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1.	2017 In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2 Journal article (peer-reviewed)
2.	Fenstermacher, M.E., et al. (author) DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy 2022 In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4 Journal article (peer-reviewed)abstract DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
3.	Bancroft, EK, et al. (author) Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study 2014 In: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 66:3, s. 489-499 Journal article (peer-reviewed)
4.	Scirica, BM, et al. (author) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus 2013 In: The New England journal of medicine. - 1533-4406. ; 369:14, s. 1317-1326 Journal article (peer-reviewed)
5.	O'Donnell-Luria, AH, et al. (author) Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy 2019 In: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 104:6, s. 1210-1222 Journal article (peer-reviewed)
6.	Ade, P. A. R., et al. (author) Planck intermediate results XL. The Sunyaev-Zeldovich signal from the Virgo cluster 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596 Journal article (peer-reviewed)abstract The Virgo cluster is the largest Sunyaev-Zeldovich (SZ) source in the sky, both in terms of angular size and total integrated flux. Planck's wide angular scale and frequency coverage, together with its high sensitivity, enable a detailed study of this big object through the SZ effect. Virgo is well resolved by Planck, showing an elongated structure that correlates well with the morphology observed from X-rays, but extends beyond the observed X-ray signal. We find good agreement between the SZ signal (or Compton parameter, y(c)) observed by Planck and the expected signal inferred from X-ray observations and simple analytical models. Owing to its proximity to us, the gas beyond the virial radius in Virgo can be studied with unprecedented sensitivity by integrating the SZ signal over tens of square degrees. We study the signal in the outskirts of Virgo and compare it with analytical models and a constrained simulation of the environment of Virgo. Planck data suggest that significant amounts of low-density plasma surround Virgo, out to twice the virial radius. We find the SZ signal in the outskirts of Virgo to be consistent with a simple model that extrapolates the inferred pressure at lower radii, while assuming that the temperature stays in the keV range beyond the virial radius. The observed signal is also consistent with simulations and points to a shallow pressure profile in the outskirts of the cluster. This reservoir of gas at large radii can be linked with the hottest phase of the elusive warm/hot intergalactic medium. Taking the lack of symmetry of Virgo into account, we find that a prolate model is favoured by the combination of SZ and X-ray data, in agreement with predictions. Finally, based on the combination of the same SZ and X-ray data, we constrain the total amount of gas in Virgo. Under the hypothesis that the abundance of baryons in Virgo is representative of the cosmic average, we also infer a distance for Virgo of approximately 18 Mpc, in good agreement with previous estimates.
7.	Ade, P. A. R., et al. (author) Planck intermediate results XXXIX. The Planck list of high-redshift source candidates 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596 Journal article (peer-reviewed)abstract The Planck mission, thanks to its large frequency range and all-sky coverage, has a unique potential for systematically detecting the brightest, and rarest, submillimetre sources on the sky, including distant objects in the high-redshift Universe traced by their dust emission. A novel method, based on a component-separation procedure using a combination of Planck and IRAS data, has been validated and characterized on numerous simulations, and applied to select the most luminous cold submillimetre sources with spectral energy distributions peaking between 353 and 857 GHz at 5' resolution. A total of 2151 Planck high-z source candidates (the PHZ) have been detected in the cleanest 26% of the sky, with flux density at 545 GHz above 500 mJy. Embedded in the cosmic infrared background close to the confusion limit, these high-z candidates exhibit colder colours than their surroundings, consistent with redshifts z > 2, assuming a dust temperature of T-xgal = 35K and a spectral index of beta(xgal) = 1.5. Exhibiting extremely high luminosities, larger than 10(14) L-circle dot, the PHZ objects may be made of multiple galaxies or clumps at high redshift, as suggested by a first statistical analysis based on a comparison with number count models. Furthermore, first follow-up observations obtained from optical to submillimetre wavelengths, which can be found in companion papers, have confirmed that this list consists of two distinct populations. A small fraction (around 3%) of the sources have been identified as strongly gravitationally lensed star-forming galaxies at redshift 2 to 4, while the vast majority of the PHZ sources appear as overdensities of dusty star-forming galaxies, having colours consistent with being at z > 2, and may be considered as proto-cluster candidates. The PHZ provides an original sample, which is complementary to the Planck Sunyaev-Zeldovich Catalogue (PSZ2); by extending the population of virialized massive galaxy clusters detected below z < 1.5 through their SZ signal to a population of sources at z > 1.5, the PHZ may contain the progenitors of today's clusters. Hence the Planck list of high-redshift source candidates opens a new window on the study of the early stages of structure formation, particularly understanding the intensively star-forming phase at high-z.
8.	Adam, R., et al. (author) Planck 2015 results IX. Diffuse component separation : CMB maps 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract We present foreground-reduced cosmic microwave background (CMB) maps derived from the full Planck data set in both temperature and polarization. Compared to the corresponding Planck 2013 temperature sky maps, the total data volume is larger by a factor of 3.2 for frequencies between 30 and 70 GHz, and by 1.9 for frequencies between 100 and 857 GHz. In addition, systematic errors in the forms of temperature-topolarization leakage, analogue-to-digital conversion uncertainties, and very long time constant errors have been dramatically reduced, to the extent that the cosmological polarization signal may now be robustly recovered on angular scales l greater than or similar to 40. On the very largest scales, instrumental systematic residuals are still non-negligible compared to the expected cosmological signal, and modes with l < 20 are accordingly suppressed in the current polarization maps by high-pass filtering. As in 2013, four different CMB component separation algorithms are applied to these observations, providing a measure of stability with respect to algorithmic and modelling choices. The resulting polarization maps have rms instrumental noise ranging between 0.21 and 0.27 mu K averaged over 55' pixels, and between 4.5 and 6.1 mu K averaged over 3.'4 pixels. The cosmological parameters derived from the analysis of temperature power spectra are in agreement at the 1 sigma level with the Planck 2015 likelihood. Unresolved mismatches between the noise properties of the data and simulations prevent a satisfactory description of the higher-order statistical properties of the polarization maps. Thus, the primary applications of these polarization maps are those that do not require massive simulations for accurate estimation of uncertainties, for instance estimation of cross-spectra and cross-correlations, or stacking analyses. However, the amplitude of primordial non-Gaussianity is consistent with zero within 2 sigma for all local, equilateral, and orthogonal configurations of the bispectrum, including for polarization E-modes. Moreover, excellent agreement is found regarding the lensing B-mode power spectrum, both internally among the various component separation codes and with the best-fit Planck 2015 Lambda cold dark matter model.
9.	Adam, R., et al. (author) Planck intermediate results XLII. Large-scale Galactic magnetic fields 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596 Journal article (peer-reviewed)abstract Recent models for the large-scale Galactic magnetic fields in the literature have been largely constrained by synchrotron emission and Faraday rotation measures. We use three different but representative models to compare their predicted polarized synchrotron and dust emission with that measured by the Planck satellite. We first update these models to match the Planck synchrotron products using a common model for the cosmic-ray leptons. We discuss the impact on this analysis of the ongoing problems of component separation in the Planck microwave bands and of the uncertain cosmic-ray spectrum. In particular, the inferred degree of ordering in the magnetic fields is sensitive to these systematic uncertainties, and we further show the importance of considering the expected variations in the observables in addition to their mean morphology. We then compare the resulting simulated emission to the observed dust polarization and find that the dust predictions do not match the morphology in the Planck data but underpredict the dust polarization away from the plane. We modify one of the models to roughly match both observables at high latitudes by increasing the field ordering in the thin disc near the observer. Though this specific analysis is dependent on the component separation issues, we present the improved model as a proof of concept for how these studies can be advanced in future using complementary information from ongoing and planned observational projects.
10.	Adam, R., et al. (author) Planck intermediate results XLIII. Spectral energy distribution of dust in clusters of galaxies 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596 Journal article (peer-reviewed)abstract Although infrared (IR) overall dust emission from clusters of galaxies has been statistically detected using data from the Infrared Astronomical Satellite (IRAS), it has not been possible to sample the spectral energy distribution (SED) of this emission over its peak, and thus to break the degeneracy between dust temperature and mass. By complementing the IRAS spectral coverage with Planck satellite data from 100 to 857 GHz, we provide new constraints on the IR spectrum of thermal dust emission in clusters of galaxies. We achieve this by using a stacking approach for a sample of several hundred objects from the Planck cluster sample. This procedure averages out fluctuations from the IR sky, allowing us to reach a significant detection of the faint cluster contribution. We also use the large frequency range probed by Planck, together with component-separation techniques, to remove the contamination from both cosmic microwave background anisotropies and the thermal Sunyaev-Zeldovich effect (tSZ) signal, which dominate at v <= 353 GHz. By excluding dominant spurious signals or systematic effects, averaged detections are reported at frequencies 353 GHz <= v <= 5000 GHz. We confirm the presence of dust in clusters of galaxies at low and intermediate redshifts, yielding an SED with a shape similar to that of the Milky Way. Planck's resolution does not allow us to investigate the detailed spatial distribution of this emission (e.g. whether it comes from intergalactic dust or simply the dust content of the cluster galaxies), but the radial distribution of the emission appears to follow that of the stacked SZ signal, and thus the extent of the clusters. The recovered SED allows us to constrain the dust mass responsible for the signal and its temperature.
11.	Ade, P. A. R., et al. (author) Planck 2015 results XIX. Constraints on primordial magnetic fields 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract We compute and investigate four types of imprint of a stochastic background of primordial magnetic fields (PMFs) on the cosmic microwave background (CMB) anisotropies: the impact of PMFs on the CMB temperature and polarization spectra, which is related to their contribution to cosmological perturbations; the effect on CMB polarization induced by Faraday rotation; the impact of PMFs on the ionization history; magnetically-induced non-Gaussianities and related non-zero bispectra; and the magnetically-induced breaking of statistical isotropy. We present constraints on the amplitude of PMFs that are derived from different Planck data products, depending on the specific effect that is being analysed. Overall, Planck data constrain the amplitude of PMFs to less than a few nanoGauss, with different bounds that depend on the considered model. In particular, individual limits coming from the analysis of the CMB angular power spectra, using the Planck likelihood, are B-1 (Mpc) < 4.4 nG (where B1 Mpc is the comoving field amplitude at a scale of 1 Mpc) at 95% confidence level, assuming zero helicity. By considering the Planck likelihood, based only on parity-even angular power spectra, we obtain B-1 (Mpc) < 5.6 nG for a maximally helical field. For nearly scale-invariant PMFs we obtain B-1 (Mpc) < 2.0 nG and B-1 (Mpc) < 0.9 nG if the impact of PMFs on the ionization history of the Universe is included in the analysis. From the analysis of magnetically-induced non-Gaussianity, we obtain three different values, corresponding to three applied methods, all below 5 nG. The constraint from the magnetically-induced passive-tensor bispectrum is B-1 (Mpc) < 2.8 nG. A search for preferred directions in the magnetically-induced passive bispectrum yields B-1 (Mpc) < 4.5 nG, whereas the compensated-scalar bispectrum gives B-1 (Mpc) < 3 nG. The analysis of the Faraday rotation of CMB polarization by PMFs uses the Planck power spectra in EE and BB at 70 GHz and gives B-1 (Mpc) < 1380 nG. In our final analysis, we consider the harmonic-space correlations produced by Alfven waves, finding no significant evidence for the presence of these waves. Together, these results comprise a comprehensive set of constraints on possible PMFs with Planck data.
12.	Aghanim, N., et al. (author) Planck 2015 results XI. CMB power spectra, likelihoods, and robustness of parameters 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract This paper presents the Planck 2015 likelihoods, statistical descriptions of the 2-point correlation functions of the cosmic microwave background (CMB) temperature and polarization fluctuations that account for relevant uncertainties, both instrumental and astrophysical in nature. They are based on the same hybrid approach used for the previous release, i.e., a pixel-based likelihood at low multipoles (l < 30) and a Gaussian approximation to the distribution of cross-power spectra at higher multipoles. The main improvements are the use of more and better processed data and of Planck polarization information, along with more detailed models of foregrounds and instrumental uncertainties. The increased redundancy brought by more than doubling the amount of data analysed enables further consistency checks and enhanced immunity to systematic effects. It also improves the constraining power of Planck, in particular with regard to small-scale foreground properties. Progress in the modelling of foreground emission enables the retention of a larger fraction of the sky to determine the properties of the CMB, which also contributes to the enhanced precision of the spectra. Improvements in data processing and instrumental modelling further reduce uncertainties. Extensive tests establish the robustness and accuracy of the likelihood results, from temperature alone, from polarization alone, and from their combination. For temperature, we also perform a full likelihood analysis of realistic end-to-end simulations of the instrumental response to the sky, which were fed into the actual data processing pipeline; this does not reveal biases from residual low-level instrumental systematics. Even with the increase in precision and robustness, the Lambda CDM cosmological model continues to offer a very good fit to the Planck data. The slope of the primordial scalar fluctuations, n(s), is confirmed smaller than unity at more than 5 sigma from Planck alone. We further validate the robustness of the likelihood results against specific extensions to the baseline cosmology, which are particularly sensitive to data at high multipoles. For instance, the effective number of neutrino species remains compatible with the canonical value of 3.046. For this first detailed analysis of Planck polarization spectra, we concentrate at high multipoles on the E modes, leaving the analysis of the weaker B modes to future work. At low multipoles we use temperature maps at all Planck frequencies along with a subset of polarization data. These data take advantage of Planck's wide frequency coverage to improve the separation of CMB and foreground emission. Within the baseline Lambda CDM cosmology this requires tau = 0.078 +/- 0.019 for the reionization optical depth, which is significantly lower than estimates without the use of high-frequency data for explicit monitoring of dust emission. At high multipoles we detect residual systematic errors in E polarization, typically at the mu K-2 level; we therefore choose to retain temperature information alone for high multipoles as the recommended baseline, in particular for testing non-minimal models. Nevertheless, the high-multipole polarization spectra from Planck are already good enough to enable a separate high-precision determination of the parameters of the Lambda CDM model, showing consistency with those established independently from temperature information alone.
13.	Adam, R., et al. (author) Planck 2015 results X. Diffuse component separation : Foreground maps 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract Planck has mapped the microwave sky in temperature over nine frequency bands between 30 and 857 GHz and in polarization over seven frequency bands between 30 and 353 GHz in polarization. In this paper we consider the problem of diffuse astrophysical component separation, and process these maps within a Bayesian framework to derive an internally consistent set of full-sky astrophysical component maps. Component separation dedicated to cosmic microwave background (CMB) reconstruction is described in a companion paper. For the temperature analysis, we combine the Planck observations with the 9-yr Wilkinson Microwave Anisotropy Probe (WMAP) sky maps and the Haslam et al. 408 MHz map, to derive a joint model of CMB, synchrotron, free-free, spinning dust, CO, line emission in the 94 and 100 GHz channels, and thermal dust emission. Full-sky maps are provided for each component, with an angular resolution varying between 7: 5 and 1 degrees. Global parameters (monopoles, dipoles, relative calibration, and bandpass errors) are fitted jointly with the sky model, and best-fit values are tabulated. For polarization, the model includes CMB, synchrotron, and thermal dust emission. These models provide excellent fits to the observed data, with rms temperature residuals smaller than 4pK over 93% of the sky for all Planck frequencies up to 353 GHz, and fractional errors smaller than 1% in the remaining 7% of the sky. The main limitations of the temperature model at the lower frequencies are internal degeneracies among the spinning dust, free-free, and synchrotron components; additional observations from external low-frequency experiments will be essential to break these degeneracies. The main limitations of the temperature model at the higher frequencies are uncertainties in the 545 and 857 GHz calibration and zero-points. For polarization, the main outstanding issues are instrumental systematics in the 100-353 GHz bands on large angular scales in the form of temperature-to-polarization leakage, uncertainties in the analogue-to-digital conversion, and corrections for the very long time constant of the bolometer detectors, all of which are expected to improve in the near future.
14.	Ade, P. A. R., et al. (author) Planck 2015 results XIV. Dark energy and modified gravity 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract We study the implications of Planck data for models of dark energy (DE) and modified gravity (MG) beyond the standard cosmological constant scenario. We start with cases where the DE only directly affects the background evolution, considering Taylor expansions of the equation of state w(a), as well as principal component analysis and parameterizations related to the potential of a minimally coupled DE scalar field. When estimating the density of DE at early times, we significantly improve present constraints and find that it has to be below similar to 2% (at 95% confidence) of the critical density, even when forced to play a role for z < 50 only. We then move to general parameterizations of the DE or MG perturbations that encompass both effective field theories and the phenomenology of gravitational potentials in MG models. Lastly, we test a range of specific models, such as k-essence, f(R) theories, and coupled DE. In addition to the latest Planck data, for our main analyses, we use background constraints from baryonic acoustic oscillations, type-Ia supernovae, and local measurements of the Hubble constant. We further show the impact of measurements of the cosmological perturbations, such as redshift-space distortions and weak gravitational lensing. These additional probes are important tools for testing MG models and for breaking degeneracies that are still present in the combination of Planck and background data sets. All results that include only background parameterizations (expansion of the equation of state, early DE, general potentials in minimally-coupled scalar fields or principal component analysis) are in agreement with ACDM. When testing models that also change perturbations (even when the background is fixed to ACDM), some tensions appear in a few scenarios: the maximum one found is similar to 2 sigma for Planck TT + lowP when parameterizing observables related to the gravitational potentials with a chosen time dependence; the tension increases to, at most, 3 sigma when external data sets are included. It however disappears when including CMB lensing.
15.	Ade, P. A. R., et al. (author) Planck 2015 results XV. Gravitational lensing 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract We present the most significant measurement of the cosmic microwave background (CMB) lensing potential to date (at a level of 40 sigma), using temperature and polarization data from the Planck 2015 full-mission release. Using a polarization-only estimator, we detect lensing at a significance of 5 sigma. We cross-check the accuracy of our measurement using the wide frequency coverage and complementarity of the temperature and polarization measurements. Public products based on this measurement include an estimate of the lensing potential over approximately 70% of the sky, an estimate of the lensing potential power spectrum in bandpowers for the multipole range 40 <= L <= 400, and an associated likelihood for cosmological parameter constraints. We find good agreement between our measurement of the lensing potential power spectrum and that found in the Lambda CDM model that best fits the Planck temperature and polarization power spectra. Using the lensing likelihood alone we obtain a percent-level measurement of the parameter combination sigma(8) Omega(0.25)(m) = 0.591 +/- 0.021. We combine our determination of the lensing potential with the E-mode polarization, also measured by Planck, to generate an estimate of the lensing B-mode. We show that this lensing B-mode estimate is correlated with the B-modes observed directly by Planck at the expected level and with a statistical significance of 10 sigma, confirming Planck's sensitivity to this known sky signal. We also correlate our lensing potential estimate with the large-scale temperature anisotropies, detecting a cross-correlation at the 3 sigma level, as expected because of dark energy in the concordance Lambda CDM model.
16.	Ade, P. A. R., et al. (author) Planck 2015 results XVII. Constraints on primordial non-Gaussianity 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract The Planck full mission cosmic microwave background (CMB) temperature and E-mode polarization maps are analysed to obtain constraints on primordial non-Gaussianity (NG). Using three classes of optimal bispectrum estimators - separable template-fitting (KSW), binned, and modal we obtain consistent values for the primordial local, equilateral, and orthogonal bispectrum amplitudes, quoting as our final result from temperature alone f(NL)(local) = 2.5 +/- 5.7, f(NL)(equil) = 16 +/- 70, and f(NL)(ortho) = 34 +/- 33 (68% CL, statistical). Combining temperature and polarization data we obtain f(NL)(local) = 0.8 +/- 5.0, f(NL)(equil) = 4 +/- 43, and f(NL)(ortho) = 26 +/- 21 (68% CL, statistical). The results are based on comprehensive cross-validation of these estimators on Gaussian and non-Gaussian simulations, are stable across component separation techniques, pass an extensive suite of tests, and are consistent with estimators based on measuring the Minkowski functionals of the CMB. The effect of time-domain de-glitching systematics on the bispectrum is negligible. In spite of these test outcomes we conservatively label the results including polarization data as preliminary, owing to a known mismatch of the noise model in simulations and the data. Beyond estimates of individual shape amplitudes, we present model-independent, three-dimensional reconstructions of the Planck CMB bispectrum and derive constraints on early universe scenarios that generate primordial NG, including general single-field models of inflation, axion inflation, initial state modifications, models producing parity-violating tensor bispectra, and directionally dependent vector models. We present a wide survey of scale-dependent feature and resonance models, accounting for the look elsewhere effect in estimating the statistical significance of features. We also look for isocurvature NG, and find no signal, but we obtain constraints that improve significantly with the inclusion of polarization. The primordial trispectrum amplitude in the local model is constrained to be g(NL)(local) = (9.0 +/- 7.7) x 10(4) (68% CL statistical), and we perform an analysis of trispectrum shapes beyond the local case. The global picture that emerges is one of consistency with the premises of the Lambda CDM cosmology, namely that the structure we observe today was sourced by adiabatic, passive, Gaussian, and primordial seed perturbations.
17.	Ade, P. A. R., et al. (author) Planck 2015 results XVIII. Background geometry and topology of the Universe 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract Maps of cosmic microwave background (CMB) temperature and polarization from the 2015 release of Planck data provide the highest quality full-sky view of the surface of last scattering available to date. This enables us to detect possible departures from a globally isotropic cosmology. We present the first searches using CMB polarization for correlations induced by a possible non-trivial topology with a fundamental domain that intersects, or nearly intersects, the last-scattering surface (at comoving distance chi(rec)), both via a direct scan for matched circular patterns at the intersections and by an optimal likelihood calculation for specific topologies. We specialize to flat spaces with cubic toroidal (T3) and slab (T1) topologies, finding that explicit searches for the latter are sensitive to other topologies with antipodal symmetry. These searches yield no detection of a compact topology with a scale below the diameter of the last-scattering surface. The limits on the radius R-i of the largest sphere inscribed in the fundamental domain (at log-likelihood ratio Delta ln L > -5 relative to a simply-connected flat Planck best-fit model) are: R-i > 0.97 chi(rec) for the T3 cubic torus; and R-i > 0.56 chi(rec) for the T1 slab. The limit for the T3 cubic torus from the matched-circles search is numerically equivalent, R-i > 0.97 chi(rec) at 99% confidence level from polarization data alone. We also perform a Bayesian search for an anisotropic global Bianchi VIIh geometry. In the non-physical setting, where the Bianchi cosmology is decoupled from the standard cosmology, Planck temperature data favour the inclusion of a Bianchi component with a Bayes factor of at least 2.3 units of log-evidence. However, the cosmological parameters that generate this pattern are in strong disagreement with those found from CMB anisotropy data alone. Fitting the induced polarization pattern for this model to the Planck data requires an amplitude of -0.10 +/- 0.04 compared to the value of + 1 if the model were to be correct. In the physically motivated setting, where the Bianchi parameters are coupled and fitted simultaneously with the standard cosmological parameters, we find no evidence for a Bianchi VIIh cosmology and constrain the vorticity of such models to (omega/H)(0) < 7.6 x 10(-10) (95% CL).
18.	Ade, P. A. R., et al. (author) Planck 2015 results XX. Constraints on inflation 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract We present the implications for cosmic inflation of the Planck measurements of the cosmic microwave background (CMB) anisotropies in both temperature and polarization based on the full Planck survey, which includes more than twice the integration time of the nominal survey used for the 2013 release papers. The Planck full mission temperature data and a first release of polarization data on large angular scales measure the spectral index of curvature perturbations to be n(s) = 0.968 +/- 0.006 and tightly constrain its scale dependence to dn(s)/dln k = -0.003 +/- 0.007 when combined with the Planck lensing likelihood. When the Planck high-l polarization data are included, the results are consistent and uncertainties are further reduced. The upper bound on the tensor-to-scalar ratio is r(0).(002) < 0.11 (95% CL). This upper limit is consistent with the B-mode polarization constraint r < 0.12 (95% CL) obtained from a joint analysis of the BICEP2/Keck Array and Planck data. These results imply that V(phi) proportional to phi(2) and natural inflation are now disfavoured compared to models predicting a smaller tensor-to-scalar ratio, such as R-2 inflation. We search for several physically motivated deviations from a simple power-law spectrum of curvature perturbations, including those motivated by a reconstruction of the inflaton potential not relying on the slow-roll approximation. We find that such models are not preferred, either according to a Bayesian model comparison or according to a frequentist simulation-based analysis. Three independent methods reconstructing the primordial power spectrum consistently recover a featureless and smooth P-R (k) over the range of scales 0.008 Mpc(-1) less than or similar to k less than or similar to 0.1 Mpc(-1). At large scales, each method finds deviations from a power law, connected to a deficit at multipoles l approximate to 20-40 in the temperature power spectrum, but at an uncompelling statistical significance owing to the large cosmic variance present at these multipoles. By combining power spectrum and non-Gaussianity bounds, we constrain models with generalized Lagrangians, including Galileon models and axion monodromy models. The Planck data are consistent with adiabatic primordial perturbations, and the estimated values for the parameters of the base Lambda cold dark matter (Lambda CDM) model are not significantly altered when more general initial conditions are admitted. In correlated mixed adiabatic and isocurvature models, the 95% CL upper bound for the non-adiabatic contribution to the observed CMB temperature variance is vertical bar alpha(non-adi)vertical bar < 1.9%, 4.0%, and 2.9% for CDM, neutrino density, and neutrino velocity isocurvature modes, respectively. We have tested inflationary models producing an anisotropic modulation of the primordial curvature power spectrum finding that the dipolar modulation in the CMB temperature field induced by a CDM isocurvature perturbation is not preferred at a statistically significant level. We also establish tight constraints on a possible quadrupolar modulation of the curvature perturbation. These results are consistent with the Planck 2013 analysis based on the nominal mission data and further constrain slow-roll single-field inflationary models, as expected from the increased precision of Planck data using the full set of observations.
19.	Ade, P. A. R., et al. (author) Planck 2015 results XXV. Diffuse low-frequency Galactic foregrounds 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract We discuss the Galactic foreground emission between 20 and 100 GHz based on observations by Planck and WMAP. The total intensity in this part of the spectrum is dominated by free-free and spinning dust emission, whereas the polarized intensity is dominated by synchrotron emission. The Commander component-separation tool has been used to separate the various astrophysical processes in total intensity. Comparison with radio recombination line templates verifies the recovery of the free-free emission along the Galactic plane. Comparison of the high-latitude H alpha emission with our free-free map shows residuals that correlate with dust optical depth, consistent with a fraction (approximate to 30%) of H alpha having been scattered by high-latitude dust. We highlight a number of diffuse spinning dust morphological features at high latitude. There is substantial spatial variation in the spinning dust spectrum, with the emission peak (in I-v) ranging from below 20 GHz to more than 50 GHz. There is a strong tendency for the spinning dust component near many prominent H Pi regions to have a higher peak frequency, suggesting that this increase in peak frequency is associated with dust in the photo-dissociation regions around the nebulae. The emissivity of spinning dust in these diffuse regions is of the same order as previous detections in the literature. Over the entire sky, the Commander solution finds more anomalous microwave emission (AME) than the WMAP component maps, at the expense of synchrotron and free-free emission. This can be explained by the difficulty in separating multiple broadband components with a limited number of frequency maps. Future surveys, particularly at 5-20 GHz, will greatly improve the separation by constraining the synchrotron spectrum. We combine Planck and WMAP data to make the highest signal-to-noise ratio maps yet of the intensity of the all-sky polarized synchrotron emission at frequencies above a few GHz. Most of the high-latitude polarized emission is associated with distinct large-scale loops and spurs, and we re-discuss their structure. We argue that nearly all the emission at 40 degrees > l > -90 degrees is part of the Loop I structure, and show that the emission extends much further in to the southern Galactic hemisphere than previously recognised, giving Loop I an ovoid rather than circular outline. However, it does not continue as far as the Fermi bubble/microwave haze, making it less probable that these are part of the same structure. We identify a number of new faint features in the polarized sky, including a dearth of polarized synchrotron emission directly correlated with a narrow, roughly 20 degrees long filament seen in H alpha at high Galactic latitude. Finally, we look for evidence of polarized AME, however many AME regions are significantly contaminated by polarized synchrotron emission, and we find a 2 sigma upper limit of 1.6% in the Perseus region.
20.	Ade, P. A. R., et al. (author) Planck 2015 results XXVI. The Second Planck Catalogue of Compact Sources 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract The Second Planck Catalogue of Compact Sources is a list of discrete objects detected in single-frequency maps from the full duration of the Planck mission and supersedes previous versions. It consists of compact sources, both Galactic and extragalactic, detected over the entire sky. Compact sources detected in the lower frequency channels are assigned to the PCCS2, while at higher frequencies they are assigned to one of two subcatalogues, the PCCS2 or PCCS2E, depending on their location on the sky. The first of these (PCCS2) covers most of the sky and allows the user to produce subsamples at higher reliabilities than the target 80% integral reliability of the catalogue. The second ( PCCS2E) contains sources detected in sky regions where the diffuse emission makes it difficult to quantify the reliability of the detections. Both the PCCS2 and PCCS2E include polarization measurements, in the form of polarized flux densities, or upper limits, and orientation angles for all seven polarization-sensitive Planck channels. The improved data-processing of the full-mission maps and their reduced noise levels allow us to increase the number of objects in the catalogue, improving its completeness for the target 80% reliability as compared with the previous versions, the PCCS and the Early Release Compact Source Catalogue (ERCSC).
21.	Ade, P. A. R., et al. (author) Planck intermediate results XLI. A map of lensing-induced B-modes 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596 Journal article (peer-reviewed)abstract The secondary cosmic microwave background (CMB) B-modes stem from the post-decoupling distortion of the polarization E-modes due to the gravitational lensing effect of large-scale structures. These lensing-induced B-modes constitute both a valuable probe of the dark matter distribution and an important contaminant for the extraction of the primary CMB B-modes from inflation. Planck provides accurate nearly all-sky measurements of both the polarization E-modes and the integrated mass distribution via the reconstruction of the CMB lensing potential. By combining these two data products, we have produced an all-sky template map of the lensing-induced B-modes using a real-space algorithm that minimizes the impact of sky masks. The cross-correlation of this template with an observed (primordial and secondary) B-mode map can be used to measure the lensing B-mode power spectrum at multipoles up to 2000. In particular, when cross-correlating with the B-mode contribution directly derived from the Planck polarization maps, we obtain lensing-induced B-mode power spectrum measurement at a significance level of 12 sigma, which agrees with the theoretical expectation derived from the Planck best-fit Lambda cold dark matter model. This unique nearly all-sky secondary B-mode template, which includes the lensing-induced information from intermediate to small (10 less than or similar to l less than or similar to 1000) angular scales, is delivered as part of the Planck 2015 public data release. It will be particularly useful for experiments searching for primordial B-modes, such as BICEP2/Keck Array or LiteBIRD, since it will enable an estimate to be made of the lensing-induced contribution to the measured total CMB B-modes.
22.	Ade, P. A. R., et al. (author) XXI. The integrated Sachs-Wolfe effect 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594 Journal article (peer-reviewed)abstract This paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4 sigma where most of the signal-to-noise is due to the Planck lensing and the NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at approximate to 3 sigma (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Omega(Lambda) is detected at more than 3 sigma. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with Lambda CDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by combining the information encoded in all the previously mentioned LSS tracers. In particular, we construct a map of the ISW secondary anisotropies and the corresponding uncertainties map, obtained from simulations. We also explore the reconstruction of the ISW anisotropies caused by the large-scale structure traced by the 2MASS Photometric Redshift Survey (2MPZ) by directly inverting the density field into the gravitational potential field.
23.	Varela, AR, et al. (author) Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity-GoPA! 2015 and 2020 Surveys 2023 In: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 20:2, s. 112-128 Journal article (peer-reviewed)abstract Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion.
24.	Werren, John H, et al. (author) Functional and evolutionary insights from the genomes of three parasitoid Nasonia species. 2010 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8 Journal article (peer-reviewed)abstract We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
25.	Andersen, M, et al. (author) The Asian Pharmacoepidemiology Network (AsPEN): promoting multi-national collaboration for pharmacoepidemiologic research in Asia 2013 In: Pharmacoepidemiology and drug safety. - : Wiley. - 1099-1557 .- 1053-8569. ; 22:7, s. 700-704 Journal article (peer-reviewed)
26.	Duggal, N, et al. (author) INVESTIGATING THE ROLE OF ACCELERATED IMMUNESENESCENCE IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS 2022 In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1152-1152 Conference paper (other academic/artistic)abstract Advancing age is recognised as a major risk factor for autoimmune inflammatory conditions, such as Rheumatoid Arthritis (RA). Despite strong associations with older age we understand little of the role ageing processes play in disease pathogenesis in RA. The immune system undergoes a dramatic remodelling with age, termed immunesenescence, which contributes towards increased risk of autoimmunity1. Previous research in patients with established RA has shown certain features of immunesenescence, such as thymic atrophy and telomere shortening in T cells, at a younger age2,3.ObjectivesIn this study we aimed to determine if immunesenescence is seen in the very earliest stages of RA and therefore might be a contributor to RA pathogenesis rather than a result of the disease.MethodsWe have assessed aspects of the aged immune phenotype by immunostaining and flow cytometry4 in adults with arthralgia (n=25), undifferentiated arthritis (UA; n=41), confirmed RA of less than 3 months (n=25) and more than 3 months duration (n=78) and compared these to age and sex matched healthy controls (n=38). Nanostring methodology was used to determine gene expression changes associated with the development of RA.ResultsWe observed increased features of T and B cell immunesenescence in DMARD-naïve recently diagnosed RA patients driven by reduced naïve T cells (p<0.01) and B cells (p<0.01), increased senescent (CD28-ve, CD57+ve, KLRG1+ve) T cells (p<0.01), an increased Th17/Treg ratio (p<0.01) and increased frequency of age-associated B cells (p<0.01). With the exception of naïve T cell frequency, which was reduced in UA patients (p<0.05), these changes were not seen in the very early stages of RA, namely patients with arthralgia and UA. These data suggest that immunesenescence only occurs once disease is established. Furthermore, using nanostring we have identified several biological ageing processes (DNA damage, autophagy) associated with this state of immunesenescence in RA.ConclusionAccelerated immune ageing is an early feature of RA and biological ageing processes represent novel targets to modulate disease progression.References[1]Duggal NA, Upton JA, Phillips AC, Sapey E, Lord JM (2013) An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity. Aging Cell 12:873-881.[2]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[3]Steer SE, Williams FMK, Kato B, Gardner JP, Norman PJ, Hall MA, Kimra M, Vaughan R, Aviv A, Spector T (2007) Reduced telomere length in rheumatoid arthritis in independent of disease activity and duration. Ann Rheum Dis 66:476-480.[4]Duggal NA, Pollock RD, Lazarus NR, Harridge S, Lord JM (2018). Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell 17:e12750Disclosure of InterestsNone declared
27.	Kminek, G, et al. (author) COSPAR Sample Safety Assessment Framework (SSAF) 2022 In: Astrobiology. - : Mary Ann Liebert Inc.. - 1531-1074 .- 1557-8070. ; 22:S1, s. S186-S216 Journal article (peer-reviewed)abstract The Committee on Space Research (COSPAR) Sample Safety Assessment Framework (SSAF) has been developed by a COSPAR appointed Working Group. The objective of the sample safety assessment would be to evaluate whether samples returned from Mars could be harmful for Earth's systems (e.g., environment, biosphere, geochemical cycles). During the Working Group's deliberations, it became clear that a comprehensive assessment to predict the effects of introducing life in new environments or ecologies is difficult and practically impossible, even for terrestrial life and certainly more so for unknown extraterrestrial life. To manage expectations, the scope of the SSAF was adjusted to evaluate only whether the presence of martian life can be excluded in samples returned from Mars. If the presence of martian life cannot be excluded, a Hold & Critical Review must be established to evaluate the risk management measures and decide on the next steps. The SSAF starts from a positive hypothesis (there is martian life in the samples), which is complementary to the null-hypothesis (there is no martian life in the samples) typically used for science. Testing the positive hypothesis includes four elements: (1) Bayesian statistics, (2) subsampling strategy, (3) test sequence, and (4) decision criteria. The test sequence capability covers self-replicating and non-self-replicating biology and biologically active molecules. Most of the investigations associated with the SSAF would need to be carried out within biological containment. The SSAF is described in sufficient detail to support planning activities for a Sample Receiving Facility (SRF) and for preparing science announcements, while at the same time acknowledging that further work is required before a detailed Sample Safety Assessment Protocol (SSAP) can be developed. The three major open issues to be addressed to optimize and implement the SSAF are (1) setting a value for the level of assurance to effectively exclude the presence of martian life in the samples, (2) carrying out an analogue test program, and (3) acquiring relevant contamination knowledge from all Mars Sample Return (MSR) flight and ground elements. Although the SSAF was developed specifically for assessing samples from Mars in the context of the currently planned NASA-ESA MSR Campaign, this framework and the basic safety approach are applicable to any other Mars sample return mission concept, with minor adjustments in the execution part related to the specific nature of the samples to be returned. The SSAF is also considered a sound basis for other COSPAR Planetary Protection Category V, restricted Earth return missions beyond Mars. It is anticipated that the SSAF will be subject to future review by the various MSR stakeholders. © Gerhard Kminek et al., 2022;
28.	Park, BJ, et al. (author) Cross-National or Multi-Database Research Networks: A New Initiative in Asia-Pacific Region and Ongoing Initiatives in Europe and United States 2012 In: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY. - 1053-8569. ; 21, s. 194-195 Conference paper (other academic/artistic)
29.	Pratt, N, et al. (author) Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study 2013 In: Pharmacoepidemiology and drug safety. - : Wiley. - 1099-1557 .- 1053-8569. ; 22:9, s. 915-924 Journal article (peer-reviewed)
30.	Sharma-Oates, A, et al. (author) INCREASED BIOLOGICAL AGE IN MALE PARTICIPANTS OF SWEDISH AND UK RHEUMATOID ARTHRITIS COHORTS IS NOT LINKED TO DISEASE 2022 In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1177-1177 Conference paper (other academic/artistic)abstract Immunesenescence in the adaptive immune system, subsequent to thymic involution, results in compromised immunity and increased susceptibility to autoimmune disease and chronic inflammation. There are reports in the literature that immunesenescence, including thymic atrophy and telomere shortening, is accelerated in patients with rheumatoid arthritis (RA)1. What is unclear is whether RA includes accelerated biological ageing overall in addition to immune ageing which may help to explain the increased risk of age-related diseases in RA2. Recent studies have identified a set of DNA methylated sites across the genome that are highly correlated with chronological age and mortality, termed epigenetic clocks3,4 or DNAm age (DNAma), and can be used to determine an individual’s biological age.ObjectivesThe aim of our study is to determine if the biological epigenetic clocks of RA patients are accelerated.MethodsWe evaluated the Horvath3 and Hannum4 epigenetic clocks of control and RA patients using published DNAm data sets, accessions GSE42861 (EIRA, Swedish cohort of 342 RA patients and 328 non-RA controls) and E-MTAB-6988 (77 RA discordant monozygotic twins).ResultsWe did not detect significant differences between DNAma of RA and non-RA twins. Similarly, there were no significant differences between the DNAma of RA patients and controls from the Swedish EIRA cohort. However, we detected a significant acceleration in DNAma of male discordant twins, both RA and non-RA, by 5.4 years (p=3.29e-5) and 2.8 years (p=0.04) using the Hannum and Horvath clocks, respectively. Male participants, both control and RA patients, from the EIRA cohort also exhibited an accelerated DNAma, by 1.5 years (p=7.55e-5) using the Hannum clock but using the Horvath clock a significant DNAma acceleration, by 1.4 years (p=0.002) was detected in male RA patients from the EIRA cohort.ConclusionOverall, we detected a significant biological age acceleration in male participants from both RA and control groups and only found a significant difference between DNAma of Non-RA controls and RA patients for one of the epigenetic clocks. Further analysis using additional cohort data and biological clock algorithms is needed to confirm our findings.References[1]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[2]Meune C, et al. (2009) Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatol 48:1309-1313.[3]Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115.[4]Hannum G, et al (2013) Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell 49:359-367.AcknowledgementsThe study was funded by FOREUMDisclosure of InterestsNone declared
31.	Trpchevska, N, et al. (author) Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss 2022 In: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 109:6, s. 1077-1091 Journal article (peer-reviewed)
32.	Allen, K. D., et al. (author) Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative 2023 In: Osteoarthritis and Cartilage. - : ELSEVIER SCI LTD. - 1063-4584 .- 1522-9653. ; 31:7, s. 954-965 Journal article (peer-reviewed)abstract Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by & GE;80% of participants were retained, and participants could suggest addi-tional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if & GE;80% rated it & GE;6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if & GE;80% of participants rated it & GE;9 and as "optional" if & GE;80% rated it & GE;7. Results: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. Conclusion: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
33.	Dahal, Prabin, et al. (author) Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis 2019 In: Malaria Journal. - : BMC. - 1475-2875. ; 18 Journal article (peer-reviewed)abstract Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
34.	Dahal, Prabin, et al. (author) Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis 2022 In: Malaria Journal. - : Springer Nature. - 1475-2875. ; 21 Journal article (peer-reviewed)abstract Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
35.	Fushitani, Mizuho, et al. (author) Time-resolved photoelectron imaging of complex resonances in molecular nitrogen 2021 In: The Journal of chemical physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 154:14 Journal article (peer-reviewed)abstract We have used the FERMI free-electron laser to perform time-resolved photoelectron imaging experiments on a complex group of resonances near 15.38 eV in the absorption spectrum of molecular nitrogen, N2, under jet-cooled conditions. The new data complement and extend the earlier work of Fushitani et al. [Opt. Express 27, 19702–19711 (2019)], who recorded time-resolved photoelectron spectra for this same group of resonances. Time-dependent oscillations are observed in both the photoelectron yields and the photoelectron angular distributions, providing insight into the interactions among the resonant intermediate states. In addition, for most states, we observe an exponential decay of the photoelectron yield that depends on the ionic final state. This observation can be rationalized by the different lifetimes for the intermediate states contributing to a particular ionization channel. Although there are nine resonances within the group, we show that by detecting individual photoelectron final states and their angular dependence, we can identify and differentiate quantum pathways within this complex system.
36.	Gringras, P., et al. (author) Weighted blankets and sleep in autistic children - A randomized controlled trial 2014 In: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 134:2, s. 298-306 Journal article (peer-reviewed)abstract OBJECTIVE:To assess the effectiveness of a weighted-blanket intervention in treating severe sleep problems in children with autism spectrum disorder (ASD).METHODS:This phase III trial was a randomized, placebo-controlled crossover design. Participants were aged between 5 years and 16 years 10 months, with a confirmed ASD diagnosis and severe sleep problems, refractory to community-based interventions. The interventions were either a commercially available weighted blanket or otherwise identical usual weight blanket (control), introduced at bedtime; each was used for a 2-week period before crossover to the other blanket. Primary outcome was total sleep time (TST) recorded by actigraphy over each 2-week period. Secondary outcomes included actigraphically recorded sleeponset latency, sleep efficiency, assessments of child behavior, family functioning, and adverse events. Sleep was also measured by using parent-report diaries.RESULTS:Seventy-three children were randomized and analysis conducted on 67 children who completed the study. Using objective measures, the weighted blanket, compared with the control blanket, did not increase TST as measured by actigraphy and adjusted for baseline TST. There were no group differences in any other objective or subjective measure of sleep, including behavioral outcomes. On subjective preference measures, parents and children favored the weighted blanket.CONCLUSIONS:The use of a weighted blanket did not help children with ASD sleep for a longer period of time, fall asleep significantly faster, or wake less often. However, the weighted blanket was favored by children and parents, and blankets were well tolerated over this period.
37.	Jalloh, MF, et al. (author) Integrated digital system for community engagement and community-based surveillance during the 2014-2016 Ebola outbreak in Sierra Leone: lessons for future health emergencies 2020 In: BMJ global health. - : BMJ. - 2059-7908. ; 5:12 Journal article (peer-reviewed)abstract Community engagement and community-based surveillance are essential components of responding to infectious disease outbreaks, but real-time data reporting remains a challenge. In the 2014–2016 Ebola outbreak in Sierra Leone, the Social Mobilisation Action Consortium was formed to scale-up structured, data-driven community engagement. The consortium became operational across all 14 districts and supported an expansive network of 2500 community mobilisers, 6000 faith leaders and 42 partner radio stations. The benefit of a more agile digital reporting system became apparent within few months of implementing paper-based reporting given the need to rapidly use the data to inform the fast-evolving epidemic. In this paper, we aim to document the design, deployment and implementation of a digital reporting system used in six high transmission districts. We highlight lessons learnt from our experience in scaling up the digital reporting system during an unprecedented public health crisis. The lessons learnt from our experience in Sierra Leone have important implications for designing and implementing similar digital reporting systems for community engagement and community-based surveillance during public health emergencies.
38.	Kalman, L. V., et al. (author) Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting 2016 In: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185 Journal article (peer-reviewed)abstract This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
39.	Law, PJ, et al. (author) Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia 2017 In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 14175- Journal article (peer-reviewed)abstract Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
40.	Lynch, Kate D, et al. (author) Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases. 2020 In: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:1 Journal article (peer-reviewed)abstract Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n= 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P= .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P= .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
41.	Maurits, M, et al. (author) GWAS Identified New Genes in Synovial Fibroblasts Linked to Early Remission in RA 2022 In: ARTHRITIS & RHEUMATOLOGY. - 2326-5191. ; 74, s. 2265-2269 Conference paper (other academic/artistic)
42.	Peng, B, et al. (author) LipidCreator workbench to probe the lipidomic landscape 2020 In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 2057- Journal article (peer-reviewed)abstract Mass spectrometry (MS)-based targeted lipidomics enables the robust quantification of selected lipids under various biological conditions but comprehensive software tools to support such analyses are lacking. Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.
43.	Raman, SR, et al. (author) Trends in attention-deficit hyperactivity disorder medication use: a retrospective observational study using population-based databases 2018 In: The lancet. Psychiatry. - 2215-0374. ; 5:10, s. 824-835 Journal article (peer-reviewed)
44.	Raman, SR, et al. (author) Utilization of Attention Deficit Hyperactivity Disorder Medications (ADHD) by Adults in 13 Countries 2017 In: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY. - 1053-8569. ; 26, s. 333-333 Conference paper (other academic/artistic)
45.	Sava, G P, et al. (author) Common variation at 12q24.13 (OAS3) influences chronic lymphocytic leukemia risk. 2015 In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 29:3, s. 748-751 Journal article (peer-reviewed)
46.	Schuemie, M. J., et al. (author) Vaccine Safety Surveillance Using Routinely Collected Healthcare Data-An Empirical Evaluation of Epidemiological Designs 2022 In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13 Journal article (peer-reviewed)abstract Background: Routinely collected healthcare data such as administrative claims and electronic health records (EHR) can complement clinical trials and spontaneous reports to detect previously unknown risks of vaccines, but uncertainty remains about the behavior of alternative epidemiologic designs to detect and declare a true risk early.Methods: Using three claims and one EHR database, we evaluate several variants of the case-control, comparative cohort, historical comparator, and self-controlled designs against historical vaccinations using real negative control outcomes (outcomes with no evidence to suggest that they could be caused by the vaccines) and simulated positive control outcomes.Results: Most methods show large type 1 error, often identifying false positive signals. The cohort method appears either positively or negatively biased, depending on the choice of comparator index date. Empirical calibration using effect-size estimates for negative control outcomes can bring type 1 error closer to nominal, often at the cost of increasing type 2 error. After calibration, the self-controlled case series (SCCS) design most rapidly detects small true effect sizes, while the historical comparator performs well for strong effects.Conclusion: When applying any method for vaccine safety surveillance we recommend considering the potential for systematic error, especially due to confounding, which for many designs appears to be substantial. Adjusting for age and sex alone is likely not sufficient to address differences between vaccinated and unvaccinated, and for the cohort method the choice of index date is important for the comparability of the groups. Analysis of negative control outcomes allows both quantification of the systematic error and, if desired, subsequent empirical calibration to restore type 1 error to its nominal value. In order to detect weaker signals, one may have to accept a higher type 1 error.
47.	Williams, R. D., et al. (author) Seek COVER: using a disease proxy to rapidly develop and validate a personalized risk calculator for COVID-19 outcomes in an international network 2022 In: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 22:1 Journal article (peer-reviewed)abstract Background: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient’s risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. Methods: We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. Results: Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69–0.81, COVER-I: 0.73–0.91, and COVER-F: 0.72–0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. Conclusions: This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use. © 2022, The Author(s).
48.	Zhou, Weihua, et al. (author) Purine metabolism regulates DNA repair and therapy resistance in glioblastoma 2020 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1 Journal article (peer-reviewed)abstract Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.

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