Assessing the content validity of the revised Health of the Nation Outcome Scales 65+: the HoNOS Older Adults

Aims and method: Recently, the Health of the Nation Outcome Scales (HoNOS) 65+ was revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA). Results: All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested that additional older adult-specific examples be included in the glossary (e.g., for scales measuring depressed mood, problems with relationships, and problems with activities of daily living). Clinical implications: Experts agreed that the HoNOS OA measures important constructs. Training may be needed to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Using a business model approach and marketing techniques for recruitment to clinical trials

Peer reviewedPublisher PD

A z=1.85 galaxy group in CEERS: evolved, dustless, massive intra-halo light and a brightest group galaxy in the making

We present CEERS JWST/NIRCam imaging of a massive galaxy group at z=1.85, to explore the early JWST view on massive group formation in the distant Universe. The group contains >16 members (including 6 spectros. confirmations) down to log10(Mstar/Msun)=8.5, including the brightest group galaxy (BGG) in the process of actively assembling at this redshift. The BGG is comprised of multiple merging components extending ~3.6" (30kpc) across the sky. The BGG contributes 69% of the group's total galactic stellar mass, with one of the merging components containing 76% of the total mass of the BGG and a SFR>1810Msun/yr. Most importantly, we detect intra-halo light (IHL) in several HST and JWST/NIRCam bands, allowing us to construct a state-of-the-art rest-frame UV-NIR Spectral Energy Distribution of the IHL for the first time at this high redshift. This allows stellar population characterisation of both the IHL and member galaxies, as well as the morphology distribution of group galaxies vs. their star-formation activity when coupled with Herschel data. We create a stacked image of the IHL, giving us a sensitivity to extended emission of 28.5 mag/arcsec2 at rest-frame 1um. We find that the IHL is extremely dust poor (Av~0), containing an evolved stellar population of log10(t50/yr)=8.8, corresponding to a formation epoch for 50% of the stellar material 0.63Gyr before z=1.85. There is no evidence of ongoing star-formation in the IHL. The IHL in this group at z=1.85 contributes ~10% of the total stellar mass, comparable with what is observed in local clusters. This suggests that the evolution of the IHL fraction is more self-similar with redshift than predicted by some models, challenging our understanding of IHL formation during the assembly of high-redshift clusters. JWST is unveiling a new side of group formation at this redshift, which will evolve into Virgo-like structures in the local Universe.Comment: 14 pages + appendix, 11 figures, 4 tables. Accepted to A&A on 15th May 202

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

First Look at z > 1 Bars in the Rest-Frame Near-Infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of {\it{JWST}} CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at $z>1$ based on rest-frame NIR F444W images of high resolution (~1.3 kpc at z ~ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at $z>1$ with spectroscopic redshifts, including the two highest redshift bars at ~2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at $z$ ~ 1.1-2.3 presented in our study have projected semi-major axes of ~2.9-4.3 kpc and projected ellipticities of ~0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ~ $1 \times 10^{10}$ to $2 \times 10^{11}$ $M_{\odot}$, star formation rates of ~ 21-295 $M_{\odot}$ yr$^{-1}$, and several have potential nearby companions. Our finding of bars at $z$ ~1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-10 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ~ 0.Comment: 16 pages, 5 figures. Accepted for Publication in Astrophysical Journal Letter

First Look at z > 1 Bars in the Rest-frame Near-infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of JWST CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at z &gt; 1 based on rest-frame NIR F444W images of high resolution (∼1.3 kpc at z ∼ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at z &gt; 1 with spectroscopic redshifts, including the two highest-redshift bars at z ∼ 2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at z ∼ 1.1-2.3 presented in our study have projected semimajor axes of ∼2.9-4.3 kpc and projected ellipticities of ∼0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ∼1 × 10 10 to 2 × 10 11 M ⊙ and star formation rates of ∼21-295 M ⊙ yr −1, and several have potential nearby companions. Our finding of bars at z ∼ 1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-11 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ∼ 0.</p

CEERS Key Paper V: A triality on the nature of HST-dark galaxies

The new capabilities that JWST offers in the near- and mid-infrared (IR) are used to investigate in unprecedented detail the nature of optical/near-IR faint, mid-IR bright sources, HST-dark galaxies among them. We gather JWST data from the CEERS survey in the EGS, jointly with HST data, and analyze spatially resolved optical-to-mid-IR spectral energy distributions (SEDs) to estimate both photometric redshifts in 2 dimensions and stellar populations properties in a pixel-by-pixel basis. We select 138 galaxies with F150W-F356W>1.5 mag, F356W<27.5 mag. The nature of these sources is threefold: (1) 71% are dusty star-forming galaxies at 2<z<6 with masses 9<log M/M_sun<11 and a variety of specific SFRs (100 Gyr^-1); (2) 18% are quiescent/dormant (i.e., subject to reignition and rejuvenation) galaxies at 3<z<5, masses log M/M_sun~10 and post-starburst stellar mass-weighted ages (0.5-1 Gyr); and (3) 11% are strong young starbursts with indications of high-EW emission lines (typically, [OIII]+Hbeta) at 6<z<7 and log M/M_sun~9.5. The sample is dominated by disk-like galaxies with a remarkable compactness for XELG-z6 (effective radii smaller than 0.4 kpc). Large attenuations in SFGs, 2<A(V)<5 mag, are found within 1.5 times the effective radius, approximately 2 kpc, while QGs present A(V)~0.2 mag. Our SED-fitting technique reproduces the expected dust emission luminosities of IR-bright and sub-millimeter galaxies. This study implies high levels of star formation activity between z~20 and z~10, where virtually 100% of our galaxies had already formed 10^8 M_sun of their stellar content, 60% of them had assembled 10^9 M_sun, and 10% up to 10^10 M_sun (in situ or ex situ). (abridged)Comment: Published in CEERS ApJL Focus Issue, ApJL 946, L1

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.D F. Easton was recipient of the CR-UK grant C1287/A10118. R A. Eeles was recipient of the CR-UK grant C5047/A10692 and B E. Henderson was recipient of the NIH grant 1U19CA148537-01This is the author accepted manuscript. The final version is available via AACR at http://cebp.aacrjournals.org/content/early/2015/04/02/1055-9965.EPI-14-0317.long

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio