Objective To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of ...life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease.Design Randomised controlled trial.Setting Two university hospitals in Copenhagen, Denmark.Participants 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up.Intervention Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care.Main outcome measures European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo2max).Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables.Results Adjusted for baseline score, disease, and demographic covariates, the intervention group showed an estimated improvement at six weeks for the primary outcome, fatigue, of −6.6 points (95% confidence interval −12.3 to −0.9, P=0.02; effect size=0.33, 0.04 to 0.61). Significant effects were seen on vitality (effect size 0.55, 95% CI 0.27 to 0.82), physical functioning (0.37, 0.09 to 0.65), role physical (0.37, 0.10 to 0.64), role emotional (0.32, 0.05 to 0.59), and mental health (0.28, 0.02 to 0.56) scores. Improvement was noted in physical capacity: estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min (95% CI 0.1 to 0.2, P<0.0001) and for muscular strength (leg press) was 29.7 kg (23.4 to 34.9, P<0.0001). No significant effect was seen on global health status/quality of life.Conclusion A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease. The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life.Trial registration Current Controlled trials ISRCTN05322922.
Precision cosmology with Type Ia supernovae (SNe Ia) makes use of the fact that SN Ia luminosities depend on their light-curve shapes and colours. Using Supernova Legacy Survey (SNLS) and other data, ...we show that there is an additional dependence on the global characteristics of their host galaxies: events of the same light-curve shape and colour are, on average, 0.08 mag (≃4.0σ) brighter in massive host galaxies (presumably metal-rich) and galaxies with low specific star formation rates (sSFR). These trends do not depend on any assumed cosmological model, and are independent of the SN light-curve width: both fast and slow-declining events show the same trends. SNe Ia in galaxies with a low sSFR also have a smaller slope (‘β’) between their luminosities and colours with ∼2.7σ significance, and a smaller scatter on SN Ia Hubble diagrams (at 95 per cent confidence), though the significance of these effects is dependent on the reddest SNe. SN Ia colours are similar between low-mass and high-mass hosts, leading us to interpret their luminosity differences as an intrinsic property of the SNe and not of some external factor such as dust. If the host stellar mass is interpreted as a metallicity indicator using galaxy mass–metallicity relations, the luminosity trends are in qualitative agreement with theoretical predictions. We show that the average stellar mass, and therefore the average metallicity, of our SN Ia host galaxies decreases with redshift. The SN Ia luminosity differences consequently introduce a systematic error in cosmological analyses, comparable to the current statistical uncertainties on parameters such as w, the equation of state of dark energy. We show that the use of two SN Ia absolute magnitudes, one for events in high-mass (metal-rich) galaxies and the other for events in low-mass (metal-poor) galaxies, adequately corrects for the differences. Cosmological fits incorporating these terms give a significant reduction in χ2 (3.8σ–4.5σ); linear corrections based on host parameters do not perform as well. We conclude that all future SN Ia cosmological analyses should use a correction of this (or similar) form to control demographic shifts in the underlying galaxy population.
We present observational constraints on the nature of dark energy using the Supernova Legacy Survey three-year sample (SNLS3) of Guy et al. and Conley et al. We use the 472 Type Ia supernovae (SNe ...Ia) in this sample, accounting for recently discovered correlations between SN Ia luminosity and host galaxy properties, and include the effects of all identified systematic uncertainties directly in the cosmological fits. Combining the SNLS3 data with the full WMAP7 power spectrum, the Sloan Digital Sky Survey luminous red galaxy power spectrum, and a prior on the Hubble constant H 0 from SHOES, in a flat universe we find Delta *W m = 0.269 ? 0.015 and w = --1.061+0.069 -- 0.068 (where the uncertainties include all statistical and SN Ia systematic errors)--a 6.5% measure of the dark energy equation-of-state parameter w. The statistical and systematic uncertainties are approximately equal, with the systematic uncertainties dominated by the photometric calibration of the SN Ia fluxes--without these calibration effects, systematics contribute only a ~2% error in w. When relaxing the assumption of flatness, we find Delta *W m = 0.271 ? 0.015, Delta *W k = --0.002 ? 0.006, and w = --1.069+0.091 -- 0.092. Parameterizing the time evolution of w as w(a) = w 0 + wa (1 -- a) gives w 0 = --0.905 ? 0.196, wa = --0.984+1.094 -- 1.097 in a flat universe. All of our results are consistent with a flat, w = --1 universe. The size of the SNLS3 sample allows various tests to be performed with the SNe segregated according to their light curve and host galaxy properties. We find that the cosmological constraints derived from these different subsamples are consistent. There is evidence that the coefficient, Delta *b, relating SN Ia luminosity and color, varies with host parameters at >4 Delta *s significance (in addition to the known SN luminosity-host relation); however, this has only a small effect on the cosmological results and is currently a subdominant systematic.
Aims. We present photometric properties and distance measurements of 252high redshift Type Ia supernovae (0.15 < z < 1.1) discovered during the first three years of the Supernova Legacy Survey ...(SNLS). These events were detected and their multi-colour light curves measured using the MegaPrime/MegaCam instrument at the Canada-France-Hawaii Telescope (CFHT), by repeatedly imaging four one-square degree fields in four bands. Follow-up spectroscopy was performed at the VLT, Gemini and Keck telescopes to confirm the nature of the supernovae and to measure their redshifts. Methods. Systematic uncertainties arising from light curve modeling are studied, making use of two techniques to derive the peak magnitude, shape and colour of the supernovae, and taking advantage of a precise calibration of the SNLS fields. Results. A flat ΛCDM cosmological fit to 231SNLS high redshift type Ia supernovae alone gives ΩM = 0.211 ± 0.034(stat) ± 0.069(sys). The dominant systematic uncertainty comes from uncertainties in the photometric calibration. Systematic uncertainties from light curve fitters come next with a total contribution of ± 0.026 on ΩM. No clear evidence is found for a possible evolution of the slope (β) of the colour-luminosity relation with redshift.
Optical long-slit spectroscopy at the Gemini-North telescope using the Gemini Multi-Object Spectrograph (GMOS) was used to classify targets from the Supernova Legacy Survey (SNLS) from 2005 July and ...2006 May-2008 May. During this time, 95 objects were observed. Where possible, the objects' redshifts (z) were measured from narrow emission or absorption features in the host galaxy spectrum, otherwise they were measured from the broader supernova features. We present spectra of 68 confirmed or probable SNe Ia from SNLS with redshifts in the range 0.17 ≤z≤ 1.02. In combination with earlier SNLS Gemini and VLT spectra, we used these new observations to measure pseudo-equivalent widths (EWs) of three spectral features - Ca ii H&K, Si ii and Mg ii- in 144 objects and compared them to the EWs of low-redshift SNe Ia from a sample drawn from the literature. No signs of changes with z are seen for the Ca ii H&K and Mg ii features. Systematically lower EW Si ii is seen at high redshift, but this can be explained by a change in demographics of the SNe Ia population within a two-component model combined with an observed correlation between EW Si ii and photometric light-curve stretch.
Aims. To investigate the effect of gravitational lensing of supernovae in large ongoing surveys. Methods. We simulate the effect of gravitational lensing magnification on individual supernovae using ...observational data input from two large supernova surveys. To estimate the magnification due to matter in the foreground, we simulate galaxy catalogs and compute the magnification along individual lines of sight using the multiple lens plane algorithm. The dark matter haloes of the galaxies are modelled as gravitational lenses using singular isothermal sphere or Navarro-Frenk-White profiles. Scaling laws between luminosity and mass, provided by Faber-Jackson and Tully-Fisher relations, are used to estimate the masses of the haloes. Results. While our simulations show that the SDSSII supernova survey is marginally affected by gravitational lensing, we find that the effect will be measurable in the SNLS survey that probes higher redshifts. Our simulations show that the probability to measure a significant ($3\sigma$) correlation between the Hubble diagram residuals and the calculated lensing magnification is $\ga$$95\%$ in the SNLS data. Moreover, with this data it should be possible to constrain the normalisation of the masses of the lensing galaxy haloes at the $1\sigma$ and $2\sigma$ confidence level with ∼$30\%$ and ~$ 60\%$ accuracy, respectively.
Aims. The observed brightness of type Ia supernovae is affected by gravitational lensing caused by the mass distribution along the line of sight, which introduces an additional dispersion into the ...Hubble diagram. We look for evidence of lensing in the SuperNova Legacy Survey 3-year data set. Methods. We investigate the correlation between the residuals from the Hubble diagram and the gravitational magnification based on a modeling of the mass distribution of foreground galaxies. A deep photometric catalog, photometric redshifts, and well established mass luminosity relations are used. Results. We find evidence of a lensing signal with a 2.3σ significance. The current result is limited by the number of SNe, their redshift distribution, and the other sources of scatter in the Hubble diagram. Separating the galaxy population into a red and a blue sample has a positive impact on the significance of the signal detection. On the other hand, increasing the depth of the galaxy catalog, the precision of photometric redshifts or reducing the scatter in the mass luminosity relations have little effect. We show that for the full SuperNova Legacy Survey sample (~400 spectroscopically confirmed type Ia SNe and ~200 photometrically identified type Ia SNe), there is an 80% probability of detecting the lensing signal with a 3σ significance.
We combine high-redshift Type Ia supernovae from the first three years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality ...joint sample of 472 SNe (123 low-z, 93 SDSS, 242 SNLS, and 14 Hubble Space Telescope). SN data alone require cosmic acceleration at >99.999% confidence, including systematic effects. For the dark energy equation of state parameter (assumed constant out to at least z = 1.4) in a flat universe, we find w = --0.91+0.16 --0.20(stat)+0.07 --0.14(sys) from SNe only, consistent with a cosmological constant. Our fits include a correction for the recently discovered relationship between host-galaxy mass and SN absolute brightness. We pay particular attention to systematic uncertainties, characterizing them using a systematic covariance matrix that incorporates the redshift dependence of these effects, as well as the shape-luminosity and color-luminosity relationships. Unlike previous work, we include the effects of systematic terms on the empirical light-curve models. The total systematic uncertainty is dominated by calibration terms. We describe how the systematic uncertainties can be reduced with soon to be available improved nearby and intermediate-redshift samples, particularly those calibrated onto USNO/SDSS-like systems.
We have previously described (R S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cycloheptadisoxazol-4-yl)propionic acid (4-AHCP) as a highly effective agonist at non-N-methyl-d-aspartate (non-NMDA) glutamate ...(Glu) receptors in vivo, which is more potent than (R S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) but inactive at NMDA receptors. However, 4-AHCP was found to be much weaker than AMPA as an inhibitor of 3HAMPA binding and to have limited effect in a 3Hkainic acid binding assay using rat cortical membranes. To shed light on the mechanism(s) underlying this quite enigmatic pharmacological profile of 4-AHCP, we have now developed a synthesis of (S)-4-AHCP (6) and (R)-4-AHCP (7). At cloned metabotropic Glu receptors mGluR1α (group I), mGluR2 (group II), and mGluR4a (group III), neither 6 nor 7 showed significant agonist or antagonist effects. The stereoisomer 6, but not 7, activated cloned AMPA receptor subunits GluR1o, GluR3o, and GluR4o with EC50 values in the range 4.5−15 μM and the coexpressed kainate-preferring subunits GluR6 + KA2 (EC50 = 6.4 μM). Compound 6, but not 7, proved to be a very potent agonist (EC50 = 0.13 μM) at the kainate-preferring GluR5 subunit, equipotent with (S)-2-amino-3-(5-tert-butyl-3-hydroxyisothiazol-4-yl)propionic acid (S)-Thio-ATPA, 4 and almost 4 times more potent than (S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid (S)-ATPA, 3. Compound 6 thus represents a new structural class of GluR5 agonists. Molecular modeling and docking to a crystal structure of the extracellular binding domain of the AMPA subunit GluR2 has enabled identification of the probable active conformation and binding mode of 6. We are able to rationalize the observed selectivities by comparing the docking of 4 and 6 to subtype constructs, i.e., a crystal structure of the extracellular binding domain of GluR2 and a homology model of GluR5.
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