ABSTRACT IMPACT: This work represents a novel way in which genetic information can be used to improve clinical decision making as it pertains to both treatment and management of congenital heart disease. OBJECTIVES/GOALS: Our lab found that MYH6 variants are both enriched in hypoplastic left heart syndrome (HLHS) and associated with decreased cardiac transplant-free survival. To elucidate the mechanisms of MYH6 variant pathogenicity, we are assessing their impact on atrial function during HLHS development and progression. METHODS/STUDY POPULATION: We are using 2D speckle-based tracking to retrospectively evaluate echocardiograms (echos) from 51 HLHS patients, 17 with MYH6 variants and 34 matched controls. Atrial function will be assessed by myocardial strain and strain rate at seven time points, beginning at the time of the patients’ earliest prenatal echo, and ending with their last available echo before death or cardiac transplant. Early left atrial function will examine the role of MYH6 variants in the development of HLHS in vivo, while longitudinal right atrial function will be assessed in order to look for differences that could be contributing to the decreased transplant-free survival seen in MYH6 variant carriers. RESULTS/ANTICIPATED RESULTS: We hypothesize that MYH6 variants cause HLHS by impairing early left atrial (LA) contractility, resulting in altered left ventricular hemodynamics and consequent hypoplasia. We therefore expect to find diminished prenatal LA function in HLHS patients with MYH6 variants. We also hypothesize that MYH6 variants continue to impair right atrial (RA) function in surgically-reconstructed HLHS hearts, necessitating earlier transplantation. Accordingly, we expect variant carriers to exhibit lower RA function at birth versus controls. We expect differences between groups to persist over time, and possibly increase in magnitude. In HLHS patients with MYH6 variants, we anticipate declining RA function will precede right ventricular function and therefore be an early indicator of transplant need. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study represents a novel way in which genetic information can inform clinical decision-making. Identifying MYH6 variants as an early cause of HLHS offers chances for intervention. Understanding long-term effects of MYH6 on right atrial function in HLHS may aid in cardiac transplant risk stratification, thus improving patient outcomes.

Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.

The estimation of interstellar dust masses is an important pursuit in our understanding of both local and early Universe – see e.g. the “dust budget crisis”. One of the most used methods of estimating dust masses – dust emission fitting – requires an estimate of the dust opacity at far-infrared and submillimeter wavelengths, but in most models this quantity is based on extrapolation rather than on actual measurements. It is becoming more and more evident that the opacity in typical dust models differs from that of dust analogs measured in the lab, meaning that astronomical dust mass estimations may need to be revised. To estimate the systematic errors introduced by this mismatch, we calculated dust emission for a model where dust far-infrared opacity is the same as that measured in lab samples, then we fit the synthetic emission with a typical (modified blackbody) dust model. Our results show that, if interstellar dust is indeed similar to the lab dust analogs, most fits may overestimate dust masses by as much as an order of magnitude.

Aristotle's Ethica Eudemia (Eth. Eud.) and Ethica Nicomachea (Eth. Nic.), as is well known and much discussed, contain three books in common (Eth. Eud. 4–6 = Eth. Nic. 5–7). Less well known, at least until Dieter Harlfinger alerted scholars to the fact in 1971, is that some of the manuscripts of Eth. Eud. do, contrary to the then prevailing consensus, contain the text of these common books. Even less well known is that Harlfinger's discovery was anticipated some 50 years before by Walter Ashburner, who had uncovered this fact about Eth. Eud. MSS in the Laurentian library of Florence. Ashburner's anticipation of Harlfinger, however, is not the real value of his article. Its value rather is that it contains collations of readings for the common books, and thereby gives us an excellent resource for examining the text of the common books as this text is contained in exclusively Eth. Eud. MSS. The Eth. Eud. tradition of the common books has hitherto received little attention. Modern editions of Eth. Eud. do not include these books, and editions of Eth. Nic. have other MSS for the purpose. Ashburner's collations are the more valuable because they are taken from (among others) the one MS that, in Harlfinger's learned stemma, appears as the archetype for all the rest.