Novel copy number variants in children with autism and additional developmental anomalies

Autism is a neurodevelopmental disorder characterized by three core symptom domains: ritualistic-repetitive behaviors, impaired social interaction, and impaired communication and language development. Recent studies have highlighted etiologically relevant recurrent copy number changes in autism, such as 16p11.2 deletions and duplications, as well as a significant role for unique, novel variants. We used Affymetrix 250K GeneChip Microarray technology (either NspI or StyI) to detect microdeletions and duplications in a subset of children from the Autism Genetic Resource Exchange (AGRE). In order to enrich our sample for potentially pathogenic CNVs we selected children with autism who had additional features suggestive of chromosomal loss associated with developmental disturbance (positive criteria filter) but who had normal cytogenetic testing (negative criteria filter). We identified families with the following features: at least one child with autism who also had facial dysmorphology, limb or digit abnormalities, or ocular abnormalities. To detect changes in copy number we used a publicly available program, Copy Number Analyser for GeneChip® (CNAG) Ver. 2.0. We identified novel deletions and duplications on chromosomes 1q24.2, 3p26.2, 4q34.2, and 6q24.3. Several of these deletions and duplications include new and interesting candidate genes for autism such as syntaxin binding protein 5 (STXBP5 also known as tomosyn) and leucine rich repeat neuronal 1 (LRRN1 also known as NLRR1). Lastly, our data suggest that rare and potentially pathogenic microdeletions and duplications may have a substantially higher prevalence in children with autism and additional developmental anomalies than in children with autism alone

Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity.

We have investigated the composition and function of membrane microparticles released from platelets exposed to the C5b-9 proteins of the complement system. Gel-filtered human platelets were incubated with sub-lytic amounts of the purified C5b-9 proteins and the distribution of surface antigens was analyzed using monoclonal antibodies and flow cytometry. C5b-9 assembly caused secretory fusion of the \u3b1-granule membrane with the plasma membrane and the release of membrane vesicles (approximately 0.1-\u3bcm diameter) that contained the plasma membrane glycoproteins (GP) GP Ib and GP IIb-IIIa as well as the \u3b1-granule membrane protein GMP-140. These microparticles were highly enriched in the C9 neoantigen of the C5b-9 complex. The apparent surface density of C5b-9 on the microparticles was approximately 103-fold higher than on the platelet itself, suggesting that the vesicles were selectively shed from the plasma membrane at the site of C5b-9 insertion. C5b-9 induced the expression of an activation-dependent epitope (recognized by monoclonal antibody, PAC1) in GP IIb-IIIa on the platelet surface but not in GP IIb-IIIa on the microparticles. The surface of the microparticles was also highly enriched in \u3b1-granule-derived coagulation factor V (or Va), accounting for nearly half of all the membrane-bound factor V detected. The number of potential membrane binding sites for factor Va was probed by adding saturating concentrations of factor Va light chain. Under these conditions, the density of factor Va binding sites on the microparticle surface exceeded that on the C5b-9-treated platelet by three to four orders of magnitude. Moreover, the microparticles provided most of the membrane surface for conversion of prothrombin to thrombin by VaXa. These studies demonstrate that the microparticles shed by C5b-9-treated platelets (and not the platelets themselves) provide the principal binding sites for coagulation factor Va and the principal catalytic surface for the prothrombinase complex. Platelet-derived microparticles formed during complement activation in vivo could provide a membrane surface that facilitates the assembly and dissemination of procoagulant enzyme complexes

Examining the Role of Patient Experience Surveys in Measuring Health Care Quality

Patient care experience surveys evaluate the degree to which care is patient-centered. This article reviews the literature on the association between patient experiences and other measures of health care quality. Research indicates that better patient care experiences are associated with higher levels of adherence to recommended prevention and treatment processes, better clinical outcomes, better patient safety within hospitals, and less health care utilization. Patient experience measures that are collected using psychometrically sound instruments, employing recommended sample sizes and adjustment procedures, and implemented according to standard protocols are intrinsically meaningful and are appropriate complements for clinical process and outcome measures in public reporting and pay-for-performance programs