Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry

Introduction The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers. Methods We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View™; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI. Results Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145–354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89). Conclusions Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center’s first cases

Family Outcomes After the Pediatric Intensive Care Unit: A Scoping Review

Background: Intensivists are increasingly attuned to the post-discharge outcomes experienced by families because patient recovery and family outcomes are interdependent after childhood critical illness. In this scoping review of international contemporary literature, we describe the evidence of family effects and functioning post-PICU as well as outcome measures used in order to identify strengths and weaknesses in the literature.Methods: We reviewed all articles published between 1970 and 2017 in PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), or the Cochrane Controlled Trials Registry. Our search used a combination of terms for the concept of “critical care/illness” combined with additional terms for the pre-specified domains of social, cognitive, emotional, physical, health-related quality of life (HRQL), and family functioning.Results: We identified 71 articles reporting on the post-PICU experience of more than 2,400 parents and 3,600 families of PICU survivors in 8 countries. These articles used 101 different metrics to assess the various aspects of family outcomes; 34 articles also included open-ended interviews. Overall, most families experienced significant disruption in at least 5 out of 6 of our family outcomes subdomains, with themes of decline in mental health, physical health, family cohesion, and family finances identified. Almost all articles represented relatively small, single-center or disease-specific observational studies. There was disproportionate representation of families of higher socioeconomic status and Caucasian race, and there was much more data about mothers compared to fathers. There was also very limited information regarding outcomes for siblings and extended family members after a child’s PICU stay. Conclusions: Significant opportunities remain for research exploring family functioning after PICU discharge. We recommend that future work include more diverse populations with respect to the critically ill child as well as family characteristics, include more intervention studies, and enrich existing knowledge about outcomes for siblings and extended family

Galaxy Zoo: Quantifying Morphological Indicators of Galaxy Interaction

We use Galaxy Zoo 2 visual classifications to study the morphological signatures of interaction between similar-mass galaxy pairs in the Sloan Digital Sky Survey. We find that many observable features correlate with projected pair separation; not only obvious indicators of merging, disturbance and tidal tails, but also more regular features, such as spiral arms and bars. These trends are robustly quantified, using a control sample to account for observational biases, producing measurements of the strength and separation scale of various morphological responses to pair interaction. For example, we find that the presence of spiral features is enhanced at scales < 70 h^-1 kpc, probably due to both increased star formation and the formation of tidal tails. On the other hand, the likelihood of identifying a bar decreases significantly in pairs with separations < 30 h^-1 kpc, suggesting that bars are suppressed by close interactions between galaxies of similar mass. We go on to show how morphological indicators of physical interactions provide a way of significantly refining standard estimates for the frequency of close pair interactions, based on velocity offset and projected separation. The presence of loosely wound spiral arms is found to be a particularly reliable signal of an interaction, for projected pair separations up to ~100 h^-1 kpc. We use this indicator to demonstrate our method, constraining the fraction of low-redshift galaxies in truly interacting pairs, with M_* > 10^9.5 M_Sun and mass ratio < 4, to be between 0.4 - 2.7 per cent.Comment: Accepted to MNRAS on November 12, 201

Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.

BACKGROUND: Genetic mutations underlying familial Alzheimer\u27s disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain. METHODS: We engineered a novel App knock-in mouse model (App RESULTS: Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App DISCUSSION: Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology

Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Using Service Blueprinting to Analyze Restaurant Service Efficiency

A time and motion study of 152 transactions at six restaurants operated by a full-service casual chain in Florida illustrates the use of service blueprinting as a method for analyzing service process efficiency. At management’s request, the researchers conducted the time and motion study to observe the extent to which individual servers followed company-mandated policies and procedures, and how well those procedures worked. Although this is a case study only and the observations cannot be generalized, the researchers noted a mixed picture with regard to policy observance and service efficiency. The restaurant chain uses a wine presentation process as a suggestive selling technique on greeting guests, but in this study the wine presentation resulted in a smaller than anticipated number of glasses sold. Moreover, unlike most suggestive selling, the wine presentation was a separate process that did not mesh with the meal order and delivery. In addition, rather than follow policy and drop checks when they check back on entrées, servers were waiting until the end of the meal to present the check, often when guests requested it. This policy omission may have added time to the table occupancy and reduced table turns. One procedure that was regularly observed—and worked successfully—was the “food ready” policy, in which any server would carry food to any table when that food was ready (instead of having the food stand until the “official” server could get it). These examples demonstrate how a comparison of actual performance to the service blueprint can show areas of inefficiency, both in terms of failure to follow policy and in terms of policies that are not as effective as expected