Confinement of Skyrmions in Nanoscale FeGe Device-like Structures

Skyrmion-based devices have been proposed as a promising solution for low-energy data storage. These devices include racetrack or logic structures and require skyrmions to be confined in regions with dimensions comparable to the size of a single skyrmion. Here we examine skyrmions in FeGe device shapes using Lorentz transmission electron microscopy to reveal the consequences of skyrmion confinement in a device-like structure. Dumbbell-shaped elements were created by focused ion beam milling to provide regions where single skyrmions are confined adjacent to areas containing a skyrmion lattice. Simple block shapes of equivalent dimensions were also prepared to allow a direct comparison with skyrmion formation in a less complex, yet still confined, device geometry. The impact of applying a magnetic field and varying the temperature on the formation of skyrmions within the shapes was examined. This revealed that it is not just confinement within a small device structure that controls the position and number of skyrmions but that a complex device geometry changes the skyrmion behavior, including allowing skyrmions to form at lower applied magnetic fields than in simple shapes. The impact of edges in complex shapes is observed to be significant in changing the behavior of the magnetic textures formed. This could allow methods to be developed to control both the position and number of skyrmions within device structures

Direct observation of propagating spin waves in the 2D van der Waals ferromagnet Fe5GeTe2

Magnetism in reduced dimensionalities is of great fundamental interest while also providing perspectives for applications of materials with novel functionalities. In particular, spin dynamics in two dimensions (2D) have become a focus of recent research. Here, we report the observation of coherent propagating spin-wave dynamics in a ∼30 nm thick flake of 2D van der Waals ferromagnet Fe5GeTe2 using X-ray microscopy. Both phase and amplitude information were obtained by direct imaging below TC for frequencies from 2.77 to 3.84 GHz, and the corresponding spin-wave wavelengths were measured to be between 1.5 and 0.5 μm. Thus, parts of the magnonic dispersion relation were determined despite a relatively high magnetic damping of the material. Numerically solving an analytic multilayer model allowed us to corroborate the experimental dispersion relation and predict the influence of changes in the saturation magnetization or interlayer coupling, which could be exploited in future applications by temperature control or stacking of 2D-heterostructures

Gabapentin for chronic pelvic pain in women (GaPP2):a multicentre, randomised, double-blind, placebo-controlled trial

BackgroundChronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.MethodsWe performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.FindingsParticipants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.InterpretationThis study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.FundingNational Institute for Health Research

Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing

Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

Polymorphism in Cu2ZnSnS4 and new off-stoichiometric crystal structure types

Cu2ZnSnS4 (CZTS) is a very promising material for the absorber layer in sustainable thin-film solar cells. Its photovoltaic performance is currently limited by crystal structure disorder, which causes fluctuations in electrostatic potential that decrease open-circuit voltage. The origin of this disorder is still not fully understood. This work investigates five samples of CZTS over a range of compositions, fabricated by solid-state reaction. Their crystal structures are conclusively identified using high-resolution anomalous X-ray diffraction. Three of the samples display two distinct CZTS phases, evident in minute splitting of some diffraction peaks (by ~0.02°) due to different c/a lattice parameter ratios. These are attributed to different composition types of CZTS, defined by different charge-neutral defect complexes. In addition to such types previously reported, two new types are proposed: G-type, in which [2CuSn3- + CuZn- + Cui+ + 3VS2+] defects are prevalent, and H-type, in which [3Si2- + VCu- + ZnCu+ + 2SnCu3+] defects are prevalent. In both cases, the defects probably do not form a single complex due to their large number. Above the order-disorder phase transition the two CZTS phases generally converge to a single phase. A mechanism of phase formation in CZTS is thus proposed. This is the first time CZTS crystal structures have been investigated with sufficiently high resolution to distinguish these different CZTS phases, thereby establishing polymorphic behavior in CZTS

Topological defect-mediated skyrmion annihilation in three dimensions

The creation and annihilation of magnetic skyrmions are mediated by three-dimensional topological defects known as Bloch points. Investigation of such dynamical processes is important both for understanding the emergence of exotic topological spin textures, and for future engineering of skyrmions in technological applications. However, while the annihilation of skyrmions has been extensively investigated in two dimensions, in three dimensions the phase transitions are considerably more complex. We report field-dependent experimental measurements of metastable skyrmion lifetimes in an archetypal chiral magnet, revealing two distinct regimes. Comparison to supporting three-dimensional geodesic nudged elastic band simulations indicates that these correspond to skyrmion annihilation into either the helical and conical states, each exhibiting a different transition mechanism. The results highlight that the lowest energy magnetic configuration of the system plays a crucial role when considering the emergence and stability of topological spin structures via defect-mediated dynamics

Confinement of Skyrmions in Nanoscale FeGe Device-like Structures

Skyrmion-based devices have been proposed as a promising solution for low-energy data storage. These devices include racetrack or logic structures and require skyrmions to be confined in regions with dimensions comparable to the size of a single skyrmion. Here we examine skyrmions in FeGe device shapes using Lorentz transmission electron microscopy to reveal the consequences of skyrmion confinement in a device-like structure. Dumbbell-shaped elements were created by focused ion beam milling to provide regions where single skyrmions are confined adjacent to areas containing a skyrmion lattice. Simple block shapes of equivalent dimensions were also prepared to allow a direct comparison with skyrmion formation in a less complex, yet still confined, device geometry. The impact of applying a magnetic field and varying the temperature on the formation of skyrmions within the shapes was examined. This revealed that it is not just confinement within a small device structure that controls the position and number of skyrmions but that a complex device geometry changes the skyrmion behavior, including allowing skyrmions to form at lower applied magnetic fields than in simple shapes. The impact of edges in complex shapes is observed to be significant in changing the behavior of the magnetic textures formed. This could allow methods to be developed to control both the position and number of skyrmions within device structures