Iterative estimating equations: Linear convergence and asymptotic properties

We propose an iterative estimating equations procedure for analysis of longitudinal data. We show that, under very mild conditions, the probability that the procedure converges at an exponential rate tends to one as the sample size increases to infinity. Furthermore, we show that the limiting estimator is consistent and asymptotically efficient, as expected. The method applies to semiparametric regression models with unspecified covariances among the observations. In the special case of linear models, the procedure reduces to iterative reweighted least squares. Finite sample performance of the procedure is studied by simulations, and compared with other methods. A numerical example from a medical study is considered to illustrate the application of the method.Comment: Published in at http://dx.doi.org/10.1214/009053607000000208 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Performance stability and degradation mechanism of La0.6Sr0.4Co0.2Fe0.8O3-δ cathodes under solid oxide fuel cells operation conditions

The performance stability and degradation mechanism of La0.6Sr0.4Co0.2Fe0.8O3d (LSCF)cathodes and LSCF impregnated Gd0.1Ce0.9O2d (LSCF-GDC) cathodes are investigated undersolid oxide fuel cell operation conditions. LSCF and LSCF-GDC cathodes show initiallyperformance improvement but degrade under cathodic polarization treatment at 750 C for120 h. The results confirm the grain growth and agglomeration of LSCF and in particularGDC-LSCF cathodes as well as the formation of SrCoOx particles on the surface of LSCFunder cathodic polarization conditions. The direct observation of SrCoOx formation hasbeen made possible on the surface of dense LSCF electrode plate on GDC electrolyte. Theformation of SrCoOx is most likely due to the interaction between the segregated Sr and Cofrom LSCF lattice under polarization conditions. The formation of SrCoOx would contributeto the deterioration of the electrocatalytic activity of the LSCF-based electrodes for the O2reduction in addition to the agglomeration and microstructure coarsenin

Dynamic Brazilian Tests of Granite Under Coupled Static and Dynamic Loads

Rocks in underground projects at great depth, which are under high static stresses, may be subjected to dynamic disturbance at the same time. In our previous work (Li et al. Int J Rock Mech Min Sci 45(5):739–748, 2008), the dynamic compressive behaviour of pre-stressed rocks was investigated using coupled-load equipment. The current work is devoted to the investigation of the dynamic tensile behaviour of granite rocks under coupled loads using the Brazilian disc (BD) method with the aid of a high-speed camera. Through wave analyses, stress measurements and crack photography, the fundamental problems of BD tests, such as stress equilibrium and crack initiation, were investigated by the consideration of different loading stresses with abruptly or slowly rising stress waves. The specially shaped striker method was used for the coupled-load test; this generates a slowly rising stress wave, which allows gradual stress accumulation in the specimen, whilst maintaining the load at both ends of the specimen in an equilibrium state. The test results showed that the tensile strength of the granite under coupled loads decreases with increases in the static pre-stresses, which might lead to modifications of the blasting design or support design in deep underground projects. Furthermore, the failure patterns of specimens under coupled loads have been investigated

Circular RNA circNOL10 Inhibits Lung Cancer Development by Promoting SCLM1-Mediated Transcriptional Regulation of the Humanin Polypeptide Family

circNOL10 is a circular RNA expressed at low levels in lung cancer, though its functions in lung cancer remain unknown. Here, the function and molecular mechanism of circNOL10 in lung cancer development are investigated using in vitro and in vivo studies, and it is shown that circNOL10 significantly inhibits the development of lung cancer and that circNOL10 expression is co‐regulated by methylation of its parental gene Pre‐NOL10 and by splicing factor epithelial splicing regulatory protein 1 (ESRP1). circNOL10 promotes the expression of transcription factor sex comb on midleg‐like 1 (SCML1) by inhibiting transcription factor ubiquitination and thus also affects regulation of the humanin (HN) polypeptide family by SCML1. circNOL10 also affects mitochondrial function through regulating the humanin polypeptide family and affecting multiple signaling pathways, ultimately inhibiting cell proliferation and cell cycle progression, and promoting the apoptosis of lung cancer cells, thereby inhibiting lung cancer development. This study investigates the functions and molecular mechanisms of circNOL10 in the development of lung cancer and reveals its involvement in the transcriptional regulation of the HN polypeptide family by SCML1. The results also demonstrate the inhibitory effect of HN on lung cancer cells growth. These findings may identify novel targets for the molecular therapy of lung cancer

Reduced SV2A and GABAA_A receptor levels in the brains of type 2 diabetic rats revealed by [18^{18}F]SDM-8 and [18^{18}F]flumazenil PET

PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer's disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2 A (SV2A), γ-aminobutyric acid type A (GABA$_A$) receptor, amyloid-β, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats. Methods: Positron emission tomography (PET) using [$^{18}$F]SDM-8 (SV2A), [$^{18}$F]flumazenil (GABA$_A$ receptor), [$^{18}$F]florbetapir (amyloid-β), [$^{18}$F]PM-PBB3 (tau), and [$^{18}$F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and SpragueDawley (SD) rats. Immunofluorescence staining, Thioflavin S staining, proteomic profiling and pathway analysis were performed on the brain tissues of ZDF and SD rats. Results: Reduced cortical [$^{18}$F]SDM-8 uptake and cortical and hippocampal [$^{18}$F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. The regional uptake of [$^{18}$F]florbetapir and [$^{18}$F]PM-PBB3 was comparable in the brains of 12-month-old ZDF and SD rats. Immunofluorescence staining revealed Thioflavin S-negative, phospho-tau-positive inclusions in the cortex and hypothalamus in the brains of ZDF rats and the absence of amyloid-beta deposits. The level of GABA$_A$ receptors was lower in the cortex of ZDF rats than SD rats. Proteomic analysis further demonstrated that, compared with SD rats, synaptic-related proteins and pathways were downregulated in the hippocampus of ZDF rats. Conclusion: These findings provide in vivo evidence for regional reductions in SV2A and GABA$_A$ receptor levels in the brains of aged T2DM ZDF rats

A stability study of impregnated LSCF–GDC composite cathodes of solid oxide fuel cells

The performance degradation of composite cathodes of La0.6Sr0.4Co0.2Fe0.8O3−δ and Gd-doped ceria (LSCF–GDC), prepared by impregnating the porous GDC scaffold with a nitrate solution containing La, Sr, Co and Fe in desired composition, is investigated at 750 °C and open circuit in air for 500 h. The performance of the impregnated LSCF–GDC composite cathodes deteriorates after testing at 750 °C for 500 h; the electrode polarization resistance (Rp) increases from 0.38 to 0.83 Ω cm2, and the electrode ohmic resistance (Ro) increases from 1.79 to 2.14 Ω cm2. The grain growth and coarsening of impregnated LSCF nanoparticles are responsible for the performance degradation of the cathodes. XPS analysis shows the enrichment of cobalt on the surface of the infiltrated LSCF–GDC cathodes and such surface segregation could also contribute to the degradation of the electrocatalytic activity of the cathodes. Introducing MgO and LaNi0.6Fe0.4O3 phases can effectively suppress the coarsening of LSCF nanoparticles and enhance the stability of the cathodes. However, the enhancing effect is related to the conductivity and electrocatalytic activity of the introduced phases

Expression of plasma methylated Septin9 gene and its clinical significance in patients with gastric cancer

Background and purpose: Gastric cancer is one of the most common malignant tumors in our country. The diagnosis and treatment process of gastric cancer lacks of sensitive and specific biomarker. This study aimed to explore the expression of plasma methylated Septin9 gene (mSEPT9) and its clinical significance in patients with gastric cancer. Methods: From April 2020 to November 2020, 221 patients with gastric cancer and 34 patients with no evidence of disease who visited Zhongshan Hospital Fudan University were enrolled. The status of mSEPT9 was detected by polymerase chain reaction (PCR) fluorescence probe method, and relative mSEPT9 value was determined by the ΔΔCt method. Detailed clinical data including pathological characteristics (patients characteristics and pathology characteristics) and serum biomarkers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA)12-5, CA19-9 and CA72-4] were collected and analyzed. Paired t test, χ2 test and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. Results: The positive rate, sensitivity and specificity of plasma mSEPT9 were 35%, 35% and 100%, respectively in untreated patients with gastric cancer. The positive rate of mSEPT9 was higher in patients with blood vessel invasion, serosa invasion and lymphatic metastasis, which was 46.87% vs 12.50%, 45.16% vs 14.29%, 75.00% vs 40.00%, respectively (P<0.05). The positive rate of mSEPT9 was higher in progressive disease (PD) patients than in partial response (PR) and stable disease (SD) patients, which were 68.75% and 17.74%, the differences were statistically significant (P<0.05). mSEPT9 level before PD and at the time of PD showed statistically significance. Conclusion: Plasma mSEPT9 detection demonstrates a more satisfactory diagnostic performance in gastric cancer than traditional serum biomarkers. The biomarker can provide information regarding severity with high positive rate among PD patients. The status and level of mSEPT9 were of clinical significance in evaluating tumor burden and predicting treatment response

Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors.A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18-89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use.Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73).Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA.American College of Rheumatology R01HL089744 K24AR064310 Clinical and Translational Science Award at the University of Pennsylvania from the National Center for Research Resources 8UL1TR000003 American College of Rheumatology Research and Education Foundation NIH K23AR063764 Doris Duke Charitable Foundation Center for Clinical Epidemiology and Biostatistics Icelandic Research Fund 120433021 R01AG025152 K23HL097151-0

Increased Vesicular Monoamine Transporter 2 (VMAT2) and Dopamine Transporter (DAT) Expression in Adolescent Brain Development: A Longitudinal Micro-PET/CT Study in Rodent

Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT.Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18F-PF-(+)-DTBZ, 11C-CFT, and 18F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum).Results: Variable uptake of 18F-PF-(+)-DTBZ and 11C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18F-PF-(+)-DTBZ and 11C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively).Conclusion: Age-dependent increases of striatal of 18F-FDG, 18F-PF-(+)-DTBZ, and 11C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation

Barriers to and Facilitators of a Career as a Physician‐Scientist Among Rheumatologists in the US

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113102/1/acr22569.pd