Multiple and Fast: The Accretion of Ordinary Chondrite Parent Bodies

Although petrologic, chemical and isotopic studies of ordinary chondrites and meteorites in general have largely helped establish a chronology of the earliest events of planetesimal formation and their evolution, there are several questions that cannot be resolved via laboratory measurements and/or experiments only. Here we propose rationale for several new constraints on the formation and evolution of ordinary chondrite parent bodies (and by extension most planetesimals) from newly available spectral measurements and mineralogical analysis of main belt S-type asteroids (83 objects) and unequilibrated ordinary chondrite meteorites (53 samples). Based on the latter, we suggest spectral data may be used to distinguish whether an ordinary chondrite was formed near the surface or in the interior of its parent body. If these constraints are correct, the suggested implications include that: i) large groups of compositionally similar asteroids are a natural outcome of planetesimal formation and, consequently, meteorites within a given class can originate from multiple parent bodies; ii) the surfaces of large (up to ~200km) S-type main-belt asteroids expose mostly the interiors of the primordial bodies, a likely consequence of impacts by small asteroids (D<10km) in the early solar system (Ciesla et al. 2013); iii) the duration of accretion of the H chondrite parent bodies was likely short (instantaneous or in less then ~10^5 yr but certainly not as long as 1 Myr); iv) LL-like bodies formed closer to the Sun than H-like bodies, a possible consequence of radial mixing and size sorting of chondrules in the protoplanetary disk prior to accretion.Comment: Accepted for publication in Ap

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BACKGROUND: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. METHODS: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. RESULTS: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). CONCLUSIONS: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab

OBJECTIVE: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. METHODS: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. RESULTS: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. CONCLUSIONS: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach

A Critical Examination of the X-Wind Model for Chondrule and Calcium-rich, Aluminum-rich Inclusion Formation and Radionuclide Production

Meteoritic data, especially regarding chondrules and calcium-rich, aluminum-rich inclusions (CAIs), and isotopic evidence for short-lived radionuclides (SLRs) in the solar nebula, potentially can constrain how planetary systems form. Intepretation of these data demands an astrophysical model, and the "X-wind" model of Shu et al. (1996) and collaborators has been advanced to explain the origin of chondrules, CAIs and SLRs. It posits that chondrules and CAIs were thermally processed < 0.1 AU from the protostar, then flung by a magnetocentrifugal outflow to the 2-3 AU region to be incorporated into chondrites. Here we critically examine key assumptions and predictions of the X-wind model. We find a number of internal inconsistencies: theory and observation show no solid material exists at 0.1 AU; particles at 0.1 AU cannot escape being accreted into the star; particles at 0.1 AU will collide at speeds high enough to destroy them; thermal sputtering will prevent growth of particles; and launching of particles in magnetocentrifugal outflows is not modeled, and may not be possible. We also identify a number of incorrect predictions of the X-wind model: the oxygen fugacity where CAIs form is orders of magnitude too oxidizing; chondrule cooling rates are orders of magnitude lower than those experienced by barred olivine chondrules; chondrule-matrix complementarity is not predicted; and the SLRs are not produced in their observed proportions. We conclude that the X-wind model is not relevant to chondrule and CAI formation and SLR production. We discuss more plausible models for chondrule and CAI formation and SLR production.Comment: Accepted for publication in The Astrophysical Journa

Differences in management approaches for lupus nephritis within the UK

\ua9 The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.Objectives: Outcomes of therapy for LN are often suboptimal. Guidelines offer varied options for treatment of LN and treatment strategies may differ between clinicians and regions. We aimed to assess variations in the usual practice of UK physicians who treat LN. Methods: We conducted an online survey of simulated LN cases for UK rheumatologists and nephrologists to identify treatment preferences for class IV and class V LN. Results: Of 77 respondents, 48 (62.3%) were rheumatologists and 29 (37.7%) were nephrologists. A total of 37 (48.0%) reported having a joint clinic between nephrologists and rheumatologists, 54 (70.0%) reported having a multidisciplinary team meeting for LN and 26 (33.7%) reported having a specialized lupus nurse. Of the respondents, 58 (75%) reported arranging a renal biopsy before starting the treatment. A total of 20 (69%) of the nephrologists, but only 13 (27%) rheumatologists, reported having a formal departmental protocol for treating patients with LN (P &lt; 0.001). The first-choice treatment of class IV LN in pre-menopausal patients was MMF [41 (53.2%)], followed by CYC [15 (19.6%)], rituximab [RTX; 12 (12.5%)] or a combination of immunosuppressive drugs [9 (11.7%)] with differences between nephrologists’ and rheumatologists’ choices (P \ubc 0.026). For class V LN, MMF was the preferred initial treatment, irrespective of whether proteinuria was in the nephrotic range or not. RTX was the preferred second-line therapy for non-responders. Conclusion: There was variation in the use of protocols, specialist clinic service provision, biopsies and primary and secondary treatment choices for LN reported by nephrologists and rheumatologists in the UK

Fluid evolution in CM carbonaceous chondrites tracked through the oxygen isotopic compositions of carbonates

The oxygen isotopic compositions of calcite grains in four CM carbonaceous chondrites have been determined by NanoSIMS, and results reveal that aqueous solutions evolved in a similar manner between parent body regions with different intensities of aqueous alteration. Two types of calcite were identified in Murchison, Mighei, Cold Bokkeveld and LaPaz Icefield 031166 by differences in their petrographic properties and oxygen isotope values. Type 1 calcite occurs as small equant grains that formed by filling of pore spaces in meteorite matrices during the earliest stages of alteration. On average, the type 1 grains have a δ18O of ∼32–36‰ (VSMOW), and Δ17O of between ∼2‰ and −1‰. Most grains of type 2 calcite precipitated after type 1. They contain micropores and inclusions, and have replaced ferromagnesian silicate minerals. Type 2 calcite has an average δ18O of ∼21–24‰ (VSMOW) and a Δ17O of between ∼−1‰ and −3‰. Such consistent isotopic differences between the two calcite types show that they formed in discrete episodes and from solutions whose δ18O and δ17O values had changed by reaction with parent body silicates, as predicted by the closed-system model for aqueous alteration. Temperatures are likely to have increased over the timespan of calcite precipitation, possibly owing to exothermic serpentinisation. The most highly altered CM chondrites commonly contain dolomite in addition to calcite. Dolomite grains in two previously studied CM chondrites have a narrow range in δ18O (∼25–29‰ VSMOW), with Δ17O ∼−1‰ to −3‰. These grains are likely to have precipitated between types 1 and 2 calcite, and in response to a transient heating event and/or a brief increase in fluid magnesium/calcium ratios. In spite of this evidence for localised excursions in temperature and/or solution chemistry, the carbonate oxygen isotope record shows that fluid evolution was comparable between many parent body regions. The CM carbonaceous chondrites studied here therefore sample either several parent bodies with a very similar initial composition and evolution or, more probably, a single C-type asteroid

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Continuous-time quantum walks for MAX-CUT are hot

By exploiting the link between time-independent Hamiltonians and thermalisation, heuristic predictions on the performance of continuous-time quantum walks for MAX-CUT are made. The resulting predictions depend on the number of triangles in the underlying MAX-CUT graph. We extend these results to the time-dependent setting with multi-stage quantum walks and Floquet systems. The approach followed here provides a novel way of understanding the role of unitary dynamics in tackling combinatorial optimisation problems with continuous-time quantum algorithms.Comment: 25 pages, 29 figure

Controlled-atmosphere thermal demagnetization and paleointensity analyses of extraterrestrial rocks

We describe a system for conducting thermal demagnetization of extraterrestrial rocks in a controlled atmosphere appropriate for a wide range of oxygen fugacities within the stability domain of iron. Thermal demagnetization and Thellier-Thellier paleointensity experiments on lunar basalt synthetic analogs show that the controlled atmosphere prevents oxidation of magnetic carriers. When combined with multidomain paleointensity techniques, this opens the possibility of highly accurate thermal demagnetization and paleointensity measurements on rocks from the Moon and asteroids.United States. National Aeronautics and Space Administration (Grant NNX12AH80G)

Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end-stage kidney disease and associated with poor outcomes after kidney transplantation from early disease recurrence. Prophylactic eculizumab treatment at the time of transplantation is used in selected patients with aHUS. We report a retrospective case note review describing transplant outcomes in patients with aHUS transplanted between 1978 and 2017, including those patients treated with eculizumab. / Methods: The National Renal Complement Therapeutics Centre database identified 118 kidney transplants in 86 recipients who had a confirmed diagnosis of aHUS. Thirty-eight kidney transplants were performed in 38 recipients who received prophylactic eculizumab. The cohort not treated with eculizumab comprised 80 transplants in 60 recipients and was refined to produce a comparable cohort of 33 transplants in 32 medium and high-risk recipients implanted since 2002. Complement pathway genetic screening was performed. Graft survival was censored for graft function at last follow-up or patient death. Graft survival without eculizumab treatment is described by complement defect status and by Kidney Disease: Improving Global Outcomes risk stratification. / Results: Prophylactic eculizumab treatment improved renal allograft survival (P = 0.006) in medium and high-risk recipients with 1-y survival of 97% versus 64% in untreated patients. Our data supports the risk stratification advised by Kidney Disease: Improving Global Outcomes. / Conclusions: Prophylactic eculizumab treatment dramatically improves graft survival making transplantation a viable therapeutic option in aHUS