Doctors at Risk: A Problem As Viewed by Decision Analysis

The authors closely analyze a case in which a Peer Review Organization cited a physician for treatment with potential for significant adverse effect. They also critique the regulatory scheme under which peer review occurs and conclude that such regulation interferes with physicians\u27 primary obligations, fails to encourage cost-effective behavior and may decrease the quality of medical care

Glacial and Postglacial Deposits of Northeastern Ohio

Author Institution: Department of Geology, University of AkronRecent high levels of Lake Erie have produced severe erosion and mass wasting along the shore. At the same time they have created excellent exposures of glacial and postglacial deposits east of Cleveland, Ohio. Glacial deposits consist of an older Coastal till and the Late Wisconsinan Ashtabula Till, whereas postglacial deposits generally are gravels, sands and silts. Lithofacies of the Ashtabula Till exposed at Sims Park in Euclid, Ohio, include sheared, massive diamicts and resedimented diamicts. The lowest sheared massive diamict previously identified as the Coastal till possibly represents a lodgement till deposited by Ashtabula ice. Beach deposits at Mentor Headlands resulted from construction of manmade structures. At Camp Isaac Jogues, deltaic sands overlie a sequence of diamicts, which has an unusually high carbonate content when compared to other sections along the shore. The geometry of the overlying sands and the facies sequence strongly suggest a river-dominated deltaic system. Two sand pits in beach ridges (one at the Warren level and the other at the Arkona level) farther inland contain coarse-grained facies that may represent an outwash plain or coastal barrier overlain by dune sand. A log dated at 13-4 ka was found at the Arkona level, 1 km south of the second pit

A 3D in vitro model of the human breast duct:A method to unravel myoepithelial-luminal interactions in the progression of breast cancer

Abstract Background 3D modelling fulfils a critical role in research, allowing for complex cell behaviour and interactions to be studied in physiomimetic conditions. With tissue banks becoming established for a number of cancers, researchers now have access to primary patient cells, providing the perfect building blocks to recreate and interrogate intricate cellular systems in the laboratory. The ducts of the human breast are composed of an inner layer of luminal cells supported by an outer layer of myoepithelial cells. In early-stage ductal carcinoma in situ, cancerous luminal cells are confined to the ductal space by an intact myoepithelial layer. Understanding the relationship between myoepithelial and luminal cells in the development of cancer is critical for the development of new therapies and prognostic markers. This requires the generation of new models that allows for the manipulation of these two cell types in a physiological setting. Methods Using access to the Breast Cancer Now Tissue Bank, we isolated pure populations of myoepithelial and luminal cells from human reduction mammoplasty specimens and placed them into 2D culture. These cells were infected with lentiviral particles encoding either fluorescent proteins, to facilitate cell tracking, or an inducible human epidermal growth factor receptor 2 (HER2) expression construct. Myoepithelial and luminal cells were then recombined in collagen gels, and the resulting cellular structures were analysed by confocal microscopy. Results Myoepithelial and luminal cells isolated from reduction mammoplasty specimens can be grown separately in 2D culture and retain their differentiated state. When recombined in collagen gels, these cells reform into physiologically reflective bilayer structures. Inducible expression of HER2 in the luminal compartment, once the bilayer has formed, leads to robust luminal filling, recapitulating ductal carcinoma in situ, and can be blocked with anti-HER2 therapies. Conclusions This model allows for the interaction between myoepithelial and luminal cells to be investigated in an in-vitro environment and paves the way to study early events in breast cancer development with the potential to act as a powerful drug discovery platform

Rotating traversable wormholes

The general form of a stationary, axially symmetric traversable wormhole is discussed. This provides an explicit class of rotating wormholes that generalize the static, spherically symmetric ones first considered by Morris and Thorne. In agreement with general analyses, it is verified that such a wormhole generically violates the null energy condition at the throat. However, for suitable model wormholes, there can be classes of geodesics falling through it which do not encounter any energy-condition-violating matter. The possible presence of an ergoregion surrounding the throat is also noted.Comment: 15 pages, harvmac; 1 figure in PicTeX; minor changes; to appear in Phys. Rev.

Particle swarming of sensor correction filters

Reducing the impact of seismic activity on the motion of suspended optics is essential for the operation of ground-based gravitational wave detectors. During periods of increased seismic activity, low-frequency ground translation and tilt cause the Advanced LIGO observatories to lose 'lock', reducing their duty cycles. This paper applies modern global-optimisation algorithms to aid in the design of the 'sensor correction' filter, used in the control of the active platforms. It is shown that a particle swarm algorithm that minimises a cost-function approximating the differential root mean squared velocity between platforms can produce control filters that perform better across most frequencies in the control bandwidth than those currently installed. These tests were conducted using training data from the LIGO Hanford Observatory seismic instruments and simulations of the Horizontal Access Module Internal Seismic Isolation platforms. These results show that new methods of producing control filters are ready for use at LIGO. The filters were implemented at LIGO's Hanford Observatory, and use the resulting data to refine the cost function. © 2020 IOP Publishing Ltd Printed in the U

Invited Article: First flight in space of a wide-field-of-view soft x-ray imager using lobster-eye optics: Instrument description and initial flight results

We describe the development, launch into space, and initial results from a prototype wide field-of-view soft X-ray imager that employs lobster-eye optics and targets heliophysics, planetary, and astrophysics science. The sheath transport observer for the redistribution of mass is the first instrument using this type of optics launched into space and provides proof-of-concept for future flight instruments capable of imaging structures such as the terrestrial cusp, the entire dayside magnetosheath from outside the magnetosphere, comets, the Moon, and the solar wind interaction with planetary bodies like Venus and Mars [Kuntz et al., Astrophys. J. (in press)]

Holographic Protection of Chronology in Universes of the Godel Type

We analyze the structure of supersymmetric Godel-like cosmological solutions of string theory. Just as the original four-dimensional Godel universe, these solutions represent rotating, topologically trivial cosmologies with a homogeneous metric and closed timelike curves. First we focus on "phenomenological" aspects of holography, and identify the preferred holographic screens associated with inertial comoving observers in Godel universes. We find that holography can serve as a chronology protection agency: The closed timelike curves are either hidden behind the holographic screen, or broken by it into causal pieces. In fact, holography in Godel universes has many features in common with de Sitter space, suggesting that Godel universes could represent a supersymmetric laboratory for addressing the conceptual puzzles of de Sitter holography. Then we initiate the investigation of "microscopic" aspects of holography of Godel universes in string theory. We show that Godel universes are T-dual to pp-waves, and use this fact to generate new Godel-like solutions of string and M-theory by T-dualizing known supersymmetric pp-wave solutions.Comment: 35 pages, 5 figures. v2: typos corrected, references adde

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

Population genomics of domestic and wild yeasts

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation