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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.
Silk and carbon nanomaterials, such as graphene oxide, graphene, and carbon nanotubes, have complementary mechanical properties that feature superior toughness and strength, respectively. Different strategies have been devoted to developing silk/carbon nanocomposites, but challenges remain to fully integrate the mechanical advantages of these two components into one synergistic material system. In this article, we provide a critical summary of structure–mechanics relationships in silk/carbon nanocomposites and highlight the impact of the interaction between silk and carbon nanomaterials on mechanical properties of the hybrid materials. We describe the challenges involved and directions for future designs of silk/carbon nanocomposites.
Common practices for invasive species control and management include physical, chemical, and biological approaches. The first two approaches have clear limitations and may lead to unintended (negative) consequences, unless carefully planned and implemented. For example, physical removal rarely completely eradicates the targeted invasive species and can cause disturbances that facilitate new invasions by nonnative species from nearby habitats. Chemical treatments can harm native, and especially rare, species through unanticipated side effects. Biological methods may be classified as biocontrol and the ecological approach. Similar to physical and chemical methods, biocontrol also has limitations and sometimes leads to unintended consequences. Therefore, a relatively safer and more practical choice may be the ecological approach, which has two major components: (1) restoration of native species and (2) biomass manipulation of the restored community, such as selective grazing or prescribed burning (to achieve and maintain viable population sizes). Restoration requires well-planned and implemented planting designs that consider alpha-, beta-, and gamma-diversity and the abundance of native and invasive component species at local, landscape, and regional levels. Given the extensive destruction or degradation of natural habitats around the world, restoration could be most effective for enhancing ecosystem resilience and resistance to biotic invasions. At the same time, ecosystems in human-dominated landscapes, especially those newly restored, require close monitoring and careful intervention (e.g., through biomass manipulation), especially when successional trajectories are not moving as intended. Biomass management frequently uses prescribed burning, grazing, harvesting, and thinning to maintain overall ecosystem health and sustainability. Thus, the resulting optimal, balanced, and relatively stable ecological conditions could more effectively limit the spread and establishment of invasive species. Here we review the literature (especially within the last decade) on ecological approaches that involve biodiversity, biomass, and productivity, three key community/ecosystem variables that reciprocally influence one another. We focus on the common and most feasible ecological practices that can aid in resisting new invasions and/or suppressing the dominance of existing invasive species. We contend that, because of the strong influences from neighboring areas (i.e., as exotic species pools), local restoration and management efforts in the future need to consider the regional context and projected climate changes.
In two experiments, we examined the function of procedural justice in signaling individuals’ value to the group by arguing that individuals treated fairly are more likely to engage in proactive preventive behavior, a behavior that involves proactively revising or correcting the mistakes and intentional deceptions of coworkers. In addition, we extend Staw and Boettger’s (1990) work on task revision and demonstrate that procedural justice and goal setting have compensatory effects, such that procedural justice can be combined with performance goals to reap the valuable aspects of goal setting while minimizing some of the unintended side-effects. Our findings also contribute to the ongoing discussion of the mixed effects of goal setting, as well as the effects of multiple goal assignment.
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.
The golden snub-nosed monkey (Rhinopithecus roxellana) is an endangered species endemic to China. Relatively little is known about the taxonomic status of soil-transmitted helminths (STH) in these monkeys. Trichuris spp. (syn. Trichocephalus) are among the most important STHs, causing significant socio-economic losses and public health concerns. To date, five Trichuris species have been reported in golden monkeys, including a novel species, T. rhinopiptheroxella, based on morphology. In the present study, molecular and morphological analysis was conducted on adult Trichuris worms obtained from a dead golden snub-nosed monkey, to better understand their taxonomic status. Morphology indicated that the adult Trichuris worms were similar to T. rhinopiptheroxella. To further ascertain their phylogenetic position, the complete mitochondrial (mt) genome of these worms was sequenced and characterized. The mt genome of T. rhinopiptheroxella is 14,186 bp, encoding 37 genes. Phylogenetic analysis based on the concatenated amino acids of 12 protein-coding genes (with the exception of atp8) indicated that T. rhinopiptheroxella was genetically distinct and exhibited 27.5–27.8% genetic distance between T. rhinopiptheroxella and other Trichuris spp. Our results support T. rhinopiptheroxella as a valid Trichuris species and suggest that mt DNA could serve as a marker for future studies on the classification, evolution and molecular epidemiology of Trichuris spp. from golden snub-nosed monkeys.
To compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypes
As part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.
The study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non–CTX-M ESBLs were detected.
Clinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.
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.
An updated compilation of published and new data of major-ion (Ca, Cl, K, Mg, Na, NO3, SO4) and methylsulfonate (MS) concentrations in snow from 520 Antarctic sites is provided by the national ITASE (International Trans-Antarctic Scientific Expedition) programmes of Australia, Brazil, China, Germany, Italy, Japan, Korea, New Zealand, Norway, the United Kingdom, the United States and the national Antarctic programme of Finland. The comparison shows that snow chemistry concentrations vary by up to four orders of magnitude across Antarctica and exhibit distinct geographical patterns. The Antarctic-wide comparison of glaciochemical records provides a unique opportunity to improve our understanding of the fundamental factors that ultimately control the chemistry of snow or ice samples. This paper aims to initiate data compilation and administration in order to provide a framework for facilitation of Antarctic-wide snow chemistry discussions across all ITASE nations and other contributing groups. The data are made available through the ITASE web page (http://www2.umaine.edu/itase/content/syngroups/snowchem.html) and will be updated with new data as they are provided. In addition, recommendations for future research efforts are summarized.
We demonstrate high vertical yield InAs1-xSbx (0 < x ≤ 0.18) nanowire arrays grown on InP (111)B substrates by calalyst-free selective-area metal-organic chemical vapor deposition. High antimony composition is achieved by pulsing the arsenic flow to reduce the effective arsenic partial pressure while keeping the antimony partial pressure fixed. This increases the antimony vapor phase composition while allowing the antimony partial pressure to be kept low enough to avoid antimony condensation on the growth mask. InAsSb nanowire arrays show strong emission by photoluminescence at 77 K, covering a wavelength range of 3.77 – 5.08 μm. These results pave the way to engineering optical properties and enabling hybrid integration for nanoscale mid-wavelength infrared optical devices.
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).
Older employees face a severe employability problem, partly because of dominant stereotypes about them. This study investigates stereotypes of older employees in corporate and news media. Drawing on the Stereotype Content Model, we content analysed newspaper coverage and corporate media of 50 large-scale Dutch organisations, published between 2006 and 2013. The data revealed that stereotypical portrayals of older employees are more common in news media than in corporate media and mixed in terms of valence. Specifically, older employees were positively portrayed with regard to warmth stereotypes, such as trustworthiness, but negatively with regard to competence stereotypes, such as technological competence and adaptability. Additionally, stereotypical portrayals that do not clearly belong to warmth or competence dimensions are found, such as the mentoring role stereotype and the costly stereotype. Because competence stereotypes weigh more heavily in employers’ productivity perceptions, these media portrayals might contribute to the employability problem of older employees. We suggest that older employees could benefit from a more realistic media debate about their skills and capacities.
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.
Previous studies have shown that the intake of freeze-dried strawberry powder (FDSP) improves select markers of cardiovascular health in adults with cardiovascular risk factors; however, whether these improvements can be observed in at-risk adolescents is unknown. A randomised, double-blind, cross-over study enrolled twenty-five overweight or obese males, aged 14–18 years, to consume 50 g of a FDSP or a control powder, daily for 1 week. Before and after each test period, measures of microvascular function, plasma nitrate/nitrite, platelet reactivity and blood lipids were collected at baseline and acutely 1 h after FDSP intake. Acute plasma nitrate/nitrite levels increased 1 h after consuming the FDSP during Study Visit 1 before daily FDSP intake (P<0·001) and during Study Visit 2 after 1 week of FDSP intake (P<0·001) compared with control powder intake. As a group, fasting nitrate/nitrite levels did not significantly change after 1 week of control or FDSP intake. However, for those individuals where fasting nitrate levels increased after short-term FDSP intake compared with controls, an increase in reactive hyperaemia index (RHI) was observed (P=0·014), whereas RHI was unchanged in those individuals who did not have a significant increase in nitrate (P=0·396). Taken together, these data support the concept that strawberries can provide vascular health benefits to heavier adolescent males.
The genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits.
We recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities.
We found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L–THA.L), left rectus to right thalamus (REC.L–THA.R), left superior orbital cortex to left thalamus (ORBsup.L–THA.L) and left superior orbital cortex to right thalamus (ORBsup.L–THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10−8) using REC.L–THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10–6, corrected p = 0.05).
Overall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.
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.