PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response.

PurposeThe purpose of our study is to determine if there is a relationship between dose deposition measured by PET/MRI and individual lesion response to yttrium-90 ((90)Y) microsphere radioembolization.Materials and methods26 patients undergoing lobar treatment with (90)Y microspheres underwent PET/MRI within 66 h of treatment and had follow-up imaging available. Adequate visualization of tumor was available in 24 patients, and contours were drawn on simultaneously acquired PET/MRI data. Dose volume histograms (DVHs) were extracted from dose maps, which were generated using a voxelized dose kernel. Similar contours to capture dimensional and volumetric change of tumors were drawn on follow-up imaging. Response was analyzed using both RECIST and volumetric RECIST (vRECIST) criteria.ResultsA total of 8 hepatocellular carcinoma (HCC), 4 neuroendocrine tumor (NET), 9 colorectal metastases (CRC) patients, and 3 patients with other metastatic disease met inclusion criteria. Average dose was useful in predicting response between responders and non-responders for all lesion types and for CRC lesions alone using both response criteria (p < 0.05). D70 (minimum dose to 70 % of volume) was also useful in predicting response when using vRECIST. No significant trend was seen in the other tumor types. For CRC lesions, an average dose of 29.8 Gy offered 76.9 % sensitivity and 75.9 % specificity for response.ConclusionsPET/MRI of (90)Y microsphere distribution showed significantly higher DVH values for responders than non-responders in patients with CRC. DVH analysis of (90)Y microsphere distribution following treatment may be an important predictor of response and could be used to guide future adaptive therapy trials

Tracing Galaxy Formation with Stellar Halos II: Relating Substructure in Phase- and Abundance-Space to Accretion Histories

This paper explores the mapping between the observable properties of a stellar halo in phase- and abundance-space and the parent galaxy's accretion history in terms of the characteristic epoch of accretion and mass and orbits of progenitor objects. The study utilizes a suite of eleven stellar halo models constructed within the context of a standard LCDM cosmology. The results demonstrate that coordinate-space studies are sensitive to the recent (0-8 Gyears ago) merger histories of galaxies (this timescale corresponds to the last few to tens of percent of mass accretion for a Milky-Way-type galaxy). Specifically, the {\it frequency, sky coverage} and {\it fraction of stars} in substructures in the stellar halo as a function of surface brightness are indicators of the importance of recent merging and of the luminosity function of infalling dwarfs. The {\it morphology} of features serves as a guide to the orbital distribution of those dwarfs. Constraints on the earlier merger history (> 8 Gyears ago) can be gleaned from the abundance patterns in halo stars: within our models, dramatic differences in the dominant epoch of accretion or luminosity function of progenitor objects leave clear signatures in the [alpha/Fe] and [Fe/H] distributions of the stellar halo - halos dominated by very early accretion have higher average [alpha/Fe], while those dominated by high luminosity satellites have higher [Fe/H]. This intuition can be applied to reconstruct much about the merger histories of nearby galaxies from current and future data sets.Comment: 21 pages, 20 figures. To appear in the Astrophysical Journa

Exploring Halo Substructure with Giant Stars. XV. Discovery of a Connection between the Monoceros Ring and the Triangulum-Andromeda Overdensity?

Thanks to modern sky surveys, over twenty stellar streams and overdensity structures have been discovered in the halo of the Milky Way. In this paper, we present an analysis of spectroscopic observations of individual stars from one such structure, "A13", first identified as an overdensity using the M giant catalog from the Two Micron All-Sky Survey. Our spectroscopic observations show that stars identified with A13 have a velocity dispersion of $\lesssim$ 40 $\mathrm{km~s^{-1}}$, implying that it is a genuine coherent structure rather than a chance super-position of random halo stars. From its position on the sky, distance ($\sim$15~kpc heliocentric), and kinematical properties, A13 is likely to be an extension of another low Galactic latitude substructure -- the Galactic Anticenter Stellar Structure (also known as the Monoceros Ring) -- towards smaller Galactic longitude and farther distance. Furthermore, the kinematics of A13 also connect it with another structure in the southern Galactic hemisphere -- the Triangulum-Andromeda overdensity. We discuss these three connected structures within the context of a previously proposed scenario that one or all of these features originate from the disk of the Milky Way.Comment: 12 pages, 9 figures. Accepted for publication in Ap

Probing the Halo From the Solar Vicinity to the Outer Galaxy: Connecting Stars in Local Velocity Structures to Large-Scale Clouds

(Abridged) This paper presents the first connections made between two local features in velocity-space found in a survey of M giant stars and stellar spatial inhomogeneities on global scales. Comparison to cosmological, chemodynamical stellar halo models confirm that the M giant population is particularly sensitive to rare, recent and massive accretion events. These events can give rise to local observed velocity sequences - a signature of a small fraction of debris from a common progenitor, passing at high velocity through the survey volume, near the pericenters of their eccentric orbits. The majority of the debris is found in much larger structures, whose morphologies are more cloud-like than stream-like and which lie at the orbital apocenters. Adopting this interpretation, the full-space motions represented by the observed velocity features are derived under the assumption that the members within each sequence share a common velocity. Orbit integrations are then used to trace the past and future trajectories of these stars across the sky revealing plausible associations with large, previously-discovered, cloud-like structures. The connections made between nearby velocity structures and these distant clouds represent preliminary steps towards developing coherent maps of such giant debris systems. These maps promise to provide new insights into the origin of debris clouds, new probes of Galactic history and structure, and new constraints on the high-velocity tails of the local dark matter distribution that are essential for interpreting direct detection experiments.Comment: submitted to the Astrophysical Journal, 40 pages, 13 figure

Neuroinflammation and Neurologic Deficits in Diabetes Linked to Brain Accumulation of Amylin

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function. METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. We exploited this fact by comparing rats overexpressing human amylin in the pancreas (HIP rats) with their littermate rats which express only wild-type (WT) non-amyloidogenic rodent amylin. Cage activity, rotarod and novel object recognition tests were performed on animals nine months of age or older. Amylin deposition in the brain was documented by immunohistochemistry, and western blot. We also measured neuroinflammation by immunohistochemistry, quantitative real-time PCR and cytokine protein levels. RESULTS: Compared to WT rats, HIP rats show i) reduced exploratory drive, ii) impaired recognition memory and iii) no ability to improve the performance on the rotarod. The development of neurological deficits is associated with amylin accumulation in the brain. The level of oligomerized amylin in supernatant fractions and pellets from brain homogenates is almost double in HIP rats compared with WT littermates (P \u3c 0.05). Large amylin deposits (\u3e50 μm diameter) were also occasionally seen in HIP rat brains. Accumulation of oligomerized amylin alters the brain structure at the molecular level. Immunohistochemistry analysis with an ED1 antibody indicates possible activated microglia/macrophages which are clustering in areas positive for amylin infiltration. Multiple inflammatory markers are expressed in HIP rat brains as opposed to WT rats, confirming that amylin deposition in the brain induces a neuroinflammatory response. CONCLUSIONS: Hyperamylinemia promotes accumulation of oligomerized amylin in the brain leading to neurological deficits through an oligomerized amylin-mediated inflammatory response. Additional studies are needed to determine whether brain amylin accumulation may predispose to diabetic brain injury and cognitive decline

Need for better and broader training in cardio-obstetrics: A national survey of cardiologists, cardiovascular team members, and cardiology fellows in training

Background Team-based models of cardio-obstetrics care have been developed to address the increasing rate of maternal mortality from cardiovascular diseases. Cardiovascular clinician and trainee knowledge and comfort with this topic, and the extent of implementation of an interdisciplinary approach to cardio-obstetrics, are unknown. Methods and Results We aimed to assess the current state of cardio-obstetrics knowledge, practices, and services provided by US cardiovascular clinicians and trainees. A survey developed in conjunction with the American College of Cardiology was circulated to a representative sample of cardiologists (N=311), cardiovascular team members (N=51), and fellows in training (N=139) from June 18, 2020, to July 29, 2020. Knowledge and attitudes about the provision of cardiovascular care to pregnant patients and the prevalence and composition of cardio-obstetrics teams were assessed. The widest knowledge gaps on the care of pregnant compared with nonpregnant patients were reported for medication safety (42%), acute coronary syndromes (39%), aortopathies (40%), and valvular heart disease (30%). Most respondents (76%) lack access to a dedicated cardio-obstetrics team, and only 29% of practicing cardiologists received cardio-obstetrics didactics during training. One third of fellows in training reported seeing pregnant women 0 to 1 time per year, and 12% of fellows in training report formal training in cardio-obstetrics. Conclusions Formalized training in cardio-obstetrics is uncommon, and limited access to multidisciplinary cardio-obstetrics teams and large knowledge gaps exist among cardiovascular clinicians. Augmentation of cardio-obstetrics education across career stages is needed to reduce these deficits. These survey results are an initial step toward developing a standard expectation for clinicians\u27 training in cardio-obstetrics

Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).

<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p

The accretion origin of the Milky Way's stellar halo

We have used data from the Sloan Digital Sky Survey (SDSS) Data Release 5 to explore the overall structure and substructure of the stellar halo of the Milky Way using about 4 million color-selected main sequence turn-off stars. We fit oblate and triaxial broken power-law models to the data, and found a `best-fit' oblateness of the stellar halo 0.5<c/a<0.8, and halo stellar masses between Galactocentric radii of 1 and 40kpc of (3.7+/-1.2)x10^8 M_sun. The density profile of the stellar halo is approximately r^{-3}; it is possible that the power law slope is shallower inside 20kpc and steeper outside that radius. Yet, we found that all smooth and symmetric models were very poor fits to the distribution of stellar halo stars because the data exhibit a great deal of spatial substructure. We quantified deviations from a smooth oblate/triaxial model using the RMS of the data around the model profile on scales >~100pc, after accounting for the (known) contribution of Poisson uncertainties. The fractional RMS deviation of the actual stellar distribution from any smooth, parameterized halo model is >~40%: hence, the stellar halo is highly structured. We compared the observations with simulations of galactic stellar halos formed entirely from the accretion of satellites in a cosmological context by analysing the simulations in the same way as the data. While the masses, overall profiles, and degree of substructure in the simulated stellar halos show considerable scatter, the properties and degree of substructure in the Milky Way's halo match well the properties of a `typical' stellar halo built exclusively out of the debris from disrupted satellite galaxies. Our results therefore point towards a picture in which an important fraction of the Milky Way's stellar halo has been accreted from satellite galaxies.Comment: Submitted to the Astrophysical Journal. 14 pages; 11 figure

A novel syndrome of paediatric cataract, dysmorphism, ectodermal features, and developmental delay in Australian Aboriginal family maps to 1p35.3-p36.32

Background: A novel phenotype consisting of cataract, mental retardation, erythematous skin rash and facial dysmorphism was recently described in an extended pedigree of Australian Aboriginal descent. Large scale chromosomal re-arrangements had previously been ruled out. We have conducted a genome-wide scan to map the linkage region in this family.Methods: Genome-wide linkage analysis using Single Nucleotide Polymorphism (SNP) markers on the Affymetrix 10K SNP array was conducted and analysed using MERLIN. Three positional candidate genes (ZBTB17, EPHA2 and EPHB2) were sequenced to screen for segregating mutations. Results: Under a fully penetrant, dominant model, the locus for this unique phenotype was mapped to chromosome 1p35.3-p36.32 with a maximum LOD score of 2.41. The critical region spans 48.7 cM between markers rs966321 and rs1441834 and encompasses 527 transcripts from 364 annotated genes. No coding mutations were identified in three positional candidate genes EPHA2, EPHB2 or ZBTB17. The region overlaps with a previously reported region for Volkmann cataract and the phenotype has similarity to that reported for 1p36 monosomy. Conclusions: The gene for this syndrome is located in a 25.6 Mb region on 1p35.3-p36.32. The known cataract gene in this region (EPHA2) does not harbour mutations in this family, suggesting that at least one additional gene for cataract is present in this region.Kathryn Hattersley, Kate J Laurie, Jan E Liebelt, Jozef Gecz, Shane R Durkin, Jamie E Craig and Kathryn P Burdo

Imaging and Neuro-Oncology Clinical Trials of the National Clinical Trials Network (NCTN)

Imaging in neuro-oncology clinical trials can be used to validate patient eligibility, stage at presentation, response to therapy, and radiation therapy. A number of National Clinical Trials Network trials illustrating this are presented. Through the Imaging and Radiation Oncology Core’s quality assurance processes for data acquisition and review, there are uniform data and imaging sets for review. Once the trial endpoints have been analyzed and published, the clinical trial information including pathology, imaging, and radiation therapy objects can be moved to a public archive for use by investigators interested in translational science and the application of new informatics tools for trial analysis