Rodent Aβ Modulates the Solubility and Distribution of Amyloid Deposits in Transgenic Mice

The amino acid sequence of amyloid precursor protein (APP) is highly conserved, and age-related Abeta aggregates have been described in a variety of vertebrate animals, with the notable exception of mice and rats. Three amino acid substitutions distinguish mouse and human Abeta that might contribute to their differing properties in vivo. To examine the amyloidogenic potential of mouse Abeta, we studied several lines of transgenic mice overexpressing wild-type mouse amyloid precursor protein (moAPP) either alone or in conjunction with mutant PS1 (PS1dE9). Neither overexpression of moAPP alone nor co-expression with PS1dE9 caused mice to develop Alzheimer-type amyloid pathology by 24 months of age. We further tested whether mouse Abeta could accelerate the deposition of human Abeta by crossing the moAPP transgenic mice to a bigenic line expressing human APPswe with PS1dE9. The triple transgenic animals (moAPP x APPswe/PS1dE9) produced 20% more Abeta but formed amyloid deposits no faster and to no greater extent than APPswe/PS1dE9 siblings. Instead, the additional mouse Abeta increased the detergent solubility of accumulated amyloid and exacerbated amyloid deposition in the vasculature. These findings suggest that, although mouse Abeta does not influence the rate of amyloid formation, the incorporation of Abeta peptides with differing sequences alters the solubility and localization of the resulting aggregates

Do Hospitalists or Physicians with Greater Inpatient HIV Experience Improve HIV Care in the Era of Highly Active Antiretroviral Therapy? Results from a Multicenter Trial of Academic Hospitalists

Background. Little is known about the effect of provider type and experience on outcomes, resource use, and processes of care of hospitalized patients with human immunodeficiency virus (HIV) infection. Hospitalists are caring for this population with increasing frequency. Methods. Data from a natural experiment in which patients were assigned to physicians on the basis of call cycle was used to study the effects of provider type—that is, hospitalist versus non hospitalist—and HIV-specific inpatient experience on resource use, outcomes, and selected measures of processes of care at 6 academic institutions. Administrative data, inpatient interviews, 30-day follow-up interviews, and the National Death Index were used to measure outcomes. Results. A total of 1207 patients were included in the analysis. There were few differences in resource use, outcomes, and processes of care by provider type and experience with HIV-infected inpatients. Patients who received hospitalist care demonstrated a trend toward increased length of hospital stay compared with patients who did not receive hospitalist care (6.0 days vs. 5.2 days; Pp .13). Inpatient providers with moderate experience with HIV-infected patients were more likely to coordinate care with outpatient providers (odds ratio, 2.40; Pp .05) than were those with the least experience with HIV-infected patients, but this pattern did not extend to providers with the highest level of experience. Conclusion. Provider type and attending physician experience with HIV-infected inpatients had minimal effect on the quality of care of HIV-infected inpatients. Approaches other than provider experience, such as the use of multidisciplinary inpatient teams, may be better targets for future studies of the outcomes, processes of care, and resource use of HIV-infected inpatients

Discovery of a Transiting Adolescent Sub-Neptune Exoplanet with K2

The role of stellar age in the measured properties and occurrence rates of exoplanets is not well understood. This is in part due to a paucity of known young planets and the uncertainties in age-dating for most exoplanet host stars. Exoplanets with well-constrained ages, particularly those which are young, are useful as benchmarks for studies aiming to constrain the evolutionary timescales relevant for planets. Such timescales may concern orbital migration, gravitational contraction, or atmospheric photo-evaporation, among other mechanisms. Here we report the discovery of an adolescent transiting sub-Neptune from K2 photometry of the low-mass star K2-284. From multiple age indicators we estimate the age of the star to be 120 Myr, with a 68% confidence interval of 100-760 Myr. The size of K2-284 b ($R_P$ = 2.8 $\pm$ 0.1 $R_\oplus$) combined with its youth make it an intriguing case study for photo-evaporation models, which predict enhanced atmospheric mass loss during early evolutionary stages.Comment: Accepted to AJ, 36 pages, 17 figures, 5 table

Embryonic Stem Cells Are Redirected to Non-Tumorigenic Epithelial Cell Fate by Interaction with the Mammary Microenvironment

Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We demonstrate that these progeny, marked by LacZ expression, differentiate into multiple epithelial subtypes including steroid receptor positive luminal cells and myoepithelial cells indicating that the ES cells are capable of epithelial multipotency in this context but do not form teratomas. In addition, in secondary transplants, ES cell progeny proliferate, contribute apparently normal mammary progeny, maintain their multipotency and do not produce teratomas

Unveiling the Active Nucleus of Centaurus A

We report new HST WFPC2 and NICMOS observations of the center of the nearest radio galaxy Centaurus A (NGC 5128) and discuss their implications for our understanding of the active nucleus and jet. We detect the active nucleus in the near-IR (K and H) and, for the first time, in the optical (I and V), deriving the spectral energy distribution of the nucleus from the radio to X-rays. The optical and part of the near-IR emission can be explained by the extrapolation of the X-ray power law reddened by A_V~14mag, a value consistent with other independent estimates. The 20pc-scale nuclear disk discovered by Schreier et al. (1998) is detected in the [FeII] 1.64mic line and presents a morphology similar to that observed in Pa alpha with a [FeII]/Pa alpha ratio typical of low ionization Seyfert galaxies and LINERs. NICMOS 3 Pa alpha observations in a 50"x50" circumnuclear region suggest enhanced star formation (~0.3Msun/yr) at the edges of the putative bar seen with ISO, perhaps due to shocks driven into the gas. The light profile, reconstructed from V, H and K observations, shows that Centaurus A has a core profile with a resolved break at ~4" and suggests a black--hole mass of ~10^9 Msun. A linear blue structure aligned with the radio/X-ray jet may indicate a channel of relatively low reddening in which dust has been swept away by the jet.Comment: 19 pages, 13 figures, Astrophysical Journal, in press. High quality figures available at http://www.arcetri.astro.it/~marconi/colpic.htm

60 Validated Planets from K2 Campaigns 5-8

We present a uniform analysis of 155 candidates from the second year of NASA's $K2$ mission (Campaigns 5-8), yielding 60 statistically validated planets spanning a range of properties, with median values of $R_p$ = 2.5 $R_\oplus$, $P$ = 7.1 d, $T_\mathrm{eq}$ = 811 K, and $J$ = 11.3 mag. The sample includes 24 planets in 11 multi-planetary systems, as well as 18 false positives, and 77 remaining planet candidates. Of particular interest are 18 planets smaller than 2 $R_\oplus$, five orbiting stars brighter than $J$ = 10 mag, and a system of four small planets orbiting the solar-type star EPIC 212157262. We compute planetary transit parameters and false positive probabilities using a robust statistical framework and present a complete analysis incorporating the results of an intensive campaign of high resolution imaging and spectroscopic observations. This work brings the $K2$ yield to over 360 planets, and by extrapolation we expect that $K2$ will have discovered $\sim$600 planets before the expected depletion of its on-board fuel in late 2018.Comment: 33 pages, 13 figures, 5 tables, accepted for publication in A

NASA's Solar Dynamics Observatory (SDO): A Systems Approach to a Complex Mission

The Solar Dynamics Observatory (SDO) includes three advanced instruments, massive science data volume, stringent science data completeness requirements, and a custom ground station to meet mission demands. The strict instrument science requirements imposed a number of challenging drivers on the overall mission system design, leading the SDO team to adopt an integrated systems engineering presence across all aspects of the mission to ensure that mission science requirements would be met. Key strategies were devised to address these system level drivers and mitigate identified threats to mission success. The global systems engineering team approach ensured that key drivers and risk areas were rigorously addressed through all phases of the mission, leading to the successful SDO launch and on-orbit operation. Since launch, SDO's on-orbit performance has met all mission science requirements and enabled groundbreaking science observations, expanding our understanding of the Sun and its dynamic processes

Issues with variability in electronic health record data about race and ethnicity: Descriptive analysis of the National COVID Cohort Collaborative Data Enclave

BACKGROUND: The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity are collected and structured by health care organizations. OBJECTIVE: This study aims to evaluate and describe variations in how health care systems collect and report information about the race and ethnicity of their patients and to assess how well these data are integrated when aggregated into a large clinical database. METHODS: At the time of our analysis, the National COVID Cohort Collaborative (N3C) Data Enclave contained records from 6.5 million patients contributed by 56 health care institutions. We quantified the variability in the harmonized race and ethnicity data in the N3C Data Enclave by analyzing the conformance to health care standards for such data. We conducted a descriptive analysis by comparing the harmonized data available for research purposes in the database to the original source data contributed by health care institutions. To make the comparison, we tabulated the original source codes, enumerating how many patients had been reported with each encoded value and how many distinct ways each category was reported. The nonconforming data were also cross tabulated by 3 factors: patient ethnicity, the number of data partners using each code, and which data models utilized those particular encodings. For the nonconforming data, we used an inductive approach to sort the source encodings into categories. For example, values such as Declined were grouped with Refused, and Multiple Race was grouped with Two or more races and Multiracial. RESULTS: No matching concept was the second largest harmonized concept used by the N3C to describe the race of patients in their database. In addition, 20.7% of the race data did not conform to the standard; the largest category was data that were missing. Hispanic or Latino patients were overrepresented in the nonconforming racial data, and data from American Indian or Alaska Native patients were obscured. Although only a small proportion of the source data had not been mapped to the correct concepts (0.6%), Black or African American and Hispanic/Latino patients were overrepresented in this category. CONCLUSIONS: Differences in how race and ethnicity data are conceptualized and encoded by health care institutions can affect the quality of the data in aggregated clinical databases. The impact of data quality issues in the N3C Data Enclave was not equal across all races and ethnicities, which has the potential to introduce bias in analyses and conclusions drawn from these data. Transparency about how data have been transformed can help users make accurate analyses and inferences and eventually better guide clinical care and public policy

Issues With Variability in Electronic Health Record Data About Race and Ethnicity: Descriptive Analysis of the National COVID Cohort Collaborative Data Enclave

Background:The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity are collected and structured by health care organizations. Objective:This study aims to evaluate and describe variations in how health care systems collect and report information about the race and ethnicity of their patients and to assess how well these data are integrated when aggregated into a large clinical database. Methods:At the time of our analysis, the National COVID Cohort Collaborative (N3C) Data Enclave contained records from 6.5 million patients contributed by 56 health care institutions. We quantified the variability in the harmonized race and ethnicity data in the N3C Data Enclave by analyzing the conformance to health care standards for such data. We conducted a descriptive analysis by comparing the harmonized data available for research purposes in the database to the original source data contributed by health care institutions. To make the comparison, we tabulated the original source codes, enumerating how many patients had been reported with each encoded value and how many distinct ways each category was reported. The nonconforming data were also cross tabulated by 3 factors: patient ethnicity, the number of data partners using each code, and which data models utilized those particular encodings. For the nonconforming data, we used an inductive approach to sort the source encodings into categories. For example, values such as “Declined” were grouped with “Refused,” and “Multiple Race” was grouped with “Two or more races” and “Multiracial.” Results:“No matching concept” was the second largest harmonized concept used by the N3C to describe the race of patients in their database. In addition, 20.7% of the race data did not conform to the standard; the largest category was data that were missing. Hispanic or Latino patients were overrepresented in the nonconforming racial data, and data from American Indian or Alaska Native patients were obscured. Although only a small proportion of the source data had not been mapped to the correct concepts (0.6%), Black or African American and Hispanic/Latino patients were overrepresented in this category. Conclusions:Differences in how race and ethnicity data are conceptualized and encoded by health care institutions can affect the quality of the data in aggregated clinical databases. The impact of data quality issues in the N3C Data Enclave was not equal across all races and ethnicities, which has the potential to introduce bias in analyses and conclusions drawn from these data. Transparency about how data have been transformed can help users make accurate analyses and inferences and eventually better guide clinical care and public policy