Cardiovascular Damage in Alzheimer Disease: Autopsy Findings From the Bryan ADRC

Autopsy information on cardiovascular damage was investigated for pathologically confirmed Alzheimer disease (AD) patients (n = 84) and non-AD control patients (n = 60). The 51 relevant items were entered into a grade-of-membership model to describe vascular damage in AD. Five latent groups were identified “I: early-onset AD,” “II: controls, cancer,” “III: controls, extensive atherosclerosis,” “IV: late-onset AD, male,” and “V: late-onset AD, female.” Expectedly, Groups IV and V had elevated APOE ϵ4 frequency. Unexpectedly, there was limited atherosclerosis and frequent myocardial valve and ventricular damage. The findings do not indicate a strong relationship between atherosclerosis and AD, although both are associated with the APOE ϵ4. Instead, autopsy findings of extensive atherosclerosis were associated with possible, not probable or definite AD, and premature death. They are consistent with the hypothesis that brain hypoperfusion contributes to dementia, possibly to AD pathogenesis, and raise the possibility that the APOE allele ϵ4 contributes directly to heart valve and myocardial damage

uvbyCa H beta CCD Photometry of Clusters. VII. The Intermediate-Age Anticenter Cluster Melotte 71

CCD photometry on the intermediate-band uvbyCa H beta system is presented for the anticenter, intermediate-age open cluster, Melotte 71. Restricting the data to probable single members of the cluster using the color-magnitude diagram and the photometric indices alone generates a sample of 48 F dwarfs on the unevolved main sequence. The average E(b-y) = 0.148 +/- 0.003 (s.e.m.) or E(B-V) = 0.202 +/- 0.004 (s.e.m.), where the errors refer to internal errors alone. With this reddening, [Fe/H] is derived from both m1 and hk, using H beta and b-y as the temperature index, with excellent agreement among the four approaches and a final weighted average of [Fe/H] = -0.17 +/- 0.02 (s.e.m.) for the cluster, on a scale where the Hyades has [Fe/H] = +0.12. When adjusted for the higher reddening estimate, the previous metallicity estimates from Washington photometry and from spectroscopy are now in agreement with the intermediate-band result. From comparisons to isochrones of appropriate metallicity, the cluster age and distance are determined as 0.9 +/- 0.1 Gyr and (m-M) = 12.2 +/- 0.1 or (m-M)_0 = 11.6 +/- 0.1. At this distance from the sun, Mel 71 has a galactocentric distance of 10.0 kpc on a scale where the sun is 8.5 kpc from the galactic center. Based upon its age, distance, and elemental abundances, Mel 71 appears to be a less populous analog to NGC 3960.Comment: Accepted for Astronomical Journal. 38 page latex file includes 11 figures and short version of data table. Full table will appear in online AJ or may be requested from author

Dynamically Driven Evolution of the Interstellar Medium in M51

We report the highest-fidelity observations of the spiral galaxy M51 in CO emission, revealing the evolution of giant molecular clouds (GMCs) vis-a-vis the large-scale galactic structure and dynamics. The most massive GMCs (so-called GMAs) are first assembled and then broken up as the gas flow through the spiral arms. The GMAs and their H2 molecules are not fully dissociated into atomic gas as predicted in stellar feedback scenarios, but are fragmented into smaller GMCs upon leaving the spiral arms. The remnants of GMAs are detected as the chains of GMCs that emerge from the spiral arms into interarm regions. The kinematic shear within the spiral arms is sufficient to unbind the GMAs against self-gravity. We conclude that the evolution of GMCs is driven by large-scale galactic dynamics --their coagulation into GMAs is due to spiral arm streaming motions upon entering the arms, followed by fragmentation due to shear as they leave the arms on the downstream side. In M51, the majority of the gas remains molecular from arm entry through the inter-arm region and into the next spiral arm passage.Comment: 6 pages, including 3 figures. Accepted, ApJ

Observing the Sun with Atacama Large Millimeter/submillimeter Array (ALMA): High Resolution Interferometric Imaging

Observations of the Sun at millimeter and submillimeter wavelengths offer a unique probe into the structure, dynamics, and heating of the chromosphere; the structure of sunspots; the formation and eruption of prominences and filaments; and energetic phenomena such as jets and flares. High-resolution observations of the Sun at millimeter and submillimeter wavelengths are challenging due to the intense, extended, low- contrast, and dynamic nature of emission from the quiet Sun, and the extremely intense and variable nature of emissions associated with energetic phenomena. The Atacama Large Millimeter/submillimeter Array (ALMA) was designed with solar observations in mind. The requirements for solar observations are significantly different from observations of sidereal sources and special measures are necessary to successfully carry out this type of observations. We describe the commissioning efforts that enable the use of two frequency bands, the 3 mm band (Band 3) and the 1.25 mm band (Band 6), for continuum interferometric-imaging observations of the Sun with ALMA. Examples of high-resolution synthesized images obtained using the newly commissioned modes during the solar commissioning campaign held in December 2015 are presented. Although only 30 of the eventual 66 ALMA antennas were used for the campaign, the solar images synthesized from the ALMA commissioning data reveal new features of the solar atmosphere that demonstrate the potential power of ALMA solar observations. The ongoing expansion of ALMA and solar-commissioning efforts will continue to enable new and unique solar observing capabilities.Comment: 22 pages, 12 figures, accepted for publication in Solar Physic

Observing the Sun with the Atacama Large Millimeter-submillimeter Array (ALMA): Fast-Scan Single-Dish Mapping

The Atacama Large Millimeter-submillimeter Array (ALMA) radio telescope has commenced science observations of the Sun starting in late 2016. Since the Sun is much larger than the field of view of individual ALMA dishes, the ALMA interferometer is unable to measure the background level of solar emission when observing the solar disk. The absolute temperature scale is a critical measurement for much of ALMA solar science, including the understanding of energy transfer through the solar atmosphere, the properties of prominences, and the study of shock heating in the chromosphere. In order to provide an absolute temperature scale, ALMA solar observing will take advantage of the remarkable fast-scanning capabilities of the ALMA 12m dishes to make single-dish maps of the full Sun. This article reports on the results of an extensive commissioning effort to optimize the mapping procedure, and it describes the nature of the resulting data. Amplitude calibration is discussed in detail: a path that utilizes the two loads in the ALMA calibration system as well as sky measurements is described and applied to commissioning data. Inspection of a large number of single-dish datasets shows significant variation in the resulting temperatures, and based on the temperature distributions we derive quiet-Sun values at disk center of 7300 K at lambda=3 mm and 5900 K at lambda=1.3 mm. These values have statistical uncertainties of order 100 K, but systematic uncertainties in the temperature scale that may be significantly larger. Example images are presented from two periods with very different levels of solar activity. At a resolution of order 25 arcsec, the 1.3 mm wavelength images show temperatures on the disk that vary over about a 2000 K range.Comment: Solar Physics, accepted: 24 pages, 13 figure

Dynamically Driven Evolution of the Interstellar Medium in M51

Massive star formation occurs in giant molecular clouds (GMCs); an understanding of the evolution of GMCs is a prerequisite to develop theories of star formation and galaxy evolution. We report the highest-fidelity observations of the grand-design spiral galaxy M51 in carbon monoxide (CO) emission, revealing the evolution of GMCs vis-a-vis the large-scale galactic structure and dynamics. The most massive GMCs (giant molecular associations (GMAs)) are first assembled and then broken up as the gas flow through the spiral arms. The GMAs and their H_2 molecules are not fully dissociated into atomic gas as predicted in stellar feedback scenarios, but are fragmented into smaller GMCs upon leaving the spiral arms. The remnants of GMAs are detected as the chains of GMCs that emerge from the spiral arms into interarm regions. The kinematic shear within the spiral arms is sufficient to unbind the GMAs against self-gravity. We conclude that the evolution of GMCs is driven by large-scale galactic dynamics—their coagulation into GMAs is due to spiral arm streaming motions upon entering the arms, followed by fragmentation due to shear as they leave the arms on the downstream side. In M51, the majority of the gas remains molecular from arm entry through the interarm region and into the next spiral arm passage

Adolescents' perspectives on a school-based physical activity intervention: A mixed method study.

Purpose:To examine adolescent experiences and perspectives of the GoActive intervention (ISRCTN31583496) using mixed methods process evaluation to determine satisfaction with intervention components and interpret adolescents' experiences of the intervention process in order to provide insights for future intervention design. Methods:Participants (n = 1542; 13.2 ±  0.4 years, mean ± SD) provided questionnaire data at baseline (shyness, activity level) and post-intervention (intervention acceptability, satisfaction with components). Between-group differences (boys vs. girls and shy/inactive vs. others) were tested with linear regression models, accounting for school clustering. Data from 16 individual interviews (shy/inactive) and 11 focus groups with 48 participants (mean = 4; range 2-7) were thematically coded. Qualitative and quantitative data were merged in an integrative mixed methods convergence matrix, which denoted convergence and dissonance across datasets. Results:Effect sizes for quantitative results were small and may not represent substantial between-group differences. Boys (vs. girls) preferred class-based sessions (β = 0.2, 95% confidence interval (CI): 0.1-0.3); qualitative data suggested that this was because boys preferred competition, which was supported quantitatively (β = 0.2, 95%CI: 0.1-0.3). Shy/inactive students did not enjoy the competition (β = -0.3, 95%CI: -0.5 to -0.1). Boys enjoyed trying new activities more (β = 0.1, 95%CI: 0.1-0.2); qualitative data indicated a desire to try new activities across all subgroups but identified barriers to choosing unfamiliar activities with self-imposed choice restriction leading to boredom. Qualitative data highlighted critique of mentorship; adolescents liked the idea, but older mentors did not meet expectations. Conclusion:We interpreted adolescent perspectives of intervention components and implementation to provide insights into future complex interventions aimed at increasing young people's physical activity in school-based settings. The intervention component mentorship was liked in principle, but implementation issues undesirably impacted satisfaction; competition was disliked by girls and shy/inactive students. The results highlight the importance of considering gender differences in preference of competition and extensive mentorship training

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers