WISDOM: history and early demise - was it inevitable?

In 1989, the UK Medical Research Council (MRC) agreed that, if feasible, a randomized controlled trial to assess the long-term risks and benefits of hormone replacement therapy (HRT) was a priority. Feasibility work began in 1990 and demonstrated that a large-scale multicenter trial was possible. An application for funding for a main trial was submitted to MRC in 1993 and, after extensive review, funding was released in late 1996. Set-up work for the trial - the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) - began in 1997 with recruitment in 1999. In October 2002, following the early discontinuation of one arm of the US Women's Health Initiative HRT trial, the MRC decided to stop the WISDOM trial. This article, by the principal UK investigators of WISDOM, sets out the background and history of the trial

The RMS Survey: Far-Infrared Photometry of Young Massive Stars

Context: The Red MSX Source (RMS) survey is a multi-wavelength campaign of follow-up observations of a colour-selected sample of candidate massive young stellar objects (MYSOs) in the galactic plane. This survey is returning the largest well-selected sample of MYSOs to date, while identifying other dust contaminant sources with similar mid-infrared colours including a large number of new ultra-compact (UC)HII regions. Aims:To measure the far-infrared (IR) flux, which lies near the peak of the spectral energy distribution (SED) of MYSOs and UCHII regions, so that, together with distance information, the luminosity of these sources can be obtained. Methods:Less than 50% of RMS sources are associated with IRAS point sources with detections at 60 micron and 100 micron, though the vast majority are visible in Spitzer MIPSGAL or IRAS Galaxy Atlas (IGA) images. However, standard aperture photometry is not appropriate for these data due to crowding of sources and strong spatially variable far-IR background emission in the galactic plane. A new technique using a 2-dimensional fit to the background in an annulus around each source is therefore used to obtain far-IR photometry for young RMS sources. Results:Far-IR fluxes are obtained for a total of 1113 RMS candidates identified as young sources. Of these 734 have flux measurements using IGA 60 micron and 100 micron images and 724 using MIPSGAL 70 micron images, with 345 having measurements in both data sets.Comment: 10 pages, 10 figures, 2 Tables, accepted to A&A. A full version of table 1 is available from the lead author or at the CDS upon publicatio

Spectacle lens fabrication in an optometric practice

Recently many of our classmates have asked questions concerning the actual set-up of an ophthalmic lens fabrication lab in an optometric practice. Our colleagues and peers not only want to know about feasibility, investment, space, equipment, and prices, but also how to perform the actual process of spectacle making. As graduating optometrists some of our classmates will enter into an association with an older established optometrist and some will go into solo practice. In either case one of their duties may be doing the actual lab work in spectacle fabrication. This is very common practice in the current optometric community. As more and more optometrists become involved with lab work, the need for a manual of this type is obvious. A literature search proved fruitless in obtaining any source that covers the breadth and scope of the edging process in its entirety. Optometric and optician\u27s publications sometimes deal with various aspects of the spectacle fabrication process, but we have found these to be too general and in the style of an overview or snapshot . We were unable to find any source containing the actual mechanisms involved. A previous research project involved a video tape of the edging process from a local laboratory, and was aimed toward explaining how the edging process is accomplished. We feel that the tape was good in that it oriented the viewer as to how this is done . However, the thrust of our project is to explain, step-by-step, how to edge lenses in an optometric office. The manual will be written from the perspective of How to do it , rather than how it is done . To our knowledge, this work will be the first of its kind, and will represent a compilation of technical information obtained from manufacturers of laboratory equipment, combined with textbook information, and original writings based on our training and experience as laboratory 1 opticians. The authors do not intend this manual to be a statement saying that professional optometrists should spend their time edging lenses. To the contrary, we feel that the optometrist should spend his/her time doing what he/she was trained to do, that is, providing vision care. If however, a spectacle fabrication lab is to be incorporated into an optometric practice, two things are necessary. First, the optometrist needs to know the processes involved as well as the equipment required in order to set up the lab. Second, he/she needs a working knowledge of the basic mechanics and procedures involved, in order to train personnel if necessary

Bimodal Fluorescence-Magnetic Resonance Contrast Agent for Apoptosis Imaging

Effective cancer therapy largely depends on inducing apoptosis in cancer cells via chemotherapy and/or radiation. Monitoring apoptosis in real-time provides invaluable information for evaluating cancer therapy response and screening preclinical anticancer drugs. In this work, we describe the design, synthesis, characterization, and in vitro evaluation of caspase probe 1 (CP1), a bimodal fluorescence-magnetic resonance (FL-MR) probe that exhibits simultaneous FL-MR turn-on response to caspase-3/7. Both caspases exist as inactive zymogens in normal cells but are activated during apoptosis and are unique biomarkers for this process. CP1 has three distinct components: a DOTA-Gd­(III) chelate that provides the MR signal enhancement, tetraphenylethylene as the aggregation induced emission luminogen (AIEgen), and DEVD peptide which is a substrate for caspase-3/7. In response to caspase-3/7, the water-soluble peptide DEVD is cleaved and the remaining Gd­(III)-AIEgen (Gad-AIE) conjugate aggregates leading to increased FL-MR signals. CP1 exhibited sensitive and selective dual FL-MR turn-on response to caspase-3/7 in vitro and was successfully tested by fluorescence imaging of apoptotic cells. Remarkably, we were able to use the FL response of CP1 to quantify the exact concentrations of inactive and active agents and accurately predict the MR signal in vitro. We have demonstrated that the aggregation-driven FL-MR probe design is a unique method for MR signal quantification. This probe design platform can be adapted for a variety of different imaging targets, opening new and exciting avenues for multimodal molecular imaging

Long-Lived Neutralino NLSPs

We investigate the collider signatures of heavy, long-lived, neutral particles that decay to charged particles plus missing energy. Specifically, we focus on the case of a neutralino NLSP decaying to Z and gravitino within the context of General Gauge Mediation. We show that a combination of searches using the inner detector and the muon spectrometer yields a wide range of potential early LHC discoveries for NLSP lifetimes ranging from 10^(-1)-10^5 mm. We further show that events from Z(l+l-) can be used for detailed kinematic reconstruction, leading to accurate determinations of the neutralino mass and lifetime. In particular, we examine the prospects for detailed event study at ATLAS using the ECAL (making use of its timing and pointing capabilities) together with the TRT, or using the muon spectrometer alone. Finally, we also demonstrate that there is a region in parameter space where the Tevatron could potentially discover new physics in the delayed Z(l+l-)+MET channel. While our discussion centers on gauge mediation, many of the results apply to any scenario with a long-lived neutral particle decaying to charged particles.Comment: 31 pages, 12 figure

General Neutralino NLSPs at the Early LHC

Gauge mediated supersymmetry breaking (GMSB) is a theoretically well-motivated framework with rich and varied collider phenomenology. In this paper, we study the Tevatron limits and LHC discovery potential for a wide class of GMSB scenarios in which the next-to-lightest superpartner (NLSP) is a promptly-decaying neutralino. These scenarios give rise to signatures involving hard photons, $W$'s, $Z$'s, jets and/or higgses, plus missing energy. In order to characterize these signatures, we define a small number of minimal spectra, in the context of General Gauge Mediation, which are parameterized by the mass of the NLSP and the gluino. Using these minimal spectra, we determine the most promising discovery channels for general neutralino NLSPs. We find that the 2010 dataset can already cover new ground with strong production for all NLSP types. With the upcoming 2011-2012 dataset, we find that the LHC will also have sensitivity to direct electroweak production of neutralino NLSPs.Comment: 26 page

A Pyramid Scheme for Particle Physics

We introduce a new model, the Pyramid Scheme, of direct mediation of SUSY breaking, which is compatible with the idea of Cosmological SUSY Breaking (CSB). It uses the trinification scheme of grand unification and avoids problems with Landau poles in standard model gauge couplings. It also avoids problems, which have recently come to light, associated with rapid stellar cooling due to emission of the pseudo Nambu-Goldstone Boson (PNGB) of spontaneously broken hidden sector baryon number. With a certain pattern of R-symmetry breaking masses, a pattern more or less required by CSB, the Pyramid Scheme leads to a dark matter candidate that decays predominantly into leptons, with cross sections compatible with a variety of recent observations. The dark matter particle is not a thermal WIMP but a particle with new strong interactions, produced in the late decay of some other scalar, perhaps the superpartner of the QCD axion, with a reheat temperature in the TeV range. This is compatible with a variety of scenarios for baryogenesis, including some novel ones which exploit specific features of the Pyramid Scheme.Comment: JHEP Latex, 32 pages, 1 figur

Embedded Star Formation in the Eagle Nebula with Spitzer/GLIMPSE

We present new Spitzer photometry of the Eagle Nebula (M16, containing the optical cluster NGC 6611) combined with near-infrared photometry from 2MASS. We use dust radiative transfer models, mid-infrared and near-infrared color-color analysis, and mid-infrared spectral indices to analyze point source spectral energy distributions, select candidate young stellar objects (YSOs), and constrain their mass and evolutionary state. Comparison of the different protostellar selection methods shows that mid-infrared methods are consistent, but as has been known for some time, near-infrared-only analysis misses some young objects. We reveal more than 400 protostellar candidates, including one massive young stellar object (YSO) that has not been previously highlighted. The YSO distribution supports a picture of distributed low-level star formation, with no strong evidence of triggered star formation in the ``pillars''. We confirm the youth of NGC 6611 by a large fraction of infrared-excess sources, and reveal a younger cluster of YSOs in the nearby molecular cloud. Analysis of the YSO clustering properties shows a possible imprint of the molecular cloud's Jeans length. Multiwavelength mid-IR imaging thus allows us to analyze the protostellar population, to measure the dust temperature and column density, and to relate these in a consistent picture of star formation in M16.Comment: 16p preprint - ApJ accepte

The Status of GMSB After 1/fb at the LHC

We thoroughly investigate the current status of supersymmetry in light of the latest searches at the LHC, using General Gauge Mediation (GGM) as a well-motivated signature generator that leads to many different simplified models. We consider all possible promptly-decaying NLSPs in GGM, and by carefully reinterpreting the existing LHC searches, we derive limits on both colored and electroweak SUSY production. Overall, the coverage of GGM parameter space is quite good, but much discovery potential still remains even at 7 TeV. We identify several regions of parameter space where the current searches are the weakest, typically in models with electroweak production, third generation sfermions or squeezed spectra, and we suggest how ATLAS and CMS might modify their search strategies given the understanding of GMSB at 1/fb. In particular, we propose the use of leptonic $M_{T2}$ to suppress $t{\bar t}$ backgrounds. Because we express our results in terms of simplified models, they have broader applicability beyond the GGM framework, and give a global view of the current LHC reach. Our results on 3rd generation squark NLSPs in particular can be viewed as setting direct limits on naturalness.Comment: 44 pages, refs added, typos fixed, improved MC statistics in fig 1

Methods for delivering the UK's multi-centre prison-based naloxone-on-release pilot randomised trial (N-ALIVE): Europe's largest prison-based randomised controlled trial

INTRODUCTION AND AIMS: Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin use by injection have a high risk of drug-related death in the first weeks after prison-release. The N-ALIVE trial was planned as a large prison-based randomised controlled trial (RCT) to test the effectiveness of naloxone-on-release in the prevention of fatal opiate overdoses soon after release. The N-ALIVE pilot trial was conducted to test the main trial's assumptions on recruitment of prisons and prisoners, and the logistics for ensuring that participants received their N-ALIVE pack on release. DESIGN AND METHODS: Adult prisoners who had ever injected heroin, were incarcerated for ≥7 days and were expected to be released within 3 months were eligible. Participants were randomised to receive, on liberation, a pack containing a single 'rescue' injection of naloxone or a control pack with no naloxone syringe. The trial was double-blind prior to prison-release. RESULTS: We randomised 1685 prisoners (842 naloxone; 843 control) across 16 prisons in England. We stopped randomisation on 8 December 2014 because only one-third of administrations of naloxone-on-release were to the randomised ex-prisoner; two-thirds were to others whom we were not tracing. DISCUSSION AND CONCLUSIONS: Prevention RCTs are seldom conducted within prisons; we demonstrated the feasibility of conducting a multi-prison RCT to prevent fatality from opioid overdose in the outside community. We terminated the N-ALIVE trial due to the infeasibility of individualised randomisation to naloxone-on-release. Large RCTs are feasible within prisons