We present for the first time a detailed and comprehensive analysis of the experimental results that set the current world sensitivity limit on the magnitude of the electric dipole moment (EDM) of ...the neutron. We have extended and enhanced our earlier analysis to include recent developments in the understanding of the effects of gravity in depolarizing ultracold neutrons (UCN); an improved calculation of the spectrum of the neutrons; and conservative estimates of other possible systematic errors, which are also shown to be consistent with more recent measurements undertaken with the apparatus. We obtain a net result of $d_\mathrm{n} = -0.21 \pm 1.82 \times10^{-26}$ $e$cm, which may be interpreted as a slightly revised upper limit on the magnitude of the EDM of $3.0 \times10^{-26}$ $e$cm (90% CL) or $ 3.6 \times10^{-26}$ $e$cm (95% CL). This paper is dedicated by the remaining authors to the memory of Prof. J. Michael Pendlebury.
Summary
Background
In reported systematic reviews and meta‐analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not ...differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference.
Objectives
This systematic review and meta‐analysis aimed to explore this possibility.
Methods
Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495).
Results
We analysed 51 RCTs. Of these, 21 included at least one anti‐tumour necrosis factor (TNF)‐α arm, 15 one anti‐interleukin (IL)‐17 arm, 11 one anti‐IL‐23 arm and nine one anti‐IL‐12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88–1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02–1·65). By drug class, the RRs were for anti‐TNF‐α, 1·68 (95% CI 1·11–2·54; no missing data); anti‐IL‐17, 1·28 (95% CI 0·88–1·85; no missing data); anti‐IL‐23, 0·95 (95% CI 0·59–1·52; no missing data) and anti‐IL‐12/23, 1·18 (95% CI 0·72–1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events.
Conclusions
On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.
What is already known about this topic?
Systematic reviews and meta‐analyses assessing the safety of biologic treatments for plaque‐type psoriasis in randomized controlled trials concluded that the proportion of serious adverse events (SAEs) was not significantly different between biologic and placebo groups.
What does this study add?
On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic group than in the placebo group, especially for anti‐tumour necrosis factor‐α treatments.
Given the rare events, we could not highlight whether this higher risk of SAEs was related to adverse events of special interest.
Linked Comment: Dávila?Seijo. Br J Dermatol 2021; 184:385.
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•Implementation of code for fitting zero- to ultralow-field (ZULF) NMR data.•Spin-spin couplings determined with uncertainty as low as 200μHz.•Improved precision for some couplings by ...up to 100×.•Spin-spin couplings reported for neat liquids (no 2H lock solvents, etc.).
We present a method which allows for the extraction of physical quantities directly from zero- to ultralow-field nuclear magnetic resonance (ZULF NMR) data. A numerical density matrix evolution is used to simulate ZULF NMR spectra of several molecules in order to fit experimental data. The method is utilized to determine the indirect spin-spin couplings (J-couplings) in these systems, which is achieved with precision of 10-2–10-4Hz. The simulated and measured spectra are compared to earlier research. Agreement and improved precision are achieved for most of the J-coupling estimates. The availability of fast, flexible fitting method for ZULF NMR enables a new generation of precision-measurement experiments for spin-dependent interactions and physics beyond the Standard Model.
The Global Network of Optical Magnetometers to search for Exotic physics (GNOME) is a network of geographically separated, time-synchronized, optically pumped atomic magnetometers that is being used ...to search for correlated transient signals heralding exotic physics. The GNOME is sensitive to nuclear- and electron-spin couplings to exotic fields from astrophysical sources such as compact dark-matter objects (for example, axion stars and domain walls). Properties of the GNOME sensors such as sensitivity, bandwidth, and noise characteristics are studied in the present work, and features of the network’s operation (e.g., data acquisition, format, storage, and diagnostics) are described. Characterization of the GNOME is a key prerequisite to searches for and identification of exotic physics signatures.
We present a magnetometer based on optically pumped Cs atoms that measures the magnitude and direction of a 1 μT magnetic field. Multiple circularly polarized laser beams were used to probe the free ...spin precession of the Cs atoms. The design was optimized for long-time stability and achieves a scalar resolution better than 300 fT for integration times ranging from 80 ms to 1000 s. The best scalar resolution of less than 80 fT was reached with integration times of 1.6 to 6 s. We were able to measure the magnetic field direction with a resolution better than 10 μrad for integration times from 10 s up to 2000 s.
We report a new limit on a possible short range spin-dependent interaction from the precise measurement of the ratio of Larmor precession frequencies of stored ultracold neutrons and Hg199 atoms ...confined in the same volume. The measurement was performed in a ∼1μT vertical magnetic holding field with the apparatus searching for a permanent electric dipole moment of the neutron at the Paul Scherrer Institute. A possible coupling between freely precessing polarized neutron spins and unpolarized nucleons of the wall material can be investigated by searching for a tiny change of the precession frequencies of neutron and mercury spins. Such a frequency change can be interpreted as a consequence of a short range spin-dependent interaction that could possibly be mediated by axions or axion-like particles. The interaction strength is proportional to the CP violating product of scalar and pseudoscalar coupling constants gSgP. Our result confirms limits from complementary experiments with spin-polarized nuclei in a model-independent way. Limits from other neutron experiments are improved by up to two orders of magnitude in the interaction range of 10−6<λ<10−4m.
We describe a spin-echo method for ultracold neutrons (UCNs) confined in a precession chamber and exposed to a |B0|=1 μT magnetic field. We have demonstrated that the analysis of UCN spin-echo ...resonance signals in combination with knowledge of the ambient magnetic field provides an excellent method by which to reconstruct the energy spectrum of a confined ensemble of neutrons. The method takes advantage of the relative dephasing of spins arising from a gravitationally induced striation of stored UCNs of different energies, and also permits an improved determination of the vertical magnetic-field gradient with an exceptional accuracy of 1.1 pT/cm. This novel combination of a well-known nuclear resonance method and gravitationally induced vertical striation is unique in the realm of nuclear and particle physics and should prove to be invaluable for the assessment of systematic effects in precision experiments such as searches for an electric dipole moment of the neutron or the measurement of the neutron lifetime.
We compare the expected effects of so-called gravitationally enhanced depolarization of ultracold neutrons to measurements carried out in a spin-precession chamber exposed to a variety of vertical ...magnetic-field gradients. In particular, we have investigated the dependence upon these field gradients of spin depolarization rates and also of shifts in the measured neutron Larmor precession frequency. We find excellent qualitative agreement, with gravitationally enhanced depolarization accounting for several previously unexplained features in the data.
An analytic solution to the magnetostatic inverse problem in the framework of vector spherical harmonic basis functions is presented. This formalism is used for the design of a spherical magnetic ...field compensation system and its performance is compared with an already existing rectangular coil system. The proposed set of spherical coils with 15 degrees of freedom achieves a shielding factor of 1000 or better in a large part of the volume enclosed by the coils for a dipolar type external perturbation.
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