Objective
Health outcomes in rheumatoid arthritis (RA) have improved significantly over the past 2 decades. However, research suggests that disparities exist by race/ethnicity and socioeconomic ...status, with certain vulnerable populations remaining understudied. Our objective was to assess disparities in disease activity and function by race/ethnicity and explore the impact of language and immigrant status at clinics serving diverse populations.
Methods
We examined a cross‐sectional study of 498 adults with confirmed RA at 2 rheumatology clinics: a university hospital clinic and a public county hospital clinic. Outcomes included the Disease Activity Score in 28 joints (DAS28) and its components, and the Health Assessment Questionnaire (HAQ), a measure of function. We estimated multivariable linear regression models including interaction terms for race/ethnicity and clinic site.
Results
After adjusting for age, sex, education, disease duration, rheumatoid factor status, and medication use, clinically meaningful and statistically significant differences in DAS28 and HAQ scores were seen by race/ethnicity, language, and immigrant status. Lower disease activity and better function was observed among whites compared to nonwhites at the university hospital. This same pattern was observed for disease activity by language (English compared to non‐English) and immigrant status (US‐born compared to immigrant) at the university clinic. No significant differences in outcomes were found at the county clinic.
Conclusion
The relationship between social determinants and RA disease activity varied significantly across clinic setting with pronounced variation at the university, but not at the county clinic. These disparities may be a result of events that preceded access to subspecialty care, poor adherence, or health care delivery system differences.
The multiple-recycle fuel cycle for uranium-238 considered here, if practically realized, can bring revolutionary changes in nuclear energy. A full use of uranium-238 implies a practically infinite ...resource for power generation. Besides the energy, the fuel cycle net output is only fission products, which are co-products rather than waste. For the same amount of energy produced, the amount of fission products is two orders of magnitude less compared with the amount of spent nuclear fuel generated in currently exploited nuclear energy production scenarios. Using the simplest isotope balance model, key features of the multiple-recycle fuel cycle for uranium-238 are investigated. The repetition of this cycle results in smooth transformation of the initial fuel to ‘stationary’ fuel without strong variations in the fractional isotope content. Deficit of delayed neutrons is a threat of the fuel cycle considered as well as other fuel cycles that use plutonium. It has a dramatic impact on reactor controllability and safety. A solution to this threat could be a subcritical nuclear reactor with an external neutron source. In this paper, use of a stellarator–mirror (SM) fusion–fission hybrid for the multiple-recycle fuel cycle for uranium-238 is analysed. A summary of the experimental and theoretical studies on the SM hybrid is given. Preliminary results for principal design of a SM hybrid nuclear reactor for the multiple-recycle fuel cycle for uranium-238 are presented.
The MCNPX Monte-Carlo code has been used to model the neutron transport in a sub-critical fast fission reactor driven by a fusion neutron source. A stellarator-mirror device is considered as the ...fusion neutron source. The principal composition for a fission blanket of a mirror fusion–fission hybrid is devised from the calculations. Heat load on the first wall, the distribution of the neutron fields in the reactor, the neutron spectrum and the distribution of energy release in the blanket are calculated. The possibility of tritium breeding inside the installation in quantities that meet the needs of the fusion neutron source is analyzed. The portion of the plasma column generates fusion neutrons that mainly do not reach the fission reactor core is proposed to be surrounded by a vessel filled with borated water to absorb the flying out neutrons. The flux of the neutrons escaping from the device to surrounding space is also calculated.
Heterogeneity in disease course and treatment response among patients with MCD/FSGS necessitates a granular evaluation of kidney tissue features. This study aimed to identify histologic and ...ultrastructural descriptors of structural changes most predictive of clinical outcomes in the Nephrotic Syndrome Study Network (NEPTUNE).
Forty-eight histologic (37 glomerular, 9 tubulointerstitial, 2 vascular) and 20 ultrastructural descriptors were quantified by applying the NEPTUNE Digital Pathology Scoring System to NEPTUNE kidney biopsies. Outcomes included time from biopsy to disease progression, first complete remission of proteinuria, and treatment response. Relative importance of pathology and clinical predictors was obtained from random forest models, and predictive discrimination was assessed.
Among 224 participants (34% Black, 24% Hispanic), model performance was excellent, with predictive discrimination of 0.9 for disease progression, 0.85 for complete remission, and 0.81 for treatment response. The most predictive descriptors of outcomes included both conventional-
, global sclerosis or segmental sclerosis and interstitial fibrosis/tubular atrophy-and novel features, including adhesion, interstitial foam cells, deflation, periglomerular fibrosis, mononuclear white blood cells, endothelial cell abnormalities, microvillous transformation, and acute tubular injury.
The most predictive descriptors of clinical outcomes among MCD/FSGS patients reflected structural changes in multiple renal compartments. Reporting these descriptors should be standardized to guide prognostication of proteinuric glomerular diseases.
The current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies nor the ...clinical and molecular heterogeneity of these diseases.
Prospective observational cohort study.
221 MCD and FSGS patients enrolled in the Nephrotic Syndrome Study Network (NEPTUNE).
The NEPTUNE Digital Pathology Scoring System (NDPSS) was applied to generate scores for 37 glomerular descriptors.
Time from biopsy to complete proteinuria remission, time from biopsy to kidney disease progression (40% estimated glomerular filtration rate eGFR decline or kidney failure), and eGFR over time.
Cluster analysis was used to group patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for associations with outcomes using adjusted Cox models and linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes between clusters and identify genes associated with individual descriptors driving cluster membership.
Three clusters were identified: X (n = 56), Y (n = 68), and Z (n = 97). Clusters Y and Z had higher probabilities of proteinuria remission (HRs of 1.95 95% CI, 0.99-3.85 and 3.29 95% CI, 1.52-7.13, respectively), lower hazards of disease progression (HRs of 0.22 95% CI, 0.08-0.57 and 0.11 95% CI, 0.03-0.45, respectively), and lower loss of eGFR over time compared with X. Cluster X had 1,920 genes that were differentially expressed compared with Y+Z; these reflected activation of pathways of immune response and inflammation. Six descriptors driving the clusters individually correlated with clinical outcomes and gene expression.
Low prevalence of some descriptors and biopsy at a single time point.
The NDPSS allows for categorization of FSGS/MCD patients into clinically and biologically relevant subgroups, and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems.
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Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because ...the molecular mechanisms underlying APOL1’s pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS.
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The MCNPX numerical code has been used to model the neutron transport in a mirror based fusion-fission reactor. The purpose is to find a principal design of the fission mantle which fits to the ...neutron source and to calculate the leakage of neutrons through the mantle surface of the fission reactor.
The fission reactor part has a cylindrical shape with an outer radius 1.66 m and a 4 m length. The fuel has the isotopic composition of the spent nuclear fuel from PWR after uranium-238 removal. Inside the fission reactor core is a vacuum chamber with a radius 0.5 m containing a 4 m long hot plasma producing fusion neutrons. To sustain the hot ion plasma which is responsible for the fusion neutron production, neutral beam injection is considered.
Calculation results for the radial leakage of neutrons through the mantle surface of the fission reactor are presented. These calculations predict that the power released with neutrons from the reactor to outer space would be small and will not exceed the value of 6 kW while the reactor thermal power is 1 GWth.
We conducted this study to test the hypothesis that plasma zonulin levels are elevated in pediatric patients with nephrotic syndrome compared to healthy controls.
Plasma zonulin levels were measured ...by ELISA in 114 children enrolled in the NEPTUNE study. Clinical and laboratory data were retrieved from the NEPTUNE database.
The median age of the patients was 10 (IQR = 5 to 14) years, 59 were male, 64 had minimal change disease, 47 focal segmental glomerulosclerosis, median eGFR was 96 (IQR = 80 to 114) ml/min/1.73 m
, and median urine protein:creatinine ratio was 0.5 (IQR = 0.1 to 3.4) (g:g). The plasma zonulin level was 14.2 ± 5.0 vs. 10.2 ± 2.5 ng/ml in healthy adults in a report using the same assay kit,
= 0.0025. These findings were confirmed in an independent cohort of children with nephrotic syndrome compared to healthy age-matched controls,
= 0.01. Zonulin concentrations did not differ in children with minimal change disease vs. focal segmental glomerulosclerosis, frequently relapsing vs. steroid-dependent vs. steroid-resistant clinical course, and were not influenced by the immunosuppressive treatment regimen. There was no relationship between plasma zonulin levels and the absolute or percentage change in proteinuria from enrollment until the time of the zonulin assay.
Plasma zonulin levels are elevated in childhood nephrotic syndrome regardless of level of proteinuria or specific treatment. The cause of the high plasma zonulin levels and whether zonulin contributes to glomerular injury requires further study.
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