OBJECTIVES/GOALS: There is no objective, biologic tool to detect concussion or guide clinical management. We previously showed that saliva microRNA (miRNA) levels differ in children with concussion and may predict symptom duration. The purpose of this study was to validate the utility of saliva miRNA and define longitudinal trends during the recovery period. METHODS/STUDY POPULATION: We collected concussion symptom burden (SCAT-5), cognitive performance (DANA), balance measures (ClearEdge), and saliva from 150 children (7-21 years) with concussion over 5 time-points: 0-2, 3-6, 7-14, 15-29, and 30-60 days post-injury. Saliva miRNA levels within the 443 concussion samples were quantified with RNA sequencing and compared to 218 samples from age- and sex-matched controls (healthy and post-exercise participants). Non-parametric ANOVA assessed RNA levels across time-points, and between concussions/controls. Machine learning was used to build logistic regression algorithms differentiating concussions/controls, and symptomatic/recovered concussion participants. Relationships between miRNAs and concussion phenotypes were explored with Spearman’s Rank correlations. RESULTS/ANTICIPATED RESULTS: Fifteen miRNAs differed across control and concussion participants (FDR < 0.05). Within concussion participants, all 15 miRNAs trended back toward control levels by 30-60 days post injury. A regression algorithm employing 6 of the 15 miRNAs differentiated control and concussion participants with an area under the curve (AUC) of 0.78 in a training set (n = 244) and 0.84 in a naïve test set (n = 24). Similarly, 6 miRNAs were able to differentiate symptomatic (SCAT-5 symptom score > 7) and asymptomatic concussion participants with an AUC of 0.73 in a training set (n = 219) and 0.76 in a naïve test set (n = 44). Furthermore, 5 miRNAs showed significant (R > 0.3; FDR < 0.05) associations with subjective and/or objective measures of concussion-related symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Saliva miRNAs levels are altered in children with concussion, and display predictable longitudinal trends following injury. Saliva miRNA measurement represents a non-invasive, objective tool that could be rapidly assessed to provide biologic evidence for clinicians managing pediatric concussion. CONFLICT OF INTEREST DESCRIPTION: I serve as a paid consultant and scientific advisory board member for Quadrant Biosciences, who has funded a portion of this work and licensed the findings from the Penn State College of Medicine.

It seems obvious that agreements to cut tariffs will raise trade between their signatories. But recent studies show that some agreements widely considered to be landmarks in economic history had either a remarkably small impact on trade or none at all. Among those agreements are the Cobden-Chevalier Treaties and the long series of tariff accords concluded under the auspices of the GATT/WTO. Both sets of agreements cut import duties on many goods that applied to all trading partners entitled to most-favored-nation treatment, but neither increased aggregate trade between their members. This article examines the agreements concluded by the United States under the 1934 Reciprocal Trade Agreements Act (RTAA). The authors use an original data set that records changes in tariffs and US imports at the product-line level for each of the twenty-seven bilateral agreements. No comparable data exist either for the nineteenth-century trade network or for the postwar trade regime. The results show that the RTAA treaties failed to raise aggregate US imports from its treaty partners. They also show that these agreements did lead to a large and significant rise in US imports of specific products from specific countries. Because the same bargaining protocol that produced the RTAA agreements also governed the European treaty network and the GATT/WTO, the argument advanced in this article can also help to explain why neither treaty exerted a significant impact on aggregate trade between their signatories.

This article uses a replication experiment of ninety-four specifications from sixteen different studies to show the severity of the problem of selection on unobservables. Using a variety of approaches, it shows that membership in the General Agreement on Tariffs and Trade/World Trade Organization has a significant effect on a surprisingly high number of dependent variables (34 per cent) that have little or no theoretical relationship to the WTO. To make the exercise even more conservative, the study demonstrates that membership in a low-impact environmental treaty, the Convention on Trade in Endangered Species, yields similarly high false positive rates. The authors advocate theoretically informed sensitivity analysis, showing how prior theoretical knowledge conditions the crucial choice of covariates for sensitivity tests. While the current study focuses on international institutions, the arguments also apply to other subfields and applications.

This paper considers the problem of a reinforced elliptical hole in a plate under the action of a principal stress system of the type found in cylindrical and ellipsoidal pressure vessels. That is, stress systems in which the ratio of the principal stresses is not greater than two to one. It is shown that when the ratio of the major and minor axes of the ellipse can be chosen arbitrarily, practical reinforcements can be designed to give a maximum stress around the hole which is only slightly greater than the maximum stress in a similarly loaded plate with no hole. General expressions are obtained for the stress distribution in the plate around the hole, for the stress acting on a normal cross section of the reinforcement, and for the cross-sectional area of a reinforcement which gives a small stress concentration. These are used to find the variation in the stress distribution around the hole due to reinforcements having different cross-sectional areas when the applied principal stresses are in the ratio of two to one and Poisson's ratio for the material of the plate and reinforcement has practical values.

The First World War is often cited as proof par excellence of the flaws in the liberal peace argument because the adversaries it engaged had been each other’s major pre-war trading partners. Although commonly assumed to have wreaked havoc on the trade of the states it engaged, the war’s impact on commerce has rarely been rigorously examined. Using an original dataset, this study shows that the Great War triggered substitution processes that reduced its trade-related costs. Although recourse to second-best alternatives always induces efficiency losses, the costs of adjustment were small relative to the other costs that states incurred during the war. The analysis shows that the Great War is not the egregious exception to the theory that conventional wisdom has long assumed it to be. At the same time, it makes clear that the deterrent power of trade varies inversely with belligerents’ ability to access the markets of alternative trading partners.

This paper focuses on the variability of judicialization across preferential trade agreements (PTAs) and their impact on trade flows. We develop a categorization of PTAs that contrasts enforcement mechanisms with the level of trade policy discretion allowed by a trade agreement and the degree of flexibility allowed for members. Utilizing an original dataset of PTAs signed by countries in Asia, which has emerged as one of the most active regions of PTA formation and which exhibits wide variability in levels of judicialization, we compare the effects of trade policy discretion, flexibility provisions, and enforcement mechanisms in PTAs on trade flows. We examine the empirical strength of our theoretical framework distinguishing between discretion, flexibility, and enforcement using confirmatory factor analysis. The empirical analysis then goes on to examine their respective effects on trade flows. The results show that agreements with strong commitments, that is, those that remove more trade policy discretion from a government, lead to a greater expansion of trade between signatories. Enforcement and flexibility mechanisms, however, have mixed effects.

Despite mixed empirical evidence, in the past two decades central bank independence (CBI) has been on the rise under the assumption that it ensures price stability. Using an encompassing theoretical approach and new yearly data for de jure CBI (seventy-eight countries, 1973–2008), we reexamine this relationship, distinguishing the role of printing less money (discipline) from the public's beliefs about the central bank's likely actions (credibility). Democracies differ from dictatorships in the likelihood of political interference and changes to the law because of the presence of political opposition and the freedom to expose government actions. CBI in democracies should be directly reflected in lower money supply growth. Besides being more disciplinarian, it also ensures a more robust money demand by reducing inflation expectations and, therefore, inflation. Empirical results are robust and support a discipline effect conditioned by political institutions, as well as a credibility effect.

Recent studies cast doubt on the value added of international trade agreements and institutions. Using a new data set that consists of about 35,000 observations on the trade of fifty-four nations between 1919 and 1938, we examine whether this skepticism also applies to the infamous interwar trade blocs. Traditional historical accounts attribute to them a large drop in international trade and a rise in the political tensions that would later erupt in World War II. In this study, we show that no bloc raised trade among its members as a whole or decreased trade between members and nonmembers. However, our findings are not wholly consistent with the skepticism recent studies express. We argue that conflicts of interest among the great powers encouraged the emergence of the bloc system and also gave rise to intrabloc trade shifts consistent with the political interests of their great-power hubs. The political-military alliances these conflicts created also reduced trade between their signatories, and we argue more generally that the causal chain runs from politics to trade. As a result, measuring only the effect of agreements and institutions on aggregate trade between their members can generate inaccurate estimates of their value added.

The Dawn spacecraft orbited Asteroid (4) Vesta for a year, and returned disk-resolved images and spectra covering visible and near-infrared wavelengths at scales as high as 20 m/pix. The visible geometric albedo of Vesta is ~ 0.36. The disk-integrated phase function of Vesta in the visible wavelengths derived from Dawn approach data, previous ground-based observations, and Rosetta OSIRIS observations is consistent with an IAU H-G phase law with H=3.2 mag and G=0.28. Hapke's modeling yields a disk-averaged single-scattering albedo of 0.50, an asymmetry factor of -0.25, and a roughness parameter of ~20 deg at 700 nm wavelength. Vesta's surface displays the largest albedo variations observed so far on asteroids, ranging from ~0.10 to ~0.76 in geometric albedo in the visible wavelengths. The phase function of Vesta displays obvious systematic variations with respect to wavelength, with steeper slopes within the 1- and 2-micron pyroxene bands, consistent with previous ground-based observations and laboratory measurement of HED meteorites showing deeper bands at higher phase angles. The relatively high albedo of Vesta suggests significant contribution of multiple scattering. The non-linear effect of multiple scattering and the possible systematic variations of phase function with albedo across the surface of Vesta may invalidate the traditional algorithm of applying photometric correction on airless planetary surfaces.

Reciprocal trade agreements (RTAs) have proliferated rapidly in Asia in recent years, an unprecedented phenomenon in a region in which state-led institution-building efforts were largely unsuccessful during the Cold War years. In this article, we investigate the qualitative provisions of RTAs in Asia, focusing on agreements that are professedly geared toward trade liberalization through reciprocal exchanges of trade concessions. We build on the concept of credible commitment—that states “tie their hands” through international agreements and thus signal strong commitment to trade liberalization. We argue that a broad range of agreement provisions will affect an RTA's ability to achieve its primary objective: trade liberalization. We present a coding scheme that measures the strength of a wide variety of provisions in the legal texts of RTAs. Using quantitative analysis, we analyze the impact of various components of Asia's RTAs on participants' trade flows.