Proportion of Osteoporotic Women Remaining at Risk for Fracture Despite Adherence to Oral Bisphosphonates

Background Adherence to oral bisphosphonates is often low, but even adherent patients may remain at elevated fracture risk. The goal of this study was to estimate the proportion of bisphosphonate-adherent women remaining at high risk of fracture. Methods A retrospective cohort of women aged 50 years and older, adherent to oral bisphosphonates for at least two years was identified, and data were extracted from a multi-system health information exchange. Adherence was defined as having a dispensed medication possession ratio ≥ 0.8. The primary outcome was clinical occurrence of: low trauma fracture (months 7–36), persistent T-score ≤ − 2.5 (months 13–36), decrease in bone mineral density (BMD) at any skeletal site ≥ 5%, or the composite of any one of these outcomes. Results Of 7435 adherent women, 3110 had either pre- or post-adherent DXA data. In the full cohort, 7% had an incident osteoporotic fracture. In 601 women having both pre- and post-adherent DXA to evaluate BMD change, 6% had fractures, 22% had a post-treatment T-score ≤ − 2.5, and 16% had BMD decrease by ≥ 5%. The composite outcomes occurred in 35%. Incident fracture was predicted by age, previous fracture, and a variety of co-morbidities, but not by race, glucocorticoid treatment or type of bisphosphonate. Conclusion Despite bisphosphonate adherence, 7% had incident osteoporotic fractures and 35% had either fracture, decreases in BMD, or persistent osteoporotic BMD, representing a substantial proportion of treated patients in clinical practices remaining at risk for future fractures. Further studies are required to determine the best achievable goals for osteoporosis therapy, and which patients would benefit from alternate therapies

Exome sequencing: the sweet spot before whole genomes

The development of massively parallel sequencing technologies, coupled with new massively parallel DNA enrichment technologies (genomic capture), has allowed the sequencing of targeted regions of the human genome in rapidly increasing numbers of samples. Genomic capture can target specific areas in the genome, including genes of interest and linkage regions, but this limits the study to what is already known. Exome capture allows an unbiased investigation of the complete protein-coding regions in the genome. Researchers can use exome capture to focus on a critical part of the human genome, allowing larger numbers of samples than are currently practical with whole-genome sequencing. In this review, we briefly describe some of the methodologies currently used for genomic and exome capture and highlight recent applications of this technology

Public opinion on energy crops in the landscape: considerations for the expansion of renewable energy from biomass

Public attitudes were assessed towards two dedicated biomass crops – Miscanthus and Short Rotation Coppice (SRC), particularly regarding their visual impacts in the landscape. Results are based on responses to photographic and computer-generated images as the crops are still relatively scarce in the landscape. A questionnaire survey indicated little public concern about potential landscape aesthetics but more concern about attendant built infrastructure. Focus group meetings and interviews indicated support for biomass end uses that bring direct benefits to local communities. Questions arise as to how well the imagery used was able to portray the true nature of these tall, dense, perennial plants but based on the responses obtained and given the caveat that there was limited personal experience of the crops, it appears unlikely that wide-scale planting of biomass crops will give rise to substantial public concern in relation to their visual impact in the landscape

Pain Squad+ smartphone app to support real-time pain treatment for adolescents with cancer: protocol for a randomised controlled trial.

INTRODUCTION: Pain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes. METHODS AND ANALYSIS: This will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 1:1:1 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are significant comorbidities, end-of-life status or enrolment in a concurrent pain study. The primary aim is to determine the effect of Pain Squad+, with and without nurse support, on pain intensity in adolescents with cancer, when compared with a waitlist control group. The secondary aims are to determine the immediate and sustained effect over time of using Pain Squad+, with and without nurse support, as per prospective outcome measurements of pain interference, HRQL, pain self-efficacy and cost. Linear mixed models with baseline scores as a covariate will be used. Qualitative interviews with adolescents from all trial arms will be conducted and analysed. ETHICS AND DISSEMINATION: This trial is approved by the Hospital for Sick Children Research Ethics Board. Results will provide data to guide adolescents with cancer and healthcare teams in treating pain. Dissemination will occur through partnerships with stakeholder groups, scientific meetings, publications, mass media releases and consumer detailing. TRIAL REGISTRATION NUMBER: NCT03632343

Discovery of Pulsed γ\gamma-rays from PSR J0034-0534 with the Fermi LAT: A Case for Co-located Radio and γ\gamma-ray Emission Regions

Millisecond pulsars (MSPs) have been firmly established as a class of gamma-ray emitters via the detection of pulsations above 0.1 GeV from eight MSPs by the Fermi Large Area Telescope (LAT). Using thirteen months of LAT data significant gamma-ray pulsations at the radio period have been detected from the MSP PSR J0034-0534, making it the ninth clear MSP detection by the LAT. The gamma-ray light curve shows two peaks separated by 0.274$\pm$0.015 in phase which are very nearly aligned with the radio peaks, a phenomenon seen only in the Crab pulsar until now. The $\geq$0.1 GeV spectrum of this pulsar is well fit by an exponentially cutoff power law with a cutoff energy of 1.8$\pm 0.6\pm$0.1 GeV and a photon index of 1.5$\pm 0.2\pm$0.1, first errors are statistical and second are systematic. The near-alignment of the radio and gamma-ray peaks strongly suggests that the radio and gamma-ray emission regions are co-located and both are the result of caustic formation.Comment: 20 pages, 3 figures, 2 tables. Accepted for publication in Ap

Fermi Large Area Telescope Observations of the Crab Pulsar and Nebula

We report on gamma-ray observations of the Crab Pulsar and Nebula using 8 months of survey data with the Fermi Large Area Telescope (LAT). The high quality light curve obtained using the ephemeris provided by the Nancay and Jodrell Bank radio telescopes shows two main peaks stable in phase with energy. The first gamma-ray peak leads the radio main pulse by (281 \pm 12 \pm 21) mus, giving new constraints on the production site of non-thermal emission in pulsar magnetospheres. The improved sensitivity and the unprecedented statistics afforded by the LAT enable precise measurement of the Crab Pulsar spectral parameters: cut-off energy at E_c = (5.8 \pm 0.5 \pm 1.2) GeV, spectral index of Gamma = (1.97 \pm 0.02 \pm 0.06) and integral photon flux above 100 MeV of (2.09 \pm 0.03 \pm 0.18) x 10^{-6} cm^{-2} s^{-1}. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Pulsed gamma-ray photons are observed up to ~ 20 GeV which precludes emission near the stellar surface, below altitudes of around 4 to 5 stellar radii in phase intervals encompassing the two main peaks. The spectrum of the nebula in the energy range 100 MeV - 300 GeV is well described by the sum of two power-laws of indices Gamma_{sync} = (3.99 \pm 0.12 \pm 0.08) and Gamma_{IC} = (1.64 \pm 0.05 \pm 0.07), corresponding to the falling edge of the synchrotron and the rising edge of the inverse Compton components, respectively. This latter, which links up naturally with the spectral data points of Cherenkov experiments, is well reproduced via inverse Compton scattering from standard Magnetohydrodynamics (MHD) nebula models, and does not require any additional radiation mechanism.Comment: 17 pages, 9 figures, Accepted for publications in Astrophysical Journa

PSR J1907+0602: A Radio-Faint Gamma-Ray Pulsar Powering a Bright TeV Pulsar Wind Nebula

We present multiwavelength studies of the 106.6 ms gamma-ray pulsar PSR J1907+06 near the TeV source MGRO J1908+06. Timing observations with Fermi result in a precise position determination for the pulsar of R.A. = 19h07m547(2), decl. = +06:02:16(2) placing the pulsar firmly within the TeV source extent, suggesting the TeV source is the pulsar wind nebula of PSR J1907+0602. Pulsed gamma-ray emission is clearly visible at energies from 100 MeV to above 10 GeV. The phase-averaged power-law index in the energy range E > 0.1 GeV is = 1.76 \pm 0.05 with an exponential cutoff energy E_{c} = 3.6 \pm 0.5 GeV. We present the energy-dependent gamma-ray pulsed light curve as well as limits on off-pulse emission associated with the TeV source. We also report the detection of very faint (flux density of ~3.4 microJy) radio pulsations with the Arecibo telescope at 1.5 GHz having a dispersion measure DM = 82.1 \pm 1.1 cm^{-3}pc. This indicates a distance of 3.2 \pm 0.6 kpc and a pseudo-luminosity of L_{1400} ~ 0.035 mJy kpc^2. A Chandra ACIS observation revealed an absorbed, possibly extended, compact <(4 arcsec) X-ray source with significant non-thermal emission at R.A. = 19h07m54.76, decl. = +06:02:14.6 with a flux of 2.3^{+0.6}_{-1.4} X 10^{-14} erg cm^{-2} s^{-1}. From archival ASCA observations, we place upper limits on any arcminute scale 2--10 keV X-ray emission of ~ 1 X 10^{-13} erg cm^{-2} s^{-1}. The implied distance to the pulsar is compatible with that of the supernova remnant G40.5-0.5, located on the far side of the TeV nebula from PSR J1907+0602, and the S74 molecular cloud on the nearer side which we discuss as potential birth sites

Fermi Large Area Telescope observations of the Vela-X Pulsar Wind Nebula

We report on gamma-ray observations in the off-pulse window of the Vela pulsar PSR B0833-45, using 11 months of survey data from the Fermi Large Area Telescope (LAT). This pulsar is located in the 8 degree diameter Vela supernova remnant, which contains several regions of non-thermal emission detected in the radio, X-ray and gamma-ray bands. The gamma-ray emission detected by the LAT lies within one of these regions, the 2*3 degrees area south of the pulsar known as Vela-X. The LAT flux is signicantly spatially extended with a best-fit radius of 0.88 +/- 0.12 degrees for an assumed radially symmetric uniform disk. The 200 MeV to 20 GeV LAT spectrum of this source is well described by a power-law with a spectral index of 2.41 +/- 0.09 +/- 0.15 and integral flux above 100 MeV of (4.73 +/- 0.63 +/- 1.32) * 10^{-7} cm^{-2} s^{-1}. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Detailed morphological and spectral analyses give strong constraints on the energetics and magnetic field of the pulsar wind nebula (PWN) system and favor a scenario with two distinct electron populations.Comment: 21 pages, 5 figures, accepted for publication in Astrophysical Journa