The Louisville Twin Study (LTS) is nationally recognized as one of the largest and most comprehensive studies of child development related to multiple birth status. The LTS is unique because of the extensive longitudinal face-to-face assessments, the frequency of data collection, the inclusion of data on additional family members (i.e., parents, siblings, grandparents; and later, twins’ own spouses and children), and the variety of data collection methods used. Data preservation efforts began in 2008 and are largely complete, although efforts are ongoing to obtain funding to convert the electronic data to a newer format. A pilot study was completed in the summer of 2018 to bring the twins, who are now middle-aged, back for testing. A grant is currently under review to extend the pilot study to include all former participants who are now ≥40 years of age. Opportunities for collaboration are welcome.

Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.

Post-disaster archaeological investigations at Jaffna Fort have revealed material demonstrating pre-colonial contact, shedding new light on the importance of the site in Indian Ocean trade and communications networks before European occupation.

This study connects Mexico’s imports of U.S. broiler meat with its imports of feed products. Two demand systems for Mexico are estimated: a two-stage Almost Ideal Demand System (AIDS) model for broiler meat and a demand for feed derived from a translog cost function representing the production of Mexican chickens. The models are estimated using data from 1997 to 2016. Given a change in policy where Mexico completely replaces U.S. broiler meat imports, the imports of U.S. feed products will increase. If Mexico does not completely replace U.S. imports with domestic broiler production, our model suggests that Mexican imports of U.S. feed fall.

OBJECTIVES/SPECIFIC AIMS: 1) Determine the mutational landscape, including translocation, mutations and mutational signatures as well as copy number variations of pPCL and identify significant differences to non pPCL MM. 2) Determine whether genetic changes pertinent to pPCL could be explored as therapeutic targets to improve the dismal prognosis of this patient population. METHODS/STUDY POPULATION: Samples from overall 19 pPCL patients that presented to the Myeloma Center, UAMS between 2000-2018 were used for this study. We performed gene expression profiling (GEP; Affymetrix U133 Plus 2.0) of matched circulating peripheral PCs and bone marrow (BM) PCs from 13 patients. Whole exome sequencing (WES) was performed on purified CD138+ PCs from BM aspirates from 19 pPCL patients with a median depth of 61x. CD34+ sorted cells, taken at the time of stem cell harvest from the same 19 patients, were used as controls. Translocations and mutations were called using Manta and Strelka and annotated as previously reported. Copy number was determined by Sequenza. RESULTS/ANTICIPATED RESULTS: 1) GEP from the BM and circulating peripheral PCs showed that the expression patterns of the two samples from each individual clustered together, indicating that circulating PCs and BM PCs in pPCL result from the same clone and are biologically clearly related. 2) The clinical characteristics from the patient cohort used for WES analysis were as follows: median age was 58 years (range 36–77), females accounted for 74% (14/19), an elevated creatinine level was found in 78% (14/18) and an elevated LDH level in 71% (10/14). All patients presented with an ISS stage of III. Median OS of the whole dataset was poor at 22 months, which is consistent with OS from previously reported pPCL cohorts. 3) Primary Immunoglobulin translocations were common and identified in 63% (12/19) of patients, including MAF translocations, which are known to carry high risk in 42% (8/19) of patients [t(14;16), 32% and t(14;20), 10%] followed by t(11;14) (16%) and t(4;14) (10%). Furthermore, 32% (6/19) of patients had at least one MYC translocation, which are known to play a crucial role in disease progression. 4) The mutational burden of pPCL consisted of a median of 98 non-silent mutations per sample, suggesting that the mutational landscape of pPCL is highly complex and harbors more coding mutations than non-pPCL MM. 5) Driver mutations, that previously have been described in non-pPCL MM showed a different prevalence and distribution in pPCL, including KRAS and TP53 with 47% (9/19) and 37% (7/19) affected patients respectively compared to 21% and 5% in non-PCL MM. PIK3CA (5%), PRDM1 (10%), EP300 (10%) and NF1 (10%) were also enriched in the pPCL group compared to previously reported cases in non-pPCL MM. 6) Biallelic inactivation of TP53 – a feature of Double Hit myeloma - was found in 6/19 (32%) samples, indicating a predominance of high risk genomic features compared to non-pPCL MM. Furthermore, analysis of mutational signatures in pPCL showed that aberrant APOBEC activity was highly prevalent only in patients with a MAF translocation, but not in other translocation groups. DISCUSSION/SIGNIFICANCE OF IMPACT: In conclusion we present one of the first WES datasets on pPCL with the largest patient cohort reported to date and show that pPCL is a highly complex disease. The aggressive disease behavior can, at least in part, be explained by a high prevalence of MAF and MYC translocations, TP53 and KRAS mutations as well as bi-allelic inactivation of TP53. It is of interest that only KRAS but not NRAS mutations are highly enriched in pPCL. From all highly prevalent genomic alterations in pPCL, only KRAS mutations offer a potential for already available therapeutically targeting with MEK inhibitors, which should be further explored.

We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.

Motivated by the dynamics within terrestrial bodies, we consider a rotating, strongly thermally stratified fluid within a spherical shell subject to a prescribed laterally inhomogeneous heat-flux condition at the outer boundary. Using a numerical model, we explore a broad range of three key dimensionless numbers: a thermal stratification parameter (the relative size of boundary temperature gradients to imposed vertical temperature gradients), $10^{-3}\leqslant S\leqslant 10^{4}$ , a buoyancy parameter (the strength of applied boundary heat-flux anomalies), $10^{-2}\leqslant B\leqslant 10^{6}$ , and the Ekman number (ratio of viscous to Coriolis forces), $10^{-6}\leqslant E\leqslant 10^{-4}$ . We find both steady and time-dependent solutions and delineate the regime boundaries. We focus on steady-state solutions, for which a clear transition is found between a low $S$ regime, in which buoyancy dominates the dynamics, and a high $S$ regime, in which stratification dominates. For the low- $S$ regime, we find that the characteristic flow speed scales as $B^{2/3}$ , whereas for high- $S$ , the radial and horizontal velocities scale respectively as $u_{r}\sim S^{-1}$ , $u_{h}\sim S^{-3/4}B^{1/4}$ and are confined within a thin layer of depth $(SB)^{-1/4}$ at the outer edge of the domain. For the Earth, if lower mantle heterogeneous structure is due principally to chemical anomalies, we estimate that the core is in the high- $S$ regime and steady flows arising from strong outer boundary thermal anomalies cannot penetrate the stable layer. However, if the mantle heterogeneities are due to thermal anomalies and the heat-flux variation is large, the core will be in a low- $S$ regime in which the stable layer is likely penetrated by boundary-driven flows.

Linear disturbance development in the von Kármán boundary layer on an infinite rotating-disc is investigated for an extensive range of azimuthal mode numbers $n$ . The study expands upon earlier investigations that were limited to those values of $n$ located near the onset of absolute instability (Lingwood, J. Fluid Mech., vol. 299, 1995, pp. 17–33), where disturbances to the genuine inhomogeneous flow were shown to be globally stable (Davies & Carpenter, J. Fluid Mech., vol. 486, 2003, pp. 287–329). Numerical simulations corresponding to azimuthal mode numbers greater than the conditions for critical absolute instability display a form of global linear instability that is characterised by a faster than exponential temporal growth, similar in appearance to that found on the rotating-disc with mass suction (Thomas & Davies, J. Fluid Mech., vol. 724, 2010, pp. 510–526) and other globally unstable flows (Huerre & Monkewitz, Annu. Rev. Fluid Mech., vol. 22, 1990, pp. 473–537). Solutions indicate that a change in the global behaviour arises for  $n\in [80:100]$ that is marginally greater than those disturbances studied previously. Furthermore, the Reynolds number associated with the larger azimuthal mode numbers coincides with the upper bound of experimental predictions for transition. Thus, the local–global linear stability of the infinite rotating-disc is similar to the scenario outlined by Huerre & Monkewitz (1990) that states a region of local absolute instability is necessary but not sufficient for global instability to ensue. Conditions are derived to predict the azimuthal mode number needed to bring about a change in global behaviour, based on solutions of the linearised complex Ginzburg–Landau equation coupled with numerical simulations of disturbances to the radially homogeneous flow. The long term response is governed by a detuning effect, based on radial variations of the temporal frequency and matching shifts in temporal growth that increases for larger $n$ , eventually attaining values sufficient to engineer global linear instability. The analysis is extended to include mass transfer through the disc surface, with similar conclusions drawn for disturbances to large enough azimuthal mode numbers. Finally, we conclude that the high $n$ modes are unlikely to have a strong influence on disturbance development and transition in the von Kármán flow, as they will be unable to establish themselves across an extended radial range before nonlinear effects are triggered by the huge growth associated with the wavepacket maxima of the lower $n$ -valued convective instabilities.

Archaeometrists use a variety of analytical methods to determine trace elements in ancient Greek silver coins, for provenance studies, understanding social and technological change, and authentication. One analytical problem which is little documented is understanding the horizontal spatial heterogeneity of coin elemental composition in micro-sampled areas, which are usually assumed to be uniform. This study analysed ten ancient Greek coins representative of silver circulating in the Aegean region in the sixth to third centuries BC. Scanning electron microscopy with energy dispersive spectrometry was used to map the spatial distribution of elements on coins that were abraded to remove the patina. Time of flight-secondary ion mass spectrometry was then conducted on selected coins, mapping an area ~100 × 100 µm and depth profiling from 0 to 10 µm. These data revealed the three-dimensional elemental complexity of the coins, in particular, the heterogeneity both in the patina and beneath it. These data will guide future authentication and provenance studies of larger sample sets of ancient Greek coins including the use of line scanning for laser ablation inductively coupled plasma mass spectrometry data collection rather than spot analyses, and non-destructive analytical techniques such as X-ray fluorescence spectrometry.

Convection in the metallic cores of terrestrial planets is likely to be subjected to lateral variations in heat flux through the outer boundary imposed by creeping flow in the overlying silicate mantles. Boundary anomalies can significantly influence global diagnostics of core convection when the Rayleigh number, $Ra$ , is weakly supercritical; however, little is known about the strongly supercritical regime appropriate for planets. We perform numerical simulations of rapidly rotating convection in a spherical shell geometry and impose two patterns of boundary heat flow heterogeneity: a hemispherical $Y_{1}^{1}$ spherical harmonic pattern; and one derived from seismic tomography of the Earth’s lower mantle. We consider Ekman numbers $10^{-4}\leqslant E\leqslant 10^{-6}$ , flux-based Rayleigh numbers up to ${\sim}800$ times critical, and a Prandtl number of unity. The amplitude of the lateral variation in heat flux is characterised by $q_{L}^{\ast }=0$ , 2.3, 5.0, the peak-to-peak amplitude of the outer boundary heat flux divided by its mean. We find that the Nusselt number, $Nu$ , can be increased by up to ${\sim}25\,\%$ relative to the equivalent homogeneous case due to boundary-induced correlations between the radial velocity and temperature anomalies near the top of the shell. The $Nu$ enhancement tends to become greater as the amplitude and length scale of the boundary heterogeneity are increased and as the system becomes more supercritical. This $Ra$ dependence can steepen the $Nu\propto Ra^{\unicode[STIX]{x1D6FE}}$ scaling in the rotationally dominated regime, with $\unicode[STIX]{x1D6FE}$ for our most extreme case approximately 20 % greater than the equivalent homogeneous scaling. Therefore, it may be important to consider boundary heterogeneity when extrapolating numerical results to planetary conditions.

It has been recognised for many years that the first fraction of meltwater from a melting snowpack contains a much higher concentration of ions than that of the bulk (or average) snow of which the pack is comprised (Foster 1978, Johannessen and Henriksen 1978). This process leads to the so called “acid flush” in the spring and can have severe ecological effects on lakes and streams (Hagen and Langeland 1973, Leivestad and Muniz 1976, National Research Council of Canada 1981). We have studied elution of ions through a snowpack on Folgefonna near Bergen, Norway, and in the laboratory. In the field we collected meltwater samples at hourly intervals for a period of 4 d at the start of the melt season, and analyzed them for pH, , Cl−, Na+, Mg2+, Ca2+ and K+. 2 m cores were also collected at the beginning and end of the experiment in order to study bulk changes in snow composition. The meltwaters showed a diurnal cycle with high ionic concentrations around noon, with and levels rising by factors of up to four and six-fold compared to the average concentrations on the first day. Cl− levels peaked much later, after the and levels had decreased, and only reached 2.3 times their lowest concentrations. pH values were strongly correlated with and levels, suggesting that a significant proportion of these anions were in the form of strong acids.

The laboratory experiments involved slow melting of snow samples collected in the Cairngorm mountains, Scotland, and also showed that and (and also Mg2+ and K+) ions were removed from the snow preferentially whilst Na+ and Cl− tended to remain longer. The position of H+ within the ion elution sequence is unclear due to uncertainties in the absolute determination of pH in the field measurements, but the laboratory experiments confirm the differential rates of elution shown in the Norwegian snowpack and reaffirms its importance in the acidification of streams during spring.