Brca2 and Trp53 deficiency cooperate in the progression of mouse prostate tumourigenesis.

Epidemiological studies have shown that one of the strongest risk factors for prostate cancer is a family history of the disease, suggesting that inherited factors play a major role in prostate cancer susceptibility. Germline mutations in BRCA2 predispose to breast and ovarian cancer with its predominant tumour suppressor function thought to be the repair of DNA double-strand breaks. BRCA2 has also been implicated in prostate cancer etiology, but it is unclear the impact that mutations in this gene have on prostate tumourigenesis. Here we have undertaken a genetic analysis in the mouse to determine the role of Brca2 in the adult prostate. We show that deletion of Brca2 specifically in prostate epithelia results in focal hyperplasia and low-grade prostate intraepithelial neoplasia (PIN) in animals over 12 months of age. Simultaneous deletion of Brca2 and the tumour suppressor Trp53 in prostate epithelia gave rise to focal hyperplasia and atypical cells at 6 months, leading to high-grade PIN in animals from 12 months. Epithelial cells in these lesions show an increase in DNA damage and have higher levels of proliferation, but also elevated apoptosis. Castration of Brca2;Trp53 mutant animals led to regression of PIN lesions, but atypical cells persisted that continued to proliferate and express nuclear androgen receptor. This study provides evidence that Brca2 can act as a tumour suppressor in the prostate, and the model we describe should prove useful in the development of new therapeutic approaches

Aiming Higher: Results From a State Scorecard on Health System Performance

Assesses state variation across key dimensions of health system performance -- access, quality, avoidable hospital use and costs, equity, and healthy lives -- and assigns overall state rankings as well as ranks on each dimension

Cosmology with velocity dispersion counts: an alternative to measuring cluster halo masses

The evolution of galaxy cluster counts is a powerful probe of several fundamental cosmological parameters. A number of recent studies using this probe have claimed tension with the cosmology preferred by the analysis of the Planck primary CMB data, in the sense that there are fewer clusters observed than predicted based on the primary CMB cosmology. One possible resolution to this problem is systematic errors in the absolute halo mass calibration in cluster studies, which is required to convert the standard theoretical prediction (the halo mass function) into counts as a function of the observable (e.g., X-ray luminosity, Sunyaev-Zel'dovich flux, optical richness). Here we propose an alternative strategy, which is to directly compare predicted and observed cluster counts as a function of the one-dimensional velocity dispersion of the cluster galaxies. We argue that the velocity dispersion of groups/clusters can be theoretically predicted as robustly as mass but, unlike mass, it can also be directly observed, thus circumventing the main systematic bias in traditional cluster counts studies. With the aid of the BAHAMAS suite of cosmological hydrodynamical simulations, we demonstrate the potential of the velocity dispersion counts for discriminating even similar $\Lambda$CDM models. These predictions can be compared with the results from existing redshift surveys such as the highly-complete Galaxy And Mass Assembly (GAMA) survey, and upcoming wide-field spectroscopic surveys such as the Wide Area Vista Extragalactic Survey (WAVES) and the Dark Energy Survey Instrument (DESI).Comment: 15 pages, 13 figures. Accepted for publication in MNRAS. New section on cosmological forecasts adde

Why Not the Best? Results From the National Scorecard on U.S. Health System Performance, 2011

Assesses the U.S. healthcare system's average performance in 2007-09 as measured by forty-two indicators of health outcomes, quality, access, efficiency, and equity compared with the 2006 and 2008 scorecards and with domestic and international benchmarks

Organizing the U.S. Health Care Delivery System for High Performance

Analyzes the fragmentation of the healthcare delivery system and makes policy recommendations -- including payment reform, regulatory changes, and infrastructure -- for creating mechanisms to coordinate care across providers and settings

Investigating Heating and Cooling in the BCS & B55 Cluster Samples

We study clusters in the BCS cluster sample which are observed by Chandra and are more distant than redshift, z>0.1. We select from this subsample the clusters which have both a short central cooling time and a central temperature drop, and also those with a central radio source. Six of the clusters have clear bubbles near the centre. We calculate the heating by these bubbles and express it as the ratio r_heat/r_cool=1.34+/-0.20. This result is used to calculate the average size of bubbles expected in all clusters with central radio sources. In three cases the predicted bubble sizes approximately match the observed radio lobe dimensions. We combine this cluster sample with the B55 sample studied in earlier work to increase the total sample size and redshift range. This extended sample contains 71 clusters in the redshift range 0<z<0.4. The average distance out to which the bubbles offset the X-ray cooling in the combined sample is at least r_heat/r_cool=0.92+/-0.11. The distribution of central cooling times for the combined sample shows no clusters with clear bubbles and t_cool>1.2Gyr. An investigation of the evolution of cluster parameters within the redshift range of the combined samples does not show any clear variation with redshift.Comment: 12 pages, 9 figures, accepted for publication in MNRA

Health System Performance for the High-Need Patient: A Look at Access to Care and Patient Care Experiences

Achieving a high-performing health system will require improving outcomes and reducing costs for high-need, high-cost patients—those who use the most health care services and account for a disproportionately large share of health care spending. Goal: To compare the health care experiences of adults with high needs—those with three or more chronic diseases and a functional limitation in the ability to care for themselves or perform routine daily tasks—to all adults and to those with multiple chronic diseases but no functional limitations. Methods: Analysis of data from the 2009–2011 Medical Expenditure Panel Survey. Key findings: High-need adults were more likely to report having an unmet medical need and less likely to report having good patient–provider communication. High-need adults reported roughly similar ease of obtaining specialist referrals as other adults and greater likelihood of having a medical home. While adults with private health insurance reported the fewest unmet needs overall, privately insured highneed adults reported the greatest difficulties having their needs met. Conclusion: The health care system needs to work better for the highest-need, most-complex patients. This study's findings highlight the importance of tailoring interventions to address their need

Advanced tracking systems design and analysis

The results of an assessment of several types of high-accuracy tracking systems proposed to track the spacecraft in the National Aeronautics and Space Administration (NASA) Advanced Tracking and Data Relay Satellite System (ATDRSS) are summarized. Tracking systems based on the use of interferometry and ranging are investigated. For each system, the top-level system design and operations concept are provided. A comparative system assessment is presented in terms of orbit determination performance, ATDRSS impacts, life-cycle cost, and technological risk

Dust-forming molecules in VY Canis Majoris (and Betelgeuse)

The formation of inorganic dust in circumstellar environments of evolved stars is poorly understood. Spectra of molecules thought to be most important for the nucleation, i.e. AlO, TiO, and TiO2, have been recently detected in the red supergiant VY CMa. These molecules are effectively formed in VY CMa and the observations suggest that non-equilibrium chemistry must be involved in their formation and nucleation into dust. In addition to exploring the recent observations of VY CMa, we briefly discuss the possibility of detecting these molecules in the dust-poor circumstellar environment of Betelgeuse.Comment: contribution to Betelgeuse Workshop 2012: "The physics of Red Supergiants: recent advances and open questions", 26-29 Nov 2012 Paris (France

Pure rotational spectra of TiO and TiO_2 in VY Canis Majoris

We report the first detection of pure rotational transitions of TiO and TiO_2 at (sub-)millimeter wavelengths towards the red supergiant VY CMa. A rotational temperature, T_rot, of about 250 K was derived for TiO_2. Although T_rot was not well constrained for TiO, it is likely somewhat higher than that of TiO_2. The detection of the Ti oxides confirms that they are formed in the circumstellar envelopes of cool oxygen-rich stars and may be the "seeds" of inorganic-dust formation, but alternative explanations for our observation of TiO and TiO_2 in the cooler regions of the envelope cannot be ruled out at this time. The observations suggest that a significant fraction of the oxides is not converted to dust, but instead remains in the gas phase throughout the outflow.Comment: to appear in Astronomy and Astrophysic