Publications (109)432.3 Total impact

Article: Modified KnappHartung randomeffects metaanalysis recommended for applications in rare diseases
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ABSTRACT: BACKGROUND: Randomeffects metaanalysis is commonly performed by first deriving an estimate of the betweenstudy variation, the heterogeneity, and subsequently using this as the basis for combining results, i.e., for estimating the effect, the figure of primary interest. The heterogeneity estimate however is commonly associated with substantial uncertainty, especially in contexts where there are only few studies available, such as in small populations and rare diseases. METHODS: Confidence intervals and tests for the effect may be constructed via a simple normal approximation, or via a Studentt distribution, using the HartungKnappSidikJonkman (HKSJ) approach in order to account for the estimation uncertainty in the heterogeneity parameter. The modified KnappHartung method (mKH) applies an ad hoc correction and has been proposed to prevent counterintuitive effects and to yield more conservative inference. We performed a simulation study to investigate the behaviour of the standard HKSJ and modified mKH procedures in a range of circumstances, with a focus on the common case of metaanalysis based on only a few studies. RESULTS: The standard HKSJ procedure works well when the treatment effect estimates to be combined are of comparable precision, but nominal error levels are exceeded when standard errors vary considerably between studies (e.g. due to variations in study size). Application of the modification on the other hand yields more conservative results with error rates closer to the nominal level. Differences are most pronounced in the common case of few studies of varying size or precision. CONCLUSIONS: When applying the HKSJ method, the specifics of the adjustment are crucial. Use of the modified mKH procedure is recommended, especially when only a few studies contribute to the metaanalysis.  [Show abstract] [Hide abstract]
ABSTRACT: To our knowledge, no previous metaanalysis has attempted to compare the efficacy of pharmacological, psychological and combined treatments for the three main anxiety disorders (panic disorder, generalized anxiety disorder and social phobia). Prepost and treated versus control effect sizes (ES) were calculated for all evaluable randomizedcontrolled studies (n=234), involving 37 333 patients. Medications were associated with a significantly higher average prepost ES [Cohen's d=2.02 (1.902.15); 28 051 patients] than psychotherapies [1.22 (1.141.30); 6992 patients; P<0.0001]. ES were 2.25 for serotoninnoradrenaline reuptake inhibitors (n=23 study arms), 2.15 for benzodiazepines (n=42), 2.09 for selective serotonin reuptake inhibitors (n=62) and 1.83 for tricyclic antidepressants (n=15). ES for psychotherapies were mindfulness therapies, 1.56 (n=4); relaxation, 1.36 (n=17); individual cognitive behavioural/exposure therapy (CBT), 1.30 (n=93); group CBT, 1.22 (n=18); psychodynamic therapy 1.17 (n=5); therapies without facetoface contact (e.g. Internet therapies), 1.11 (n=34); eye movement desensitization reprocessing, 1.03 (n=3); and interpersonal therapy 0.78 (n=4). The ES was 2.12 (n=16) for CBT/drug combinations. Exercise had an ES of 1.23 (n=3). For control groups, ES were 1.29 for placebo pills (n=111), 0.83 for psychological placebos (n=16) and 0.20 for waitlists (n=50). In direct comparisons with control groups, all investigated drugs, except for citalopram, opipramol and moclobemide, were significantly more effective than placebo. Individual CBT was more effective than waiting list, psychological placebo and pill placebo. When looking at the average prepost ES, medications were more effective than psychotherapies. Prepost ES for psychotherapies did not differ from pill placebos; this finding cannot be explained by heterogeneity, publication bias or allegiance effects. However, the decision on whether to choose psychotherapy, medications or a combination of the two should be left to the patient as drugs may have side effects, interactions and contraindications.International clinical psychopharmacology 04/2015; 30(4). DOI:10.1097/YIC.0000000000000078 · 3.10 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: In 20092010, the Laser Interferometer Gravitationalwave Observa tory (LIGO) operated together with international partners Virgo and GEO600 as a network to search for gravitational waves of astrophysical origin. The sensitiv ity of these detectors was limited by a combination of noise sources inherent to the instrumental design and its environment, often localized in time or frequency, that couple into the gravitationalwave readout. Here we review the performance of the LIGO instruments during this epoch, the work done to characterize the de tectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of LIGO to a variety of astrophysical sources.Classical and Quantum Gravity 10/2014; 32(11). DOI:10.1088/02649381/32/11/115012 · 3.10 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Searches for a stochastic gravitationalwave background (SGWB) using terrestrial detectors typically involve crosscorrelating data from pairs of detectors. The sensitivity of such crosscorrelation analyses depends, among other things, on the separation between the two detectors: the smaller the separation, the better the sensitivity. Hence, a colocated detector pair is more sensitive to a gravitationalwave background than a noncolocated detector pair. However, colocated detectors are also expected to suffer from correlated noise from instrumental and environmental effects that could contaminate the measurement of the background. Hence, methods to identify and mitigate the effects of correlated noise are necessary to achieve the potential increase in sensitivity of colocated detectors. Here we report on the first SGWB analysis using the two LIGO Hanford detectors and address the complications arising from correlated environmental noise. We apply correlated noise identification and mitigation techniques to data taken by the two LIGO Hanford detectors, H1 and H2, during LIGO's fifth science run. At low frequencies, 40  460 Hz, we are unable to sufficiently mitigate the correlated noise to a level where we may confidently measure or bound the stochastic gravitationalwave signal. However, at high frequencies, 4601000 Hz, these techniques are sufficient to set a $95\%$ confidence level (C.L.) upper limit on the gravitationalwave energy density of \Omega(f)<7.7 x 10^{4} (f/ 900 Hz)^3, which improves on the previous upper limit by a factor of $\sim 180$. In doing so, we demonstrate techniques that will be useful for future searches using advanced detectors, where correlated noise (e.g., from global magnetic fields) may affect even widely separated detectors.Physical Review D 10/2014; 91(2). DOI:10.1103/PhysRevD.91.022003 · 4.86 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: The Advanced LIGO and Advanced Virgo gravitational wave (GW) detectors will begin operation in the coming years, with compact binary coalescence events a likely source for the first detections. The gravitational waveforms emitted directly encode information about the sources, including the masses and spins of the compact objects. Recovering the physical parameters of the sources from the GW observations is a key analysis task. This work describes the LALInference software library for Bayesian parameter estimation of compact binary coalescence (CBC) signals, which builds on several previous methods to provide a welltested toolkit which has already been used for several studies. We are able to show using three independent sampling algorithms that our implementation consistently converges on the same results, giving confidence in the parameter estimates thus obtained. We demonstrate this with a detailed comparison on three compact binary systems: a binary neutron star, a neutron starblack hole binary and a binary black hole, where we show a crosscomparison of results. These systems were analysed with nonspinning, aligned spin and generic spin configurations respectively, showing that consistent results can be obtained even with the full 15dimensional parameter space of the generic spin configurations. We also demonstrate statistically that the Bayesian credible intervals we recover correspond to frequentist confidence intervals under correct prior assumptions by analysing a set of 100 signals drawn from the prior. We discuss the computational cost of these algorithms, and describe the general and problemspecific sampling techniques we have used to improve the efficiency of sampling the CBC parameter space.Physical Review D 09/2014; 91(4). DOI:10.1103/PhysRevD.91.042003 · 4.86 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: We report on an allsky search for periodic gravitational waves in the frequency range 50–1000 Hz with the first derivative of frequency in the range −8.9 × 10−10 Hz s−1 to zero in two years of data collected during LIGO's fifth science run. Our results employ a Hough transform technique, introducing a χ2 test and analysis of coincidences between the signal levels in years 1 and 2 of observations that offers a significant improvement in the product of strain sensitivity with compute cycles per data sample compared to previously published searches. Since our search yields no surviving candidates, we present results taking the form of frequency dependent, 95% confidence upper limits on the strain amplitude h0. The most stringent upper limit from year 1 is 1.0 × 10−24 in the 158.00–158.25 Hz band. In year 2, the most stringent upper limit is 8.9 × 10−25 in the 146.50–146.75 Hz band. This improved detection pipeline, which is computationally efficient by at least two orders of magnitude better than our flagship Einstein@Home search, will be important for 'quicklook' searches in the Advanced LIGO and Virgo detector era.Classical and Quantum Gravity 04/2014; 31(8):085014. DOI:10.1088/02649381/31/8/085014 · 3.10 Impact Factor 
Dataset: 13119

Dataset: 84 local APF20 617

Dataset: 122
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ABSTRACT: During the LIGO and Virgo joint science runs in 20092010, gravitational wave (GW) data from three interferometer detectors were analyzed within minutes to select GW candidate events and infer their apparent sky positions. Target coordinates were transmitted to several telescopes for followup observations aimed at the detection of an associated optical transient. Images were obtained for eight such GW candidates. We present the methods used to analyze the image data as well as the transient search results. No optical transient was identified with a convincing association with any of these candidates, and none of the GW triggers showed strong evidence for being astrophysical in nature. We compare the sensitivities of these observations to several model light curves from possible sources of interest, and discuss prospects for future joint GWoptical observations of this type.The Astrophysical Journal Supplement Series 02/2014; 211(1):25. DOI:10.1088/00670049/211/1/7 · 14.14 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Background: Interleukin2 receptor antagonists (IL2RA) are frequently used as induction therapy in liver transplant recipients to decrease the risk of acute rejection while allowing the reduction of concomitant immunosuppression. The exact association with the use of IL2RA however is uncertain. Methods: We performed a systematic literature search for relevant studies. Random effects models were used to assess the incidence of acute rejection, steroidresistant rejection, graft loss, patient death, and adverse drug reaction, with or without IL2RA. Results: Six studies (2 randomized and 4 nonrandomized) met the elegibility criteria. Acute rejection at 6 months or later favored the use of IL2RA significantly (relative risk [RR] 0.38; 95% confidence interval [CI] 0.220.66, pvalue [p] = 0.0005). Although not statistically significant, IL2RA showed a substantial reduction of the risk of steroidresistant rejection (RR 0.32; CI 0.191.03, p = 0.0594). Graft loss and patient death showed a reductive tendency through the use of IL2RA. Conclusions: The use of IL2RA is safe and is associated with a statistically significantly lower incidence of acute rejection after transplantation and substantial reduction of steroidresistant rejection, graft loss and patient death.Pediatric Transplantation 02/2014; 18(8). DOI:10.1111/petr.12362 · 1.63 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: The problem of reconstructing the sky position of compact binary coalescences detected via gravitational waves is a central one for future observations with the groundbased network of gravitationalwave laser interferometers, such as Advanced LIGO and Advanced Virgo. Different techniques for sky localisation have been independently developed. They can be divided in two broad categories: fully coherent Bayesian techniques, which are highlatency and aimed at indepth studies of all the parameters of a source, including sky position, and "triangulationbased" techniques, which exploit the data products from the search stage of the analysis to provide an almost realtime approximation of the posterior probability density function of the sky location of a detection candidate. These techniques have previously been applied to data collected during the last science runs of gravitationalwave detectors operating in the socalled initial configuration. Here, we develop and analyse methods for assessing the selfconsistency of parameter estimation methods and carrying out fair comparisons between different algorithms, addressing issues of efficiency and optimality. These methods are general, and can be applied to parameter estimation problems other than sky localisation. We apply these methods to two existing sky localisation techniques representing the two abovementioned categories, using a set of simulated inspiralonly signals from compact binary systems with total mass $\le 20\,M_\odot$ and nonspinning components. We compare the relative advantages and costs of the two techniques and show that sky location uncertainties are on average a factor $\approx 20$ smaller for fully coherent techniques than for the specific variant of the "triangulationbased" technique used during the last science runs, at the expense of a factor $\approx 1000$ longer processing time.Physical Review D 12/2013; 89(8). DOI:10.1103/PhysRevD.89.084060 · 4.86 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: The analysis of count data is commonly done using Poisson models. Negative binomial models are a straightforward and readily motivated generalization for the case of overdispersed data, that is, when the observed variance is greater than expected under a Poissonian model. Rate and overdispersion parameters then need to be considered jointly, which in general is not trivial. Here, we are concerned with evidence synthesis in the case where the reporting of data is rather heterogeneous, that is, events are reported either in terms of mean event counts, the proportion of eventfree patients, or rate estimates and standard errors. Either figure carries some information about the relevant parameters, and it is the joint modeling that allows for coherent inference on the parameters of interest. The methods are motivated and illustrated by a systematic review in chronic obstructive pulmonary disease. © 2015 WILEYVCH Verlag GmbH & Co. KGaA, Weinheim.Biometrical Journal 12/2013; DOI:10.1002/bimj.201300288 · 1.24 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Cosmic string cusps produce powerful bursts of gravitational waves (GWs). These bursts provide the most promising observational signature of cosmic strings. In this letter we report stringent limits on cosmic string models obtained from the analysis of 625 days of observation with the LIGO and Virgo GW detectors. A significant fraction of the cosmic string parameter space is ruled out. This result complements and improves existing limits from searches for a stochastic background of GWs using cosmic microwave background and pulsar timing data. In particular, if the size of loops is given by gravitational backreaction, we place upper limits on the string tension $G\mu$ below $10^{8}$ in some regions of the cosmic string parameter space.Physical Review Letters 10/2013; DOI:10.1103/PhysRevLett.112.131101 · 7.51 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Long gammaray bursts (GRBs) have been linked to extreme corecollapse supernovae from massive stars. Gravitational waves (GW) offer a probe of the physics behind long GRBs. We investigate models of longlived (~101000s) GW emission associated with the accretion disk of a collapsed star or with its protoneutron star remnant. Using data from LIGO's fifth science run, and GRB triggers from the swift experiment, we perform a search for unmodeled longlived GW transients. Finding no evidence of GW emission, we place 90% confidence level upper limits on the GW fluence at Earth from long GRBs for three waveforms inspired by a model of GWs from accretion disk instabilities. These limits range from F<3.5 ergs cm^2 to $F<1200 ergs cm^2, depending on the GRB and on the model, allowing us to probe optimistic scenarios of GW production out to distances as far as ~33 Mpc. Advanced detectors are expected to achieve strain sensitivities 10x better than initial LIGO, potentially allowing us to probe the engines of the nearest long GRBs.Physical Review D 09/2013; 88:122004. DOI:10.1103/PhysRevD.88.122004 · 4.86 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: We present the results of a directed search for continuous gravitational waves from unknown, isolated neutron stars in the Galactic Center region, performed on two years of data from LIGO's fifth science run from two LIGO detectors. The search uses a semicoherent approach, analyzing coherently 630 segments, each spanning 11.5 hours, and then incoherently combining the results of the single segments. It covers gravitational wave frequencies in a range from 78 to 496 Hz and a frequencydependent range of first order spindown values down to 7.86 x 10^8 Hz/s at the highest frequency. No gravitational waves were detected. We place 90% confidence upper limits on the gravitational wave amplitude of sources at the Galactic Center. Placing 90% confidence upper limits on the gravitational wave amplitude of sources at the Galactic Center, we reach ~3.35x10^25 for frequencies near 150 Hz. These upper limits are the most constraining to date for a largeparameterspace search for continuous gravitational wave signals.Physical Review D 09/2013; DOI:10.1103/PhysRevD.88.102002 · 4.86 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitationalwave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spindown luminosities. We reach within a factor of five of the canonical spindown limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spindown limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most uptodate results from all pulsars searched for during the operations of the firstgeneration LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.The Astrophysical Journal 09/2013; 785(2):18. DOI:10.1088/0004637X/785/2/119 · 6.28 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Background: Recent systematic reviews of randomized controlled trials (RCTs) in relapsing multiple sclerosis (RMS) suggest a decrease in annualized relapse rates (ARRs) over calendar time as well as over the course of a study in placebo groups. Methods: We updated a recent systematic review of placebo controlled randomized trials in RMS. Data on expanded disability status scale (EDSS) and ARR were extracted. Results: A total of 62 RCTs including 19,783 patients was identified. The previously observed decreases in ARR in placebo groups between and within studies could be confirmed. In contrast, the mean EDSS scores did not decline over calendar time and neither could a decrease during the studies be observed. The treatment effects in terms of mean EDSS did not change significantly over the years with the average treatment effect being of the same order of magnitude as the annual progression observed in placebo groups. When focusing on comparisons between active treatments and placebo, both measures tended to agree in their direction of effect. Conclusion: This study allowed us to start to understand some of the conflicting data that have emerged about the role of relapses in disability by demonstrating the coexistence of natural history and treatment related effects.  [Show abstract] [Hide abstract]
ABSTRACT: Background: Recent systematic reviews of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS) highlighted a number of shortcomings of the annualized relapse rate (ARR) as trial outcome including decreasing placebo ARR over the past two decades and regression to the mean effects. However, the exact relationship of such effects to other commonly used measures of disease severity is unknown. Methods: We conducted a systematic review of RCTs in RMS. Data on expanded disability status scale (EDSS) and ARR were extracted. Results: A total of 64 RCTs including 20,115 patients was identified. Mean EDSS, the most commonly provided disability outcome, remained stable in placebo groups over the past 30 years while ARR decreased substantially. Furthermore, ARR suffers from regression to the mean effects which we did not observe in mean EDSS. However, treatment effects on both scales were correlated (Spearman's $\rho$=0.58, p<0.001). The association between mean EDSS values and disability progression is of the same order of magnitude as the association between ARR and disability progression. Conclusion: While the interpretability of mean EDSS values has its limitations, it remains being commonly quoted and it provides a useful measure of disability, especially allowing for better intertrial comparison than ARR. 
Article: Enhanced sensitivity of the LIGO gravitational wave detector by using squeezed states of light
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ABSTRACT: Nearly a century after Einstein first predicted the existence of gravitational waves, a global network of Earthbased gravitational wave observatories1, 2, 3, 4 is seeking to directly detect this faint radiation using precision laser interferometry. Photon shot noise, due to the quantum nature of light, imposes a fundamental limit on the attometrelevel sensitivity of the kilometrescale Michelson interferometers deployed for this task. Here, we inject squeezed states to improve the performance of one of the detectors of the Laser Interferometer GravitationalWave Observatory (LIGO) beyond the quantum noise limit, most notably in the frequency region down to 150 Hz, critically important for several astrophysical sources, with no deterioration of performance observed at any frequency. With the injection of squeezed states, this LIGO detector demonstrated the best broadband sensitivity to gravitational waves ever achieved, with important implications for observing the gravitationalwave Universe with unprecedented sensitivity.Nature Photonics 07/2013; 7(8):613. DOI:10.1038/nphoton.2013.177 · 29.96 Impact Factor
Publication Stats
2k  Citations  
432.30  Total Impact Points  
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Institutions

2014

Max Planck Institute for Gravitational Physics (AlbertEinsteinInstitute)
Potsdam, Brandenburg, Germany 
Universitair Medisch Centrum Groningen
Groningen, Groningen, Netherlands


2013–2014

Max Planck Institute of Physics
München, Bavaria, Germany 
Universitätsklinikum Freiburg
Freiburg an der Elbe, Lower Saxony, Germany


2008–2013

Leibniz Universität Hannover
Hanover, Lower Saxony, Germany 
Northwestern University
 Department of Physics and Astronomy
Evanston, Illinois, United States


2006–2013

University of Auckland
 Department of Statistics
Auckland, Auckland, New Zealand


2009

Princeton University
 Department of Physics
Princeton, New Jersey, United States 
MaxPlanckInstitut für Gravitationsphysik, Teilinstitut Hannover
Hanover, Lower Saxony, Germany
