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The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
The feasibility of non-destructive detection and classification of in-shell insect-infested almonds was examined by using multispectral imaging (MSI) technology combined with chemometrics. Differentiation of reflectance spectral data between intact and insect-infested almonds was attempted by using analytical approaches based on principal component analysis and support vector machines, classification accuracy rates as high as 99.1% in the calibration set and 97.5% in the prediction set were achieved. Meanwhile, the in-shell almonds were categorized into three classes (intact, slightly infested and severely infested) based on the degree of damage caused by insect infestation and were characterized quantitatively by the analysis of shell/kernel weight ratio. A three-class model for the identification of intact, slightly infested and severely infested almonds yielded acceptable classification performance (95.6% accuracy in the calibration set and 93.3% in the prediction set). These results revealed that MSI technology combined with chemometrics may be a promising approach for the non-destructive detection of hidden insect damage in almonds and could be used for industrial applications.
In vivo and in vitro trials were conducted to assess the effects of tributyrin (TB) supplementation on short-chain fatty acid (SFCA) concentrations, fibrolytic enzyme activity, nutrient digestibility and methanogenesis in adult sheep. Nine 12-month-old ruminally cannulated Small Tail ewes (initial body weight 55 ± 5.0 kg) without pregnancy were used for the in vitro trial. In vitro substrate made to offer TB at 0, 2, 4, 6 and 8 g/kg on a dry matter (DM) basis was incubated by ruminal microbes for 72 h at 39°C. Forty-five adult Small Tail ewes used for the in vivo trial were randomly assigned to five treatments with nine animals each for an 18-d period according to body weight (55 ± 5.0 kg). Total mixed ration fed to ewes was also used to offer TB at 0, 2, 4, 6 and 8 g/kg on a DM basis. The in vitro trial showed that TB supplementation linearly increased apparent digestibility of DM, crude protein, neutral detergent fibre and acid detergent fibre, and enhanced gas production and methane emissions. The in vivo trial showed that TB supplementation decreased DM intake, but enhanced ruminal fermentation efficiency. Both in vitro and in vivo trials showed that TB supplementation enhanced total SFCA concentrations and carboxymethyl cellulase activity. The results indicate that TB supplementation might exert advantage effects on rumen microbial metabolism, despite having an enhancing effect on methanogenesis.
The Proterozoic Sushina Hill Complex is the only agpaitic complex, reported from India and is characterized by a eudialyte-rinkite-bearing nepheline syenite. The complex is considered a ‘metamorphosed agpaitic complex'. This study describes the mineral assemblages formed during successive stages of evolution from magmatic to hydrothermal stages and low-temperature subsolidus re-equilibration assemblage. The primary-late magmatic assemblage is characterized by albite, orthoclase, unaltered nepheline, zoned diopside-hedenbergite, rinkite, late magmatic eudialyte and magnesio-arfvedsonite formed at ∼700°C with maximum aSiO2 of 0.60. In contrast, a deuteric assemblage (400-348°C) is represented by aegirine-jadeite-rich clinopyroxene, post-magmatic eudialyte, sodalite, analcime and the decomposition assemblages formed after eudialyte with decreasing aSiO2 (0.52-0.48). A further low-temperature subsolidus assemblage (≤250°C) represented by late-forming natrolite could be either related to regressive stages of metamorphism or a continuum of the subsolidus processes. Considering the P/T range of the greenschist - lower-amphibolite facies of metamorphism it is evident that the incorporation of a jadeite component within pyroxene is related to a subsolidus process between ∼400°C and 348°C in a silica deficient environment. We emphasize that the deuteric fluid itself acted as an agent of metamorphism and the decomposition assemblage formed after eudialyte is retained even after metamorphism due to the convergence of subsolidus and metamorphic domains. The formation of jadeite-rich aegirine is not considered to result from metamorphism. Overall it is near-impossible to discern any bona fide metamorphic textures or mineral assemblages in these syenites which appear to preserve a relict mineralogy regardless of their occurrence in country rocks which have experienced greenschist - amphibolite facies metamorphism. The Sushina complex is very similar in this respect to the Norra Kärr complex (Sweden).
Social networks facilitate the transmission of hepatitis C virus (HCV) in people who inject drugs (PWID). The aim of this study was to assess how certain network structural characteristics are related to HCV infections in PWID and to determine the most susceptible individuals for HCV transmission in a network of PWID. PWID (N = 80) from central China were recruited from a previous follow-up case-control study. Demographic and behavioural information was obtained from a computerized database for each group. HCV RNA was extracted from blood specimens. Sequences were used to construct a phylogenetic tree and to determine genetic distances. Socio-metric social links were established between participants. Network measures were calculated using UCINET. Three HCV genotypes were identified, covering five subtypes. The density of the social networks for the whole sample (N = 80), case group (n = 31) and control group (n = 49) was 0.038, 0.054 and 0.008, respectively. PWID infected with HCV were in frequent contact with others within their group. There were four pairs of nodes with genotypic distances of 0.000 that were identified and clustered in subtypes 6a and 1b; each subject pair was linked and found in one clique. Three of the five most active nodes were infected with HCV. These three nodes served as a bridge, contributing to the connection of other nodes. These findings identify susceptible individuals for HCV transmission in PWID based on their frequent contact with others in the network. These results provide data that could be used for modelling HCV transmission patterns and in public health policies.
Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F2 pigs from a White Duroc×Erhualian F2 cross. The most significant SNP (ALGA0022658, P=5.59×10−13) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r2>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).
The objective of the present study was to investigate the effect of dietary neutral detergent fibre (NDF) : crude protein (CP) ratio on duodenal microbial crude protein (MCP) flow and nitrogen (N) losses. The study was completed in a 5 × 5 Latin square design with five lactating Holstein dairy cows and 5 high-concentrate total mixed rations (TMR) with different forage combinations, typical for Northern China. The rations with a fixed forage-to-concentrate ratio (39 : 61) resulted in different dietary NDF : CP ratios: TMR1 3·03 : 1 (428·2 g NDF/kg : 141·4 g CP/kg); TMR2 2·74 : 1 (392·7 g NDF/kg : 143·2 g CP/kg); TMR3 2·55 : 1 (368·3 g NDF/kg : 144·4 g CP/kg); TMR4 1·84 : 1 (304·8 g NDF/kg : 165·8 g CP/kg); TMR5 1·60 : 1 (285·0 g NDF/kg : 178·0 g CP/kg). Rumen content, milk, blood, urine and faeces were sampled on the last 3 days of five 18-day periods. Purine derivatives in the urine samples were determined to estimate rumen MCP flow into the small intestine. Milk yield and milk protein yield increased linearly with decreasing dietary NDF : CP ratio although slight differences in dry matter intake were observed due to feed intake restriction. Diurnal ammonia N in the rumen and duodenal MCP flow increased linearly, but blood urea N, urinary N and faecal N linearly decreased with decreasing dietary NDF : CP ratio. The enhanced N utilization in the maize-silage-based TMRs (TMR4–5) in comparison with maize-stover-based TMRs (TMR1–3) increased milk yield and the synthesis of milk protein instead of milk fat in the lactating cows, probably due to high transfer of ammonia N into rumen MCP with a considerable increase of dietary non-fibre carbohydrate content and the decrease of NDF : CP ratio. The present results indicate that not only increasing dietary non-structural carbohydrate content but also adjusting the ratio of structural carbohydrate to CP ratio are important diet formulation strategies for mitigating N losses in lactating cows.
In 2009, we examined HIV and sexually transmitted infections (STIs) in 750 female sex workers (FSWs) in Shanghai using a cross-sectional survey. Participants (mean age 27 years) were interviewed and tested for HIV and selected STIs. Prevalence was: HIV 0·13%, chlamydia 14·7%, gonorrhoea 3·5% and syphilis 1·3%. In a demographic multivariate model, younger age, higher income and originating from provinces other than Zhejiang and Shanghai were independently associated with STI. In a social and sexual behavioural model, women working in small venues with fewer clients per week, use of drugs, and higher price charged per sex act indicated a greater risk for STI. Although HIV appears rare in Shanghai FSWs, chlamydial infection is common, especially in women aged <25 years (prevalence 19·6%). Since STI and HIV share similar risk factors, preventive intervention measures should be implemented immediately based on the venues and characteristics of FSWs to prevent future spread of HIV.
The effects of source field plates on AlGaN/GaN High Electron Mobility Transistor reliability under off-state stress conditions were investigated using step-stress cycling. The source field plate enhanced the drain breakdown voltage from 55V to 155V and the critical voltage for off-state gate stress from 40V to 65V, relative to devices without the field plate. Transmission electron microscopy was used to examine the degradation of the gate contacts. The presence of cracking that appeared on both source and drain side of the gate edges was attributed to the inverse piezoelectric effect. In addition, a thin oxide layer was observed between the Ni gate contact and the AlGaN layer, and both Ni and oxygen had diffused into the AlGaN layer. The critical degradation voltage of AlGaN/GaN High Electron Mobility Transistors during off-state electrical stress was determined as a function of Ni/Au gate dimensions (0.1-0.17μm). Devices with different gate length and gate-drain distances were found to exhibit the onset of degradation at different source-drain biases but similar electric field strengths, showing that the degradation mechanism is primarily field-driven. The temperature dependence of sub-threshold drain current versus gate voltage at a constant drain bias voltage were used to determine the trap densities in AlGaN/GaN high electron mobility transistors (HEMTs) before and after the off-state stress. Two different trap densities were obtained for the measurements conducted at 300-493K and 493-573K, respectively.
The unit-cell parameters of andalusite and sillimanite have been measured by high-T powder X-ray diffraction up to 1000°C at ambient pressure. Within the temperature range investigated, all the unit-cell parameters varied smoothly, indicating no phase transition. The volume-temperature data were fitted with a polynomial expression for the thermal expansion coefficient (αT = a0 + a1T + a2T-2). yielding a0 = 2.55(2) × 10–5K–1, al = 0 and a2 = 0 for andalusite, and a0 = 1.40(4) × 10–5K–1a1 = 7.1(8) × 10–9K–2 and a2 = 0 for sillimanite. Using the new thermal expansion data determined in the present study and compressional data from the literature, the P-T phase relations of the kyanite-andalusite-sillimanite system were calculated thermodynamically, with the invariant point located at ∼523°C and 3.93 kbar.
Selective emitter structure has long been regarded as a good and relatively simple approach to improve the energy conversion efficiency of Si wafer-based single-junction photovoltaic (PV) cells. Recently emerged double printing method, on the other hand, potentially has the capability of improving the efficiency with no requirement for device structure modification. The manufacturability of these two approaches has been studied on a mass-production platform at JA Solar recently with large scale sampling. The experimental results collected from over two hundred thousand cells demonstrated that both approaches are capable of achieving significant conversion-efficiency gain in a cost-effective way with high yield rate on the PV industry commonly used mass production platform currently adopted by the vast majority of cell manufacturers
A new magnetron sputtering strategy is introduced that utilizes high plasma density (~5mA.cm-2) to avoid or reduce high temperature processing. The technique uses magnetrons of opposing magnetic polarity to create a “closed field” in which the plasma density is enhanced without the need for high applied Voltages. A batch system has been used which employs a rotating vertical drum as the substrate carrier and a symmetrical array of linear magnetrons. The magnetrons are fitted with target materials for each of the thin films required in the photovoltaic (PV) stack including the CdTe absorber layer, CdS window layer, metal contact using the conventional superstrate configuration. The “closed field” sputtering technology allows scale up not only for larger batch system designs but it is also configurable for “in-line” or “roll to roll” formats for large scale production. The morphology of each of the layers is characterized using a variety of structural and optical techniques including Field Emission Gun SEM and X-ray diffraction (XRD).
The fabrication of nanoporous aluminum oxide (Al2O3) membranes for large scale production of nanowires is performed at room temperature by a two-step anodization of commercially available aluminum foil tapes. During the anodization process, an oxide barrier layer is formed at the interface with aluminum. In the present work, the removal of the barrier is performed by (i) ramping down the voltage with a rate in the range of 0.5 V per 60s to 2 V per 60s and (ii) immersing the substrate in 50% phosphoric acid for up to 5 minutes. Depending on the removal conditions, several morphologies at the oxide-aluminum interface are observed by Scanning Electron Microscopy (SEM). Ramping down the voltage at less than 0.3 V per 15s combined by immersion in 50% phosphoric acid for less than 3 minutes is found to open the barrier layer of the nanopores. The pores have root-like structure with branches as small as few nanometers due to the slow voltage ramping. Several amorphous anodized Al2O3 (AAO) templates with pore diameter ranging from 30 to 40 nm and with length up to 25 μm were prepared by two-step anodization for the cathodic electrodeposition of photoactive nanowire semiconductors such as copper indium diselenide and cadmium sulfide.
Gestation length and maternal ability are important to improve the sow reproduction efficiency and their offspring survival. To map quantitative trait loci (QTL) for gestation length and maternal ability related traits including piglet survival rate and average body weight of piglets at weaning, more than 200 F2 sows from a White Duroc × Erhualian resource population were phenotyped. A genome-wide scan was performed with 194 microsatellite markers covering the whole pig genome. QTL analysis was carried out using a composite regression interval mapping method via QTL express. The results showed that total number of born piglets was significantly correlated with gestation length (r = −0.13, P < 0.05). Three QTL were detected on pig chromosome (SSC)2, 8 and 12 for gestation length. The QTL on SSC2 achieved the 5% genome-wide significant level and the QTL on SSC8 was consistent with previous reports. Four suggestive QTL were identified for maternal ability related traits including 1 QTL for survival rate of piglets at weaning on SSC8, 3 QTL for average body weight of piglet at weaning on SSC3, 11 and 13.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhoea in neonatal and postweaning pigs. F41 is one of ETEC fimbriae that adhere to the small intestinal epithelium and lead to development of diarrhoea. The genetic architecture of susceptibility to ETEC F41 remains elusive in pigs. In this study, we determined the in vitro adhesion phenotypes of ETEC F41 in a total of 835 F2 animals from a White Duroc × Erhualian intercross, and performed a genome scan using both F2 and half-sib analyses with 183 microsatellite markers to detect quantitative trait loci (QTL) for porcine susceptibility to ETEC F41. The two analyses consistently revealed a 1% genome-wide significant QTL on pig chromosome 4. Moreover, we determined F41 adhesion phenotypes in 14 purebred Erhualian and 14 White Duroc pigs. The results showed that both the founder breeds are segregating for the F41 adhesion phenotype, while less percentage of Erhualian pigs were adhesive to ETEC F41 compared to White Duroc pigs.
Adipocyte size and number are correlated with fat deposition, which is of major concern to human health and pork producers. To identify quantitative trait loci (QTL) for adipocyte size and number in pigs, a total of 341 F2 animals at 240 days in a White Duroc × Erhualian cross were measured for the area, perimeters, volume and number of adipocyte in abdominal fat. A genome scan was performed on these animals and their parents and grandparents with 183 microsatellite markers spanning the pig genome. Five chromosomal regions showed effects on the traits measured, predominantly on adipocyte size, on pig chromosome (SSC) 1, 4, 7 and 9. Neither of these QTL has been reported before this study. The QTL for adipocyte size detected in this study perfectly correspond to the previously reported QTL for fatness traits on SSC1, 4 and 7. The most significant association was evidenced at 58 cM on SSC7. At the locus, the favorable allele decreasing adipocyte size was unusually originated from the obese Erhualian breed. Only a suggestive QTL was detected for adipocyte number on SSC9. The results shed new lights on the understanding of the genetic basis of fatness traits in pigs.
The electrical properties of Ni-based ohmic contacts N-face p-type GaN are presented. The specific contact resistance of N-face p-GaN exhibits a liner decrease from 1.01 × cm2 to 9.05 × 10-3 Ω cm2 for the as-deposited and the annealed Ni/Au contacts, respectively, with increasing annealing temperature Furthermore, the specific contact resistance could be decreased by four orders of magnitude to 1.03 × 10-4 Ω cm2 as a result of surface treatment using an alcohol-based (NH4)2S solution. The depth profile data measured by the intensity of O1s core peak in the x-ray photoemission spectra showed that the alcohol-based (NH4)2S treatment was effective in removing of the surface oxide layer of GaN. In addition, a Ga 2p core-level peak showed a red-shift of binding energy by 0.3 eV by alcohol-based (NH4)2S treatment, indicating that the surface Fermi level was shifted toward the valence-band edge. Thus, the low ohmic contact behavior observed in our treated sample might be explained in terms of the removal of the oxide layer and reducing the barrier heights by reduced band-bending effect.
We report on a method based on cross-sectional scanning photoelectron microscopy and spectroscopy (XSPEM/S) for studying electronic structure of III-nitride surfaces and interfaces on a submicrometer scale. Cross-sectional III-nitride surfaces prepared by in situ cleavage were investigated to eliminate the polarization effects associated with the interface charges/dipoles normal to the cleaved surface. In contrast to the as-grown polar surfaces which show strong surface band bending, the cleaved nonpolar surfaces have been found to be under the flat-band conditions. Therefore, both doping and compositional junctions can be directly visualized at the cleaved nonpolar surfaces. Additionally, we show that the “intrinsic” valence band offsets at the cleaved III-nitride heterojunctions can be unambiguously determined.