This study provides a morphological and phylogenetic characterization of two novel species of the order Haplosporida (Haplosporidium carcini n. sp., and H. cranc n. sp.) infecting the common shore crab Carcinus maenas collected at one location in Swansea Bay, South Wales, UK. Both parasites were observed in the haemolymph, gills and hepatopancreas. The prevalence of clinical infections (i.e. parasites seen directly in fresh haemolymph preparations) was low, at ~1%, whereas subclinical levels, detected by polymerase chain reaction, were slightly higher at ~2%. Although no spores were found in any of the infected crabs examined histologically (n = 334), the morphology of monokaryotic and dikaryotic unicellular stages of the parasites enabled differentiation between the two new species. Phylogenetic analyses of the new species based on the small subunit (SSU) rDNA gene placed H. cranc in a clade of otherwise uncharacterized environmental sequences from marine samples, and H. carcini in a clade with other crustacean-associated lineages.

A sphere sinking through a chemical gradient drags fluid with it, deforming the gradient. The sphere leaves a trail of gradient enhancement that persists longer than the velocity disturbance in the Reynolds $10^{-2}\leqslant Re\leqslant 10^{2}$ , Froude $10^{-1}\leqslant Fr\leqslant 10^{3}$ and Péclet $10^{2}<Pe\leqslant 10^{6}$ regime considered here. We quantify the enhancement of the gradient and the diffusive flux in the trail of disturbed chemical left by the passing sphere using a combination of numerical simulations and scaling analyses. When $Fr$ is large and buoyancy forces are negligible, dragged isosurfaces of chemical form a boundary layer of thickness $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}$ around the sphere with diameter $l$ . We derive the scaling $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}/l\sim \mathit{Pe}^{-1/3}$ from the balance of advection and diffusion in the chemical boundary layer. The sphere displaces a single isosurface of chemical a maximum distance $\mathit{L}_{Def}$ that increases as $\mathit{L}_{Def}/l\sim l/\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}\sim \mathit{Pe}^{1/3}$ . Increased flux through the chemical boundary layer moving with the sphere is described by a Sherwood number, $Sh\sim l/\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}\sim \mathit{Pe}^{1/3}$ . The gradient enhancement trail extends much farther than $\mathit{L}_{Def}$ as displaced isosurfaces slowly return to their original positions through diffusion. In the reference frame of a chemical isosurface moving past the sphere, a new quantity describing the Lagrangian flux is found to scale as $\mathit{M}\sim (\mathit{L}_{Def}/l)^{2}\sim \mathit{Pe}^{2/3}$ . The greater $\mathit{Pe}$ dependence of $\mathit{M}$ versus $Sh$ demonstrates the importance of the deformation trail for determining the total flux of chemical in the system. For $\mathit{Fr}\geqslant 10$ , buoyancy forces are weak compared to the motion of the sphere and the preceding results are retained. Below $\mathit{Fr}=10$ , an additional Froude dependence is found and $l/\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}\sim Sh\sim Re^{1/6}Fr^{-1/6}Pe^{1/3}$ . Buoyancy forces suppress gradient deformation downstream, resulting in $\mathit{L}_{Def}/l\sim Re^{-1/3}Fr^{1/3}Pe^{1/3}$ and $\mathit{M}\sim Re^{-1/3}Fr^{1/3}Pe^{2/3}$ . The productivity of marine plankton – and therefore global carbon and oxygen cycles – depends on the availability of microscale gradients of chemicals. Because most plankton exist in the fluids regime under consideration, this work describes a new mechanism by which sinking particles and plankton can stir weak ambient chemical gradients a distance $\mathit{L}_{Def}$ and increase chemical flux in the trail by a factor of  $\mathit{M}$ .

Archaeological research in the Maya lowlands has identified special deposits that offer essential information about the abandonment of Classic Maya centers. We argue that some of the “problematical deposits” associated with terminal architecture may be more accurately described as peri-abandonment deposits since they temporally and behaviorally relate to the activities associated with the final use of ceremonial space. Here, we describe several peri-abandonment deposits that were identified in Group B at the site of Baking Pot, located in western Belize. Using detailed stratigraphic and contextual information, artifact assemblages, and calendar dates recorded on polychrome vessels recovered in the deposits, we describe the nature of activities associated with the formation of peri-abandonment deposits at Baking Pot in the eighth to ninth centuries. We find patterning in the spatial locations of deposits in the corners of plazas and courtyards at Baking Pot, with variability in artifact assemblages between specific deposits.

Any knot in $S^{3}$ can be reduced to a slice knot by crossing changes. Indeed, this slice knot can be taken to be the unknot. In this paper we study the question of when the same holds for knots in homology spheres. We show that a knot in a homology sphere is nullhomotopic in a smooth homology ball if and only if that knot is smoothly concordant to a knot that is homotopic to a smoothly slice knot. As a consequence, we prove that the equivalence relation on knots in homology spheres given by cobounding immersed annuli in a homology cobordism is generated by concordance in homology cobordisms together with homotopy in a homology sphere.

We construct links of arbitrarily many components each component of which is slice and yet are not concordant to any link with even one unknotted component. The only tool we use comes from the Alexander modules.

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.

Recent observations of globular clusters imposed major revisions to the previous paradigm, in which they were considered to be isotropic in velocity space and non-rotating. However, the theory of collisionless spheroids with some kinematic richness has seldom been studied. We present here a first step in this direction, owing to new results regarding the linear stability of rotating Plummer spheres, with varying anisotropy in velocity space and total amount of angular momentum. We extend the well-known radial orbit instability to rotating systems, and discover a new regime of instability in fast rotating, tangentially anisotropic systems.

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.

Physical activity (PA) may be therapeutic for people with severe mental illness (SMI) who generally have low PA and experience numerous life style-related medical complications. We conducted a meta-review of PA interventions and their impact on health outcomes for people with SMI, including schizophrenia-spectrum disorders, major depressive disorder (MDD) and bipolar disorder. We searched major electronic databases until January 2018 for systematic reviews with/without meta-analysis that investigated PA for any SMI. We rated the quality of studies with the AMSTAR tool, grading the quality of evidence, and identifying gaps, future research needs and clinical practice recommendations. For MDD, consistent evidence indicated that PA can improve depressive symptoms versus control conditions, with effects comparable to those of antidepressants and psychotherapy. PA can also improve cardiorespiratory fitness and quality of life in people with MDD, although the impact on physical health outcomes was limited. There were no differences in adverse events versus control conditions. For MDD, larger effect sizes were seen when PA was delivered at moderate-vigorous intensity and supervised by an exercise specialist. For schizophrenia-spectrum disorders, evidence indicates that aerobic PA can reduce psychiatric symptoms, improves cognition and various subdomains, cardiorespiratory fitness, whilst evidence for the impact on anthropometric measures was inconsistent. There was a paucity of studies investigating PA in bipolar disorder, precluding any definitive recommendations. No cost effectiveness analyses in any SMI condition were identified. We make multiple recommendations to fill existing research gaps and increase the use of PA in routine clinical care aimed at improving psychiatric and medical outcomes.

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.