Memorandum on Reopening the Dodd-Frank Act Section 956 Incentive Compensation Rule

Professor Michael Herz, along with four other administrative law professors, sent a letter to six agencies about legal options regarding a long-delayed rule aimed at executive compensation

Fontan-Associated Dyslipidemia

Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥ 18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8–34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, P\u3c 0.0001), low‐density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, P\u3c 0.0001), and high‐density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, P\u3c 0.0001) than controls. In those with a Fontan, high‐density lipoprotein cholesterol was inversely correlated with body mass index (r=−0.30, P\u3c 0.0001), high‐sensitivity C‐reactive protein (r=−0.27, P=0.0006), and alanine aminotransferase (r=−0.18, P=0.02) but not with other liver disease markers. Lower high‐density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04–1.81 [P=0.03]). This relationship was attenuated when log high‐sensitivity C‐reactive protein was added to the model (HR, 1.26; 95% CI, 0.95–1.67 [P=0.10]). Total cholesterol, low‐density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high‐density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan‐associated liver disease and lipid metabolism

The Lantern Vol. 28, No. 2, Spring 1961

• A New Bedlam • A Priori • Germ Warfare • Verse for a Sympathy Card • On Lamartine\u27s Crucifix • On Art • Hope • Hymn to the Morning • An Educator Speaks • Come Out • Insemination • A Day\u27s Hope • Laura • Walking Together • 20 September 1960 • 15 October 1960 • The Governor\u27s Dog • One of the Gang • Poem • Knowledge is Freedom • To Conservative Child • Seventeen American Skating Careers at the Zenithhttps://digitalcommons.ursinus.edu/lantern/1080/thumbnail.jp

Epigenetic patterns in blood associated with lipid traits predict incident coronary heart disease events and are enriched for results from genome-wide association studies

Background- Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. Methods and Results- To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P < 1.08E-07) and replicated 33 (at Bonferroni-corrected P < 0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglyceridesand high-density lipoprotein cholesterol (HDL- C; cg27243685; P= 8.1E-26 and 9.3E-19) was associated with cis-expression of a reverse cholesterol transporter (ABCG1; P= 7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P= 0.0007). We found significant cis-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (P-TC = 0.004, PHDL-C = 0.008 and P-triglycerides = 0.00003) and coronary heart disease ( P= 0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. Conclusions-We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events

Riding the Wave: Reconciling the Roles of Disease and Climate Change in Amphibian Declines

We review the evidence for the role of climate change in triggering disease outbreaks of chytridiomycosis, an emerging infectious disease of amphibians. Both climatic anomalies and disease-related extirpations are recent phenomena, and effects of both are especially noticeable at high elevations in tropical areas, making it difficult to determine whether they are operating separately or synergistically. We compiled reports of amphibian declines from Lower Central America and Andean South America to create maps and statistical models to test our hypothesis of spatiotemporal spread of the pathogen Batrachochytrium dendrobatidis (Bd), and to update the elevational patterns of decline in frogs belonging to the genus Atelopus. We evaluated claims of climate change influencing the spread of Bd by including error into estimates of the relationship between air temperature and last year observed. Available data support the hypothesis of multiple introductions of this invasive pathogen into South America and subsequent spread along the primary Andean cordilleras. Additional analyses found no evidence to support the hypothesis that climate change has been driving outbreaks of amphibian chytridiomycosis, as has been posited in the climate-linked epidemic hypothesis. Future studies should increase retrospective surveys of museum specimens from throughout the Andes and should study the landscape genetics of Bd to map fine-scale patterns of geographic spread to identify transmission routes and processes

Riding the Wave: Reconciling the Roles of Disease and Climate Change in Amphibian Declines

We review the evidence for the role of climate change in triggering disease outbreaks of chytridiomycosis, an emerging infectious disease of amphibians. Both climatic anomalies and disease-related extirpations are recent phenomena, and effects of both are especially noticeable at high elevations in tropical areas, making it difficult to determine whether they are operating separately or synergistically. We compiled reports of amphibian declines from Lower Central America and Andean South America to create maps and statistical models to test our hypothesis of spatiotemporal spread of the pathogen Batrachochytrium dendrobatidis (Bd), and to update the elevational patterns of decline in frogs belonging to the genus Atelopus. We evaluated claims of climate change influencing the spread of Bd by including error into estimates of the relationship between air temperature and last year observed. Available data support the hypothesis of multiple introductions of this invasive pathogen into South America and subsequent spread along the primary Andean cordilleras. Additional analyses found no evidence to support the hypothesis that climate change has been driving outbreaks of amphibian chytridiomycosis, as has been posited in the climate-linked epidemic hypothesis. Future studies should increase retrospective surveys of museum specimens from throughout the Andes and should study the landscape genetics of Bd to map fine-scale patterns of geographic spread to identify transmission routes and processes

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases

Mechanisms of Assortative Mating in Speciation with Gene Flow: Connecting Theory and Empirical Research

The large body of theory on speciation with gene flow has brought to light fundamental differences in the effects of two types of mating rules on speciation: preference/trait rules, in which divergence in both (female) preferences and (male) mating traits is necessary for assortment, and matching rules, in which individuals mate with like individuals on the basis of the presence of traits or alleles that they have in common. These rules can emerge from a variety of behavioral or other mechanisms in ways that are not always obvious. We discuss the theoretical properties of both types of rules and explain why speciation is generally thought to be more likely under matching rather than preference/trait rules. We furthermore discuss whether specific assortative mating mechanisms fall under a preference/trait or matching rule, present empirical evidence for these mechanisms, and propose empirical tests that could distinguish between them. The synthesis of the theoretical literature on these assortative mating rules with empirical studies of the mechanisms by which they act can provide important insights into the occurrence of speciation with gene flow. Finally, by providing a clear framework we hope to inspire greater alignment in the ways that both theoreticians and empiricists study mating rules and how these rules affect speciation through maintaining or eroding barriers to gene flow among closely related species or populations

Thy1+ Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive Lymphocytes

While immunological memory has long been considered the province of T- and B- lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1+ subset of natural killer (NK) cells. We demonstrate that immune protection against infection from a lethal dose of virus can be adoptively transferred with memory hepatic Thy1+ NK cells that were primed with live virus. Our results also indicate that, like classical immunological memory, stronger innate memory responses form in response to priming with live virus than a highly attenuated vector. These results demonstrate that a defined innate memory cell population alone can provide host protection against a lethal systemic infection through viral clearance