Immunologic assessment and KMT2D mutation detection in Kabuki syndrome.

Kabuki or Niikawa-Kuroki syndrome (KS) is a rare disorder with multiple malformations and recurrent infections, especially otitis media. This study aimed to investigate the genetic defects in Kabuki syndrome and determine if immune status is related to recurrent otitis media. Fourteen patients from 12 unrelated families were enrolled in the 9-year study period (2005-2013). All had Kabuki faces, cleft palate, developmental delay, mental retardation, and the short fifth finger. Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. Immunologic analysis revealed lower memory CD19+ cells (11/13), lower memory CD4+ cells (8/13), undetectable anti-HBs antibodies (7/13), and antibody deficiency (7/13), including lower IgA (4), IgG (2), and IgG2 (1). Naïve emigrant lymphocytes, lymphocyte proliferation function, complement activity, and superoxide production in polymorphonuclear cells were all normal. All the patients had KMT2D mutations and 10 novel mutations of R1252X, R1757X,Y1998C, P2550R fs2604X, Q4013X, G5379X, E5425K, R5432X, R5432W, and R5500W. Resembling the phenotype of common variable immunodeficiency, KS patients with antibody deficiency, decreased memory cells, and poor vaccine response increased susceptibility to recurrent otitis media. Large-scale prospective studies are warranted to determine if regular immunoglobulin supplementation decreases the frequency of otitis media and severity of hearing impairment.

Does targeted pre-load optimisation by stroke volume variation attenuate a reduction in cardiac output in the prone position.

The prone position can reduce cardiac output by up to 25% due to reduced preload. We hypothesised that preload optimisation targeted to stroke volume variation before turning prone might alleviate this. A supine threshold stroke volume variation of 14% in a preliminary study identified patients whose cardiac outputs would decline when turned prone. In 45 patients, cardiac output declined only in the group whose supine stroke volume variation was high (mean (SD) 5.1 (2.0) to 3.9 (1.9) l.min(-1) ; p < 0.001), but not in patients in whom it was low, or in those in whom stroke volume variation was high, but who received volume preload (p = 0.525 and 0.941, respectively). We conclude that targeted preload optimisation using a supine stroke volume variation value < 14% is effective in preventing falls in cardiac output induced by the prone position.

A unified Bayesian framework for exact inference of area under the receiver operating characteristic curve.

The area under the receiver operating characteristic curve is a widely used measure for evaluating the performance of a diagnostic test. Common approaches for inference on area under the receiver operating characteristic curve are usually based upon approximation. For example, the normal approximation based inference tends to suffer from the problem of low accuracy for small sample size. Frequentist empirical likelihood based approaches for area under the receiver operating characteristic curve estimation may perform better, but are usually conducted through approximation in order to reduce the computational burden, thus the inference is not exact. By contrast, we proposed an exact inferential procedure by adapting the empirical likelihood into a Bayesian framework and draw inference from the posterior samples of the area under the receiver operating characteristic curve obtained via a Gibbs sampler. The full conditional distributions within the Gibbs sampler only involve empirical likelihoods with linear constraints, which greatly simplify the computation. To further enhance the applicability and flexibility of the Bayesian empirical likelihood, we extend our method to the estimation of partial area under the receiver operating characteristic curve, comparison of multiple tests, and the doubly robust estimation of area under the receiver operating characteristic curve in the presence of missing test results. Simulation studies confirm the desirable performance of the proposed methods, and a real application is presented to illustrate its usefulness.

Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology.

We developed genetic-epigenetic tissue mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung transplant recipients, we showed that, at 72 hr after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles, and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring, and cancer screening.

Relationship of Socioeconomic Status Indicators to Obesity in Hispanic and Non-Hispanic White Middle-Aged Women: A Population Study.

BACKGROUND: Obesity rates differ between Hispanic and White (non-Hispanic) women in the United States, with higher rates among Hispanic women. Socioeconomic processes contribute to this disparity both at the individual and the environmental level. Understanding these complex relationships requires multilevel analyses within cohorts of women that have a shared environment. In population-based samples of Hispanic and White (non-Hispanic) women from the same neighborhoods, we evaluated within each ethnic group a) The association of individual-level socioeconomic status (SES) with body mass index (BMI); and b) The additional contribution of neighborhood-level measures of SES. METHODS: Using population-based multi-stage sampling methods, we oversampled low SES and Hispanic block groups. During household screening, we identified women aged 30 to 50 years. Among White women, we specifically oversampled women with low educational levels. 515 Hispanic and 503 White women completed baseline. Height and weight were measured. Baseline surveys, in Spanish and English, included four measures of SES. Three measures of area-level SES were examined. Analysis of loge BMI on each SES measure used linear mixed models, incorporating design effects. RESULTS: Among White women, low education, social status, and neighborhood SES were associated with higher BMI (p < 0.001, p < 0.0001, and p < 0.05, respectively), independent of other SES measures. Although the highest grouped category of education, income and subjective social status within the Hispanic cohort had the lowest mean estimated BMI, the point estimates across categories were not monotonic, and had wide confidence intervals. As a result, in contrast to the findings among White women, no statistically significant associations were found between BMI and measures of SES among Hispanic women. DISCUSSION: Neighborhood and individual measures of SES operate differently in Hispanic compared with White women. We had assumed the measures we included to be most salient and operate similarly for both groups of women. Rather the salient factors for Hispanic women have yet to be identified. Improved understanding may ultimately inform the design of culturally-relevant multilevel obesity prevention strategies.

The Intrinsic (3)

A near-UV triplet emission from [Au(2)(dcpm)(2)](ClO(4))(2) has been discovered. Studies on the spectroscopic properties of the complexes [Au(2)(dcpm)(2)]Y(2) (Y=ClO(4)(-), PF(6)(-), CF(3)SO(3)(-), [Au(CN)(2)](-), Cl(-), and I(-); dcpm=bis(dicyclohexylphosphanyl)methane) support the assignment of the high-energy emissions at 360-368 nm to the (3)[dsigma*psigma] excited state, adducts of which exhibit exciplex emissions in the visible region with solvent or counterions (see schematic diagram).