Synchronous and proportional deglacial changes in Atlantic meridional overturning and northeast Brazilian precipitation

Changes in heat transport associated with fluctuations in the strength of the Atlantic meridional overturning circulation (AMOC) are widely considered to affect the position of the Intertropical Convergence Zone (ITCZ), but the temporal immediacy of this teleconnection has to date not been resolved. Based on a high-resolution marine sediment sequence over the last deglaciation, we provide evidence for a synchronous and near-linear link between changes in the Atlantic interhemispheric sea surface temperature difference and continental precipitation over northeast Brazil. The tight coupling between AMOC strength, sea surface temperature difference, and precipitation changes over northeast Brazil unambiguously points to a rapid and proportional adjustment of the ITCZ location to past changes in the Atlantic meridional heat transport

A tabletop Optically Pumped Magnetometer setup for the monitoring of magnetic nanoparticle clustering and immobilization using Thermal Noise Magnetometry

Many characterization techniques for magnetic nanoparticles depend on the usage of external fields. This is not the case in Thermal Noise Magnetometry (TNM), where thermal fluctuations in the magnetic signal of magnetic nanoparticle ensembles are measured without any external excitation. This can provide valuable information about the fundamental dynamical properties of the particles, due to the purely observative experiments of this relatively new technique. Until now, TNM signals have been detected only by a superconducting quantum interference device (SQUID) sensor. We present a tabletop setup using Optically Pumped Magnetometers (OPMs) in a small magnetic shield, offering a flexible and accessible alternative and show the agreement between both measurement systems for two different commercially available nanoparticle samples. We argue that the OPM setup with high accessibility complements the SQUID setup with high sensitivity and bandwidth. Furthermore, because of its excellent sensitivity in the lower frequencies, the OPM tabletop setup is well suited to monitor aggregation processes where the magnetization dynamics of the particles tend to slow down, e.g. in biological processes. As a proof of concept, we show for three different immobilization and clustering processes the changes in the noise spectrum measured in the tabletop setup: 1) the aggregation of particles due to the addition of ethanol, 2) the formation of polymer structures in the sample due to UV exposure, and 3) the cellular uptake of the particles by THP-1 cells. From our results we conclude that the tabletop setup offers a flexible and widely adoptable sensor measurement unit to monitor the immobilization and clustering of magnetic nanoparticles over time for different applications

Working Towards a Treat-to-Target Protocol in Juvenile Proliferative Lupus Nephritis - A Survey of Pediatric Rheumatologists and Nephrologists in Germany and Austria.

BackgroundTo describe treatment practices for juvenile proliferative lupus nephritis (LN) class III and IV of pediatric rheumatologists and nephrologists in Germany and Austria in preparation for a treat-to-target treatment protocol in LN.MethodsSurvey study by members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German Society for Pediatric Nephrology (GPN) on diagnostics and (concomitant) therapy of LN.ResultsFifty-eight physicians completed the survey. Overall, there was a considerable heterogeneity regarding the suggested diagnostics and management of juvenile proliferative LN. Increased urinary protein excretion, either assessed by 24 h urine collection or spot urine (protein-creatinine ratio), and reduced estimated glomerular filtration rate were specified as important parameters for indication of kidney biopsy to diagnose proliferative LN and monitoring of therapy. Corticosteroids were generally proposed for induction and maintenance therapy, most often in conjunction with either mycophenolate mofetil (MMF) or cyclophosphamide (CP) as steroid-sparing immunosuppressants. MMF was clearly preferred over CP for induction therapy of LN class III, whereas CP and MMF were equally proposed for LN class IV. MMF was most often recommended for maintenance therapy in conjunction with oral corticosteroids and continued for at least 3 years and 1 year, respectively, after remission. Hydroxychloroquine was widely accepted as a concomitant measure followed by renin-angiotensin system inhibitors in cases of arterial hypertension and/or proteinuria.ConclusionThe majority of pediatric rheumatologists and nephrologists in Germany and Austria propose the use of corticosteroids, most often in combination with either MMF or CP, for treatment of proliferative LN in children. The considerable heterogeneity of responses supports the need for a treat-to-target protocol for juvenile proliferative LN between pediatric rheumatologists and nephrologists

Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry

ObjectiveInterim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS).MethodsFrom September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit.ResultsAt the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (<18 years). The median patient age was 20.0 years (range 2.0–79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive >SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician’s global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout.ConclusionData from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.Novartis Pharma A