Spitzer Imaging of i'-drop Galaxies: Old Stars at z~6

We present new evidence for mature stellar populations with ages >100Myr in massive galaxies (M_stellar>10^10M_sun) seen at a time when the Universe was less than 1Gyr old. We analyse the prominent detections of two z~6 star-forming galaxies (SBM03#1 & #3) made at wavelengths corresponding to the rest-frame optical using the IRAC camera onboard the Spitzer Space Telescope. We had previously identified these galaxies in HST/ACS GOODS images of Chandra Deep Field South through the "i-drop" Lyman break technique, and subsequently confirmed spectroscopically with the Keck telescope. The new Spitzer photometry reveals significant Balmer/4000Ang discontinuities, indicative of dominant stellar populations with ages >100Myr. Fitting a range of population synthesis models (for normal initial mass functions) to the HST/Spitzer photometry yields ages of 250-650Myr and implied formation redshifts z~7.5-13.5 in presently-accepted world models. Remarkably, our sources have best-fit stellar masses of 1.3-3.8x10^10M_sun (95% confidence) assuming a Salpeter initial mass function. This indicates that at least some galaxies with stellar masses >20% of those of a present-day L* galaxy had already assembled within the first Gyr after the Big Bang. We also deduce that the past average star formation rate must be comparable to the current observed rate (SFR_UV~5-30M_sun/yr), suggesting that there may have been more vigorous episodes of star formation in such systems at higher redshifts. Although a small sample, limited primarily by Spitzer's detection efficiency, our result lends support to the hypothesis advocated in our earlier analyses of the Ultra Deep Field and GOODS HST/ACS data. The presence of established systems at z~6 suggests long-lived sources at earlier epochs (z>7) played a key role in reionizing the Universe.Comment: Accepted for publication in MNRAS (minor corrections made

Can we predict those with osteoarthritis who will worsen following a chronic disease management program?

Objective: To identify predictors of worsening symptoms and overall health of the treated hip or knee joint following 26 weeks of a nonsurgical chronic disease management program for hip and knee osteoarthritis (OA) and to examine the consistency of these predictors across 3 definitions of worsening. Methods: This prospective cohort study followed 539 participants of the program for 26 weeks. The 3 definitions of worsening included symptomatic worsening based on change in the Western Ontario and McMaster Universities Osteoarthritis Index Global score (WOMAC-G) measuring pain, stiffness, and function; a transition scale that asked about overall health of the treated hip or knee joint; and a composite outcome including both. Multivariate logistic regression models were constructed for the 3 definitions of worsening. Results: Complete data were available for 386 participants: mean age was 66.3 years, 69% were female, 85% reported knee joint pain as primary symptom (signal joint), 46% were waitlisted for total joint arthroplasty (TJA). TJA waitlist status, signal joint, 6-Minute Walk Test (6MWT), depressive symptoms, pain, and age were independently associated with at least 1 definition of worsening. TJA waitlist status and 6MWT remained in the multivariate models for the transition and composite definitions of worsening. Conclusion: Participants reporting worsening on the transition scale did not consistently meet the WOMAC-G definition of worsening symptoms. TJA waitlist status was predictive of the composite definition of worsening, a trend apparent for the transition definition. However, variables that predict worsening remain largely unknown. Further research is required to direct comprehensive and targeted management of patients with hip and knee OA.10 page(s

Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study

<p>Abstract</p> <p>Background</p> <p>Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO_2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse).</p> <p>Methods</p> <p>We determined VO_2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis.</p> <p>Results</p> <p>The EPO-d mice’s hematocrit was about 50% lower than that of controls (p < 0.05) and their performance level was about 25% lower (p < 0.001). A total of 1583 genes exhibited significant changes in their expression levels. However, 68 genes were strongly up-regulated (normalized ratio > 1.4) and 115 were strongly down-regulated (normalized ratio < 0.80). The transcriptome data mining analysis showed that the exercise in the EPO-d mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation.</p> <p>Conclusions</p> <p>Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail.</p