BackgroundThe accumulation of risk for the development of rheumatoid arthritis (RA) is regarded as a continuum that may start with interacting environmental and genetic factors, proceed with the... Show moreBackgroundThe accumulation of risk for the development of rheumatoid arthritis (RA) is regarded as a continuum that may start with interacting environmental and genetic factors, proceed with the initiation of autoimmunity, and result in the formation of autoantibodies such as anti-citrullinated peptide antibodies (ACPA). In parallel, at-risk individuals may be asymptomatic or experience joint pain (arthralgia) that is itself non-specific or clinically suspicious for evolving RA, even in the absence of overt arthritis. Optimal strategies for the management of people at-risk of RA, both for symptom control and to delay or prevent progression to classifiable disease, remain poorly understood. MethodsTo help address this, groups of stakeholders from academia, clinical rheumatology, industry and patient research partners have collaborated to advance understanding, define and study different phases of the at-risk state. In this current report we describe different European initiatives in the field and the successful effort to build a European Registry of at-risk people to facilitate observational and interventional research. ResultsWe outline similarities and differences between cohorts of at-risk individuals at institutions spanning several countries, and how to best combine them within the new database. Over the past 2 years, besides building the technical infrastructure, we have agreed on a core set of variables that all partners should strive to collect for harmonization purposes. ConclusionWe emphasize to address this process from different angles and touch on the biologic, epidemiologic, analytic, and regulatory aspects of collaborative studies within a meta-database of people at-risk of RA. Show less
Page, E.C.; Bancroft, E.K.; Brook, M.N.; Assel, M.; Battat, M.H. al; Thomas, S.; ... ; IMPACT Study Collaborators 2019
Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in... Show moreBackground: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.Design, setting, and participants: Men aged 40-69 yr with a germline pathogenic BRCA1/ 2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA> 3.0 ng/ml, men were offered prostate biopsy.Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p= 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. (C) 2019 The Authors. Published by Elsevier B.V. Show less
Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity... Show moreMotivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)).Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. Show less
We present the size-stellar mass relations of nearby (z = 0.01-0.02) Sloan Digital Sky Survey galaxies, for samples selected by color, morphology, Sérsic index n, and specific star formation rate.... Show moreWe present the size-stellar mass relations of nearby (z = 0.01-0.02) Sloan Digital Sky Survey galaxies, for samples selected by color, morphology, Sérsic index n, and specific star formation rate. Several commonly employed size measurement techniques are used, including single Sérsic fits, two-component Sérsic models, and a non-parametric method. Through simple simulations, we show that the non-parametric and two-component Sérsic methods provide the most robust effective radius measurements, while those based on single Sérsic profiles are often overestimates, especially for massive red/early-type galaxies. Using our robust sizes, we show for all sub-samples that the mass-size relations are shallow at low stellar masses and steepen above ~{}3-4 { imes} 10$^{10}$ M $_{☉}$. The mass-size relations for galaxies classified as late-type, low-n, and star-forming are consistent with each other, while blue galaxies follow a somewhat steeper relation. The mass-size relations of early-type, high-n, red, and quiescent galaxies all agree with each other but are somewhat steeper at the high-mass end than previous results. To test potential systematics at high redshift, we artificially redshifted our sample (including surface brightness dimming and degraded resolution) to z = 1 and re-fit the galaxies using single Sérsic profiles. The sizes of these galaxies before and after redshifting are consistent and we conclude that systematic effects in sizes and the size-mass relation at z ~{} 1 are negligible. Interestingly, since the poorer physical resolution at high redshift washes out bright galaxy substructures, single Sérsic fitting appears to provide more reliable and unbiased effective radius measurements at high z than for nearby, well-resolved galaxies. Show less
Patel, S.G.; Dokkum, P.; Franx, M.; Quadri, R.; Muzzin, A.V.; Marchesini, D.; ... ; Stefanon, M. 2013
We study the structural evolution of massive galaxies by linking progenitors and descendants at a constant cumulative number density of n $_c$ = 1.4 { imes} 10$^{-4}$ Mpc$^{-3}$ to z ~{} 3.... Show moreWe study the structural evolution of massive galaxies by linking progenitors and descendants at a constant cumulative number density of n $_c$ = 1.4 { imes} 10$^{-4}$ Mpc$^{-3}$ to z ~{} 3. Structural parameters were measured by fitting Sérsic profiles to high-resolution CANDELS HST WFC3 J $_{125}$ and H $_{160}$ imaging in the UKIDSS-UDS at 1 {lt} z {lt} 3 and ACS I $_{814}$ imaging in COSMOS at 0.25 {lt} z {lt} 1. At a given redshift, we selected the HST band that most closely samples a common rest-frame wavelength so as to minimize systematics from color gradients in galaxies. At fixed n $_c$, galaxies grow in stellar mass by a factor of ~{}3 from z ~{} 3 to z ~{} 0. The size evolution is complex: galaxies appear roughly constant in size from z ~{} 3 to z ~{} 2 and then grow rapidly to lower redshifts. The evolution in the surface mass density profiles indicates that most of the mass at r {lt} 2 kpc was in place by z ~{} 2, and that most of the new mass growth occurred at larger radii. This inside-out mass growth is therefore responsible for the larger sizes and higher Sérsic indices of the descendants toward low redshift. At z {lt} 2, the effective radius evolves with the stellar mass as r$_e$ vpropM $^{2.0}$, consistent with scenarios that find dissipationless minor mergers to be a key driver of size evolution. The progenitors at z ~{} 3 were likely star-forming disks with r$_e$ ~{} 2 kpc, based on their low Sérsic index of n ~{} 1, low median axis ratio of b/a ~{} 0.52, and typical location in the star-forming region of the U - V versus V - J diagram. By z ~{} 1.5, many of these star-forming disks disappeared, giving rise to compact quiescent galaxies. Toward lower redshifts, these galaxies continued to assemble mass at larger radii and became the local ellipticals that dominate the high-mass end of the mass function at the present epoch. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc. under NASA contract NAS 5-26555. Show less
Patel, S.G.; Dokkum, P.; Franx, M.; Quadri, R.; Muzzin, A.V.; Marchesini, D.; ... ; Stefanon, M. 2013
We study the structural evolution of massive galaxies by linking progenitors and descendants at a constant cumulative number density of n $_c$ = 1.4 { imes} 10$^{-4}$ Mpc$^{-3}$ to z ~{} 3.... Show moreWe study the structural evolution of massive galaxies by linking progenitors and descendants at a constant cumulative number density of n $_c$ = 1.4 { imes} 10$^{-4}$ Mpc$^{-3}$ to z ~{} 3. Structural parameters were measured by fitting Sérsic profiles to high-resolution CANDELS HST WFC3 J $_{125}$ and H $_{160}$ imaging in the UKIDSS-UDS at 1 {lt} z {lt} 3 and ACS I $_{814}$ imaging in COSMOS at 0.25 {lt} z {lt} 1. At a given redshift, we selected the HST band that most closely samples a common rest-frame wavelength so as to minimize systematics from color gradients in galaxies. At fixed n $_c$, galaxies grow in stellar mass by a factor of ~{}3 from z ~{} 3 to z ~{} 0. The size evolution is complex: galaxies appear roughly constant in size from z ~{} 3 to z ~{} 2 and then grow rapidly to lower redshifts. The evolution in the surface mass density profiles indicates that most of the mass at r {lt} 2 kpc was in place by z ~{} 2, and that most of the new mass growth occurred at larger radii. This inside-out mass growth is therefore responsible for the larger sizes and higher Sérsic indices of the descendants toward low redshift. At z {lt} 2, the effective radius evolves with the stellar mass as r$_e$ vpropM $^{2.0}$, consistent with scenarios that find dissipationless minor mergers to be a key driver of size evolution. The progenitors at z ~{} 3 were likely star-forming disks with r$_e$ ~{} 2 kpc, based on their low Sérsic index of n ~{} 1, low median axis ratio of b/a ~{} 0.52, and typical location in the star-forming region of the U - V versus V - J diagram. By z ~{} 1.5, many of these star-forming disks disappeared, giving rise to compact quiescent galaxies. Toward lower redshifts, these galaxies continued to assemble mass at larger radii and became the local ellipticals that dominate the high-mass end of the mass function at the present epoch. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc. under NASA contract NAS 5-26555. Show less
