Naresuan University Journal
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Aicardi-Goutières syndrome harbours abundant systemic and brain-reactive autoantibodies.
OBJECTIVES: Aicardi-Goutières syndrome (AGS) is an autoimmune disorder that shares similarities with systemic lupus erythematous. AGS inflammatory responses specially target the cerebral white matter. However, it remains uncertain why the brain is the most affected organ, and little is known about the presence of autoantibodies in AGS. Here, we aim to profile specific autoantibodies in AGS and to determine whether these autoantibodies target cerebral epitopes. METHODS: Using a multiplex microarray, we assessed the spectrum of serum autoantibodies in 56 genetically confirmed patients with AGS. We investigated the presence of immunoglobulins in AGS brain specimens using immunohistochemistry and studied the reactivity of sera against brain epitopes with proteomics. RESULTS: Serum from patients exhibited high levels of IgGs against nuclear antigens (gP210, Nup62, PCNA, Ro/SSA, Sm/RNP complex, SS-A/SS-B), components of the basement membrane (entactin, laminin), fibrinogen IV and gliadin. Upon testing whether antibodies in AGS could be found in the central nervous system, IgGs were identified to target in vivo endothelial cells in vivo and astrocytes in brain sections of deceased patients with AGS. Using a proteomics approach, we were able to confirm that IgGs in serum samples from AGS patients bind epitopes present in the cerebral white matter. CONCLUSIONS: Patients with AGS produce a broad spectrum of autoantibodies unique from other autoimmune diseases. Some of these autoantibodies target endothelial cells and astrocytes in the brain of the affected patients, perhaps explaining the prominence of neurological disease in the AGS phenotype
The management of Otitis Media with Effusion in children with cleft palate (mOMEnt)::a feasibility study and economic evaluation
Background: Cleft lip and palate are among the most common congenital malformations, with an incidence of around 1 in 700. Cleft palate (CP) results in impaired Eustachian tube function, and 90% of children with CP have otitis media with effusion (OME) histories. There are several approaches to management, including watchful waiting, the provision of hearing aids (HAs) and the insertion of ventilation tubes (VTs). However, the evidence underpinning these strategies is unclear and there is a need to determine which treatment is the most appropriate. Objectives: To identify the optimum study design, increase understanding of the impact of OME, determine the value of future research and develop a core outcome set (COS) for use in future studies. Design: The management of Otitis Media with Effusion in children with cleft palate (mOMEnt) study had four key components: (i) a survey evaluation of current clinical practice in each cleft centre; (ii) economic modelling and value of information (VOI) analysis to determine if the extent of existing decision uncertainty justifies the cost of further research; (iii) qualitative research to capture patient and parent opinion regarding willingness to participate in a trial and important outcomes; and (iv) the development of a COS for use in future effectiveness trials of OME in children with CP. Setting: The survey was carried out by e-mail with cleft centres. The qualitative research interviews took place in patients’ homes. The COS was developed with health professionals and parents using a web-based Delphi exercise and a consensus meeting. Participants: Clinicians working in the UK cleft centres, and parents and patients affected by CP and identified through two cleft clinics in the UK, or through the Cleft Lip and Palate Association. Results: The clinician survey revealed that care was predominantly delivered via a ‘hub-and-spoke’ model; there was some uncertainty about treatment strategies; it is not current practice to insert VTs at the time of palate repair; centres were in a position to take part in a future study; and the response rate to the survey was not good, representing a potential concern about future co-operation. A COS reflecting the opinions of clinicians and parents was developed, which included nine core outcomes important to both health-care professionals and parents. The qualitative research suggested that a trial would have a 25% recruitment rate, and although hearing was a key outcome, this was likely to be due to its psychosocial consequences. The VOI analysis suggested that the current uncertainty justified the costs of future research. Conclusions: There exists significant uncertainty regarding the best management strategy for persistent OME in children with clefts, reflecting a lack of high-quality evidence regarding the effectiveness of individual treatments. It is feasible, cost-effective and of significance to clinicians and parents to undertake a trial examining the effectiveness of VTs and HAs for children with CP. However, in view of concerns about recruitment rate and engagement with the clinicians, we recommend that a trial with an internal pilot is considered
Convertible bond announcement effects: why is Japan different?
U.S. and Japanese firms dominate global convertible bond issuance. Previous research 10 documents more favorable convertible bond announcement effects in Japan than in the U.S. 11 and other developed countries. Using a global sample of convertible bonds issued from 1982 12 to 2012, we find that the more favorable announcement effects of Japanese convertibles are 13 driven by their stated uses of proceeds. Japanese convertibles more often include capital expen- 14 diture as an intended use, while U.S. firms tend to mention general purposes to motivate their 15 offering. Our findings illustrate the value to firms of being more explicit when disclosing the 16 intended use of proceeds of security offerings
Loss and rebuilding: A qualitative study of late diagnosis of cleft palate
Purpose To explore the experiences of parents whose child received a late diagnosis of cleft palate (>24 hr after birth). Design and Methods Parents of 17 children and three nurses specialised in cleft care (specialist nurses) took part in a qualitative, semi-structured interview. Framework analysis was applied to data. Results Loss and rebuilding was an overarching concept—from the crescendo leading up to the bombshell of diagnosis, followed by the aftermath of dealing with the child's long-term condition. Practice implications Specialist nurses can help parents to trust healthcare professionals and to feel confident in their ability to nurture by listening, informing, and supporting
An Inverted-Sandwich Diuranium μ-η5:η5-Cyclo-P5 Complex Supported by U-P5 δ-Bonding
Trends in US Contact Lens Prescribing 2002 to 2014.
PURPOSE: To document contact lens prescribing patterns in the United States between 2002 and 2014. METHODS: A survey of contact lens prescribing trends was conducted each year between 2002 and 2014, inclusive. Randomly selected contact lens practitioners were asked to provide information relating to 10 consecutive contact lens fits between January and March each year. RESULTS: Over the 13-year survey period, 1650 survey forms were received from US practitioners representing details of 7702 contact lens fits. The mean (±SD) age of lens wearers was 33.6 (±15.2) years, of whom 65.2% were female. Rigid lens new fits decreased from 13.0% in 2002 to 9.4% in 2014. Across this period, silicone hydrogels have replaced mid water contact lens hydrogels as the soft lens material of choice. Toric lenses represented about 25 to 30% of all soft lens fits. Multifocal soft lenses are generally preferred to monovision. Daily disposable lens fits have recently increased, and in 2014, they represented 27.1% of all soft lens fits. Most lenses are prescribed on 1 to 2 weekly or monthly lens replacement regimen. Extended wear remains a minority lens wearing modality. The vast majority of those wearing reusable lenses use multipurpose lens care solutions. Lenses are mostly worn 7 d/wk. CONCLUSIONS: This survey has revealed prescribing trends and preferences in the United States over the past 13 years