A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation.

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript. These findings provide hypotheses to explain some of the phenotypic characteristics of Tskl + mice and the lethality of Tsk/Tsk embryos

Extraosseous Osteosarcoma of the Esophagus: A Case Report

Extraosseous osteosarcoma (EOO) is a malignant mesenchymal neoplasm that is located in the soft tissues without direct attachment to the skeletal system and that produces osteoid, bone, or chondroid material. EOO is an extremely rare disease, accounting for only 1% of soft tissue sarcomas, and typically presents in either an extremity or the retroperitoneum. This paper presents the case of a 45-year-old Caucasian male with extraosseous osteosarcoma of the esophagus

Study of UV Degradation on Plastic (PET) Aerosols

The present study was aimed to explore the impact of UV radiation, from ‘real world’ environmental exposure, on the degradation of plastic PET aerosol containers. Additionally, the intent was to correlate the ‘real world’ environmental exposure to artificial sunlight, using a Xenon-Arc lamp, to develop a simulated test. The standardized methodology could then be used to evaluate the integrity of the plastic aerosol container and product, without the complexity of using ‘real world’ exposure. Through this study, a lab method was developed and validated that would simulate the effect of UV radiation using the Xenon-Arc. Moreover, a correlation was made for conditions inside the Xenon-Arc chamber that were conducive to testing a plastic pressurized container

Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN

Holding and restraining children for clinical procedures within an acute care setting: an ethical consideration of the evidence

This critical reflection on the ethical concerns of current practice is underpinned by a systematic synthesis of current evidence focusing on why and how children are held or restrained for clinical procedures within acute care and the experiences of those present when a child is held against their wishes. Empirical evidence from a range of clinical settings internationally demonstrates that frequently children are held for procedures to be completed; younger children and those requiring procedures perceived as urgent are more likely to be held. Parents and health professionals express how holding children for procedures can cause feelings of moral distress expressed as uncertainty, guilt and upset and that this act breaches the trusting and protective relationship established with children. Despite this, children’s rights and alternatives to holding are not always respected or explored. Children’s experiences and perceptions are absent from current literature. Children and young people have a moral right to have their voice and protests heard and respected and for these to inform judgements of their best interests and the actions of health professionals. Without robust evidence, debate and recognition that children are frequently held against their wishes in clinical practice for procedures which may not be urgent, children’s rights will continue to be compromised

A CANDELS WFC3 Grism Study of Emission-Line Galaxies at z~2: A Mix of Nuclear Activity and Low-Metallicity Star Formation

We present Hubble Space Telescope Wide Field Camera 3 slitless grism spectroscopy of 28 emission-line galaxies at z~2, in the GOODS-S region of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). The high sensitivity of these grism observations, with 1-sigma detections of emission lines to f > 2.5x10^{-18} erg/s/cm^2, means that the galaxies in the sample are typically ~7 times less massive (median M_* = 10^{9.5} M_sun) than previously studied z~2 emission-line galaxies. Despite their lower mass, the galaxies have OIII/Hb ratios which are very similar to previously studied z~2 galaxies and much higher than the typical emission-line ratios of local galaxies. The WFC3 grism allows for unique studies of spatial gradients in emission lines, and we stack the two-dimensional spectra of the galaxies for this purpose. In the stacked data the OIII emission line is more spatially concentrated than the Hb emission line with 98.1 confidence. We additionally stack the X-ray data (all sources are individually undetected), and find that the average L(OIII)/L(0.5-10 keV) ratio is intermediate between typical z~0 obscured active galaxies and star-forming galaxies. Together the compactness of the stacked OIII spatial profile and the stacked X-ray data suggest that at least some of these low-mass, low-metallicity galaxies harbor weak active galactic nuclei.Comment: ApJ accepted. 8 pages, 6 figure

Extreme Emission Line Galaxies in CANDELS: Broad-Band Selected, Star-Bursting Dwarf Galaxies at z>1

We identify an abundant population of extreme emission line galaxies (EELGs) at redshift z~1.7 in the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS) imaging from Hubble Space Telescope/Wide Field Camera 3 (HST/WFC3). 69 EELG candidates are selected by the large contribution of exceptionally bright emission lines to their near-infrared broad-band magnitudes. Supported by spectroscopic confirmation of strong [OIII] emission lines -- with rest-frame equivalent widths ~1000\AA -- in the four candidates that have HST/WFC3 grism observations, we conclude that these objects are galaxies with 10^8 Msol in stellar mass, undergoing an enormous starburst phase with M_*/(dM_*/dt) of only ~15 Myr. These bursts may cause outflows that are strong enough to produce cored dark matter profiles in low-mass galaxies. The individual star formation rates and the co-moving number density (3.7x10^-4 Mpc^-3) can produce in ~4 Gyr much of the stellar mass density that is presently contained in 10^8-10^9 Msol dwarf galaxies. Therefore, our observations provide a strong indication that many or even most of the stars in present-day dwarf galaxies formed in strong, short-lived bursts, mostly at z>1.Comment: accepted for publication in ApJ; 10 pages; 6 figures; 1 tabl

Unfolding the recipes for conflict resolution during the new service development effort

The management of conflicts that emerge during new service development (NSD) has escaped the attention of scholars. Yet differing conflict management styles (CMS) of team members and dynamics within the team create a complex managerial challenge. Additionally, the broader literature on conflict resolution shows contradictory findings preventing a clear roadmap for practitioner use when such conflicts emerge. This study draws on complexity theory and employs fuzzy set Qualitative Comparative Analysis, drawing on data from 543 members of 116 NSD projects, to unravel conflict resolution recipes. The results reveal, in detail, the variety of causal patterns that explain the linkages between individual CMS, the dynamics of the team and two critical conflict characteristics; conflict intensity and frequency. Implications for theory and practice are identified and discussed

CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey - The Hubble Space Telescope Observations, Imaging Data Products and Mosaics

This paper describes the Hubble Space Telescope imaging data products and data reduction procedures for the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS). This survey is designed to document the evolution of galaxies and black holes at $z\sim1.5-8$, and to study Type Ia SNe beyond $z>1.5$. Five premier multi-wavelength sky regions are selected, each with extensive multiwavelength observations. The primary CANDELS data consist of imaging obtained in the Wide Field Camera 3 / infrared channel (WFC3/IR) and UVIS channel, along with the Advanced Camera for Surveys (ACS). The CANDELS/Deep survey covers \sim125 square arcminutes within GOODS-N and GOODS-S, while the remainder consists of the CANDELS/Wide survey, achieving a total of \sim800 square arcminutes across GOODS and three additional fields (EGS, COSMOS, and UDS). We summarize the observational aspects of the survey as motivated by the scientific goals and present a detailed description of the data reduction procedures and products from the survey. Our data reduction methods utilize the most up to date calibration files and image combination procedures. We have paid special attention to correcting a range of instrumental effects, including CTE degradation for ACS, removal of electronic bias-striping present in ACS data after SM4, and persistence effects and other artifacts in WFC3/IR. For each field, we release mosaics for individual epochs and eventual mosaics containing data from all epochs combined, to facilitate photometric variability studies and the deepest possible photometry. A more detailed overview of the science goals and observational design of the survey are presented in a companion paper.Comment: 39 pages, 25 figure

CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey

The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) is designed to document the first third of galactic evolution, over the approximate redshift (z) range 8--1.5. It will image >250,000 distant galaxies using three separate cameras on the Hubble Space Telescope, from the mid-ultraviolet to the near-infrared, and will find and measure Type Ia supernovae at z>1.5 to test their accuracy as standardizable candles for cosmology. Five premier multi-wavelength sky regions are selected, each with extensive ancillary data. The use of five widely separated fields mitigates cosmic variance and yields statistically robust and complete samples of galaxies down to a stellar mass of 10^9 M_\odot to z \approx 2, reaching the knee of the ultraviolet luminosity function (UVLF) of galaxies to z \approx 8. The survey covers approximately 800 arcmin^2 and is divided into two parts. The CANDELS/Deep survey (5\sigma\ point-source limit H=27.7 mag) covers \sim 125 arcmin^2 within GOODS-N and GOODS-S. The CANDELS/Wide survey includes GOODS and three additional fields (EGS, COSMOS, and UDS) and covers the full area to a 5\sigma\ point-source limit of H \gtrsim 27.0 mag. Together with the Hubble Ultra Deep Fields, the strategy creates a three-tiered "wedding cake" approach that has proven efficient for extragalactic surveys. Data from the survey are nonproprietary and are useful for a wide variety of science investigations. In this paper, we describe the basic motivations for the survey, the CANDELS team science goals and the resulting observational requirements, the field selection and geometry, and the observing design. The Hubble data processing and products are described in a companion paper.Comment: Submitted to Astrophysical Journal Supplement Series; Revised version, subsequent to referee repor