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An iterative solution method is introduced for SN transport calculations called "chaotic" iterations. For SN sweeps on parallel-decomposed meshes, a full-parallel sweep can be employed, in which processors must wait to start a sweep until incoming boundary data are received from one or more neighboring processes. This causes delays in the computation that affects efficiency. The parallel block Jacobi (PBJ) method, by contrast, is a splitting method in which all processor-local sweeps are computed using incoming data from the previous iteration with no waiting. This eliminates the delay associated with full-parallel sweeps but adversely impacts the iterative convergence rate. The chaotic iteration is a hybrid of the two possibilities, using current incoming data from neighboring processors when available and previous iteration data otherwise. Whether the boundary data are available or not depends on the communication between processes. It can be viewed as a splitting that changes from one iteration to the next, making the iteration chaotic. In this article, we prove that several iteration schemes associated with the chaotic splitting converge. The analysis presumes some splitting has been imposed at any given iteration, and so the results also apply to fixed, as well as chaotic, splittings. We present numerical results showing the convergence rate of the chaotic iterations method is between the full sweep method and the PBJ method. The numerical results also compare timings between the methods. Notably, for most of the test problems in this article, the chaotic iterations method is at least as fast as the PBJ method. [ABSTRACT FROM AUTHOR]

Alpine soils are expected to contain large amounts of labile carbon (C) which may become a further source of atmospheric CO2 as a result of global warming. However, there is little data available on these soils, and understanding of the influence of environmental factors on soil organic matter (SOM) turnover is limited. We extracted 30 cm deep cores from five grassland sites along a small elevation gradient from 2285 to 2653 m above sea level (a.s.l.) in the central Swiss Alps. Our aim was to determine the quantity, degree of stabilization and mean residence time (MRT) of SOM in relation to site factors such as temperature, soil pH, vegetation, and organic matter (OM) structure. Soil fractions obtained by size and density fractionation revealed a high proportion of labile particulate organic matter C (POM C %) mostly in the uppermost soil layers. POM C in the top 20 cm across the gradient ranged from 39.6-57.6% in comparison to 7.2-29.6% reported in previous studies for lower elevation soils (810-1960m a.s.l.). At the highest elevation, MRTs measured by means of radiocarbon dating and turnover modelling, increased between fractions of growing stability from 90 years in free POM (fPOM) to 534 years in the mineral-associated fraction (mOM). Depending on elevation and pH, plant community data indicated considerable variation in the quantity and quality of litter input, and these patterns could be reflected in the dynamics of soil C. 13C NMR data confirmed the direct relationship of OM composition to MRT. While temperature is likely to be a major cause for the slow turnover rate observed, other factors such as litter quality and soil pH, as well as the combination of all factors, play an important role in causing small-scale variability of SOM turnover. Ignoring this interplay of controlling factors may impair the performance of models to project SOM responses to environmental change. [ABSTRACT FROM AUTHOR]

Patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic disease due to mutations of the PKD1 or PKD2 gene, show signs of complement activation in the urine and cystic fluid, but their pathogenic role in cystogenesis is unclear. We tested the causal relationship between complement activation and cyst growth using a Pkd1KO renal tubular cell line and newly generated conditional Pkd1-/- C3-/- mice. Pkd1-deficient tubular cells have increased expression of complement-related genes (C3, C5, CfB, C3ar, and C5ar1), while the gene and protein expression of complement regulators DAF, CD59, and Crry is decreased. Pkd1-/- C3-/- mice are unable to fully activate the complement cascade and are characterized by a significantly slower kidney cystogenesis, preserved renal function, and reduced intrarenal inflammation compared with Pkd1-/- C3+/+ controls. Transgenic expression of the cytoplasmic C-terminal tail of Pkd1 in Pkd1KO cells lowered C5ar1 expression, restored Daf levels, and reduced cell proliferation. Consistently, both DAF overexpression and pharmacological inhibition of C5aR1 (but not C3aR) reduced Pkd1KO cell proliferation. In conclusion, the loss of Pkd1 promotes unleashed activation of locally produced complement by downregulating DAF expression in renal tubular cells. Increased C5a formation and C5aR1 activation in tubular cells promotes cyst growth, offering a new therapeutic target.

The deposition of antipodocyte autoantibodies in the glomerular subepithelial space induces primary membranous nephropathy (MN), the leading cause of nephrotic syndrome worldwide. Taking advantage of the glomerulus-on-a-chip system, we modeled human primary MN induced by anti-PLA2R antibodies. Here we show that exposure of primary human podocytes expressing PLA2R to MN serum results in IgG deposition and complement activation on their surface, leading to loss of the chip permselectivity to albumin. C3a receptor (C3aR) antagonists as well as C3AR gene silencing in podocytes reduced oxidative stress induced by MN serum and prevented albumin leakage. In contrast, inhibition of the formation of the membrane-attack-complex (MAC), previously thought to play a major role in MN pathogenesis, did not affect permselectivity to albumin. In addition, treatment with a C3aR antagonist effectively prevented proteinuria in a mouse model of MN, substantiating the chip findings. In conclusion, using a combination of pathophysiologically relevant in vitro and in vivo models, we established that C3a/C3aR signaling plays a critical role in complement-mediated MN pathogenesis, indicating an alternative therapeutic target for MN.

B cell depleting therapies permit immunosuppressive drug withdrawal and maintain remission in patients with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), but lack of biomarkers for treatment failure. Post-depletion immune cell reconstitution may identify relapsing patients, but previous characterizations suffered from methodological limitations of flow cytometry. Time-of-flight mass cytometry (CyTOF) is a comprehensive analytic modality that simultaneously quantifies over 40 cellular markers. Herein, we report CyTOF-enabled immune cell comparisons over a 12-month period from 30 children with SDNS receiving B cell depleting therapy who either relapsed (n = 17) or remained stable (n = 13). Anti-CD20 treatment depleted all B cells subsets and CD20 depleting agent choice (rituximab vs ofatumumab) did not affect B cell subset recovery. Despite equal total numbers of B cells, 5 subsets of B cells were significantly higher in relapsing individuals; all identified subsets of B cells were class-switched. T cell subsets (including T follicular helper cells and regulatory T cells) and other major immune compartments were largely unaffected by B cell depletion, and similar between relapsing and stable children. In conclusion, CyTOF analysis of immune cells from anti-CD20 antibody treated patients identifies class-switched B cells as the main subset whose expansion associates with disease relapse. Our findings set the basis for future studies exploring how identified subsets can be used to monitor treatment response and improve our understanding of the pathogenesis of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fribourg, Cioni, Ghiggeri, Cantarelli, Leventhal, Budge, Bin, Riella, Colucci, Vivarelli, Angeletti, Perin and Cravedi.)

Currently available treatments of diabetic kidney disease (DKD) remain limited despite improved understanding of DKD pathophysiology. The complement system is a central part of innate immunity, but its dysregulated activation is detrimental and results in systemic diseases with overt inflammation. Growing evidence suggests complement activation in DKD. With existent drugs and clinical success of treating other kidney diseases, complement inhibition has emerged as a potential novel therapy to halt the progression of DKD. This article will review DKD, the complement system's role in diabetic and non-diabetic disease, and the potential benefits of complement targeting therapies especially for DKD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Budge, Dellepiane, Yu and Cravedi.)

Kidney glomerulosclerosis commonly progresses to end-stage kidney failure, but pathogenic mechanisms are still poorly understood. Here, we show that podocyte expression of decay-accelerating factor (DAF/CD55), a complement C3 convertase regulator, crucially controls disease in murine models of adriamycin (ADR)-induced focal and segmental glomerulosclerosis (FSGS) and streptozotocin (STZ)-induced diabetic glomerulosclerosis. ADR induces enzymatic cleavage of DAF from podocyte surfaces, leading to complement activation. C3 deficiency or prevention of C3a receptor (C3aR) signaling abrogates disease despite DAF deficiency, confirming complement dependence. Mechanistic studies show that C3a/C3aR ligations on podocytes initiate an autocrine IL-1β/IL-1R1 signaling loop that reduces nephrin expression, causing actin cytoskeleton rearrangement. Uncoupling IL-1β/IL-1R1 signaling prevents disease, providing a causal link. Glomeruli of patients with FSGS lack DAF and stain positive for C3d, and urinary C3a positively correlates with the degree of proteinuria. Together, our data indicate that the development and progression of glomerulosclerosis involve loss of podocyte DAF, triggering local, complement-dependent, IL-1β-induced podocyte injury, potentially identifying new therapeutic targets., Competing Interests: Disclosures: J.M. Thurman reported a patent to US 7,999,082 issued "Alexion Pharmaceuticals, Inc." and a patent to US 8,703,140 B2 issued "Alexion Pharmaceuticals, Inc." J. Manrique reported personal fees from Alexion Pharmaceuticals, Inc. P.S. Heeger reported personal fees from Mallinckrodt Pharmaceuticals during the conduct of the study. No other disclosures were reported., (© 2020 Angeletti et al.)

Urinary stone disease (USD) is affecting a greater number of children and low bone mineral density (BMD) and increased skeletal fractures have been demonstrated in stone patients; however, the mechanism(s) driving bone disease remain unclear. This pilot study was undertaken to assess an adolescent kidney stone cohort's BMD and evaluate for an inverse correlation between BMD and urine concentration of lithogenic minerals and/or inflammatory levels. Prospective case-control study was carried out at a large pediatric center. 15 participants with USD (12-18 years of age, 8 female) were matched by age, sex, and body mass index to 15 controls. Lumbar and total body BMD z-score did not differ between groups. When stone formers were separated by sex, there was a significant difference between male stone formers vs. controls total body BMD z-score (Fig. 1). BMD z-score did not significantly correlate with urine calcium, oxalate, citrate or magnesium. Higher urine IL-13 did significantly correlate with higher total body BMD z-score (r = 0.677, p = 0.018). Total body BMD z-score did significantly correlate with body mass index (BMI) as expected for the control group (r = 0.6321, p = 0.0133). However, this relationship was not present in the USD group (r = - 0.1629, p = 0.5619). This is a small but hypothesis-generating study which demonstrates novel evidence of male-specific low BMD in adolescent stone formers. Furthermore, we demonstrated a positive association between urine IL-13 and total body BMD z-score USD patients as well as a lack of a positive BMD and BMI correlations in stone formers.

Purpose The primary aims of this study were to examine the speech-language correlates of decoding difficulties in children with histories of suspected childhood apraxia of speech (sCAS) and to identify predictors of low-proficiency reading levels. Method Participants were school-age children and adolescents, 7-18 years of age, diagnosed with sCAS ( n = 40) or speech sound disorder but no sCAS (SSD-no sCAS; n = 119). The sCAS and SSD-no sCAS reading groups were compared on measures of performance IQ, oral language, phonological awareness, rapid automatic naming, diadochokinetic rates, single word articulation, and multisyllable and nonsense word repetition. Logistic regression analyses were employed to identify predictors of low-proficiency reading in the sCAS and SSD-no sCAS groups. Results Sixty-five percent of the participants with sCAS compared to 24% of those with SSD-no sCAS were classified as low-proficiency readers based on nonsense and single word decoding. Analysis failed to reveal significant differences in reading, oral language, or phonological awareness between low-proficiency readers with sCAS and low-proficiency readers with SSD-no sCAS. Oral language and phonological awareness skills were the best predictors of reading level for all participants, followed by performance on multisyllabic word repetition and diadochokinetic rate. Conclusions The language and phonological awareness deficits of children with sCAS are related to their risks for reading failure. To a lesser degree, motor speech deficits and speech sound production also increase risks for reading difficulties. The findings justify early intervention for this subset of children.

Root turnover is an important carbon flux component in grassland ecosystems because it replenishes substantial parts of carbon lost from soil via heterotrophic respiration and leaching. Among the various methods to estimate root turnover, the root's radiocarbon signature has rarely been applied to grassland soils previously, although the value of this approach is known from studies in forest soils. In this paper, we utilize the root's radiocarbon signatures, at 25 plots, in mountain grasslands of the montane to alpine zone of Europe. We place the results in context of a global data base on root turnover and discuss driving factors. Root turnover rates were similar to those of a subsample of the global data, comprising a similar temperature range, but measured with different approaches, indicating that the radiocarbon method gives reliable, plausible and comparable results. Root turnover rates (0.06-1.0 y(-1)) scaled significantly and exponentially with mean annual temperatures. Root turnover rates indicated no trend with soil depth. The temperature sensitivity was significantly higher in mountain grassland, compared to the global data set, suggesting additional factors influencing root turnover. Information on management intensity from the 25 plots reveals that root turnover may be accelerated under intensive and moderate management compared to low intensity or semi-natural conditions. Because management intensity, in the studied ecosystems, co-varied with temperature, estimates on root turnover, based on mean annual temperature alone, may be biased. A greater recognition of management as a driver for root dynamics is warranted when effects of climatic change on belowground carbon dynamics are studied in mountain grasslands.

Objectives: We describe the development of a five-session psychoeducational treatment, Facilitated Integrated Mood Management (FIMM), which contains many of the core elements of longer evidence-based psychosocial treatments for bipolar disorder. FIMM incorporated a novel mood monitoring program based on mobile phone technology., Methods: Adult patients with bipolar I and II disorders (N = 19) received six sessions (Pilot I: n = 14) or five sessions (Pilot II: n = 5) of FIMM with pharmacotherapy. Treatment facilitators were novice counselors who were trained in a three-day workshop and supervised for six months. FIMM sessions focused on identifying early signs of recurrence, maintaining regular daily and nightly routines, rehearsing mood management strategies, maintaining adherence to medications, and education about substance abuse. Patients sent daily text messages or e-mails containing ratings of their mood and sleep, and weekly messages containing self-ratings on the Quick Inventory of Depressive Symptomatology (QIDS) and the Altman Self Rating Mania Scale (ASRM). Patients also completed a weekly mood management strategies questionnaire., Results: Of the 19 patients, 17 (89.5%) completed FIMM in an average of 9.2 ± 3.4 weeks (Pilot I) and 7.6 ± 0.9 weeks (Pilot II). Patients reported stable moods on the QIDS and ASRM over a 120-day period, and on average responded to 81% of the daily message prompts and 88% of the weekly QIDS and ASRM prompts. Facilitators maintained high levels of fidelity to the FIMM manual. Patients' knowledge of mood management strategies increased significantly between the first and last weeks of treatment., Conclusions: Patients with bipolar disorder can be engaged in a short program of facilitated mood management. The effects of FIMM on the course of bipolar disorder await evaluation in randomized trials. The program may be a useful adjunct to pharmacotherapy in community centers that cannot routinely administer full courses of psychosocial treatment., (© 2012 John Wiley and Sons A/S.)

Background: Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium., Methods: We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity., Findings: We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders., Interpretation: Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment., Funding: National Institute for Health Research Programme Grant for Applied Research., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Objectives: The tendency for people to endorse, as an accurate description of themselves, personality descriptions that are essentially bogus is well-attested. The study tested whether the so-called 'Barnum' effect could be predicted by individual differences in self-referential thinking, and beyond this, schizotypy more generally., Methods: 130 Participants completed four different measures of the Barnum effect followed by measures of schizotypy and self-referential thinking., Results: Both self-referential thinking and positive schizotypy independently predicted the degree of agreement with several Barnum measures including both favorable and unfavorable personality descriptions, as well as computer-generated and horoscope-based readings., Limitations: The sample is heavily represented by students and is not representative of the general population. Testing at a single point in time may have reduced differences between different indices of the Barnum effect., Conclusions: Self-referential thinking and schizotypy more generally are key contributors to the Barnum effect across a wide range of indices., (Copyright © 2010 Elsevier Ltd. All rights reserved.)