Kaliopenic nephropathy revisited

In the 'older' literature, a definitive renal pathology was described in patients with long-standing hypokalaemia and depletion of the body's potassium reserves. The topic is relevant because possibly a quite cheaply reversible element in the course of chronic kidney disease progression could be addressed. Earlier, pathologists drew attention to vacuolar changes in renal tubular epithelium accompanied by inflammatory interstitial changes in patients with potassium losses. The diagnostic term 'kaliopenic nephropathy' was coined to describe such patients. Kaliopenic nephropathy now receives less emphasis than in earlier times. However, with eating disorders, laxative abuse and other potential causes, we suggest that the syndrome should be resurrected

Industrial practitioners' mental models of adversarial machine learning

Although machine learning is widely used in practice, little is known about practitioners' understanding of potential security challenges. In this work, we close this substantial gap and contribute a qualitative study focusing on developers' mental models of the machine learning pipeline and potentially vulnerable components. Similar studies have helped in other security fields to discover root causes or improve risk communication. Our study reveals two facets of practitioners' mental models of machine learning security. Firstly, practitioners often confuse machine learning security with threats and defences that are not directly related to machine learning. Secondly, in contrast to most academic research, our participants perceive security of machine learning as not solely related to individual models, but rather in the context of entire workflows that consist of multiple components. Jointly with our additional findings, these two facets provide a foundation to substantiate mental models for machine learning security and have implications for the integration of adversarial machine learning into corporate workflows, decreasing practitioners' reported uncertainty, and appropriate regulatory frameworks for machine learning security

Unconventional spin fluctuations in the hexagonal antiferromagnet YMnO3_3

We used inelastic neutron scattering to show that well below its N\'{e}el temperature, $T_{\rm N}$, the two-dimensional (2D) XY nearly-triangular antiferromagnet YMnO$_{3}$ has a prominent {\it central peak} associated with 2D antiferromagnetic fluctuations with a characteristic life time of 0.55(5) ps, coexisting with the conventional long-lived spin-waves. Existence of the two time scales suggests competition between the N\'{e}el phase favored by weak interplane interactions, and the Kosterlitz-Thouless phase intrinsic to the 2D XY spin system.Comment: 4pages, 5figure

Calomplification — the power of generative calorimeter models

Motivated by the high computational costs of classical simulations, machine-learned generative models can be extremely useful in particle physics and elsewhere. They become especially attractive when surrogate models can efficiently learn the underlying distribution, such that a generated sample outperforms a training sample of limited size. This kind of GANplification has been observed for simple Gaussian models. We show the same effect for a physics simulation, specifically photon showers in an electromagnetic calorimeter

Caplacizumab: frequent local skin reactions

Despite the increasing role of molecular markers, differential counts and morphology of hematopoietic cells in the bone marrow (BM) remain essential diagnostic criteria in hematological diseases. However, the respective reference values for BM myelogram commonly used came from small series with limited numbers of healthy individuals. We evaluated the myelograms of 236 healthy individuals who underwent unrelated bone marrow donation. Health check-ups were performed 4 weeks prior to harvest. Samples for this study, taken from the first aspiration, were stained according to the standard Pappenheim method. Three experienced investigators assessed cellularity, megakaryopoiesis, and differential counts independently. The median donor age was 31 (range 18-51) years. Predonation tests did not reveal any relevant morbidity. Thirty-seven out of 42 hypocellular marrow samples were from younger donors up to 39 years. Content of megakaryocytes was normal in 210 specimens (89%). Gender and body mass index had significant impact on hematopoiesis, whereas age had not. The number of erythroblasts was higher (about 32%) and the proportion granulopoiesis slightly lower (about 50%) compared with previous studies. Differential counts showed also some differences with respect to individual maturation stages in these lines. Interrater comparisons showed greater reliability for the assignment of cells to the different hematopoietic cell lines than for single-cell diagnoses. This study largely confirms the results for cell counts in normal human bone marrow available from previous reports and provides some insights into factors that affect individual cell populations. It also reveals substantial variability among even experienced investigators in cytological diagnoses

CSF2-dependent monocyte education in the pathogenesis of ANCA-induced glomerulonephritis

OBJECTIVES: Myeloid cell activation by antineutrophil cytoplasmic antibody (ANCA) is pivotal for necrotising vasculitis, including necrotising crescentic glomerulonephritis (NCGN). In contrast to neutrophils, the contribution of classical monocyte (CM) and non-classical monocyte (NCM) remains poorly defined. We tested the hypothesis that CMs contribute to antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and that colony-stimulating factor-2 (CSF2, granulocyte-macrophage colony-stimulating factor (GM-CSF)) is an important monocyte-directed disease modifier.METHODS: Myeloperoxidase (MPO)-immunised MPO(-/-) mice were transplanted with haematopoietic cells from wild-type (WT) mice, C-C chemokine receptor 2 (CCR2)(-/-) mice to abrogate CM, or transcription factor CCAAT-enhancer-binding protein beta (C/EBPß)(-/-) mice to reduce NCM, respectively. Monocytes were stimulated with CSF2, and CSF2 receptor subunit beta (CSF2rb)-deficient mice were used. Urinary monocytes and CSF2 were quantified and kidney expression was analysed. CSF2-blocking antibody was used in the nephrotoxic nephritis (NTN) model. RESULTS: Compared with WT mice, CCR2(-/-) chimeric mice showed reduced circulating CM and were protected from NCGN. C/EBPß(-/-) chimeric mice lacked NCM but developed NCGN similar to WT chimeric mice. Kidney and urinary CSF2 were upregulated in AAV mice. CSF2 increased the ability of ANCA-stimulated monocytes to generate interleukin-1ß and to promote T17(H) effector cell polarisation. CSF2rb(-/-) chimeric mice harboured reduced numbers of kidney T17(H) cells and were protected from NCGN. CSF2 neutralisation reduced renal damage in the NTN model. Finally, patients with active AAV displayed increased urinary CM numbers, CSF2 levels and expression of GM-CSF in infiltrating renal cells. CONCLUSIONS: CMs but not NCMs are important for inducing kidney damage in AAV. CSF2 is a crucial pathological factor by modulating monocyte proinflammatory functions and thereby T17(H) cell polarisation

Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients

ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity-guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring