Expansion of Activated Peripheral Blood Memory B Cells in Rheumatoid Arthritis, Impact of B Cell Depletion Therapy, and Biomarkers of Response.

Although B cell depletion therapy (BCDT) is effective in a subset of rheumatoid arthritis (RA) patients, both mechanisms and biomarkers of response are poorly defined. Here we characterized abnormalities in B cell populations in RA and the impact of BCDT in order to elucidate B cell roles in the disease and response biomarkers. In active RA patients both CD27+IgD- switched memory (SM) and CD27-IgD- double negative memory (DN) peripheral blood B cells contained significantly higher fractions of CD95+ and CD21- activated cells compared to healthy controls.

Characterization of Nanoparticle Tracking Analysis for Quantification and Sizing of Submicron Particles of Therapeutic Proteins.

Submicron particles may play important roles in therapeutic protein product quality, stability, and adverse effects in patients. However, quantitation of these particles has been challenging. Nanoparticle tracking analysis (NTA) is capable of both sizing and counting submicron particles.

Urban and Rural Differences in Parental Attitudes About Influenza Vaccination and Vaccine Delivery Models.

Objectives: To assess and compare among parents of healthy children in urban and rural areas: (1) reported influenza vaccination status; (2) attitudes regarding influenza vaccination; and (3) attitudes about collaborative models for influenza vaccination delivery involving practices and public health departments.

Methods: A mail survey to random samples of parents from 2 urban and 2 rural private practices in Colorado from April 2012 to June 2012.

Results: The response rate was 58% (288/500).

Acceptability of using standing orders to deliver human papillomavirus vaccines in the outpatient obstetrician/gynecologist setting.

Objective: Standing orders, an effective method for increasing vaccination, are not widely used for HPV vaccine. This is especially so among obstetrician/gynecologists (Ob/Gyns) - the specialty many women use as their primary care provider. We sought to understand the acceptability of using standing orders for HPV vaccination among a sample of women attending outpatient Ob/Gyn clinics.

A Prospective Longitudinal Study of U.S. Children Unable to Achieve Open-Set Speech Recognition 5 Years After Cochlear Implantation.

Objective: To identify characteristics associated with the inability to progress to open-set speech recognition in children 5 years after cochlear implantation.

Study Design: Prospective, longitudinal, and multidimensional assessment of auditory development for 5 years.

Setting: Six tertiary cochlear implant (CI) referral centers in the United States.

The eyeball killer: serial killings with postmortem globe enucleation.

Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases.

The Australian Medical Schools Assessment Collaboration: benchmarking the preclinical performance of medical students.

Objectives: To report the level of participation of medical schools in the Australian Medical Schools Assessment Collaboration (AMSAC); and to measure differences in student performance related to medical school characteristics and implementation methods.

Design: Retrospective analysis of data using the Rasch statistical model to correct for missing data and variability in item difficulty. Linear model analysis of variance was used to assess differences in student performance.

Left atrial transcriptional changes associated with atrial fibrillation susceptibility and persistence.

Background: Prior transcriptional studies of atrial fibrillation (AF) have been limited to specific transcripts, animal models, chronic AF, right atria, or small samples. We sought to characterize the left atrial transcriptome in human AF to distinguish changes related to AF susceptibility and persistence.

Methods And Results: Left atrial appendages from 239 patients stratified by coronary artery disease, valve disease, and AF history (no history of AF, AF history in sinus rhythm at surgery, and AF history in AF at surgery) were selected for genome-wide mRNA microarray profiling.

Splicing factor 3b subunit 1 (Sf3b1) haploinsufficient mice display features of low risk Myelodysplastic syndromes with ring sideroblasts.

Background: The presence of somatic mutations in splicing factor 3b subunit 1 (SF3B1) in patients with Myelodysplastic syndromes with ring sideroblasts (MDS-RS) highlights the importance of the RNA-splicing machinery in MDS. We previously reported the presence of bone marrow (BM) RS in Sf3b1 heterozygous (Sf3b1 (+/-)) mice which are rarely found in mouse models of MDS. Sf3b1 (+/-) mice were originally engineered to study the interaction between polycomb genes and other proteins.

School-based health centers as patient-centered medical homes.

Objective: School-based health centers (SBHCs) have been suggested as possible patient-centered medical homes. Our objectives were to determine, in a low-income, urban population, adolescents' reasons for visiting SBHCs and the value parents place on SBHC services, and adolescents' and parents' assessment of how well SBHCs fulfill criteria for a medical home as defined by the American Academy of Pediatrics.

Methods: A cross-sectional, mailed survey of a random sample of 495 adolescent SBHC users and 497 parents of SBHC users from 10 SBHCs in Denver, CO from May to October 2012.

Effectiveness of primary care-public health collaborations in the delivery of influenza vaccine: a cluster-randomized pragmatic trial.

Objective: To assess effectiveness and feasibility of public-private collaboration in delivering influenza immunization to children.

Methods: Four pediatric and four family medicine (FM) practices in Colorado with a common public health department (PHD) were randomized at the beginning of baseline year (10/2009) to Intervention (joint community clinics and PHD nurses aiding in delivery at practices); or control involving usual care without PHD. Generalized estimating equations compared changes in rates over baseline between intervention and control practices at end of 2nd intervention year (Y2=5/2011).

Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation.

Background: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.

Methods And Results: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation.

Threading plasmonic nanoparticle strings with light.

Nanomaterials find increasing application in communications, renewable energies, electronics and sensing. Because of its unsurpassed speed and highly tuneable interaction with matter, using light to guide the self-assembly of nanomaterials can open up novel technological frontiers. However, large-scale light-induced assembly remains challenging.

Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron.

Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T).

Multi-parameter assessment of platelet inhibition and its stability during aspirin and clopidogrel therapy.

Introduction: Poor response to antiplatelet drugs is associated with adverse outcomes. We assessed platelet inhibition and its stability and tested correlation and agreement between platelet function assays.

Methods: Peripheral blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous coronary intervention (PCI) was collected at hospital discharge (visit-1) and at 30-90 days (visit-2).

A Valsalva leak-point pressure of >100 cmH2O is associated with greater success in AdVance™ sling placement for the treatment of post-prostatectomy urinary incontinence.

Objectives: To determine if there is a Valsalva leak-point pressure (VLPP) threshold that predicts for retro-urethral transobturator sling (RTS) success in men with post-prostatectomy urinary incontinence (UI).

Patients And Methods: The preoperative urodynamic parameters of all patients undergoing RTS (AdVance™) sling surgery over the last 5 years were analysed and compared with the postoperative outcomes. The sling was defined as having been successful if the patient no longer had to wear pads or merely used a pad to provide a sense of security.

Microstructural analysis of Au/TiO2-SBA-15 nanocomposite.

Properties of gold nanoparticles (AuNPs) are very different from bulk gold, in particular, highly dispersed AuNPs exhibit high catalytic activities on metal oxide supports. Catalytic activities of AuNPs are strongly dependent on: (i) size and morphology; (ii) synthesis methods; (iii) nature of the support; (iv) interaction between AuNPs and the support; and (v) oxidation state of AuNPs in the synthesized catalysts. A goal is to maintain the size and to prohibit aggregation of AuNPs, since aggregations deteriorate catalytic activities.

The penile clamp: medieval pain or makeshift gain?

Introduction And Objectives: A significant number of men are affected by post-prostatectomy urinary incontinence. If symptoms persist after conservative measures fail men are left with three choices: additional surgery, drainage or absorbent devices, or a penile compression device. Our center encountered a number of men for whom additional surgery was too dangerous and for whom drainage or absorbent devices were too cumbersome.

Acceptability of a hypothetical group B strep vaccine among pregnant and recently delivered women.

Objective: Group B Streptococcus (GBS) causes significant infant morbidity and mortality. Promising GBS vaccines are currently in clinical trials. Because GBS vaccines would be the first to specifically target pregnant women, we sought to assess acceptability of a hypothetical GBS vaccine.

Long-term B cell depletion in murine lupus eliminates autoantibody-secreting cells and is associated with alterations in the kidney plasma cell niche.

Autoantibodies to dsDNA, produced by autoreactive plasma cells (PCs), are a hallmark of systemic lupus erythematosus and play a key role in disease pathogenesis. Recent data suggest that autoreactive PCs accumulate not only in lymphoid tissues, but also in the inflamed kidney in lupus nephritis. We hypothesized that the variable efficacy of anti-CD20 (rituximab)-mediated B cell depletion in systemic lupus erythematosus may be related to the absence of an effect on autoreactive PCs in the kidney.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry.

Investigations into the fouling mechanism of parvovirus filters during filtration of freeze-thawed mAb drug substance solutions.

Filtration to remove viruses is one of the single most expensive steps in the production of mAb drug products. Therefore, virus filtration steps should be fully optimized, and any decline in flow rates warrants investigation into the causes of such membrane fouling. In the current study, it was found that freezing and thawing of a mAb bulk drug solution caused a substantial decrease in viral filter membrane flow rate.

Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.

Objectives: This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.

Background: AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.

Interfacial structure and chemistry of GaN on Ge(111).

The interface of GaN grown on Ge(111) by plasma-assisted molecular beam epitaxy is resolved by aberration corrected scanning transmission electron microscopy. A novel interfacial structure with a 5∶4 closely spaced atomic bilayer is observed that explains why the interface is flat, crystalline, and free of GeN(x). Density functional theory based total energy calculations show that the interface bilayer contains Ge and Ga atoms, with no N atoms.