Search

Background: The impact of adjunctive anti-inflammatory treatment on outcomes for patients with Kawasaki disease (KD) and coronary artery aneurysms (CAAs) is unknown. Methods: Using data from the International KD Registry in patients with ≥ medium CAA we evaluate associations of treatment with outcomes and major adverse cardiac events (MACE). Results: Medium or large CAA was present in 527 (32%) patients. All were treated with intravenous immunoglobulin (IVIG), 70% were male, and the median age was 1.3 years (interquartile range: 0.4-4.0 years). The most common acute therapies included single IVIG alone in 243 (46%), multiple IVIG in 100 (19%), multiple IVIG + corticosteroids in 75 (14%), and multiple IVIG + infliximab + corticosteroids in 44 (8%) patients. Patients who received therapy beyond single IVIG had a larger CA z-score at baseline (P < 0.001) and a higher rate of bilateral CAA (P < 0.001). Compared with IVIG alone, early adjunctive treatments (within 3 days of initial IVIG) were not associated with time to CAA regression or MACE, whereas later adjunctive therapy was associated with MACE and longer time to CAA regression. Patients receiving IVIG plus steroids vs IVIG alone had a trend towards shorter time to CAA regression and lower risk of MACE (P = 0.07). A larger CAA z-score at baseline was the strongest predictor of an increase in the CAA z-score over follow-up, lower likelihood of CAA regression, and higher risk of MACE. Conclusions: Persistence of CAA and MACE are more strongly associated with baseline severity CAA than with acute adjuvant anti-inflammatory therapy. Patients who received late adjunctive therapy are at higher risk for worse outcomes. Résumé: Contexte: L’incidence d’un traitement anti-inflammatoire d’appoint chez les patients atteints de la maladie de Kawasaki (MK) compliquée d’anévrismes coronariens est inconnue. Méthodologie: À partir de données provenant du registre international de la maladie de Kawasaki portant sur les patients ayant subi des anévrismes coronariens modérés ou importants, nous avons évalué l’incidence des différents traitements sur les résultats cliniques et les événements cardiovasculaires indésirables majeurs (ECIM). Résultats: Des anévrismes coronariens modérés ou importants ont été relevés chez 527 patients (32 %). Tous les patients recevaient des immunoglobulines administrées par voie intraveineuse (IgIV); 70 % d’entre eux étaient de sexe masculin, et leur âge médian était de 1,3 an (écart interquartile : de 0,4 an à 4,0 ans). Les traitements d’urgence les plus fréquents comprenaient un seul traitement par IgIV chez 243 patients (46 %), plusieurs traitements par IgIV chez 100 patients (19 %), une association de plusieurs traitements IgIV et de corticostéroïdes chez 75 patients (14 %) et une association de plusieurs traitements IgIV, de corticostéroïdes et d’infliximab chez 44 patients (8 %). Les patients ayant reçu un traitement autre qu’un seul traitement IgIV présentaient des scores z initiaux plus élevés pour le diamètre des artères coronaires (P < 0,001) et un taux plus élevé d’anévrismes coronariens bilatéraux (P < 0,001). En comparaison d’un traitement par IgIV seulement, les traitements d’appoint précoces (administrés dans les trois jours suivant le début du traitement par IgIV) n’ont pas eu d’incidence sur la durée avant la régression des anévrismes coronariens ni sur la survenue d’ECIM, alors que les traitements d’appoint plus tardifs ont été associés à un risque plus élevé d’ECIM et à une régression plus tardive des anévrismes coronariens. Les patients ayant reçu une association d’IgIV et de corticostéroïdes avaient tendance à présenter une régression plus rapide des anévrismes coronariens et un plus faible risque d’ECIM que ceux recevant uniquement un traitement par IgIV (P = 0,07). Un score z initial plus élevé pour un anévrisme coronarien était le facteur prédictif le plus puissant d’une augmentation du score z pendant la période de suivi, d’une probabilité plus faible de régression de l’anévrisme et d’un risque plus élevé d’ECIM. Conclusions: La gravité initiale de l’anévrisme coronarien est plus fortement associée à la persistance de l’anévrisme et à la survenue d’ECIM que le recours à un traitement anti-inflammatoire d’urgence en appoint. Les patients recevant un traitement d’appoint tardif étaient par ailleurs plus susceptibles de présenter des résultats défavorables.

Dysfunction of the gastrointestinal system, and to the autophagy lysososmal pathway (ALP) have been reported in Parkinson’s disease. Here the authors report epigenetic disruption of ALP related genes in the appendix of individuals with Parkinson’s disease.

Abstract Background Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson’s disease (PD), but its molecular determinants are unknown. Here, we identify divergent epigenetic patterns involved in hemispheric asymmetry by profiling DNA methylation in isolated prefrontal cortex neurons from control and PD brain hemispheres. DNA methylation is fine-mapped at enhancers and promoters, genome-wide, by targeted bisulfite sequencing in two independent sample cohorts. Results We find that neurons of the human prefrontal cortex exhibit hemispheric differences in DNA methylation. Hemispheric asymmetry in neuronal DNA methylation patterns is largely mediated by differential CpH methylation, and chromatin conformation analysis finds that it targets thousands of genes. With aging, there is a loss of hemispheric asymmetry in neuronal epigenomes, such that hemispheres epigenetically converge in late life. In neurons of PD patients, hemispheric asymmetry in DNA methylation is greater than in controls and involves many PD risk genes. Epigenetic, transcriptomic, and proteomic differences between PD hemispheres correspond to the lateralization of PD symptoms, with abnormalities being most prevalent in the hemisphere matched to side of symptom predominance. Hemispheric asymmetry and symptom lateralization in PD is linked to genes affecting neurodevelopment, immune activation, and synaptic transmission. PD patients with a long disease course have greater hemispheric asymmetry in neuronal epigenomes than those with a short disease course. Conclusions Hemispheric differences in DNA methylation patterns are prevalent in neurons and may affect the progression and symptoms of PD.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a gestational disease caused by maternal immune responses against fetal platelets. Using a FNAIT mouse model and human trophoblast cell lines, here the authors show that uterine natural killer cell-mediated trophoblast apoptosis contributes to FNAIT pathogenesis.

Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.

Abstract For decades, superfluid helium has attracted the interest of the scientific community as an extremely pure realisation of a quantum liquid, only accessible at temperatures close to absolute zero. Previously, helium films have only been observed directly using X-rays. However, this method is limited to temperatures above 1 K due to the high levels of energy deposition, and it also suffers from an inability to distinguish between helium isotopes. Here we show that a 3He layer on top of a phase separated mixture film at 170 mK gradually dissolves into the 4He with increasing temperature. We also observe an anomaly in film behaviour near 300 mK and unexpected restoration of the layered structure at 1.5 K which is consistent with a re-entrant phase transition leading to the suppression of superfluidity in the film near 300 mK. Our successful application of neutron scattering to study helium films at ultra-low temperatures opens up new possibilities for future research.

Abstract Magnetic skyrmions are topologically protected magnetization vortices that form three-dimensional strings in chiral magnets. With the manipulation of skyrmions being key to their application in devices, the focus has been on their dynamics within the vortex plane, while the dynamical control of skyrmion strings remained uncharted territory. Here, we report the effective bending of three-dimensional skyrmion strings in the chiral magnet MnSi in orthogonal thermal gradients using small angle neutron scattering. This dynamical behavior is achieved by exploiting the temperature-dependent skyrmion Hall effect, which is unexpected in the framework of skyrmion dynamics. We thus provide experimental evidence for the existence of magnon friction, which was recently proposed to be a key ingredient for capturing skyrmion dynamics, requiring a modification of Thiele’s equation. Our work therefore suggests the existence of an extra degree of freedom for the manipulation of three-dimensional skyrmions.

In this paper, we determine the magnetic moment induced in graphene when grown on a cobalt film using polarised neutron reflectivity (PNR). A magnetic signal in the graphene was detected by X-ray magnetic circular dichroism (XMCD) spectra at the C K-edge. From the XMCD sum rules an estimated magnetic moment of 0.3 μB/C atom, while a more accurate estimation of 0.49 μB/C atom was obtained by carrying out a PNR measurement at 300 K. The results indicate that the higher magnetic moment in Co is counterbalanced by the larger lattice mismatch between the Co-C (1.6%) and the slightly longer bond length, inducing a magnetic moment in graphene that is similar to that reported in Ni/graphene heterostructures.

Magnetic molecules deposited on a metallic substrate constitute a method to engineer the spin properties of the molecule and has potential application in low-power information storage devices. Here, the authors investigate a superconductor/molecule/normal metal heterostructure and demonstrate spin-ordering and proximity induced superconducting properties at the metallo-molecular interface.

Abstract The experimental evidence of the exchange bias (EB) effect in epitaxial heterostructures of ferromagnetic La0.67Sr0.33MnO3 (LSMO) and paramagnetic LaNiO3 (LNO) grown on MgO(001) substrates is reported. The macroscopic magnetization measurements show a clear indication of EB in LNO/LSMO and LSMO/LNO/LSMO heterostructures. The strength of the exchange coupling rapidly reduces as the temperature is increased and almost vanishes above 50 K. Using spin dependent polarized neutron reflectometry (PNR) detailed depth dependent magnetization profiles of the heterostructures are investigated to understand the role of interface magnetism in the observed EB. PNR results establish the emergence of the interfacial ferromagnetic LNO layer of thickness ≈22–35 Å (≈6–9 unit cell) and magnetization ≈80 emu cc−1 at the LNO/LSMO interface for T

Additive manufacturing is a rapidly expanding field, encompassing many methods to manufacture parts and coatings with a wide variety of feedstock. Metal powders are one such feedstock, with a range of compositions and morphologies. Understanding subtle changes in the feedstock is critical to ensure successful consolidation and quality control of both the feedstock and manufactured part. Current standards lack the ability to finely distinguish almost acceptable powders from barely acceptable ones. Here, novel means of powder feedstock characterization for quality control are demonstrated for the solid-state AM process of cold spray, though similar methods may be extrapolated to other additive methods as well. These characterization methods aim to capture the physics of the process, which in cold spray consists of high strain rate deformation of solid-state feedstock. To capture this, in this effort powder compaction was evaluated via rapidly applied loads, flowability of otherwise non-flowable powders was evaluated with the addition of vibration, and powder electrical resistivity was evaluated through compaction between two electrodes. Several powders, including aluminum alloys, chromium, and cermet composites, were evaluated in this effort, with each case study demonstrating the need for non-traditional characterization metrics as a means of quality control and classification of these materials.

Unconventional superconductivity has been suggested to be present at the interface between bismuth and nickel in thin-film bilayers. In this work, we study the structural, magnetic, and superconducting properties of sputter deposited Bi/Ni bilayers. As-grown, our films do not display a superconducting transition; however, when stored at room temperature, after about 14 days our bilayers develop a superconducting transition up to 3.8 K. To systematically study the effect of low temperature annealing on our bilayers, we perform structural characterization with x-ray diffraction and polarized neutron reflectometry, along with magnetometry and low-temperature electrical transport measurements on samples annealed at 70^{∘}C. We show that the onset of superconductivity in our samples is coincident with the formation of ordered NiBi_{3} intermetallic alloy, a known s-wave superconductor. We calculate that the annealing process has an activation energy of (0.86±0.06)eV. As a consequence, gentle heating of the bilayers will cause formation of the superconducting NiBi_{3} at the Ni/Bi interface, which poses a challenge to studying any distinct properties of Bi/Ni bilayers without degrading that interface.

Using x-ray photoelectron emission microscopy we have observed the coexistence of ferromagnetic and antiferromagnetic phases in a (3 at%)Pd-doped FeRh epilayer. By quantitatively analyzing the resultant images we observe that as the epilayer transforms there is a change in magnetic domain symmetry from predominantly twofold at lower temperatures through to an equally weighted combination of both four and twofold symmetries at higher temperature. It is postulated that the lowered symmetry Ising-like nematic phase resides at the near-surface of the epilayer. This behavior is different to that of undoped FeRh suggesting that the variation in symmetry is driven by the competing structural and electronic interactions in the nanoscale FeRh film coupled with the effect of the chemical doping disorder.

We present a method to determine the magnetic configuration of an in-plane magnetized permalloy layer using Fourier transform holography with extended references in an off-normal geometry. We use a narrow slit as an extended holographic reference to record holograms with the sample surface orthogonal to the incident x-ray beam, as well as rotated by 30° and 45° with respect to the beam. To demonstrate the sensitivity of the technique to in-plane magnetization, we present images of flux closed ground states in thin (∼50 nm) permalloy elements, less than 1 μ m in lateral size. Images of the in-plane domain pattern which is magnetostatically imprinted into a permalloy film by the stray fields generated by an adjacent Co/Pt multilayer were obtained. It is found that, whilst the domain patterns within the two magnetic layers show a strong resemblance at remanence within a pristine sample, the similarities disappear after the sample is exposed to a saturating magnetic field.

Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder caused by maternal antibody-mediated destruction of fetal/neonatal platelets. It is the most common cause of severe thrombocytopenia in neonates, but the frequency of FNIT-related miscarriage is unknown, and the mechanism(s) underlying fetal mortality have not been explored. Furthermore, although platelet αIIbβ3 integrin and GPIbα are the major antibody targets in immune thrombocytopenia, the reported incidence of anti-GPIbα-mediated FNIT is rare. Here, we developed mouse models of FNIT mediated by antibodies specific for GPIbα and β3 integrin and compared their pathogenesis. We found, unexpectedly, that miscarriage occurred in the majority of pregnancies in our model of anti-GPIbα-mediated FNIT, which was far more frequent than in anti-β3-mediated FNIT. Dams with anti-GPIbα antibodies exhibited extensive fibrin deposition and apoptosis/necrosis in their placentas, which severely impaired placental function. Furthermore, anti-GPIbα (but not anti-β3) antiserum activated platelets and enhanced fibrin formation in vitro and thrombus formation in vivo. Importantly, treatment with either intravenous IgG or a monoclonal antibody specific for the neonatal Fc receptor efficiently prevented anti-GPIbα-mediated FNIT. Thus, the maternal immune response to fetal GPIbα causes what we believe to be a previously unidentified, nonclassical FNIT (i.e., spontaneous miscarriage but not neonatal bleeding) in mice. These results suggest that a similar pathology may have masked the severity and frequency of human anti-GPIbα-mediated FNIT, but also point to possible therapeutic interventions. [ABSTRACT FROM AUTHOR]