First Hubble Space Telescope observations of the brightest stars in the Virgo galaxy M100 = NGC 4321

As part of both the Early Release Observations from the Hubble Space Telescope and the Key Project on the Extragalactic Distance Scale, we have obtained multiwavelength BVR WFPC2 images for the face-on Virgo cluster spiral galaxy M100 = NGC 4321. We report here preliminary results from those observations, in the form of a color-magnitude diagram for -11,500 stars down to V ~ 27 mag and a luminosity function for the brightest blue stars which is found to have a slope of 0.7, in excellent agreement with previous results obtained for significantly nearer galaxies. With the increased resolution now available using WFPC2, the number of galaxies in which we can directly measure Population I stars and thereby quantify the recent evolution, as well as test stellar evolution theory, has dramatically increased by at least a factor of 100. Finally, we find that stars are present in M100 at the colors and luminosities expected for the brightest Cepheid variables in galaxies

Science with the Second Wide Field and Planetary Camera

With the commencement of Cycle 4 observations, the General Observer community will have access to the second Wide Field and Planetary Camera (WFPC-2), a replacement for the original WFPC instrument. WFPC-2, a wide-field photometric camera which covers the spectrum from 1200 to 10000 Angstroms, will be installed in the Hubble radial bay during the currently manifested December 1992 Shuttle servicing mission. Besides optical correction for the aberrated Hubble primary mirror, the WFPC-2 incorporates evolutionary improvements in photometric imaging capabilities. The CCD sensors, signal chain electronics, filter set, FUV performance, internal calibrations, and operational efficiency have all been improved through new technologies and lessons learned from WFPC operations and Hubble experience since launch. Here we provide an overview of the new instrument, beginning with the assumption that the reader is already familiar with the original WFPC now in service

Emergent Clinical Issues in Problem Gambling

The "Emergent Clinical Issues in Problem Gambling" conference took place Friday, April 9 & Saturday, April 10, 2010 at The Banff Centre, Banff, Alberta, Canada. Presentation and discussion topics included competing perspectives on etiology and conceptualization of gambling disorders.NoAlberta Gaming Research Institut

BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia

The therapeutic treatment of negative symptoms and cognitive dysfunction associated with schizophrenia is a significant unmet medical need. Preclinical literature indicates that α7 neuronal nicotinic acetylcholine (nACh) receptor agonists may provide an effective approach to treating cognitive dysfunction in schizophrenia. We report herein the discovery and evaluation of <b>1c</b> (BMS-933043), a novel and potent α7 nACh receptor partial agonist with high selectivity against other nicotinic acetylcholine receptor subtypes (>100-fold) and the 5-HT_3A receptor (>300-fold). <i>In vivo</i> activity was demonstrated in a preclinical model of cognitive impairment, mouse novel object recognition. BMS-933043 has completed Phase I clinical trials

Loss of H3K27me3 in meningiomas

BackgroundThere is a critical need for objective and reliable biomarkers of outcome in meningiomas beyond WHO classification. Loss of H3K27me3 has been reported as a prognostically unfavorable alteration in meningiomas. We sought to independently evaluate the reproducibility and prognostic value of H3K27me3 loss by immunohistochemistry (IHC) in a multicenter study.MethodsIHC staining for H3K27me3 and analyses of whole slides from 181 meningiomas across three centers was performed. Staining was analyzed by dichotomization into loss and retained immunoreactivity, and using a 3-tiered scoring system in 151 cases with clear staining. Associations of grouping with outcome were performed using Kaplan-Meier survival estimates.ResultsA total of 21 of 151 tumors (13.9%) demonstrated complete loss of H3K27me3 staining in tumor with retained endothelial staining. Overall, loss of H3K27me3 portended a worse outcome with shorter times to recurrence in our cohort, particularly for WHO grade 2 tumors which were enriched in our study. There were no differences in recurrence-free survival (RFS) for WHO grade 3 patients with retained vs loss of H3K27me3. Scoring by a 3-tiered system did not add further insights into the prognostic value of this H3K27me3 loss. Overall, loss of H3K27me3 was not independently associated with RFS after controlling for WHO grade, extent of resection, sex, age, and recurrence status of tumor on multivariable Cox regression analysis.ConclusionsLoss of H3K27me3 identifies a subset of WHO grade 2 and possibly WHO grade 1 meningiomas with increased recurrence risk. Pooled analyses of a larger cohort of samples with standardized reporting of clinical definitions and staining patterns are warranted

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study

Introduction: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. Methods and analysis: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. Ethics and dissemination: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

International audienceDuring their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100  M⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93  Gpc−3 yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits