Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery : Combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

Objectives: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6-3.2), low-moderate (LMDAS≥3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). Results: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.Peer reviewedFinal Published versio

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Community-based interventions for adolescents following traumatic brain injury: a systematic review

Background: Chronic impairment following childhood traumatic brain injury has the potential to increase risk of negative outcomes. This highlights potential value of community-based rehabilitation programs. Objectives: To identify research studies examining existing intervention programmes available in community-based rehabilitation to adolescents following TBI to assist with the transition back into the community. Methods: A systematic review of community-based interventions was conducted across different national contexts. All included studies involved a clinical population with TBI, aged 11 to 25 years inclusive. Risk of bias was rated for each included study. Results: Seventeen studies were identified for inclusion in the review, of these eleven distinct interventions were found. The quality of evidence was largely weak and highly variable. Conclusion: The results suggest some improvement in adolescent outcomes following community-based interventions, however higher quality evidence is needed to support specific interventions

Erratum: “The eighth data release of the Sloan Digital Sky Survey: first data from SDSS-III” (2011, ApJS, 193, 29)

Section 3.5 of Aihara et al. (2011) described various sources of systematic error in the astrometry of the imaging data of the Sloan Digital Sky Survey (SDSS). In addition to these sources of error, there is an additional and more serious error, which introduces a large systematic shift in the astrometry over a large area around the north celestial pole. The region has irregular boundaries but in places extends as far south as declination δ ≈ 41◦. The sense of the shift is that the positions of all sources in the affected area are offset by roughly 250 mas in a northwest direction. We have updated the SDSS online documentation to reflect these errors, and to provide detailed quality information for each SDSS field

SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2, which is now completed, measured medium-resolution (R=1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Long-Term Financial Burden of Breast Cancer: Experiences of a Diverse Cohort of Survivors Identified Through Population-Based Registries

Purpose: To evaluate the financial experiences of a racially and ethnically diverse cohort of long-term breast cancer survivors (17% African American, 40% Latina) identified through population-based registries. Methods: Longitudinal study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and reported to the SEER registries of metropolitan Los Angeles and Detroit. We surveyed 3,133 women approximately 9 months after diagnosis and 4 years later. Multivariable models evaluated correlates of self-reported decline in financial status attributed to breast cancer and of experiencing at least one type of privation (economically motivated treatment nonadherence and broader hardships related to medical expenses). Results: Among 1,502 patients responding to both surveys, median out-of-pocket expenses were less than or equal to $2,000; 17$5,000; 12% reported having medical debt 4 years postdiagnosis. Debt varied significantly by race: 9% of whites, 15% of blacks, 17% of English-speaking Latinas, and 10% of Spanish-speaking Latinas reported debt ( P = .03). Overall, 25% of women experienced financial decline at least partly attributed to breast cancer; Spanish-speaking Latinas had significantly increased odds of this decline relative to whites (odds ratio [OR], 2.76; P = .006). At least one privation was experienced by 18% of the sample; blacks (OR, 2.6; P \u3c .001) and English-speaking Latinas (OR, 2.2; P = .02) were significantly more likely to have experienced privation than whites. Conclusion: Racial and ethnic minority patients appear most vulnerable to privations and financial decline attributable to breast cancer, even after adjustment for income, education, and employment. These findings should motivate efforts to control costs and ensure communication between patients and providers regarding financial distress, particularly for vulnerable subgroups

The CKS1/CKS2 Proteostasis Axis Is Crucial to Maintain Hematopoietic Stem Cell Function

Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic, and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification, and degradation-broadly termed protein homeostasis or "proteostasis"-in these cells is still in its infancy, with very little known about how the functional state of the proteome is maintained in hematopoietic stem cells. We investigated the requirement of the small phospho-binding adaptor proteins, the cyclin-dependent kinase subunits (CKS1 and CKS2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. CKS1 and CKS2 are best known for their roles in p27 degradation and cell cycle regulation, and by studying the transcriptome and proteome of Cks1 -/- and Cks2 -/- mice, we demonstrate regulation of key signaling pathways that govern hematopoietic stem cell biology including AKT, FOXO1, and NFκB, together balancing protein homeostasis and restraining reactive oxygen species to ensure healthy hematopoietic stem cell function