Correlated Binomial Models and Correlation Structures

We discuss a general method to construct correlated binomial distributions by imposing several consistent relations on the joint probability function. We obtain self-consistency relations for the conditional correlations and conditional probabilities. The beta-binomial distribution is derived by a strong symmetric assumption on the conditional correlations. Our derivation clarifies the 'correlation' structure of the beta-binomial distribution. It is also possible to study the correlation structures of other probability distributions of exchangeable (homogeneous) correlated Bernoulli random variables. We study some distribution functions and discuss their behaviors in terms of their correlation structures.Comment: 12 pages, 7 figure

A case of chronic recurrent multifocal osteomyelýtýs successfully treated with etanercept

PubMe

MEFV mutations in systemic JIA

Background: Systemic form of juvenile idiopathic arthritis (JIA) is regarded as an autoinflammatory disease. Certain genetic polymorphisms in genes coding inflammatory proteins have been associated with the disease. On the other hand mutations of the MEFV gene cause a monogenic autoinflammatory disease, Familial Mediterranean Fever (FMF). In a previous study in adult rheumatoid arthritis 3 out of the 25 British patients who developed secondary amyloidosis had a mutation/polymorphism in the MEFV gene. Aim: To analyse whether mutaions in the MEFV gene had an association with systemic JIA. Patients and methods: MEFV mutations were screened in a total of 32 systemic JIA patients. All had been classified as systemic JIA according to the Durban JIA criteria. None had disease characteristics that met the Tel Hashomer criteria for the diagnosis of FMF. Results: 2 carrier for M694V and two patients who were homozygote for MEFV mutations. Both of these patients were among the most severe patients in the group. One had an excellent response to etanercept whereas the other was resistant to anti-TNF and other conventional treatments and had only a partial response to thalidomide. Although the number of severe mutations were increased in this small group of patients with systemic JIA the difference with the Turkish population did not reach statistical significance, but the disease causing mutation (M694V) was significantly high in the patients with systemic JIA(p = 0.02). Conclusion: However, the severe disease course in the aforementioned patients suggest that MEFV mutations may be a modifying genetic factor in systemic JIA.PubMe

Infectious Default Model with Recovery and Continuous Limit

We introduce an infectious default and recovery model for N obligors. Obligors are assumed to be exchangeable and their states are described by N Bernoulli random variables S_{i} (i=1,...,N). They are expressed by multiplying independent Bernoulli variables X_{i},Y_{ij},Y'_{ij}, and default and recovery infections are described by Y_{ij} and Y'_{ij}. We obtain the default probability function P(k) for k defaults. Taking its continuous limit, we find two nontrivial probability distributions with the reflection symmetry of S_{i} \leftrightarrow 1-S_{i}. Their profiles are singular and oscillating and we understand it theoretically. We also compare P(k) with an implied default distribution function inferred from the quotes of iTraxx-CJ. In order to explain the behavior of the implied distribution, the recovery effect may be necessary.Comment: 13 pages, 7 figure

Methane Mitigation:Methods to Reduce Emissions, on the Path to the Paris Agreement

The atmospheric methane burden is increasing rapidly, contrary to pathways compatible with the goals of the 2015 United Nations Framework Convention on Climate Change Paris Agreement. Urgent action is required to bring methane back to a pathway more in line with the Paris goals. Emission reduction from “tractable” (easier to mitigate) anthropogenic sources such as the fossil fuel industries and landfills is being much facilitated by technical advances in the past decade, which have radically improved our ability to locate, identify, quantify, and reduce emissions. Measures to reduce emissions from “intractable” (harder to mitigate) anthropogenic sources such as agriculture and biomass burning have received less attention and are also becoming more feasible, including removal from elevated-methane ambient air near to sources. The wider effort to use microbiological and dietary intervention to reduce emissions from cattle (and humans) is not addressed in detail in this essentially geophysical review. Though they cannot replace the need to reach “net-zero” emissions of CO2, significant reductions in the methane burden will ease the timescales needed to reach required CO2 reduction targets for any particular future temperature limit. There is no single magic bullet, but implementation of a wide array of mitigation and emission reduction strategies could substantially cut the global methane burden, at a cost that is relatively low compared to the parallel and necessary measures to reduce CO2, and thereby reduce the atmospheric methane burden back toward pathways consistent with the goals of the Paris Agreement

Stable isotopic signatures of methane from waste sources through atmospheric measurements

This study aimed to characterize the carbon isotopic signatures (δ13C-CH4) of several methane waste sources, predominantly in the UK, and during field campaigns in the Netherlands and Turkey. CH4 plumes emitted from waste sources were detected during mobile surveys using a cavity ring-down spectroscopy (CRDS) analyser. Air samples were collected in the plumes for subsequent isotope analysis by gas chromatography isotope ratio mass spectrometry (GC-IRMS) to characterize δ13C-CH4. The isotopic signatures were determined through a Keeling plot approach and the bivariate correlated errors and intrinsic scatter (BCES) fitting method. The δ13C-CH4 and δ2H-CH4 signatures were identified from biogas plants (−54.6 ± 5.6‰, n = 34; −314.4 ± 23‰ n = 3), landfills (−56.8 ± 2.3‰, n = 43; −268.2 ± 2.1‰, n = 2), sewage treatment plants (−51.6 ± 2.2‰, n = 15; −303.9 ± 22‰, n = 6), composting facilities (−54.7 ± 3.9‰, n = 6), a landfill leachate treatment plant (−57.1 ± 1.8‰, n = 2), one water treatment plant (−53.7 ± 0.1‰) and a waste recycling facility (−53.2 ± 0.2‰). The overall signature of 71 waste sources ranged from −64.4 to −44.3‰, with an average of −55.1 ± 4.1‰ (n = 102) for δ13C, −341 to −267‰, with an average of −300.3 ± 25‰ (n = 11) for δ2H, which can be distinguished from other source types in the UK such as gas leaks and ruminants. The study also demonstrates that δ2H-CH4 signatures, in addition to δ13C-CH4, can aid in better waste source apportionment and increase the granularity of isotope data required to improve regional modelling

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a group of related neurodevelopmental syndromes with complex genetic etiology.1 We identified a de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with cognitive and social delay. We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD;2 the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism;3 and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates. We comprehensively resequenced CNTNAP2 in 635 patients and 942 controls. Among patients, we identified a total of 27 nonsynonymous changes; 13 were rare and unique to patients and 8 of these were predicted to be deleterious by bioinformatic approaches and/or altered residues conserved across all species. One variant at a highly conserved position, I869T, was inherited by four affected children in three unrelated families, but was not found in 4010 control chromosomes (p = 0.014). Overall, this resequencing data demonstrated a modest nonsignificant increase in the burden of rare variants in cases versus controls. Nonethless, when viewed in light of two independent studies published in this issue of AJHG showing a relationship between ASD and common CNTNAP2 alleles,4,5 the cytogenetic and mutation screening data suggest that rare variants may also contribute to the pathophysiology of ASD, but place limits on the magnitude of this contribution

Rapidly progressive glomerulonephritis in a child with Henoch-Schönlein Vasculitis and familial Mediterranean fever

Henoch-Schonlein Vasculitis (HSV) is systemic small vessel vasculitis involving the skin, kidney, joints, and gastrointestinal tract. The proportion of patients reported to have renal involvement varies between 20% and 80%. Rapidly progressive glomerulonephritis (RPGN)is rare syndrome in children, characterized by clinical features of glomerulonephritis (GN) and rapid loss of renal function. We present a severe kidney involvement in a 14 year old boy with HSV in who is carring MEFV mutation. A 14 year old boy had developed sudden onset of palpable purpuric rash on his extensor surfaces of lower extremities. He had elevated an erythrocyte sedimentation rate (ESR) (45 mm/h), C-reactive protein (3.74 mg/dl), serum urea 66 mg/dl, serum creatinine 1.8 mg/dl. Also, he had hypocomplementemia. Antinuclear antibody, anti ds DNA, antineutrophil cytoplasmic antibody, anticardiolipine antibodies were negative. Urinalysis revealed macroscopic hematuria and proteinuria with a 24-h urinary protein excretion of 55 mg/m2/h. The renal biopsy specimen showed crescentic and necrotizing glomerulonephritis. He had also M694V/E148Q compound heterozygote mutation. Clinical symptoms and renal failure resolved with intermittant hemodialysis and medical therapy

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study

BACKGROUND: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). METHODS: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile. RESULTS: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (β = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (β = 0.13 [95%CI 0.06-0.19]; p = 0.0003). CONCLUSIONS: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups