Classification Criteria for Acute Posterior Multifocal Placoid Pigment Epitheliopathy

Purpose: To determine classification criteria for acute posterior multifocal placoid pigment epitheliopathy (APMPPE). / Design: Machine learning of cases with APMPPE and 8 other posterior uveitides. / Methods: Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. / Results: One thousand sixty-eight cases of posterior uveitides, including 82 cases of APMPPE, were evaluated by machine learning. Key criteria for APMPPE included: 1) choroidal lesions with a plaque-like or placoid appearance and 2) characteristic imaging on fluorescein angiography (lesions “block early and stain late diffusely”). Overall accuracy for posterior uveitides was 92.7% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for APMPPE were 5% in the training set and 0% in the validation set. / Conclusions: The criteria for APMPPE had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research

Classification Criteria For Pars Planitis

PURPOSE: To determine classification criteria for pars planitis DESIGN: Machine learning of cases with pars planitis and 4 other intermediate uveitides. METHODS: Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. RESULTS: Five hundred eighty-nine cases of intermediate uveitides, including 226 cases of pars planitis, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for pars planitis included unilateral or bilateral intermediate uveitis with either 1) snowballs in the vitreous or 2) snowbanks on the pars plana. Key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0 % in the training set and 1.7% in the validation set, respectively. CONCLUSIONS: The criteria for pars planitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research

Clinical Features and Prognosis of HLA-B27 Positive and Negative Anterior Uveitis in a Korean Population

Clinical features and prognosis of HLA-B27 positive anterior uveitis (AU) were assessed compared with HLA-B27 negative AU in a Korean population, based on the medical records of AU patients seen at a university hospital. Twenty-seven HLA-B27 negative, idiopathic AU patients (group I) and 55 HLA-B27 positive AU patients (group II) were studied. HLA-B27 positive group was further divided into 29 with associated systemic disease (seronegative spondyloarthropathy) (group IIA) and 26 without associated systemic disease (group IIB). Significantly more severe anterior chamber inflammation in terms of anterior chamber cells (P=0.006) and hypopyon formation (P=0.034) was observed with higher frequency of AU attacks (P=0.007) in the HLA-B27 positive group than in the HLA-B27 negative group. Systemic/periocular steroids were required in significantly more patients in the HLA-B27 positive group than in the HLA-B27 negative group (P=0.015). However, no significant differences were observed for final ocular and visual outcomes between these two groups. Associated systemic disease made no significant difference in the clinical features and prognosis in the HLA-B27 positive AU patients. In conclusion, despite more severe inflammation and a higher recurrence rate, HLA-B27 positive AU shows similar good final ocular and visual outcomes compared to HLA-B27 negative, idiopathic AU in a Korean population

Global mapping of highly pathogenic avian influenza H5N1 and H5Nx clade 2.3.4.4 viruses with spatial cross-validation.

Global disease suitability models are essential tools to inform surveillance systems and enable early detection. We present the first global suitability model of highly pathogenic avian influenza (HPAI) H5N1 and demonstrate that reliable predictions can be obtained at global scale. Best predictions are obtained using spatial predictor variables describing host distributions, rather than land use or eco-climatic spatial predictor variables, with a strong association with domestic duck and extensively raised chicken densities. Our results also support a more systematic use of spatial cross-validation in large-scale disease suitability modelling compared to standard random cross-validation that can lead to unreliable measure of extrapolation accuracy. A global suitability model of the H5 clade 2.3.4.4 viruses, a group of viruses that recently spread extensively in Asia and the US, shows in comparison a lower spatial extrapolation capacity than the HPAI H5N1 models, with a stronger association with intensively raised chicken densities and anthropogenic factors

Do radial oxygen loss and external aeration affect iron plaque formation and arsenic accumulation and speciation in rice?

Hydroponic experiments were conducted to investigate the effect of radial oxygen loss (ROL) and external aeration on iron (Fe) plaque formation, and arsenic (As) accumulation and speciation in rice (Oryza sativa L.). The data showed that there were significant correlations between ROL and Fe concentrations in Fe plaque produced on different genotypes of rice. There were also significant differences in the amounts of Fe plaque formed between different genotypes in different positions of roots and under different aeration conditions (aerated, normal, and stagnant treatments). In aerated treatments, rice tended to have a higher Fe plaque formation than in a stagnant solution, with the greatest formation at the root tip decreasing with increasing distances away, in accordance with a trend of spatial ROL. Genotypes with higher rates of ROL induced higher degrees of Fe plaque formation. Plaques sequestered As on rice roots, with arsenate almost double that with arsenite, leading to decreased As accumulation in both roots and shoots. The major As species detected in roots and shoots was arsenite, ranging from 34 to 78% of the total As in the different treatments and genotypes. These results contribute to our understanding of genotypic differences in As uptake by rice and the mechanisms causing rice genotypes with higher ROL to show lower overall As accumulation

Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients

Objective: To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). Methods: Multicenter study of SpA-related uveitis refractory to at least one immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. Results: Fifteen patients (13 men/2 women; 18 affected eyes; mean age 39±6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n=8), psoriatic arthritis (n=6) and non-radiographic axial SpA (n=1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n=13), sulfasalazine (n=6), pulses of methylprednisolone (n=4), azathioprine (n=3), leflunomide (n=2) and cyclosporine (n=1). Ten of them had also been treated with TNF-? blockers; etanercept (n=7), adalimumab (n=7), infliximab (n=6), and certolizumab (n=1). GLM was given at the standard dose (50 mg/sc/monthly) as monotherapy (n=7) or in combination with conventional immunosuppressive drugs (n=8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years (0 [0-0]) was significantly reduced compared to baseline findings (1 [0-3]); p=0.04). The mean best corrected visual acuity value also improved (0.84±0.3 at 2 years versus 0.62±0.3 at baseline; p=0.03). Only minor side effects were observed after a mean follow-up of 23±7 months. Conclusions: Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis

Genetic association analysis of N-methyl-d-aspartate receptor subunit gene GRIN2B and clinical response to clozapine

OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-d-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine. METHODS: GRIN2B variants were genotyped using standard TaqMan procedures in 175 European patients with schizophrenia deemed resistant or intolerant to treatment. Response was assessed using change in Brief Psychiatric Rating Scale scores following six months of clozapine therapy. Categorical and continuous response was assessed using chi-squared test and analysis of covariance, respectively. RESULTS: No associations were observed between the variants and response to clozapine. A-allele carriers of rs1072388 responded marginally better to clozapine therapy than GG-homozygotes; however, the difference was not statistically significant (p = 0.067, uncorrected). CONCLUSIONS: Our findings do not support a role for these GRIN2B variants in altering response to clozapine in our sample. Investigation of additional glutamate variants in clozapine response is warranted. Copyright © 2016 John Wiley & Sons, Ltd

Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain

RNA splicing is a key mechanism linking genetic variation with psychiatric disorders. Splicing profiles are particularly diverse in brain and difficult to accurately identify and quantify. We developed a new approach to address this challenge, combining long-range PCR and nanopore sequencing with a novel bioinformatics pipeline. We identify the full-length coding transcripts of CACNA1C in human brain. CACNA1C is a psychiatric risk gene that encodes the voltage-gated calcium channel CaV1.2. We show that CACNA1C’s transcript profile is substantially more complex than appreciated, identifying 38 novel exons and 241 novel transcripts. Importantly, many of the novel variants are abundant, and predicted to encode channels with altered function. The splicing profile varies between brain regions, especially in cerebellum. We demonstrate that human transcript diversity (and thereby protein isoform diversity) remains under-characterised, and provide a feasible and cost-effective methodology to address this. A detailed understanding of isoform diversity will be essential for the translation of psychiatric genomic findings into pathophysiological insights and novel psychopharmacological targets