with distance from θ1 Ori C and IR lines from C I, if solely arising from radiative recombination and cascade, reveal very high gas temperatures (a few 1000 K) consistent with the hot irradiated surface of small-scale dense clumps inside the PDR. The morphology of the Bar, in particular that of the H2 lines, reveals multiple prominent filaments that exhibit different characteristics. This leaves the impression of a 'terraced'transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. We attribute the different characteristics of the H2 filaments to their varying depth into the PDR and, in some cases, not reaching the C+/C/CO transition. These observations thus reveal what local conditions are required to drive the physical and chemical processes needed to explain the different characteristics of the DFs and the photochemical evolution of the AIB carriers. Conclusions. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star and planet formation as well as galaxy evolution.
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33.
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34.
  • Abbott, Benjamin W., et al. (författare)
  • Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
  • 2016
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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35.
  • Bethlehem, RAI, et al. (författare)
  • Brain charts for the human lifespan
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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36.
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37.
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38.
  • Koven, C. D., et al. (författare)
  • A simplified, data-constrained approach to estimate the permafrost carbon-climate feedback
  • 2015
  • Ingår i: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 373:2054
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (gamma sensitivity) of -14 to -19 PgC degrees C-1 on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.
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39.
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40.
  • Lane, Avery A., et al. (författare)
  • Household composition and the infant fecal microbiome : The INSPIRE study
  • 2019
  • Ingår i: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 3:169, s. 526-539
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Establishment and development of the infant gastrointestinal microbiome (GIM) varies cross-culturally and is thought to be influenced by factors such as gestational age, birth mode, diet, and antibiotic exposure. However, there is little data as to how the composition of infants' households may play a role, particularly from a cross-cultural perspective. Here, we examined relationships between infant fecal microbiome (IFM) diversity/composition and infants' household size, number of siblings, and number of other household members. Materials and methods: We analyzed 377 fecal samples from healthy, breastfeeding infants across 11 sites in eight different countries (Ethiopia, The Gambia, Ghana, Kenya, Peru, Spain, Sweden, and the United States). Fecal microbial community structure was determined by amplifying, sequencing, and classifying (to the genus level) the V1–V3 region of the bacterial 16S rRNA gene. Surveys administered to infants' mothers identified household members and composition. Results: Our results indicated that household composition (represented by the number of cohabitating siblings and other household members) did not have a measurable impact on the bacterial diversity, evenness, or richness of the IFM. However, we observed that variation in household composition categories did correspond to differential relative abundances of specific taxa, namely: Lactobacillus, Clostridium, Enterobacter, and Klebsiella. Discussion: This study, to our knowledge, is the largest cross-cultural study to date examining the association between household composition and the IFM. Our results indicate that the social environment of infants (represented here by the proxy of household composition) may influence the bacterial composition of the infant GIM, although the mechanism is unknown. A higher number and diversity of cohabitants and potential caregivers may facilitate social transmission of beneficial bacteria to the infant gastrointestinal tract, by way of shared environment or through direct physical and social contact between the maternal–infant dyad and other household members. These findings contribute to the discussion concerning ways by which infants are influenced by their social environments and add further dimensionality to the ongoing exploration of social transmission of gut microbiota and the “old friends” hypothesis.
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41.
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42.
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43.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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44.
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45.
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46.
  • Lackey, Kimberly A., et al. (författare)
  • What's normal? Microbiomes in human milk and infant feces are related to each other but vary geographically : The inspire study
  • 2019
  • Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Microbial communities in human milk and those in feces from breastfed infants vary within and across populations. However, few researchers have conducted cross-cultural comparisons between populations, and little is known about whether certain “core” taxa occur normally within or between populations and whether variation in milk microbiome is related to variation in infant fecal microbiome. The purpose of this study was to describe microbiomes of milk produced by relatively healthy women living at diverse international sites and compare these to the fecal microbiomes of their relatively healthy infants. Methods: We analyzed milk (n = 394) and infant feces (n = 377) collected from mother/infant dyads living in 11 international sites (2 each in Ethiopia, The Gambia, and the US; 1 each in Ghana, Kenya, Peru, Spain, and Sweden). The V1-V3 region of the bacterial 16S rRNA gene was sequenced to characterize and compare microbial communities within and among cohorts. Results: Core genera in feces were Streptococcus, Escherichia/Shigella, and Veillonella, and in milk were Streptococcus and Staphylococcus, although substantial variability existed within and across cohorts. For instance, relative abundance of Lactobacillus was highest in feces from rural Ethiopia and The Gambia, and lowest in feces from Peru, Spain, Sweden, and the US; Rhizobium was relatively more abundant in milk produced by women in rural Ethiopia than all other cohorts. Bacterial diversity also varied among cohorts. For example, Shannon diversity was higher in feces from Kenya than Ghana and US-California, and higher in rural Ethiopian than Ghana, Peru, Spain, Sweden, and US-California. There were limited associations between individual genera in milk and feces, but community-level analyses suggest strong, positive associations between the complex communities in these sample types. Conclusions: Our data provide additional evidence of within- and among-population differences in milk and infant fecal bacterial community membership and diversity and support for a relationship between the bacterial communities in milk and those of the recipient infant's feces. Additional research is needed to understand environmental, behavioral, and genetic factors driving this variation and association, as well as its significance for acute and chronic maternal and infant health.
  •  
47.
  • McGuire, Michelle K., et al. (författare)
  • What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically
  • 2017
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 105:5, s. 1086-1100
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human milk is a complex fluid comprised of myriad substances, with one of the most abundant substances being a group of complex carbohydrates referred to as human milk oligosaccharides (HMOs). There has been some evidence that HMO profiles differ in populations, but few studies have rigorously explored this variability. Objectives: We tested the hypothesis that HMO profiles differ in diverse populations of healthy women. Next, we examined relations between HMO and maternal anthropometric and reproductive indexes and indirectly examined whether differences were likely related to genetic or environmental variations. Design: In this cross-sectional, observational study, milk was collected from a total of 410 healthy, breastfeeding women in 11 international cohorts and analyzed for HMOs by using high-performance liquid chromatography. Results: There was an effect of the cohort (P , 0.05) on concentrations of almost all HMOs. For instance, the mean 3-fucosyllactose concentration was .4 times higher in milk collected in Sweden than in milk collected in rural Gambia (mean ± SEM: 473 6 55 compared with 103 6 16 μmol/mL, respectively; P , 0.05), and disialyllacto-N-tetraose (DSLNT) concentrations ranged from 216 ± 14 μmol/mL (in Sweden) to 870 ± 68 μmol/mL (in rural Gambia) (P , 0.05). Maternal age, time postpartum, weight, and body mass index were all correlated with several HMOs, and multiple differences in HMOs [e.g., lacto-N-neotetrose and DSLNT] were shown between ethnically similar (and likely genetically similar) populations who were living in different locations, which suggests that the environment may play a role in regulating the synthesis of HMOs. Conclusions: The results of this study support our hypothesis that normal HMO concentrations and profiles vary geographically, even in healthy women. Targeted genomic analyses are required to determine whether these differences are due at least in part to genetic variation. A careful examination of sociocultural, behavioral, and environmental factors is needed to determine their roles in this regard. This study was registered at clinicaltrials.gov as NCT02670278.
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48.
  • Pace, Ryan M., et al. (författare)
  • Variation in human milk composition is related to differences in milk and infant fecal microbial communities
  • 2021
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities.
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49.
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50.
  • Ruiz-Pavon, Lorena, et al. (författare)
  • What's normal? Immune profiling of human milk from healthy women living in different geographical and socioeconomic settings
  • 2017
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8:JUN
  • Tidskriftsartikel (refereegranskat)abstract
    • Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1ß, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1ß), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFß2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFß2, IL7, IL8, Groa, and MIP1ß were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the "core" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.
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