Black-Hole Mass and Growth Rate at z~4.8: A Short Episode of Fast Growth Followed by Short Duty Cycle Activity

We present new Gemini-North/NIRI and VLT/SINFONI H-band spectroscopy for a flux limited sample of 40 z~4.8 active galactic nuclei, selected from the Sloan Digital Sky Survey. The sample probably contains the most massive active black holes (BHs) at this redshift and spans a broad range in bolometric luminosity, 2.7x10^46< L_bol < 2.4x10^47 erg/sec. The high-quality observations and the accurate fitting of the MgII(2800A) line, enable us to study, systematically, the distribution of BH mass (M_BH) and normalized accretion rate (L/L_Edd) at z~4.8. We find that 10^8 < M_BH < 6.6x10^9 M_sun, with a median of ~8.4x10^8 M_sun. We also find that 0.2 < L/L_Edd < 3.9 with a median of ~0.6. Most of these sources had enough time to grow to their observed mass at z~4.8 from z=20, assuming a range of seed BH masses, with ~40% that are small enough to be stellar remnants. Compared to previously studied samples at z~2.4 and 3.3, the masses of the z~4.8 BHs are typically lower by ~0.5 dex. and their L/L_Edd is higher by a similar factor. The new z~4.8 sample can be considered as the progenitor population of the most massive BHs at z~2.4 and 3.3. Such an evolutionary interpretation requires that the growth of the BHs from z~4.8 to z~3.3 and z~2.4 proceeds with short duty cycles, of about 10-20%, depending on the particular growth scenario.Comment: 14 pages and 8 figures. Accepted for publication in Ap

The Rise of Massive Red Galaxies: the color-magnitude and color-stellar mass diagrams for z < ~2 from the MUltiwavelength Survey by Yale-Chile (MUSYC)

We present the color-magnitude and color-stellar mass diagrams for galaxies with z_phot < ~2, based on a K < 22 (AB) catalog of the Extended Chandra Deep Field South (ECDFS) from the MUltiwavelength Survey by Yale-Chile (MUSYC). Our main sample of 7840 galaxies contains 1297 M_* > 10^11 M_Sol galaxies in the range 0.2 < z_phot < 1.8. We show empirically that this catalog is approximately complete for M_* > 10^11 M_Sol galaxies for z_phot < 1.8. For this mass-limited sample, we show that the locus of the red sequence color-stellar mass relation evolves as Del(u-r) ~ (-0.44+/-0.02) z_phot for z_phot ~1.3, however, we are no longer able to reliably distinguish red and blue subpopulations from the observed color distribution; we show that this would require much deeper near infrared data. At 1.5 < z_phot 10^11 M_Sol galaxies is ~50% of the local value, with a red fraction of ~33%. Making a parametric fit to the observed evolution, we find n_tot(z) ~ (1+z_phot)^(-0.52+/-0.12(+/-0.20)). We find stronger evolution in the red fraction: f_red(z) ~ (1+z_phot)^(-1.17+/-0.18(+/-0.21)). Through a series of sensitivity analyses, we show that the most important sources of systematic error are: 1. systematic differences in the analysis of the z~0 and z>>0 samples; 2. systematic effects associated with details of the photometric redshift calculation; and 3. uncertainties in the photometric calibration. With this in mind, we show that our results based on photometric redshifts are consistent with a completely independent analysis which does not require redshift information for individual galaxies. Our results suggest that, at most, 1/5 of local red sequence galaxies with M_* >10^11 M_Sol were already in place at z ~ 2.Comment: Accepted for publication in ApJ. 31 pages in emulateapj format; 18 figues (14 in main text). Additional online data available through http://www.strw.leidenuniv.nl/~ent

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study

BACKGROUND: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER: NCT02413567.status: publishe

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: One year results from the first international, open-label, prospective, multicentre study

Background: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. Methods: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. Results: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. Conclusions: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. Trial registration number: NCT0241356

Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study)

Aims: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. Materials and Methods: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5–10.0% (58–86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). Results: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. Conclusions: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.SCOPUS: ar.jinfo:eu-repo/semantics/publishe