We provide an analytic method to construct a bivariate distribution function (DF) with given marginal distributions and correlation coefficient. We introduce a convenient mathematical tool, called a ...copula, to connect two DFs with any prescribed dependence structure. If the correlation of two variables is weak (Pearson's correlation coefficient |ρ| < 1/3), the Farlie–Gumbel–Morgenstern (FGM) copula provides an intuitive and natural way to construct such a bivariate DF. When the linear correlation is stronger, the FGM copula cannot work anymore. In this case, we propose using a Gaussian copula, which connects two given marginals and is directly related to the linear correlation coefficient between two variables. Using the copulas, we construct the bivariate luminosity function (BLF) and discuss its statistical properties. We focus especially on the far-infrared–far-ulatraviolet (FUV–FIR) BLF, since these two wavelength regions are related to star-formation (SF) activity. Though both the FUV and FIR are related to SF activity, the univariate LFs have a very different functional form: the former is well described by the Schechter function whilst the latter has a much more extended power-law-like luminous end. We construct the FUV–FIR BLFs using the FGM and Gaussian copulas with different strengths of correlation, and examine their statistical properties. We then discuss some further possible applications of the BLF: the problem of a multiband flux-limited sample selection, the construction of the star-formation rate (SFR) function, and the construction of the stellar mass of galaxies (M*)–specific SFR (SFR/M*) relation. The copulas turn out to be a very useful tool to investigate all these issues, especially for including complicated selection effects.
Type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA) are both chronic diseases. Although the link between metabolic abnormalities and dysregulated inflammation has received much attention, ...it is not known whether T2DM can be a risk for the development of RA. Also, observational studies have the disadvantage that the possibility of confounding factors, such as environmental factors, cannot be ruled out. Therefore, the current study performed the mendelian randomization (MR) analysis using recent large-scale genome-wide association studies datasets of T2DM and RA separately European and Asian ancestries. As a result, T2DM had an inverse causal effect on the risk of RA. This study proposed a novel hypothesis that a protective effect of T2DM for the risk of RA.
To report long-term safety from the completed extension trial of baricitinib, an oral selective Janus kinase inhibitor, in patients with active rheumatoid arthritis (RA).
Treatment-emergent adverse ...events are summarised from an integrated database (9 phase III/II/Ib and 1 long-term extension) of patients who received any baricitinib dose (All-bari-RA). Standardised incidence ratio (SIR) for malignancy (excluding non-melanoma skin cancer (NMSC)) and standardised mortality ratio (SMR) were estimated. Additional analysis was done in a subset of patients who had ever taken 2 mg or 4 mg baricitinib.
3770 patients received baricitinib (14 744 patient-years of exposure (PYE)). All-bari-RA incidence rates (IRs) per 100 patient-years at risk were 2.6, 3.0 and 0.5 for serious infections, herpes zoster and major adverse cardiovascular events (MACE), respectively. In patients aged ≥50 with ≥1 cardiovascular risk factor, the IR for MACE was 0.77 (95% CI 0.56 to 1.04). The IR for malignancy (excluding NMSC) during the first 48 weeks was 0.6 and remained stable thereafter (IR 1.0). The SIR for malignancies excluding NMSC was 1.07 (95% CI 0.90 to 1.26) and the SMR was 0.74 (95% CI 0.59 to 0.92). All-bari-RA IRs for deep vein thrombosis (DVT)/pulmonary embolism (PE), DVT and PE were 0.5 (95% CI 0.38 to 0.61), 0.4 (95% CI 0.26 to 0.45) and 0.3 (95% CI 0.18 to 0.35), respectively. No clear dose differences were noted for exposure-adjusted IRs (per 100 PYE) for deaths, serious infections, DVT/PE and MACE.
In this integrated analysis including long-term data of baricitinib from 3770 patients (median 4.6 years, up to 9.3 years) with active RA, baricitinib maintained a similar safety profile to earlier analyses. No new safety signals were identified.
NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT02265705, NCT01721044, NCT01721057, NCT01711359 and NCT01885078.
We investigated the effectiveness of tocilizumab (an anti-interleukin-6 receptor antibody) in patients with polymyalgia rheumatica (PMR).
We performed a systematic literature review from the ...inception dates until August 7, 2019 for articles reporting tocilizumab administration to treat isolated PMR.
We identified 59 patients with isolated PMR treated with tocilizumab. All studies used intravenously administered tocilizumab at a dose of 8 mg/kg monthly. Tocilizumab monotherapy was administered to 24 and combination therapy (tocilizumab + glucocorticoid) to 35 patients. Tocilizumab monotherapy achieved low disease activity scores in only 17% of patients at week 4 and in only 71% patients even at week 12. Compared to glucocorticoid monotherapy, the reduction in the cumulative glucocorticoid dose was between 58% and 70% using a combination of tocilizumab and glucocorticoids, and 33–100% of the patients eventually showed glucocorticoid-free remission. All relapses occurred in patients administered tocilizumab monotherapy. No new safety event was reported.
Tocilizumab is effective in cases of isolated PMR, particularly in combination with glucocorticoids. In addition to its glucocorticoid-sparing effect, it achieves glucocorticoid-free remission and reduces relapse rates. Tocilizumab monotherapy is not recommended.
Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren's syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause ...the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.
•Interleukin-4, but not interleukin-21 enhances IgG4 production in IgG4-related disease.•Interleukin-4 induces IgG4 production only in IgG4-related disease, but not in healthy controls.•Our findings ...can help understanding the mechanism of IgG4 class switching in IgG4-related disease.
IgG4-related disease (IgG4-RD) is a systemic disorder characterized by elevated serum IgG4 level, which is mediated by T follicular helper 2 (Tfh2) cell. However, the cytokines responsible for enhancing IgG4 production remain unclear in IgG4-RD. The aim of this study was to identify responsible Tfh2-related cytokines (interleukin (IL)-4 and IL-21) for enhancing IgG4 production in IgG4-RD. Peripheral blood mononuclear cells obtained from consecutive patients with active, untreated IgG4-RD and healthy controls were examined. The production of both IgG and IgG4 were significantly increased by stimulation with IL-4 alone as well as IL-21 alone compared to background stimulation with anti-CD40 antibody in IgG4-RD. On the other hand, the IgG4/IgG ratio was statistically higher by stimulation with IL-4 alone compared to the other Tfh2-related cytokines including IL-21 in IgG4-RD. IgG4 production was not increased by stimulation with IL-4 in healthy controls. These results suggest that IL-4 can contribute to the shift of balance of IgG subclasses toward IgG4 compared to the other Tfh2-related cytokines in IgG4-RD.
ABSTRACT
The spectral energy distribution (SED) of galaxies provides fundamental information on the related physical processes. However, the SED is significantly affected by dust in its interstellar ...medium. Dust is mainly produced by asymptotic giant branch stars and Type II supernovae. In addition, the dust mass increases through the metal accretion, and the grain size changes by the collisions between the grains. The contribution of each process and the extinction depend on the size distribution. Therefore, the SED model should treat the evolution of the dust mass and size distribution. In spite of the importance of dust evolution, many previous SED models have not considered the evolution of the total mass and size distribution in a physically consistent manner. In this work, we constructed a new radiative transfer SED model, based on our dust evolution model consistent with the chemical evolution. To reduce the computational cost, we adopted the mega-grain and the 1D plane-parallel galaxy approximation. As a fiducial case, we calculated Milky Way-like galaxy SEDs at various ages under the closed-box model. We found that a galaxy at the age of 100 Myr does not produce small grains such as polycyclic aromatic hydrocarbons. After 1 Gyr, we observed a drastic increase of infrared emission and attenuation caused by a rapid increase of dust mass. This phenomenon can be treated appropriately for the first time by our new model. This model can be used for the SED fitting to a galaxy at any stage of evolution.
Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from ...the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX
CR1
Ly6C
F4/80
I-A
/I-E
macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX
CR1
HLA-DR
CD11c
CD80
CD86
cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.
ABSTRACT
Faraday tomography offers crucial information on the magnetized astronomical objects, such as quasars, galaxies, or galaxy clusters, by observing its magnetoionic media. The observed linear ...polarization spectrum is inverse Fourier transformed to obtain the Faraday dispersion function (FDF), providing us a tomographic distribution of the magnetoionic media along the line of sight. However, this transform gives a poor reconstruction of the FDF because of the instrument’s limited wavelength coverage. The current Faraday tomography techniques’ inability to reliably solve the above inverse problem has noticeably plagued cosmic magnetism studies. We propose a new algorithm inspired by the well-studied area of signal restoration, called the Constraining and Restoring iterative Algorithm for Faraday Tomography (craft). This iterative model-independent algorithm is computationally inexpensive and only requires weak physically motivated assumptions to produce high fidelity FDF reconstructions. We demonstrate an application for a realistic synthetic model FDF of the Milky Way, where craft shows greater potential over other popular model-independent techniques. The dependence of observational frequency coverage on the various techniques’ reconstruction performance is also demonstrated for a simpler FDF. craft exhibits improvements even over model-dependent techniques (i.e. QU-fitting) by capturing complex multiscale features of the FDF amplitude and polarization angle variations within a source. The proposed approach will be of utmost importance for future cosmic magnetism studies, especially with broad-band polarization data from the Square Kilometre Array and its precursors. We make the craft code publicly available†.
The relation between the ratio of infrared (IR) and ultraviolet (UV) flux densities (the infrared excess: IRX) and the slope of the UV spectrum ( beta ) of galaxies plays a fundamental role in the ...evaluation of the dust attenuation of star-forming galaxies, especially at high redshifts. Many authors, however, have pointed out that there is a significant dispersion and/or deviation from the originally proposed IRX- beta relation depending on sample selection. We reexamined the IRX- beta relation by measuring the far- and near-UV flux densities of the original sample galaxies with GALEX and AKARI imaging data and constructed a revised formula. We found that the newly obtained IRX values were lower than the original relation because of the significant underestimation of the UV flux densities of the galaxies, caused by the small aperture of IUE. Furthermore, since the original relation was based on IRAS data that covered a wavelength range of lambda = 42-122 mu m, we obtained an appropriate IRX- beta relation with total dust emission (TIR): log (L sub(TIR)/L sub(FUV)) = log 10 super(0.4(3.06 + 1.58 beta )) - 1 + 0.22 using the data from AKARI, which has wider wavelength coverage toward longer wavelengths. This new relation is consistent with most of the preceding results for samples selected at optical and UV, though there is significant scatter around it. We also found that even the quiescent class of IR galaxies follows this new relation, though luminous and ultraluminous IR galaxies distribute completely differently as previously thought.
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