Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Electrical and optical properties of Ta-Si-N thin films deposited by reactive magnetron sputtering

The electrical and optical properties of TaxSiyNz thin films deposited by reactive magnetron sputtering from individual Ta and Si targets were studied in order to investigate the effects of nitrogen and silicon contents on both properties and their correlation to the film microstructure. Three sets of fcc-TaxSiyNz thin films were prepared: sub-stoichiometric TaxSiyN0.44, nearly stoichiometric TaxSiyN0.5, and over-stoichiometric TaxSiyN0.56. The optical properties were investigated by near-normal-incidence reflectivity and ellipsometric measurements in the optical energy range from 0.375 eV to 6.8 eV, while the d.c. electrical resistivity was measured in the van der Pauw configuration from 20 K to 300 K. The optical and electrical measurements were interpreted using the standard Drude-Lorentz model and the so-called grain boundary scattering model, respectively. The electronic properties were closely correlated with the compositional and structural modifications of the TaxSiyNz films due to variations in the stoichiometry of the fcc-TaNz system and the addition of Si atoms. According to the nitrogen and silicon contents, fcc-TaxSiyNz films can exhibit room temperature resistivity values ranging from 10(2) mu Omega cm to about 6 x 10(4) mu Omega cm. The interpretation of the experimental temperature-dependent resistivity data within the Grain Boundary Scattering model, combined with the results from optical investigations, showed that the mean electron transmission probability G and the free carriers concentration, N, are the main parameters that control the transport properties of these films. The results indicated that the correlation between electrical and optical measurements with the chemical composition and the nanostructure of the TaxSiyNz thin films provides a pertinent and consistent description of the evolution of the Ta-Si-N system from a solid solution to a nanocomposite material due to the addition of Si atoms. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4766904

Influence of bias voltage on the microstructure and physical properties of magnetron sputtered Zr–Si–N nanocomposite thin films

e report an investigation concerning the influence of ion bombardment on the nanostructure and physical properties of Zr–Si–N nanocomposite thin films. The films were deposited by reactive magnetron sputtering from individual Zr and Si targets. The Si content was varied by changing the power applied to the Si target. The increase of ion bombardment energy was obtained by applying a negative potential Ub = − 150 V to the substrate. The evolution of the film texture, grain size and lattice constant was mapped out using X-ray diffraction measurements. Zr–Si–N films deposited at a substrate temperature Ts = 510 K with a bias voltage of Ub = − 150 V exhibit less pronounced columnar structure with small crystallites having various orientations. The maximum nanohardness of 39 GPa is reached for the films at about 2.5 at.% Si, 8 nm grain size and 0.3 Si surface coverage. The increased energy of ionic species reaching the substrate when a negative bias voltage is applied seems to have the opposite effect to that of increasing substrate temperature: reduced SiNx coverage on the ZrN nanocrystallites

TaSiN nanocomposite thin films: Correlation between structure, chemical composition, and physical properties

The structural and electronic properties of fcc-TaN/SiNx nanocomposite thin films deposited by reactive magnetron sputtering have been investigated as function of the N and Si contents. Our studies have been mainly focused on three different types of nanocomposite TaxSiyNz films based on: nitrogen deficient fcc-TaN0.88, nearly stoichiometric fcc-TaN, and over-stoichiometric fcc-TaN1.2 with the Si contents in the range from 0 to about 15 at.%. The optical properties were investigated by ellipsometric measurements, while the DC. electrical resistivity was measured using the van der Pauw configuration at 300 K. The optical measurements were interpreted using the standard Drude-Lorentz model. The results showed that the electronic properties are closely correlated with both the compositional and the structural modifications of the TaxSiyNz films induced by the addition of Si atoms, and also depending on the stoichiometry of the starting fcc-TaN system. Thus, depending on both the nitrogen and the silicon contents, the fcc-TaxSiyNz films can exhibit room temperature resistivity values ranging from 10(2) mu Omega cm to about 6 x 10(4) mu Omega cm. Published by Elsevier B.V

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease