Description: Background The clinical course of advanced adrenocortical carcinoma (ACC) is heterogeneous. Our study aimed primarily to refine and make headway in the prognostic stratification of advanced ACC. Patients and methods Patients with advanced ENSAT ACC (stage III or stage IV) at diagnosis registered between 2000 and 2009 in the ENSAT database were enrolled. The primary end point was overall survival (OS). Parameters of potential prognostic relevance were selected. Univariate and multivariate analyses were carried out: model 1 ‘before surgery’; model 2 ‘post-surgery’. Results Four hundred and forty-four patients with advanced ENSAT ACC (stage III: 210; stage IV: 234) were analyzed. After a median follow-up of 55.2 months, the median OS was 24 months. A modified ENSAT (mENSAT) classification was validated: stage III (invasion of surrounding tissues/organs or the vena renalis/cava) and stage IVa, IVb, IVc (2, 3 or 〉3 metastatic organs, including N, respectively). Two- or 5-year OS was 73%, 46%, 26% and 15% or 50%, 15%, 14% and 2% for stages III, IVa, IVb and IVc, respectively. In the multivariate analysis, mENSAT stages (stages IVa, IVb, or IVc, respectively) were significantly correlated with OS ( P 〈 0.0001), as well as additional parameters: age ≥50 years ( P 〈 0.0001), tumor- or hormone-related symptoms ( P = 0.01 and 0.03, respectively) in model 1 but also the R status ( P = 0.001) and Grade (Weiss 〉6 and/or Ki67 ≥20%, P = 0.06) in model 2. Conclusion The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC.

Description: Muscle weakness and exercise intolerance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min –1 ·kg body wt –1 , maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt –1 ·day –1 inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50% of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using 31 P-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.

Description: Objectives Older adults frequently visit the emergency department (ED). Socioeconomic status (SES) has an important impact on health and ED utilisation; however, the association between SES and ED utilisation in elderly remains unclear. The aim of this study was to investigate the association between SES in older adult patients visiting the ED on outcomes. Design A retrospective study. Participants Older adults (≥65 years) visiting the ED, in the Netherlands. SES was stratified into tertiles based on average household income at zip code level: low (〈1800/month), intermediate (1800–2300/month) and high (〉2300/month). Primary outcomes Hospitalisation, inhospital mortality and 30-day ED return visits. Effect of SES on outcomes for all groups were assessed by logistic regression and adjusted for confounders. Results In total, 4828 older adults visited the ED during the study period. Low SES was associated with a higher risk of hospitalisation among community-dwelling patients compared with high SES (adjusted OR 1.3, 95% CI 1.1 to 1.7). This association was not present for intermediate SES (adjusted OR 1.1, 95% CI 0.95 to 1.4). Inhospital mortality was comparable between the low and high SES group, even after adjustment for age, comorbidity and triage level (low OR 1.4, 95% CI 0.8 to 2.6, intermediate OR 1.3, 95% CI 0.8 to 2.2). Thirty-day ED revisits among community-dwelling patients were also equal between the SES groups (low: adjusted OR 1.0, 95% CI 0.7 to 1.4, and intermediate: adjusted OR 0.8, 95% CI 0.6 to 1.1). Conclusion In older adult ED patients, low SES was associated with a higher risk of hospitalisation than high SES. However, SES had no impact on inhospital mortality and 30-day ED revisits after adjustment for confounders.

Description: The Ocean Model Intercomparison Project (OMIP) is an endorsed project in the Coupled Model Intercomparison Project Phase 6 (CMIP6). OMIP addresses CMIP6 science questions, investigating the origins and consequences of systematic model biases. It does so by providing a framework for evaluating (including assessment of systematic biases), understanding, and improving ocean, seaice, tracer, and biogeochemical components of climate and earth system models contributing to CMIP6. Among the WCRP Grand Challenges in climate science (GCs), OMIP primarily contributes to the regional sea level change and near-term (climate/decadal) prediction GCs. OMIP provides (a) an experimental protocol for global ocean/sea-ice models run with a prescribed atmospheric forcing; and (b) a protocol for ocean diagnostics to be saved as part of CMIP6. We focus here on the physical component of OMIP, with a companion paper (Orr et al., 2016) detailing methods for the inert chemistry and interactive biogeochemistry. The physical portion of the OMIP experimental protocol follows the interannual Coordinated Ocean-ice Reference Experiments (CORE-II). Since 2009, CORE-I (Normal Year Forcing) and CORE-II (Interannual Forcing) have become the standard methods to evaluate global ocean/seaice simulations and to examine mechanisms for forced ocean climate variability. The OMIP diagnostic protocol is relevant for any ocean model component of CMIP6, including the DECK (Diagnostic, Evaluation and Characterization of Klima experiments), historical simulations, FAFMIP (Flux Anomaly Forced MIP), C4MIP (Coupled Carbon Cycle Climate MIP), DAMIP (Detection and Attribution MIP), DCPP (Decadal Climate Prediction Project), ScenarioMIP, High- ResMIP (High Resolution MIP), as well as the ocean/sea-ice OMIP simulations.