Weighted estimation of the dependence function for an extreme-value distribution

Bivariate extreme-value distributions have been used in modeling extremes in environmental sciences and risk management. An important issue is estimating the dependence function, such as the Pickands dependence function. Some estimators for the Pickands dependence function have been studied by assuming that the marginals are known. Recently, Genest and Segers [Ann. Statist. 37 (2009) 2990-3022] derived the asymptotic distributions of those proposed estimators with marginal distributions replaced by the empirical distributions. In this article, we propose a class of weighted estimators including those of Genest and Segers (2009) as special cases. We propose a jackknife empirical likelihood method for constructing confidence intervals for the Pickands dependence function, which avoids estimating the complicated asymptotic variance. A simulation study demonstrates the effectiveness of our proposed jackknife empirical likelihood method.Comment: Published in at http://dx.doi.org/10.3150/11-BEJ409 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Three Chinese pedigrees of A20 haploinsufficiency: clinical, cytokine and molecular characterization

ObjectiveHaploinsufficiency of A20 (HA20) is a newly described rare autoinflammatory disease caused by TNFAIP3 gene mutations. HA20 has seldom been documented in the Chinese population. Herein, we report eight patients with HA20 from three unrelated families in China.MethodsEight Chinese Han patients were diagnosed with HA20 in our department from 2018 to 2021. Their clinical data and genotypes were carefully documented and studied. The newly identified variants were functionally verified. We also conducted a systematic literature review of HA20, and the clinical characteristics and genotype of HA20 between the Chinese population and other populations were compared.ResultsEight HA20 patients from three families comprised six adults and two children. There was one man and seven women. The clinical characteristics included recurrent oral ulcers (8/8, 100%), fever (4/8, 50%), perianal ulcer (3/8, 38%), skin lesions (2/8, 25%), arthritis (1/8, 13%), and uveitis (1/8, 13%). Three TNFAIP3 variants, A547T, c.1906+2T>G, and R271X, were identified. Two novel variants, A547T and c.1906+2T>G, were validated to be pathogenic in our study. In a literature review a total of 126 patients with HA20 reported by 35 articles were included. The clinical phenotype of Chinese HA20 patients was similar to that of patients from other populations except for a lower frequency of genital ulcers (16.7% vs. 54.4%, p < 0.01). Autoantibodies were detectable in approximately one-third of the 126 patients, among which ANA and anti-thyroid antibodies were commonly seen.ConclusionThe rarity and diversity of phenotypes make the diagnosis of HA20 a huge challenge to physicians. HA20 should be considered in child-onset patients with manifestations that resemble Behçet’s syndrome, especially those whose family members have similar symptoms. Gene testing is critically helpful for the diagnosis of HA20. Two novel TNFAIP3 variants, A547T and c.1906+2T>G, were identified in this study

The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome

ObjectiveThe pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. The N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript modification, has close associations with multiple diseases. This study aimed to investigate the role of m6A in patients with pSS.Materials and methodsThis study enrolled 44 patients with pSS, 50 age- and gender-matched healthy controls (HCs), and 11 age- and gender-matched patients with non-SS sicca. We detected the messenger RNA (mRNA) levels of m6A elements (including METTL3, WTAP, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2), ISG15, and USP18 in peripheral blood mononuclear cells (PBMCs) from patients with pSS, patients with non-SS sicca, and HCs. The clinical characteristics and laboratory findings of patients with pSS and patients with non-SS sicca were also collected. We used binary logistic regression to determine if m6A elements were risk factors for pSS.ResultsThe mRNA levels of m6A writers (METTL3 and RBM15), erasers (ALKBH5 and FTO), and readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2) were all significantly higher in PBMCs from patients with pSS than in HCs. The mRNA levels of m6A writers (METTL3 and WTAP) and readers (YTHDF2, YTHDF3, and YTHDC2) were lower in PBMCs from patients with pSS compared to patients with non-SS sicca. The expression of METTL3, RBM15, FTO, YTHDF1, YTHDF2, YTHDC1, and YTHDC2 was positively correlated with the level of C-reactive protein (CRP) of patients with pSS. The mRNA level of YTHDF1 in PBMCs from patients with pSS was negatively correlated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) score. In patients with pSS, FTO, YTHDC1, and YTHDC2 were also related to white blood cells (WBCs), neutrophils, lymphocytes, and monocytes. Increased mRNA level of ALKBH5 in PBMCs was a risk factor for pSS, as determined by binary logistic regression analysis. The mRNA level of ISG15 was positively correlated with that of FTO, YTHDF2, YTHDF3, and YTHDC2 in patients with pSS.ConclusionCompared with HCs, the expression of METTL3, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 was considerably higher in PBMCs from patients with pSS. In comparison with patients with non-SS sicca, the expression of METTL3, WTAP, YTHDF2, YTHDF3, and YTHDC2 was reduced in PBMCs from patients with pSS. The m6A elements correlating with clinical variables may indicate the disease activity and inflammation status of pSS. Elevated expression of ALKBH5 was a risk factor for pSS. The dynamic process of m6A modification is active in pSS. m6A elements (FTO, YTHDF2, YTHDF3, or YTHDC2) might target ISG15, stimulate the expression of ISG15, and activate the type I IFN signaling pathway, playing an active role in initiating the autoimmunity in pSS

Double Trouble of Air Pollution by Anthropogenic Dust

With urbanization worldwide in recent decades, anthropogenic dust (AD) emissions due to heavy urban construction and off-road vehicle use have been increasing. Its perturbations on urban air pollution at the global scale are still unclear. Based on observations, we found that a high urban AD optical depth is often accompanied by severe non-dust aerosol optical depth in the planetary boundary layer (PBL), both magnitudes even comparable. To investigate the causes, an AD emission inventory constrained by satellite retrievals is implemented in a global climate model. The results show that AD-induced surface radiative cooling of up to -15.9 +/- 4.0 W m(-2) regionally leads to reduced PBL height, which deteriorates non-dust pollution, especially over India and northern China, in addition to the tremendous direct AD contribution to pollutants. The estimated global total premature mortality due to AD is 0.8 million deaths per year and is more severe in populous regions.Peer reviewe

Development of Sequence-Tagged Site Marker Set for Identification of J, JS, and St Sub-genomes of Thinopyrum intermedium in Wheat Background

Thinopyrum intermedium (2n = 6x = 42, JJJSJSStSt) is one of the important resources for the wheat improvement. So far, a few Th. intermedium (Thi)-specific molecular markers have been reported, but the number is far from enough to meet the need of identifying alien fragments in wheat-Th. intermedium hybrids. In this study, 5,877,409 contigs were assembled using the Th. intermedium genotyping-by-sequencing (GBS) data. We obtained 5,452 non-redundant contigs containing mapped Thi-GBS markers with less than 20% similarity to the wheat genome and developed 2,019 sequence-tagged site (STS) molecular markers. Among the markers designed, 745 Thi-specific markers with amplification products in Th. intermedium but not in eight wheat landraces were further selected. The distribution of these markers in different homologous groups of Th. intermedium varied from 47 (7/12/28 on 6J/6St/6JS) to 183 (54/62/67 on 7J/7St/7JS). Furthermore, the effectiveness of these Thi-specific markers was verified using wheat-Th. intermedium partial amphidiploids, addition lines, substitution lines, and translocation lines. Markers developed in this study provide a convenient, rapid, reliable, and economical method for identifying Th. intermedium chromosomes in wheat. In addition, this set of Thi-specific markers can also be used to estimate genetic and physical locations of Th. intermedium chromatin in the introgression lines, thus providing valuable information for follow-up studies such as alien gene mining

Pilot study of tocilizumab monotherapy for active chronic periaortitis

Objectives To investigate the effectiveness and safety of TCZ (tocilizumab) monotherapy for chronic periaortitis (CP) patients at acute active stage.Methods Twelve patients with definite or possible diagnosis of CP were enrolled and received intravenous infusions of TCZ (8 mg/kg) every 4 weeks for at least 3 months. Clinical features, laboratory and imaging findings were recorded at baseline and during the follow-up. The primary endpoint was the rate of partial and complete remission after 3 months TCZ monotherapy and the secondary endpoint was the frequency of treatment related adverse events.Results Three patients (27.3%) achieved partial remission and seven patients (63.6%) obtained complete remission after 3 months TCZ treatment. The total remission rate achieved 90.9%. All patients reported improvement in clinical symptoms. Inflammatory markers such as erythrocyte sedimentation rate and C reactive protein decreased to normal levels after TCZ treatment. Nine patients (81.8%) showed remarkable shrinkage of perivascular mass greater than or equal to 50% on CT.Conclusion Our study showed that TCZ monotherapy contributed to remarkable clinical and laboratory improvement in CP patients and could be an alternative treatment option for CP

Clinical Characteristics of Systemic Lupus Erythematosus with Cirrhosis

Aim. Cirrhosis is rare in systemic lupus erythematosus (SLE) patients with a poor prognosis. This study is aimed at retrospectively analyzing our single-center experience to explore the characteristics of cirrhosis in SLE patients. Methods. SLE patients with cirrhosis from 2012 to 2019 were enrolled. SLE diagnosis was rigorously confirmed by a medical record review according to the revised 1997 American College of Rheumatology classification criteria for SLE. The diagnosis of liver cirrhosis was based on a combination of clinical, laboratory, and imaging criteria features. We conducted a case-control study in SLE patients complicated with the cirrhosis group and the age-, sex-, and entry-time-matched noncirrhosis group. Results. A total of 21 patients with SLE cirrhosis were enrolled, 3 males and 18 females. The median age at the time of cirrhosis diagnosis was 47.3±4.0 years, and the mean disease duration of SLE before cirrhosis was 4.7±1.0 years. The most common initial presentation was the involvement of the hematological system in 9 patients and then skin and mucosal involvement in 5 patients, arthritis in 4 patients, and nephritis in 3 patients. Patients with cirrhosis had a significantly higher rate of hematological system involvement (thrombocytopenia and leukopenia) and worse liver function; a higher level of immune globulin G had higher mortality (p<0.05) than patients without cirrhosis. Conclusions. Cirrhosis is a rare and severe subtype of SLE with a poor prognosis. Those patients with hematological system involvement and impaired liver function should be paid more attention

Synthesis of microporous nitrogen-rich covalent-organic framework and its application in CO2 capture

An imine-based nitrogen-rich covalent-organic framework (COF) was successfully synthesized using two triangular building units under solvothermal reaction condition. The gas adsorption properties of the obtained microporous nitrogen-rich COF were investigated. The results indicated that the activated COF material presented good up take capabilities of CO2 and CH4 at 61.2 and 43.4 cm3·g−1 at 1 atm and 273 K, respectively, showing its application potential in selective gas capture and separation