Bayesian multi-model projection of climate: bias assumptions and interannual variability

Current climate change projections are based on comprehensive multi-model ensembles of global and regional climate simulations. Application of this information to impact studies requires a combined probabilistic estimate taking into account the different models and their performance under current climatic conditions. Here we present a Bayesian statistical model for the distribution of seasonal mean surface temperatures for control and scenario periods. The model combines observational data for the control period with the output of regional climate models (RCMs) driven by different global climate models (GCMs). The proposed Bayesian methodology addresses seasonal mean temperatures and considers both changes in mean temperature and interannual variability. In addition, unlike previous studies, our methodology explicitly considers model biases that are allowed to be time-dependent (i.e. change between control and scenario period). More specifically, the model considers additive and multiplicative model biases for each RCM and introduces two plausible assumptions ("constant bias” and "constant relationship”) about extrapolating the biases from the control to the scenario period. The resulting identifiability problem is resolved by using informative priors for the bias changes. A sensitivity analysis illustrates the role of the informative prior. As an example, we present results for Alpine winter and summer temperatures for control (1961-1990) and scenario periods (2071-2100) under the SRES A2 greenhouse gas scenario. For winter, both bias assumptions yield a comparable mean warming of 3.5-3.6°C. For summer, the two different assumptions have a strong influence on the probabilistic prediction of mean warming, which amounts to 5.4°C and 3.4°C for the "constant bias” and "constant relation” assumptions, respectively. Analysis shows that the underlying reason for this large uncertainty is due to the overestimation of summer interannual variability in all models considered. Our results show the necessity to consider potential bias changes when projecting climate under an emission scenario. Further work is needed to determine how bias information can be exploited for this tas

Hermetia illucens meal as fish meal replacement for rainbow trout on farm

In a 7-week on-farm feeding trial rainbow trout(Oncorhynchus mykiss) were provided with a diet containing 28% mechanically de-fatted insect meal prepared from larvae of the black soldier fly, Hermetia illucens (HIM) and compared to a control that received a certified organic and fishmeal based diet. In the test diet insect meal replaced almost 50% of the fishmeal. The whole experiment was conducted under practical conditions on an organically certified rainbow trout farm in Switzerland. Fish of initially 66.5±2.3 g body weight were grown to 125±4.5 g and assessed for their growth performance, as well as analysed for their proximate composition, feed conversion ratio, fatty acid contents and organoleptic properties. Improved lipid utilisation and decreased protein utilisation were observed in fish fed the HIM diet. Furthermore, in a controlled degustation no differences except a slightly darker coloration of fish fed HIM were observed. The experiment demonstrated that substantial replacement of fishmeal by insect meal is possible without compromising growth, feed conversion and product quality. However, the decreased protein utilisation efficiency in HIM fed fish might lower production efficiency when applied over a whole production cycle and not only over 7 weeks

Limited diagnostic yield of non-invasive coronary angiography by 16-slice multi-detector spiral computed tomography in routine patients referred for evaluation of coronary artery disease

Aims Multislice spiral computed tomography (MSCT) is a promising non-invasive method to diagnose coronary artery disease (CAD). As no detailed comparative evaluation in consecutive patients referred for evaluation of CAD has been reported, this prospective study evaluating 2384 coronary segments in 149 consecutive patients was performed. Methods and results The coronary artery tree was analysed in 16 segments both for coronary angiography (CA) and MSCT; a luminal narrowing ≥50% based on visual assessment was considered significant. By MSCT, 77% of 2110 angiographically assessable segments could be evaluated, 94% per patient in proximal and 70% in distal segments (P<0.001). Sensitivity of MSCT to detect significant stenoses was 30% in all, but only 10% in peripheral segments. The main limitations were calcifications in 34% of segments and motion artefacts in 24% of patients. Overall diagnostic sensitivity for the presence of significant CAD was 86% but specificity was only 49%. Conclusion When compared with invasive CA, 16-slice MSCT is of limited diagnostic value for the diagnosis of CAD in consecutive patients. Despite a clinically useful sensitivity for the overall diagnosis of significant CAD, specificity is low. Thus, relevant decisions regarding the need of and suitability for possible revascularization procedures cannot be based on MSCT findings alon

Cost-effectiveness of invasive versus medical management of elderly patients with chronic symptomatic coronary artery disease: Findings of the randomized trial of invasive versus medical therapy in elderly patients with chronic angina (TIME)

Aim To compare benefits and costs of invasive versus medical management in elderly patients with chronic angina. Methods and results In a predefined subgroup of 188 patients of the Trial of Invasive versus Medical therapy in Elderly patients with chronic angina (TIME), one-year benefits were assessed as freedom from major events and improvements in symptoms and quality of live. Costs were determined as one-year costs of resource utilisation. Invasive patients had higher 30-day, but lower months 2-12 hospital and intervention costs than medical patients, resulting in somewhat higher one-year costs for invasive management (p=0.08). However, billing data available for a subgroup of patients showed higher practitioner's charges in the medical patients (adjusted p=0.0015). Incremental costs to prevent one major event by invasive management averaged CHF 10100 (95% CI: −800 to 28300) or € 6965, ranging from average CHF 5100 (€ 3515) to CHF 11600 (€ 8000) in a best, compared to a worst, case scenario. Conclusions Early increased costs of revascularization in invasive patients were balanced after one year by increased practitioners' charges and symptom-driven late revascularizations in medical patients. Therefore, the invasive strategy with improved clinical effectiveness at only marginally higher costs as medical management was cost-effective. Costs should not be an argument against invasive management of elderly patients with chronic angin

Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina - on-treatment analysis of the TIME trial

Aim To assess treatment effects of optimised medical therapy and PCI or CABG surgery on one-year outcome in patients ⩾75 years old with chronic angina. Methods and Results On-treatment analysis of the TIME data: all re-vascularised patients (REVASC \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $n=174$ \end{document}: 112 randomised to revascularisation and 62 to drugs with late revascularisation) were compared to all patients on continued drug therapy (MED \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $n=127$ \end{document}: 86 randomised to drugs and 41 to revascularisation only). Baseline characteristics of both groups were similar (age 80±4 years). Risk of death at one year (adjusted hazard ratio (HR)=1.31; 95%-CI: 0.58-2.99; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $P=0.52$ \end{document}) and of death/infarction (adjusted hazard ratio=1.77; 95%-CI 0.91-3.41; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $P=0.09$ \end{document}) were comparable between REVASC and MED patients. Furthermore, the risk of death within 30 days was even slightly lower among REVASC patients (unadjusted hazard ratio=0.73; 95%-CI: 0.21-2.53; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $P=0.98)$ \end{document}. Overall, REVASC patients had greater improvements in symptoms and well-being than MED patients \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(P{<}0.01)$ \end{document}. Surgical patients had similar mortality rates as angioplasty patients, but they also had greater symptomatic improvements \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(P{<}0.01)$ \end{document}. Conclusion Treated medically, elderly patients with chronic angina have a similarly high 30-day and one-year mortality as patients of the same age being re-vascularised; however, they can expect lower improvements in symptoms and well bein

ATP-Dependent Infra-Slow (<0.1 Hz) Oscillations in Thalamic Networks

An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at ∼0.005–0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba2+-sensitive K+ channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain

Daytime variation of perioperative myocardial injury in non-cardiac surgery and effect on outcome

Recently, daytime variation in perioperative myocardial injury (PMI) has been observed in patients undergoing cardiac surgery. We aim at investigating whether daytime variation also occurs in patients undergoing non-cardiac surgery.; In a prospective diagnostic study, we evaluated the presence of daytime variation in PMI in patients at increased cardiovascular risk undergoing non-cardiac surgery, as well as its possible impact on the incidence of acute myocardial infarction (AMI), and death during 1-year follow-up in a propensity score-matched cohort. PMI was defined as an absolute increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration of ≥14 ng/L from preoperative to postoperative measurements.; Of 1641 patients, propensity score matching defined 630 with similar baseline characteristics, half undergoing non-cardiac surgery in the morning (starting from 8:00 to 11:00) and half in the afternoon (starting from 14:00 to 17:00). There was no difference in PMI incidence between both groups (morning: 50, 15.8% (95% CI 12.3 to 20.3); afternoon: 52, 16.4% (95% CI 12.7 to 20.9), p=0.94), nor if analysing hs-cTnT release as a quantitative variable (median morning group: 3 ng/L (95% CI 1 to 7 ng/L); median afternoon group: 2 ng/L (95% CI 0 to 7 ng/L; p=0.16). During 1-year follow-up, the incidence of AMI was 1.2% (95% CI 0.4% to 3.2%) among morning surgeries versus 4.1% (95% CI 2.3% to 6.9%) among the afternoon surgeries (corrected HR for afternoon surgery 3.44, bootstrapped 95% CI 1.33 to 10.49, p log-rank=0.03), whereas no difference in mortality emerged (p=0.70).; Although there is no daytime variation in PMI in patients undergoing non-cardiac surgery, the incidence of AMI during follow-up is increased in afternoon surgeries and requires further study.; NCT02573532;Results

Perioperative Myocardial Injury After Non-cardiac Surgery: Incidence, Mortality, and Characterization

Perioperative myocardial injury (PMI) seems to be a contributor to mortality after noncardiac surgery. Because the vast majority of PMIs are asymptomatic, PMI usually is missed in the absence of systematic screening.; We performed a prospective diagnostic study enrolling consecutive patients undergoing noncardiac surgery who had a planned postoperative stay of ≥24 hours and were considered at increased cardiovascular risk. All patients received a systematic screening using serial measurements of high-sensitivity cardiac troponin T in clinical routine. PMI was defined as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements. Furthermore, mortality was compared among patients with PMI not fulfilling additional criteria (ischemic symptoms, new ECG changes, or imaging evidence of loss of viable myocardium) required for the diagnosis of spontaneous acute myocardial infarction versus those that did.; From 2014 to 2015 we included 2018 consecutive patients undergoing 2546 surgeries. Patients had a median age of 74 years and 42% were women. PMI occurred after 397 of 2546 surgeries (16%; 95% confidence interval, 14%-17%) and was accompanied by typical chest pain in 24 of 397 patients (6%) and any ischemic symptoms in 72 of 397 (18%). Crude 30-day mortality was 8.9% (95% confidence interval [CI], 5.7-12.0) in patients with PMI versus 1.5% (95% CI, 0.9-2.0) in patients without PMI (; P; &lt;0.001). Multivariable regression analysis showed an adjusted hazard ratio of 2.7 (95% CI, 1.5-4.8) for 30-day mortality. The difference was retained at 1 year with mortality rates of 22.5% (95% CI, 17.6-27.4) versus 9.3% (95% CI, 7.9-10.7). Thirty-day mortality was comparable among patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction (280/397, 71%) versus those with at least 1 additional criterion (10.4%; 95% CI, 6.7-15.7, versus 8.7%; 95% CI, 4.2-16.7;; P; =0.684).; PMI is a common complication after noncardiac surgery and, despite early detection during routine clinical screening, is associated with substantial short- and long-term mortality. Mortality seems comparable in patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction versus those patients who do.; URL: https://www.clinicaltrials.gov. Unique identifier: NCT02573532