Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in ...BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after≥36-month follow-up for all living patients.
This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150mg twice daily) plus trametinib (2mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics.
Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n= 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and<3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use.
These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, ...myocardial infarction, or death (7.2% and 6.8%, respectively; P=0.51). Stroke was more common with carotid-artery stenting than carotid endarterectomy; myocardial infarction was more common with carotid endarterectomy. The 4-year rate of stroke or death was 6.4% for carotid-artery stenting and 4.7% for carotid endarterectomy (P=0.03).
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death (7.2% and 6.8%, respectively).
Carotid-artery atherosclerosis is an important cause of ischemic stroke.
1
Carotid endarterectomy has been established as effective treatment for both symptomatic patients and asymptomatic patients.
2
–
4
Carotid-artery stenting is another option for treatment. The results of randomized trials comparing carotid-artery stenting and carotid endarterectomy for use in symptomatic patients are conflicting.
5
–
7
The primary aim of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) was to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis.
Methods
Study Design
CREST is a randomized, controlled trial with blinded end-point adjudication. Ethics review . . .
The INT/WFC Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg2 imaging survey covering Galactic latitudes |b| < 5° and longitudes ℓ = 30°–215° in the r, i, and Hα filters ...using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel−1) and to a mean 5σ depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r − Hα, r − i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys.
•We model world fossil fuel production by country including unconventional sources.•Four countries, China, USA, Canada and Australia modelled by state/province level.•Three ultimately recouverable ...resources applied, that range from 48.4 to 121.5 ZJ.•Scenarios suggest coal production peaks before 2025 due to China.•Results suggest lack of fossil fuels to deliver high IPCC scenarios: A1Fl, RCP8.5.
Detailed projections of world fossil fuel production including unconventional sources were created by country and fuel type to estimate possible future fossil fuel production. Four critical countries (China, USA, Canada and Australia) were examined in detail with projections made on the state/province level. Ultimately Recoverable Resources (URR) for fossil fuels were estimated for three scenarios: Low=48.4 ZJ, Best Guess (BG)=75.7 ZJ, High=121.5 ZJ. The scenarios were developed using Geologic Resources Supply-Demand Model (GeRS-DeMo). The Low and Best Guess (BG) scenarios suggest that world fossil fuel production may peak before 2025 and decline rapidly thereafter. The High scenario indicates that fossil fuels may have a strong growth till 2025 followed by a plateau lasting approximately 50years before declining. All three scenarios suggest that world coal production may peak before 2025 due to peaking Chinese production and that only natural gas could have strong growth in the future. In addition, by converting the fossil fuel projections to greenhouse gas emissions, the projections were compared to IPCC scenarios which indicated that based on current estimates of URR there are insufficient fossil fuels to deliver the higher emission IPCC scenarios A1Fl and RCP8.5.
We report results of a study of Planck Sunyaev–Zel'dovich effect selected galaxy cluster candidates using the Panoramic Survey Telescope & Rapid Response System (Pan-STARRS) imaging data. We first ...examine 150 Planck-confirmed galaxy clusters with spectroscopic redshifts to test our algorithm for identifying optical counterparts and measuring their redshifts; our redshifts have a typical accuracy of σ
z/(1+z) ∼ 0.022 for this sample. Using 60 random sky locations, we estimate that our chance of contamination through a random superposition is ∼3 per cent. We then examine an additional 237 Planck galaxy cluster candidates that have no redshift in the source catalogue. Of these 237 unconfirmed cluster candidates we are able to confirm 60 galaxy clusters and measure their redshifts. A further 83 candidates are so heavily contaminated by stars due to their location near the Galactic plane that we do not attempt to identify counterparts. For the remaining 94 candidates, we find no optical counterpart but use the depth of the Pan-STARRS1 data to estimate a redshift lower limit
$z_{{\rm lim}(10^{15})}$
beyond which we would not have expected to detect enough galaxies for confirmation. Scaling from the already published Planck sample, we expect that ∼12 of these unconfirmed candidates may be real clusters.
The Blanco Cosmology Survey (BCS) is a 60 night imaging survey of ~80 deg super(2) of the southern sky located in two fields: (alpha, delta) = (5 hr, -55degrees) and (23 hr, -55degrees). The survey ...was carried out between 2005 and 2008 in griz bands with the Mosaic2 imager on the Blanco 4 m telescope. The primary aim of the BCS survey is to provide the data required to optically confirm and measure photometric redshifts for Sunyaev-Zel'dovich effect selected galaxy clusters from the South Pole Telescope and the Atacama Cosmology Telescope. We process and calibrate the BCS data, carrying out point-spread function-corrected model-fitting photometry for all detected objects. The median 10sigma galaxy (point-source) depths over the survey in griz are approximately 23.3 (23.9), 23.4 (24.0), 23.0 (23.6), and 21.3 (22.1), respectively. The astrometric accuracy relative to the USNO-B survey is ~45 mas. We calibrate our absolute photometry using the stellar locus in grizJ bands, and thus our absolute photometric scale derives from the Two Micron All Sky Survey, which has ~2% accuracy. The scatter of stars about the stellar locus indicates a systematic floor in the relative stellar photometric scatter in griz that is ~1.9%, ~2.2%, ~2.7%, and ~2.7%, respectively. A simple cut in the AstrOmatic star-galaxy classifier spread_model produces a star sample with good spatial uniformity. We use the resulting photometric catalogs to calibrate photometric redshifts for the survey and demonstrate scatter deltaz/(1 + z) = 0.054 with an outlier fraction eta < 5% to z ~ 1. We highlight some selected science results to date and provide a full description of the released data products.
The FOCUS smartphone intervention was developed to provide automated real-time/real-place illness management support to individuals with schizophrenia. The system was specifically designed to be ...usable by people with psychotic disorders who may have cognitive impairment, psychotic symptoms, negative symptoms, and/or low reading levels. FOCUS offers users both prescheduled and on-demand resources to facilitate symptom management, mood regulation, medication adherence, social functioning, and improved sleep. In this study, 33 individuals with schizophrenia or schizoaffective disorder used FOCUS over a 1-month period in their own environments. Participants were able to learn how to use the intervention independently, and all but one participant completed the trial successfully and returned the smartphones intact. Completers used the system on 86.5% of days they had the device, an average of 5.2 times a day. Approximately 62% of use of the FOCUS intervention was initiated by the participants, and 38% of use was in response to automated prompts. Baseline levels of cognitive functioning, negative symptoms, persecutory ideation, and reading level were not related to participants' use of the intervention. Approximately 90% of participants rated the intervention as highly acceptable and usable. Paired samples t tests found significant reductions in psychotic symptoms, depression, and general psychopathology, after 1 month of FOCUS use. This study demonstrated the feasibility, acceptability, and preliminary efficacy of the FOCUS intervention for schizophrenia and introduces a new treatment model which has promise for extending the reach of evidence-based care beyond the confines of a physical clinic using widely available technologies.
We present a study of the optical properties of the 26 most massive galaxy clusters within the South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) 2500 deg2 survey spanning the redshift range ...0.10 < z < 1.13. We measure the radial profiles, the luminosity functions (LFs), and the halo occupation numbers (HONs) using optical data of typical depth m* + 2. The stacked radial profiles are consistent with a Navarro–Frenk–White profile of concentration
$2.84^{+0.40}_{-0.37}$
for the red sequence (RS) and
$2.36^{+0.38}_{-0.35}$
for the total population. Stacking the data in multiple redshift bins shows slight redshift evolution in the concentration when both the total population is used, and when only RS galaxies are used (at 2.1σ and 2.8σ, respectively). The stacked LF shows a faint end slope
$\alpha = -1.06^{+0.04}_{-0.03}$
for the total and
$\alpha = -0.80^{+0.04}_{-0.03}$
for the RS population. The redshift evolution of m* is consistent with a passively evolving composite stellar population (CSP) model. Adopting the CSP model predictions, we explore the redshift evolution of the Schechter parameters α and ϕ*. We find α for the total population to be consistent with no evolution (0.3σ), and mildly significant evidence of evolution for the red galaxies (1.1–2.1σ). The data show that the density ϕ*/E
2(z) decreases with redshift, in tension with the self-similar expectation at a 2.4σ level for the total population. The measured HON–mass relation has a lower normalization than previous low redshift studies. Finally, our data support HON redshift evolution at a 2.1σ level, with clusters at higher redshift containing fewer galaxies than their low-z counterparts.
The INT/WFC Photometric H... Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg... imaging survey covering Galactic latitudes |b| < 5... and longitudes ... = 30...-215... in the r, i, and Hα ...filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel...) and to a mean 5... depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r - Hα,...r - i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys. (ProQuest: ... denotes formulae/symbols omitted.)
We present measurements as part of the Southern Oxidant and Aerosol Study (SOAS) during which atmospheric aerosol particles were comprehensively characterized. We present results utilizing a Filter ...Inlet for Gases and AEROsol coupled to a chemical ionization mass spectrometer (CIMS). We focus on the volatility and composition of isoprene derived organic aerosol tracers and of the bulk organic aerosol. By utilizing the online volatility and molecular composition information provided by the FIGAERO–CIMS, we show that the vast majority of commonly reported molecular tracers of isoprene epoxydiol (IEPOX) derived secondary organic aerosol (SOA) is derived from thermal decomposition of accretion products or other low volatility organics having effective saturation vapor concentrations <10–3 μg m–3. In addition, while accounting for up to 30% of total submicrometer organic aerosol mass, the IEPOX-derived SOA has a higher volatility than the remaining bulk. That IEPOX-SOA, and more generally bulk organic aerosol in the Southeastern U.S. is comprised of effectively nonvolatile material has important implications for modeling SOA derived from isoprene, and for mechanistic interpretations of molecular tracer measurements. Our results show that partitioning theory performs well for 2-methyltetrols, once accretion product decomposition is taken into account. No significant partitioning delays due to aerosol phase or viscosity are observed, and no partitioning to particle-phase water or other unexplained mechanisms are needed to explain our results.
PDF
