Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs and infliximab

Objective: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naive rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-alpha (TNF-alpha) is involved in these effects. Method: Ninety-nine patients with early, DMARD-naive RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate, radiographs were scored with the modified Sharp-van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. Results: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-alpha production in human macrophages, indicating a possible connection between resistin and TNF-alpha. Conclusion: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-alpha antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients.Peer reviewe

A New Evolutionary Path to Type Ia Supernovae: Helium-Rich Super-Soft X-Ray Source Channel

We have found a new evolutionary path to Type Ia supernovae (SNe Ia) which has been overlooked in previous work. In this scenario, a carbon-oxygen white dwarf (C+O WD) is originated, not from an asymptotic giant branch star with a C+O core, but from a red-giant star with a helium core of $\sim 0.8-2.0 M_\odot$. The helium star, which is formed after the first common envelope evolution, evolves to form a C+O WD of $\sim 0.8-1.1 M_\odot$ with transferring a part of the helium envelope onto the secondary main-sequence star. This new evolutionary path, together with the optically thick wind from mass-accreting white dwarf, provides a much wider channel to SNe Ia than previous scenarios. A part of the progenitor systems are identified as the luminous supersoft X-ray sources or the recurrent novae like U Sco, which are characterized by the accretion of helium-rich matter. The white dwarf accretes hydrogen-rich, helium-enhanced matter from a lobe-filling, slightly evolved companion at a critical rate and blows excess matter in the wind. The white dwarf grows in mass to the Chandrasekhar mass limit and explodes as an SN Ia. A theoretical estimate indicates that this channel contributes a considerable part of the inferred rate of SNe Ia in our Galaxy, i.e., the rate is about ten times larger than the previous theoretical estimates for white dwarfs with slightly evolved companions.Comment: 19 pages including 12 figures, to be published in ApJ, 519, No.

Recruitment Constraints in Singapore's Fluted Giant Clam (Tridacna squamosa) Populations - A Dispersal Model Approach

10.1371/journal.pone.0058819PLoS ONE83

Long-term visual and treatment outcomes of whole-population pre-school visual screening (PSVS) in children:a longitudinal, retrospective, population-based cohort study

BACKGROUND: This study reports the long-term visual and treatment outcomes in a whole-population, orthoptic-delivered pre-school visual screening (PSVS) programme in Scotland and further examines their associations with socioeconomic backgrounds and home circumstances. METHODS: Retrospective case review was conducted on 430 children who failed PSVS. Outcome measures included best corrected visual acuity (BCVA), severity of amblyopia (mild, moderate and severe), binocular vision (BV) (normal, poor and none), ophthalmic diagnosis and treatment modalities. Parameters at discharge were compared to those at baseline and were measured against the Scottish index of multiple deprivation (SIMD) and Health plan indicator (HPI), which are indices of deprivation and status of home circumstances. RESULTS: The proportion of children with amblyopia reduced from 92.3% (373/404) at baseline to 29.1% (106/364) at discharge (p < 0.001). Eighty percent (291/364) had good BV at discharge compared to 29.2% (118/404) at baseline (p < 0.001). Children from more socioeconomically deprived areas (OR 2.19, 95% CI 1.01–4.30, p = 0.003) or adverse family backgrounds (OR 3.94, 95% CI 1.99–7.74, p = 0.002) were more likely to attend poorly and/or become lost to follow-up. Children from worse home circumstances were five times more likely to have residual amblyopia (OR 5.37, 95% CI 3.29–10.07, p < 0.001) and three times more likely to have poor/no BV (OR 3.41, 95% CI 2.49–4.66, p < 0.001) than those from better home circumstances. CONCLUSIONS: Orthoptic-delivered PSVS is successful at screening and managing amblyopia. Children from homes requiring social care input are less likely to attend and are more likely to have poorer visual outcomes

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

The Near-Earth Object Surveyor Mission

The Near-Earth Object (NEO) Surveyor mission is a NASA observatory designed to discover and characterize near-Earth asteroids and comets. The mission's primary objective is to find the majority of objects large enough to cause severe regional impact damage ($>$140 m in effective spherical diameter) within its five-year baseline survey. Operating at the Sun-Earth L1 Lagrange point, the mission will survey to within 45 degrees of the Sun in an effort to find the objects in the most Earth-like orbits. The survey cadence is optimized to provide observational arcs long enough to reliably distinguish near-Earth objects from more distant small bodies that cannot pose an impact hazard. Over the course of its survey, NEO Surveyor will discover $\sim$200,000 - 300,000 new NEOs down to sizes as small as $\sim$10 m and thousands of comets, significantly improving our understanding of the probability of an Earth impact over the next century.Comment: accepted to PS

A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

10.1186/1471-2334-4-34BMC Infectious Diseases4-BIDM

Reverse Engineering the Yeast RNR1 Transcriptional Control System

Transcription is controlled by multi-protein complexes binding to short non-coding regions of genomic DNA. These complexes interact combinatorially. A major goal of modern biology is to provide simple models that predict this complex behavior. The yeast gene RNR1 is transcribed periodically during the cell cycle. Here, we present a pilot study to demonstrate a new method of deciphering the logic behind transcriptional regulation. We took regular samples from cell cycle synchronized cultures of Saccharomyces cerevisiae and extracted nuclear protein. We tested these samples to measure the amount of protein that bound to seven different 16 base pair sequences of DNA that have been previously identified as protein binding locations in the promoter of the RNR1 gene. These tests were performed using surface plasmon resonance. We found that the surface plasmon resonance signals showed significant variation throughout the cell cycle. We correlated the protein binding data with previously published mRNA expression data and interpreted this to show that transcription requires protein bound to a particular site and either five different sites or one additional sites. We conclude that this demonstrates the feasibility of this approach to decipher the combinatorial logic of transcription