Citations

AbstractBackgroundIt is not known whether preclinical cognitive decline is associated with fibrillar β‐amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status.MethodsFrom a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral‐to‐cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden.ResultsAt P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners.ConclusionsAsymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.

Key Points Evidence exists that ELN criteria for response in ET and PV issued in 2009 do not provide relevant measures of benefit for patients. Revised recommendations for assessing response are provided.

ObjectivesIdeally, guidewires used during peripheral vasculature (PV) interventions could serve both as a therapy delivery platform and a diagnostic tool for real‐time vessel sizing (2‐in‐1 function).BackgroundVascular imaging modalities, like intravascular ultrasound (IVUS), used during lower PV interventions, can improve outcomes versus angiographic assessment alone, but are rarely used due to added time, cost, and required clinical training/interpretation.MethodsA 0.035″ bodied 0.035″ conductance guidewire (CGW) is described here as a vascular navigation and diagnostic real‐time PV sizing tool. When attached to a console, the CGW creates a safe, electric field to determine vascular size through simultaneous voltage measurements.ResultsThe CGW showed functionality as a workhorse guidewire on the bench (torqueability and trackability equivalent to a Wholey guidewire) and in vivo (over‐the‐wire stent deployment in domestic swine and first‐in‐man study with no major adverse events). Validation of CGW sizing versus the true diameter and IVUS was completed in 4–10 mm diameter phantoms on the bench and in swine and showed virtually no bias with excellent repeatability and accuracy (i.e., CGW repeatability: swine phantom bias = 0.03 ± 0.09 mm (1.3% error). CGW vs. true diameter: in vivo bias = 0.14 ± 0.15 mm (2.7% error). IVUS vs. true diameter: swine phantom bias = 0.01 ± 0.36 mm (4.7% error). CCW vs. IVUS: swine phantom bias = 0.13 ± 0.26mm (3.8% error)).ConclusionsReal‐time, accurate, and safe PV dimension assessment and therapy‐delivery (2‐in‐1 function) is possible using a novel workhorse 0.035″ bodied CGW. © 2013 Wiley Periodicals, Inc.

Abstract Zebrafish ( Danio rerio ) is a popular vertebrate model organism largely deployed using outbred laboratory animals. The nonisogenic nature of the zebrafish as a model system offers the opportunity to understand natural variations and their effect in modulating phenotype. In an effort to better characterize the range of natural variation in this model system and to complement the zebrafish reference genome project, the whole genome sequence of a wild zebrafish at 39-fold genome coverage was determined. Comparative analysis with the zebrafish reference genome revealed approximately 5.2 million single nucleotide variations and over 1.6 million insertion–deletion variations. This dataset thus represents a new catalog of genetic variations in the zebrafish genome. Further analysis revealed selective enrichment for variations in genes involved in immune function and response to the environment, suggesting genome-level adaptations to environmental niches. We also show that human disease gene orthologs in the sequenced wild zebrafish genome show a lower ratio of nonsynonymous to synonymous single nucleotide variations.

ObjectiveTo examine lipid profiles among statin‐naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins.MethodsInformation regarding lipid measures and statin use was gathered in a population‐based incident cohort of patients with RA (1987 American College of Rheumatology criteria first met between January 1, 1988 and January 1, 2008) and in a cohort of non‐RA subjects from the same underlying population. Only patients with no prior history of statin use were included.ResultsThe study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non‐RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol and low‐density lipoprotein (LDL) cholesterol were lower in the RA versus the non‐RA cohort (P < 0.001 and P = 0.003, respectively). The absolute and percentage change in LDL cholesterol after at least 90 days of statin use tended to be smaller in the RA versus the non‐RA cohort (P = 0.03 and P = 0.09, respectively). After at least 90 days of statin use, patients with RA were less likely to achieve therapeutic goals for LDL cholesterol than the non‐RA subjects (P = 0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (odds ratio 0.47, 95% confidence interval 0.26–0.85) was associated with lower likelihood of achieving therapeutic LDL goals.ConclusionPatients with RA had lower total cholesterol and LDL cholesterol levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non‐RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals.