We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All ...subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.
While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future ...SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.
This is the third in a series of papers studying the astrophysics and cosmology of massive, dynamically relaxed galaxy clusters. Our sample comprises 40 clusters identified as being dynamically ...relaxed and hot (i.e. massive) in Papers I and II of this series. Here we consider the thermodynamics of the intracluster medium, in particular the profiles of density, temperature and related quantities, as well as integrated measurements of gas mass, average temperature, total luminosity and centre-excluded luminosity. We fit power-law scaling relations of each of these quantities as a function of redshift and cluster mass, which can be measured precisely and with minimal bias for these relaxed clusters using hydrostatic arguments. For the thermodynamic profiles, we jointly model the density and temperature and their intrinsic scatter as a function of radius, thus also capturing the behaviour of the gas pressure and entropy. For the integrated quantities, we also jointly fit a multidimensional intrinsic covariance. Our results reinforce the view that simple hydrodynamical models provide a good description of relaxed clusters outside their centres, but that additional heating and cooling processes are important in the inner regions (radii r ... 0.5 r sub( 2500) ... 0.15 r sub( 500)). The thermodynamic profiles remain regular, with small intrinsic scatter, down to the smallest radii where deprojection is straightforward (~20 kpc); within this radius, even the most relaxed systems show clear departures from spherical symmetry. Our results suggest that heating and cooling are continuously regulated in a tight feedback loop, allowing the cluster atmosphere to remain stratified on these scales. (ProQuest: ... denotes formulae/symbols omitted.)
This is the second in a series of papers studying the astrophysics and cosmology of massive, dynamically relaxed galaxy clusters. The data set employed here consists of Chandra observations of 40 ...such clusters, identified in a comprehensive search of the Chandra archive for hot (kT ... 5 keV), massive, morphologically relaxed systems, as well as high-quality weak gravitational lensing data for a subset of these clusters. Here we present cosmological constraints from measurements of the gas mass fraction, ..., for this cluster sample. By incorporating a robust gravitational lensing calibration of the X-ray mass estimates, and restricting our measurements to the most self-similar and accurately measured regions of clusters, we significantly reduce systematic uncertainties compared to previous work. Our data for the first time constrain the intrinsic scatter in fgas, 7.4 ± 2.3 per cent in a spherical shell at radii 0.8-1.2 ... (~1/4 of the virial radius), consistent with the expected level of variation in gas depletion and non-thermal pressure for relaxed clusters. From the lowest redshift data in our sample, five clusters at z < 0.16, we obtain a constraint on a combination of the Hubble parameter and cosmic baryon fraction, ... = 0.089 ± 0.012, that is insensitive to the nature of dark energy. Combining this with standard priors on h and ... provides a tight constraint on the cosmic matter density, ... = 0.27 ± 0.04, which is similarly insensitive to dark energy. Using the entire cluster sample, extending to z > 1, we obtain consistent results for ... and interesting constraints on dark energy: ... for non-flat ...CDM (cosmological constant) models, and w = -0.98 ± 0.26 for flat models with a constant dark energy equation of state. Our results are both competitive and consistent with those from recent cosmic microwave background, Type Ia supernova and baryon acoustic oscillation data. We present constraints on more complex models of evolving dark energy from the combination of fgas data with these external data sets, and comment on the possibilities for improved fgas constraints using current and next-generation X-ray observatories and lensing data. (ProQuest: ... denotes formulae/symbols omitted.)
Globally, the corona virus disease 2019 (COVID-19) pandemic has created an interpersonally threatening context within which other people have become a source of possible threat. This study reports on ...the development and validation of a self-report measure of pandemic paranoia; that is, heightened levels of suspicion and mistrust towards others due to the COVID-19 pandemic.
An international consortium developed an initial set of 28 items for the Pandemic Paranoia Scale (PPS), which were completed by participants from the UK (
= 512), USA (
= 535), Germany (
= 516), Hong Kong (
= 454) and Australia (
= 502) using stratified quota sampling (for age, sex and educational attainment) through Qualtrics and translated for Germany and Hong Kong.
Exploratory factor analysis in the UK sample suggested a 25-item, three-factor solution (persecutory threat; paranoid conspiracy and interpersonal mistrust). Confirmatory factor analysis (CFA) on the remaining combined sample showed sufficient model fit in this independent set of data. Measurement invariance analyses suggested configural and metric invariance, but no scalar invariance across cultures/languages. A second-order factor CFA on the whole sample indicated that the three factors showed large loadings on a common second-order pandemic paranoia factor. Analyses also supported the test-retest reliability and internal and convergent validity.
The PPS offers an internationally validated and reliable method for assessing paranoia in the context of a pandemic. The PPS has the potential to enhance our understanding of the impact of the pandemic, the nature of paranoia and to assist in identifying and supporting people affected by pandemic-specific paranoia.
The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to ...analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and ...early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes.
Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance.
Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or nodes), and among these, 48% resolved (at primary site and/or nodes); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically.
Hypoxia is present in HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.
•Novel receiver with solids as heat transfer fluid.•New continuum model for multiphase heat transfer.•Continuum model validated via DEM simulations.
A novel solar receiver that uses solid particles ...as a heat transfer fluid is being developed at the National Renewable Energy Laboratory for use in concentrating solar power plants. The prototype considered here is enclosed and contains arrays of hexagonal heat transfer tubes that particles flow between. Discrete element method (DEM) simulations were completed for a laboratory-scale solar receiver for different geometric configurations, hexagon apex angles, particle sizes, and mass flow rates. The heat transfer strongly depends on the particle size, where increased heat transfer is obtained using smaller particles. At higher solids mass flow rates, more particles contact the heat transfer surfaces and the overall heat transfer increases. When a sharper apex angle was used, the particles flow through the receiver at a faster velocity, but the heat transfer decreases because the solids concentration decreases slightly at higher velocities. The DEM simulations show that the heat transfer strongly depends on the solids concentration near the heat transfer surfaces as well as particle size. A new continuum model has recently been developed (Morris et al., 2015) that accounts for both of these effects, and it was previously tested for simple systems. In the current effort, the continuum model was applied to the complex solar receiver and validated via comparison to DEM data. The results indicate that the new continuum model accurately predicts the local heat transfer coefficient and yields an overall heat transfer coefficient with an average error less than 5%.
Modified clay minerals on Mars
Sedimentary rocks exposed in Gale crater on Mars contain extensive clay minerals. Bristow
et al.
analyzed drill samples collected by the Curiosity rover as it climbed ...up sedimentary layers in the crater. They found evidence of past reactions with liquid water and sulfate brines, which could have percolated through the clay from an overlying sulfate deposit. Similar sulfate deposits are widespread across the planet and represent some of the last sedimentary rocks to form before the planet lost its surface liquid water, so the results inform our understanding of the geologic processes that occurred as Mars dried out.
Science, abg5449, this issue p.
198
Clay minerals examined by the Curiosity rover contain evidence of reactions with sulfate brines as Mars dried out.
Mars’ sedimentary rock record preserves information on geological (and potential astrobiological) processes that occurred on the planet billions of years ago. The
Curiosity
rover is exploring the lower reaches of Mount Sharp, in Gale crater on Mars. A traverse from Vera Rubin ridge to Glen Torridon has allowed
Curiosity
to examine a lateral transect of rock strata laid down in a martian lake ~3.5 billion years ago. We report spatial differences in the mineralogy of time-equivalent sedimentary rocks <400 meters apart. These differences indicate localized infiltration of silica-poor brines, generated during deposition of overlying magnesium sulfate–bearing strata. We propose that destabilization of silicate minerals driven by silica-poor brines (rarely observed on Earth) was widespread on ancient Mars, because sulfate deposits are globally distributed.
PDF
