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Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr-1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr-1. Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m-2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m-2), CO2 (34.3 mW m-2), and NOx (17.5 mW m-2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m-2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.

Over the past few decades, the geographical distribution of emissions of substances that alter the atmospheric energy balance has changed due to economic growth and air pollution regulations. Here, we show the resulting changes to aerosol and ozone abundances and their radiative forcing using recently updated emission data for the period 1990-2015, as simulated by seven global atmospheric composition models. The models broadly reproduce large-scale changes in surface aerosol and ozone based on observations (e.g.-1 to-3%yr-1 in aerosols over the USA and Europe). The global mean radiative forcing due to ozone and aerosol changes over the 1990-2015 period increased by +0.17±0.08Wm-2, with approximately one-third due to ozone. This increase is more strongly positive than that reported in IPCC AR5. The main reasons for the increased positive radiative forcing of aerosols over this period are the substantial reduction of global mean SO2 emissions, which is stronger in the new emission inventory compared to that used in the IPCC analysis, and higher black carbon emissions.

Reducing aviation emissions is important as they contribute to air pollution and climate change. Several alternative aviation fuels that may reduce life cycle emissions have been proposed. Comparative life cycle assessments (LCAs) of fuels are useful for inspecting individual fuels, but systemwide analysis remains difficult. Thus, systematic properties like fleet composition, performance, or emissions and changes to them under alternative fuels can only be partially addressed in LCAs. By integrating the geospatial fuel and emission model, AviTeam, with LCA, we can assess the mitigation potential of a fleetwide use of alternative aviation fuels on 210 000 shorter haul flights. In an optimistic case, liquid hydrogen (LH2) and power-to-liquid fuels, when produced with renewable electricity, may reduce emissions by about 950 GgCO 2 eq when assessed with the GWP100 metric and including non-CO 2 impacts for all flights considered. Mitigation potentials range from 44% on shorter flights to 56% on longer flights. Alternative aviation fuels' mitigation potential is limited because of short-lived climate forcings and additional fuel demand to accommodate LH2 fuel. Our results highlight the importance of integrating system models into LCAs and are of value to researchers and decision-makers engaged in climate change mitigation in the aviation and transport sectors.

The rate of global surface warming is crucial for tracking progress towards global climate targets, but is strongly influenced by interannual-to-decadal variability, which precludes rapid detection of the temperature response to emission mitigation. Here we use a physics based Green's function approach to filter out modulations to global mean surface temperature from sea-surface temperature (SST) patterns, and show that it results in an earlier emergence of a response to strong emissions mitigation. For observed temperatures, we find a filtered 2011-2020 surface warming rate of 0.24 °C per decade, consistent with long-term trends. Unfiltered observations show 0.35 °C per decade, partly due to the El Nino of 2015-2016. Pattern filtered warming rates can become a strong tool for the climate community to inform policy makers and stakeholder communities about the ongoing and expected climate responses to emission reductions, provided an effort is made to improve and validate standardized Green's functions., (© 2022. The Author(s).)

Introduction: Decreased fasting and oral glucose-stimulated incretin hormone concentrations following moderate-intensity continuous endurance training interventions have been reported in glucose-tolerant people, however results are conflicting. The effect of more time-efficient, very low-volume, high-intensity interval training (HIT) on circulating incretin hormone levels has never been studied. Materials and methods: Ten sedentary and overweight-to-obese participants (4 women and 6 men; age 43 ± 6 years (mean ± SD); BMI 30.2 ± 3.2 kg∙m -2 ; HbA1c 35 ± 5.1 mmol∙mol -1 (5.3 ± 0.3%); VO 2 max 30 ± 5 ml∙min -1 ∙kg -1 ) from the Copenhagen cohort of the METAPREDICT trial underwent 6 weeks of supervised low-volume HIT (3 sessions per week: 7 × 1 min at ∼100% VO 2 max separated by 1 min of active recovery). We measured glucose, insulin, C-peptide, glucagon, GLP-1 and GIP concentrations during a frequently sampled 75 g oral glucose tolerance test as well as VO 2 max and body composition before and after the intervention. Results: Training compliance was 100%. Relative VO 2 max improved after the intervention (median 2.69 ml∙min -1 ∙kg -1 , IQR [0.43; 3.14], p  = 0.037) while there were no significant effects on body weight and composition. No significant effects on oral glucose-stimulated glucose and hormone responses or estimates of insulin sensitivity and β-cell function were observed. Conclusion: Low-volume HIT improved aerobic fitness, but neither affected glucose tolerance nor oral glucose-stimulated incretin hormone responses in sedentary and overweight-to-obese people. Highlights Ten sedentary, overweight-to-obese, glucose-tolerant participants underwent 6 weeks of supervised, very low-volume HIT.Aerobic fitness improved.Fasting and oral glucose-stimulated incretin hormone concentrations were not affected.

Background: Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination., Methods: In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18-55 years with a body-mass index 27·0-39·9 kg/m 2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC 0-168 h ) and maximum concentration [C max ] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to C max [t max ], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete., Findings: Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16-2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16-4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC 0-168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and C max ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16-4·5 mg. AUC 0-168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and C max ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16-4·5 mg had a half-life of 159-195 h, with a median t max of 24-72 h. Semaglutide 2·4 mg had a half-life of 145-165 h, with a median t max of 12-24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1-5; estimated treatment difference of -6·0% [95% CI -9·9 to -2·0] for cagrilintide 1·2 mg and -7·4% [-11·2 to -3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference -7·4% [-12·8 to -2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups., Interpretation: Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination., Funding: Novo Nordisk A/S., Competing Interests: Declaration of interests LBE, KKB, MTL, and AS are employees and shareholders at Novo Nordisk A/S. MK is the principal investigator for the study and received sponsorship from Novo Nordisk. DMR is a consultant, advisory board member, speaker, clinical investigator for, and shareholder of Novo Nordisk; a clinical investigator for Boehringer Ingelheim; has received research funding from Obesinov and honoraria from Medscape. DCWL is a consultant for and has received speaker honoraria from Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, and Novo Nordisk., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO 2 ), nitrogen oxides (NO x ), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr -1 , and in terms of climate change impacts, with CO 2 emissions increasing by a factor of 6.8 to 1034 Tg CO 2 yr -1 . Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO 2 and NO x emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m -2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m -2 ), CO 2 (34.3 mW m -2 ), and NO x (17.5 mW m -2 ). Non-CO 2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m -2 . Uncertainty distributions (5%, 95%) show that non-CO 2 forcing terms contribute about 8 times more than CO 2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO 2 -warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO 2 emissions alone. CO 2 and NO x aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

A major step towards achieving the goals of the Paris agreement would be a measurable change in the evolution of global warming in response to mitigation of anthropogenic emissions. The inertia and internal variability of the climate system, however, will delay the emergence of a discernible response even to strong, sustained mitigation. Here, we investigate when we could expect a significant change in the evolution of global mean surface temperature after strong mitigation of individual climate forcers. Anthropogenic CO 2 has the highest potential for a rapidly measurable influence, combined with long term benefits, but the required mitigation is very strong. Black Carbon (BC) mitigation could be rapidly discernible, but has a low net gain in the longer term. Methane mitigation combines rapid effects on surface temperature with long term effects. For other gases or aerosols, even fully removing anthropogenic emissions is unlikely to have a discernible impact before mid-century.

Objective: Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg., Methods: The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE) IBT was a 56-week, randomized, double-blind, placebo-controlled, multicenter trial in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140) as an adjunct to IBT., Results: At week 56, mean weight loss with liraglutide 3.0 mg plus IBT was 7.5% and 4.0% with placebo combined with IBT (estimated treatment difference [95% CI]-3.4% [-5.3% to -1.6%], P = 0.0003). Significantly more individuals on liraglutide 3.0 mg than placebo achieved ≥ 5% weight loss (61.5% vs. 38.8%; odds ratio [OR] 2.5% [1.5% to 4.1%], P = 0.0003), > 10% weight loss (30.5% vs. 19.8%; OR 1.8% [1.0% to 3.1%], P = 0.0469), and > 15% weight loss (18.1% vs. 8.9%; OR 2.3% [1.1% to 4.7%], P = 0.0311). Liraglutide 3.0 mg in combination with IBT was well tolerated, with no new safety signals identified., Conclusions: In a primary care setting, Centers for Medicare and Medicaid Services-based IBT produced clinically meaningful weight loss at 56 weeks, enhanced by the addition of liraglutide 3.0 mg., (© 2020 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).)

Aims: Skeletal muscle lipid stores and mitochondrial function have been appointed as key players in obesity-induced insulin resistance. However, there are conflicting reports in the literature based on in vitro quantitative measurements. Here, we test the hypothesis that it is not the quantity but the quality that matters., Methods: This study combines quantitative and qualitative structural measurements of lipid stores and mitochondrial dynamics in skeletal muscle from lean subjects, and subjects with morbid obesity, with and without type 2 diabetes, before and after gastric bypass surgery., Results: The structural organization of muscle mitochondrial networks in type II muscle fibres from subjects with morbid obesity is impaired. In addition, the amount of skeletal muscle perilipin 2 protein per intramyocellular lipid is reduced in subjects with morbid obesity, resulting in qualitative alterations in perilipin 2 coat around some lipid droplets. Gastric bypass surgery-induced weight loss and insulin resistance remission were associated with decreases in intramyocellular lipid stores and, qualitative improvements in lipid droplets' morphology, perilipin 2 coat and mitochondrial dynamics., Conclusion: Morbid obesity leads to severe qualitative alterations of both skeletal muscle lipid stores and mitochondrial networks. The degree of structural improvements after gastric bypass surgery was proportional to the improvements in whole body insulin sensitivity, suggesting an association between these events., (© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Fine particulate matter air pollution (PM 2.5 ) is a major risk factor for premature death globally. Studies of the PM 2.5 health burden usually treat exposure to ambient air pollution (AAP) and household air pollution from solid fuels (HAP) as separate risk factors. AAP and HAP can, however, be closely interrelated. Taking as the starting point that the total exposure to PM 2.5 is what matters for health, and recognizing the curvilinear form of exposure-response functions for important health effects, we develop a method for estimating the total annual mean population-weighted personal exposure, denoted integrated population-weighted exposure (IPWE). To establish the IPWE in China, we used recent emission inventories, Chemical Transport Models, China Census data on population and residential fuel use, and estimates of the PM 2.5 exposure among solid fuel users. We found an IPWE of 151 [123-179] μg/m 3 , of which 62-74% was attributable to residential solid fuels through HAP exposure and the residential sector emissions' contribution to AAP. We found large disparities in the PM 2.5 exposure burden, with an estimated IPWE in rural populations nearly twice the level in urban populations. Using the IPWE metric, we estimated that 1.15 [1.09-1.19] million premature deaths were attributable to PM 2.5 exposure annually in the period 2010-2013. Using the same data set, but calculating premature deaths from AAP and HAP in isolation, the estimated number was nearly 50% higher. The IPWE metric enables integration across AAP and HAP in policy analyses and could mitigate the concern of a potential double counting of the health burden that may arise from treating AAP and HAP as separate health risk factors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: It has been proposed, but not yet demonstrated by convincing evidence in published articles, that insulin resistance and mitochondrial respiratory function are causally related physiological phenomena. Here, we tested the prediction that weight loss-induced increase in insulin sensitivity will correlate with a corresponding change in mitochondrial respiratory capacity over the same time period., Methods: Insulin sensitivity was evaluated using the hyperinsulinaemic-euglycaemic clamp technique, and skeletal muscle mitochondrial respiratory capacity was evaluated by high-resolution respirometry in 26 patients with obesity. Each experiment was performed ~2 months and 1-2 weeks before, and ~4 and ~19 months after Roux-en-Y gastric bypass (RYGB) surgery., Results: A substantial weight loss was observed in all patients, and insulin sensitivity increased in all patients over the 21-months time period of the study. In contrast, skeletal muscle mitochondrial respiratory capacity, intrinsic mitochondrial respiratory capacity and mitochondrial content remained unchanged over the same time period., Conclusion: Among obese patients with and without type 2 diabetes undergoing RYGB surgery, intrinsic mitochondrial respiratory capacity in skeletal muscle is not correlated with insulin sensitivity before or after the surgical intervention. Mitochondrial respiratory function may not be germane to the pathophysiology and/or aetiology of obesity and/or type 2 diabetes., (© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Aim: Metabolic health may deteriorate with age as a result of altered body composition and decreased physical activity. Endurance exercise is known to counter these changes delaying or even preventing onset of metabolic diseases. High-intensity interval training (HIIT) is a time efficient alternative to regular endurance exercise, and the aim of this study was to investigate the metabolic benefit of HIIT in older subjects., Methods: Twenty-two sedentary male (n = 11) and female (n = 11) subjects aged 63 ± 1 years performed HIIT training three times/week for 6 weeks on a bicycle ergometer. Each HIIT session consisted of five 1-minute intervals interspersed with 1½-minute rest. Prior to the first and after the last HIIT session whole-body insulin sensitivity, measured by a hyperinsulinaemic-euglycaemic clamp, plasma lipid levels, HbA1c, glycaemic parameters, body composition and maximal oxygen uptake were assessed. Muscle biopsies were obtained wherefrom content of glycogen and proteins involved in muscle glucose handling were determined., Results: Insulin sensitivity (P = .011) and maximal oxygen uptake increased (P < .05) in both genders, while plasma cholesterol (P < .05), low-density lipoprotein (P < .05), visceral fat mass (P < .05) and per cent body fat (P < .05) decreased after 6 weeks of HIIT. HbA1c decreased only in males (P = .001). Muscle glycogen content increased in both genders (P = .001) and in line GLUT4 (P < .05), glycogen synthase (P = .001) and hexokinase II (P < .05) content all increased., Conclusion: Six weeks of HIIT significantly improves metabolic health in older males and females by reducing age-related risk factors for cardiometabolic disease., (© 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Aim: The baroreflex is a key mechanism in cardiovascular regulation, and alterations in baroreceptor function are seen in many diseases, including heart failure, obesity and hypertension. We propose a new method for analysing baroreceptor function from continuous blood pressure (BP) and heart rate (HR) in both health and disease., Methods: Forty-eight-hour data series of BP and HR were collected with telemetry. Sprague Dawley rats on standard chow (n = 11) served as controls, while rats on a high-fat, high-fructose (HFHC) diet (n = 6) constituted the obese-hypertensive model. A third group of rats underwent autonomic blockade (n = 6). An autoregressive-moving-average with exogenous inputs (ARMAX) model was applied to the data and compared with the α-coefficient., Results: Autonomic blockade caused a significant reduction in the strength of the baroreflex as estimated by ARMAX [ARMAX- baroreflex sensitivity (BRS)] -0.03 ± 0.01 vs. -0.19 ± 0.04 bpm heartbeat -1) . Both methods showed a ~50% reduction in BRS in the obese-hypertensive group compared with control (body weight 531 ± 27 vs. 458 ± 19 g, P < 0.05; mean arterial pressure 119 ± 3 vs. 102 ± 1 mmHg, P < 0.05; ARMAX-BRS -0.08 ± 0.01 vs. -0.15 ± 0.01 bpm heartbeat -1 , P < 0.05; α-coefficient BRS 0.51 ± 0.07 vs. 0.89 ± 0.07 ms mmHg -1 , P < 0.05). The ARMAX method additionally showed the open-loop gain of the baroreflex to be reduced by ~50% in the obese-hypertensive group (-2.3 ± 0.3 vs. -4.1 ± 0.3 bpm, P < 0.05), while the rate constant was similar between groups., Conclusion: The ARMAX model represents an efficient method for estimating several aspects of the baroreflex. The open-loop gain of the baroreflex was attenuated in obese-hypertensive rats compared with control, while the time response was similar. The algorithm can be applied to other species including humans., (© 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Ambient air pollution from ozone and fine particulate matter is associated with premature mortality. As emissions from one continent influence air quality over others, changes in emissions can also influence human health on other continents. We estimate global air pollution-related premature mortality from exposure to PM 2.5 and ozone, and the avoided deaths from 20% anthropogenic emission reductions from six source regions, North America (NAM), Europe (EUR), South Asia (SAS), East Asia (EAS), Russia/Belarus/Ukraine (RBU) and the Middle East (MDE), three global emission sectors, Power and Industry (PIN), Ground Transportation (TRN) and Residential (RES) and one global domain (GLO), using an ensemble of global chemical transport model simulations coordinated by the second phase of the Task Force on Hemispheric Transport of Air Pollution (TF-HTAP2), and epidemiologically-derived concentration-response functions. We build on results from previous studies of the TF-HTAP by using improved atmospheric models driven by new estimates of 2010 anthropogenic emissions (excluding methane), with more source and receptor regions, new consideration of source sector impacts, and new epidemiological mortality functions. We estimate 290,000 (95% CI: 30,000, 600,000) premature O 3 -related deaths and 2.8 million (0.5 million, 4.6 million) PM 2.5 -related premature deaths globally for the baseline year 2010. While 20% emission reductions from one region generally lead to more avoided deaths within the source region than outside, reducing emissions from MDE and RBU can avoid more O 3 -related deaths outside of these regions than within, and reducing MDE emissions also avoids more PM 2.5 -related deaths outside of MDE than within. Our findings that most avoided O 3 -related deaths from emission reductions in NAM and EUR occur outside of those regions contrast with those of previous studies, while estimates of PM 2.5 -related deaths from NAM, EUR, SAS and EAS emission reductions agree well. In addition, EUR, MDE and RBU have more avoided O 3 -related deaths from reducing foreign emissions than from domestic reductions. For six regional emission reductions, the total avoided extra-regional mortality is estimated as 6,000 (-3,400, 15,500) deaths/year and 25,100 (8,200, 35,800) deaths/year through changes in O 3 and PM 2.5 , respectively. Interregional transport of air pollutants leads to more deaths through changes in PM 2.5 than in O 3 , even though O 3 is transported more on interregional scales, since PM 2.5 has a stronger influence on mortality. For NAM and EUR, our estimates of avoided mortality from regional and extra-regional emission reductions are comparable to those estimated by regional models for these same experiments. In sectoral emission reductions, TRN emissions account for the greatest fraction (26-53% of global emission reduction) of O 3 -related premature deaths in most regions, in agreement with previous studies, except for EAS (58%) and RBU (38%) where PIN emissions dominate. In contrast, PIN emission reductions have the greatest fraction (38-78% of global emission reduction) of PM 2.5 -related deaths in most regions, except for SAS (45%) where RES emission dominates, which differs with previous studies in which RES emissions dominate global health impacts. The spread of air pollutant concentration changes across models contributes most to the overall uncertainty in estimated avoided deaths, highlighting the uncertainty in results based on a single model. Despite uncertainties, the health benefits of reduced intercontinental air pollution transport suggest that international cooperation may be desirable to mitigate pollution transported over long distances.

We conducted a randomized, single-blinded study of the effect of alcohol intake during a hangover. We measured cardiovascular parameters, and the participants filled out a series of questionnaires regarding their well-being. We found, that an intake of five beers led to a significant decrease in systolic blood pressure, heart rate and self-reported feeling of palpitations. However, the self-reported sense of well-being did not improve. In addition, we found that the risk of brain freeze increased, as the beer's temperature fell.

Over the last 35 years there has been an almost 50% increase in childhood obesity worldwide. Childhood obesity is associated with increased cardiovascular morbidity and mortality in adulthood, and in children with overweight or obesity pathologic changes have been found down to the age of two years. These changes are present in vasculature, heart and autonomic nervous system and affect blood pressure control. Overweight and obesity must be prevented, detected and treated at an early age, as even a small weight loss reduces the risk of cardiovascular disease significantly.

Objective: To investigate hepatic and adipose tissue macrophage content in subjects with obesity and the role of adipose tissue macrophages in weight loss-induced improved insulin sensitivity (IS)., Methods: A cross-sectional and a longitudinal study were combined to investigate the role of macrophages in subcutaneous (SAT) and visceral (VAT) adipose tissue and the liver in obesity-induced impaired IS and improvements with weight loss. Macrophage markers (CD68, CD163, and CD206) in SAT, VAT, and the liver from patients with obesity were investigated. The same macrophage markers were investigated in SAT from 18 patients with obesity before and ∼18 months after a diet- and Roux-en-Y gastric bypass-induced weight loss., Results: SAT macrophage markers did not decrease with weight loss, but macrophage concentration may have increased, concomitant with improved IS. Hepatic macrophage markers did not correlate to VAT mass or macrophage markers, but they were higher in patients with obesity compared with patients without obesity. Hepatic anti-inflammatory macrophage markers correlated positively with hepatic IS. VAT and SAT macrophage markers did not correlate., Conclusions: The results indicate that decreased SAT macrophage content is not a primary driver for weight loss-induced IS improvements, but a better hepatic CD163 and CD206 macrophage profile may contribute to improved glycemic control. SAT macrophage markers were not predictive for VAT macrophage markers., (© 2017 The Obesity Society.)

The recent update on the US National Ambient Air Quality Standards (NAAQS) of the ground-level ozone (O 3 / can benefit from a better understanding of its source contributions in different US regions during recent years. In the Hemispheric Transport of Air Pollution experiment phase 1 (HTAP1), various global models were used to determine the O 3 source-receptor (SR) relationships among three continents in the Northern Hemisphere in 2001. In support of the HTAP phase 2 (HTAP2) experiment that studies more recent years and involves higher-resolution global models and regional models' participation, we conduct a number of regional-scale Sulfur Transport and dEposition Model (STEM) air quality base and sensitivity simulations over North America during May-June 2010. STEM's top and lateral chemical boundary conditions were downscaled from three global chemical transport models' (i.e., GEOS-Chem, RAQMS, and ECMWF C-IFS) base and sensitivity simulations in which the East Asian (EAS) anthropogenic emissions were reduced by 20 %. The mean differences between STEM surface O 3 sensitivities to the emission changes and its corresponding boundary condition model's are smaller than those among its boundary condition models, in terms of the regional/period-mean (<10 %) and the spatial distributions. An additional STEM simulation was performed in which the boundary conditions were downscaled from a RAQMS (Realtime Air Quality Modeling System) simulation without EAS anthropogenic emissions. The scalability of O 3 sensitivities to the size of the emission perturbation is spatially varying, and the full (i.e., based on a 100% emission reduction) source contribution obtained from linearly scaling the North American mean O 3 sensitivities to a 20% reduction in the EAS anthropogenic emissions may be underestimated by at least 10 %. The three boundary condition models' mean O 3 sensitivities to the 20% EAS emission perturbations are ~8% (May-June 2010)/~11% (2010 annual) lower than those estimated by eight global models, and the multi-model ensemble estimates are higher than the HTAP1 reported 2001 conditions. GEOS-Chem sensitivities indicate that the EAS anthropogenic NO x emissions matter more than the other EAS O 3 precursors to the North American O 3 , qualitatively consistent with previous adjoint sensitivity calculations. In addition to the analyses on large spatial-temporal scales relative to the HTAP1, we also show results on subcontinental and event scales that are more relevant to the US air quality management. The EAS pollution impacts are weaker during observed O 3 exceedances than on all days in most US regions except over some high-terrain western US rural/remote areas. Satellite O 3 (TES, JPL-IASI, and AIRS) and carbon monoxide (TES and AIRS) products, along with surface measurements and model calculations, show that during certain episodes stratospheric O 3 intrusions and the transported EAS pollution influenced O 3 in the western and the eastern US differently. Free-running (i.e., without chemical data assimilation) global models underpredicted the transported background O 3 during these episodes, posing difficulties for STEM to accurately simulate the surface O 3 and its source contribution. Although we effectively improved the modeled O 3 by incorporating satellite O 3 (OMI and MLS) and evaluated the quality of the HTAP2 emission inventory with the Royal Netherlands Meteorological Institute-Ozone Monitoring Instrument (KNMI-OMI) nitrogen dioxide, using observations to evaluate and improve O 3 source attribution still remains to be further explored., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Roux-en-Y gastric bypass (RYGB) leads to a major weight loss in obese patients. However, given that most patients remain obese after the weight loss, regular exercise should be part of a healthier lifestyle. The primary aim of this study was to investigate the cardiopulmonary fitness in obese patients before and after RYGB. Thirty-four patients had body composition and cardiopulmonary fitness (VO 2max ) assessed and completed questionnaires regarding physical activity and function twice before RYGB (time points A and B) and 4 and 18 months after surgery (time points C and D). Weight loss was 37 ± 2 kg during the study period. VO 2max increased (A: 21 ± 1 vs D: 29 mL/min/kg, P < 0.001), but absolute VO 2max decreased (A: 2713 ± 126 vs 2609 ± 187 mL/min, P = 0.02) and VO 2max per kilogram fat free mass did not change. Self-perceived limitations to perform exercise decreased and self-perceived physical fitness increased after RYGB. Self-reported low- and high-intensity physical activity did not change. With weight loss, self-rated fitness level increased and the limitations to perform exercise decreased in RYGB patients. Nevertheless, as shown by the lower absolute VO 2max , RYGB patients do not adopt new exercise habits following surgery., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reducing global carbon dioxide (CO2) emissions is often thought to be at odds with economic growth and poverty reduction. Using an integrated assessment modeling approach, we find that China can cap CO2 emissions at 2015 level while sustaining economic growth and reducing the urban-rural income gap by a third by 2030. As a result, the Chinese economy becomes less dependent on exports and investments, as household consumption emerges as a driver behind economic growth, in line with current policy priorities. The resulting accumulated greenhouse gas emissions reduction 2016-2030 is about 60billionton (60Mg) CO2e. A CO2 tax combined with income re-distribution initially leads to a modest warming due to reduction in sulfur dioxide (SO2) emissions. However, the net effect is eventually cooling when the effect of reduced CO2 emissions dominates due to the long-lasting climate response of CO2. The net reduction in global temperature for the remaining part of this century is about 0.03±0.02°C, corresponding in magnitude to the cooling from avoiding one year of global CO2 emissions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Key Points: Hepatic insulin resistance in patients with obesity or type 2 diabetes has been suggested to result from hepatic mitochondrial dysfunction. High-resolution respirometry (HRR) can be used to assess oxidative phosphorylation by measuring the mitochondrial oxygen consumption rate in the individual complexes of the mitochondria. By using HRR, the present study demonstrates no difference in hepatic mitochondrial oxidative phosphorylation among subjects with obesity with or without type 2 diabetes and non-obese controls. Furthermore, the amount of mitochondria, assessed by the citrate synthase activity, is not different between the three groups. Together the present findings indicate that hepatic mitochondrial oxidative phosphorylation capacity is not impaired in patients with obesity or type 2 diabetes., Abstract: Obese patients with type 2 diabetes (T2DM) and without type 2 diabetes (OB) are characterized by high hepatic lipid content and hepatic insulin resistance. This may be linked to impaired hepatic mitochondrial oxidative phosphorylation (OXPHOS) capacity. The aim of the present study was to investigate and compare hepatic mitochondrial OXPHOS capacity in T2DM, OB and non-obese controls (CON). Seventeen obese patients (nine OB and eight T2DM) and six CON patients had perioperative liver biopsies taken. Samples were divided into three parts to measure (1) complex I, II and IV linked respiration, (2) citrate synthase (CS) activity and (3) lipid droplet (LD) size and area (% of total tissue area filled by LDs). State 3 respiration of complex I, II and IV and the CS activity did not differ in OB, T2DM and CON. LD size was significantly higher in T2DM compared with CON, and LD area tended (P = 0.10) to be higher in T2DM and OB compared with CON. The present findings indicate that hepatic OXPHOS capacity is not different in patients with markedly different weight and glycaemic control. Furthermore, the results do not support impaired hepatic mitochondrial respiratory capacity playing a major role in the development of obesity-induced type 2 diabetes., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Aims: The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N = 16) and without (OB, N = 27) type 2 diabetes was studied., Methods: At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition, hepatic glucose production (HGP), insulin-mediated glucose uptake (GIR), respiratory exchange ratio, hepatic insulin sensitivity and clearance were determined. GLUT4, intramuscular triglycerides (IMTG) and glycogen content were measured in skeletal muscle., Results: Weight loss was 35-40 kg, and approximately one-third of the total improvement in GIR in T2DM was observed after the diet-induced weight loss of only ~6 kg (B). Insulin clearance, visceral fat and fasting plasma insulin also improved significantly after the diet (P < 0.05). Throughout the study, HGP, GLUT4 and glycogen content did not change significantly, but IMTG decreased significantly consistent with significant increases in GIR. Metabolic flexibility and hepatic insulin sensitivity improved after RYGB., Conclusions: Metabolic improvements of RYGB are present already after the diet-induced weight loss prior to surgery. GLUT4 content in skeletal muscle cannot and IMTG content can only partly explain increases in GIR after RYGB.

Objective. To investigate the predictive value of type 2 diabetes and lack of physical activity for mental health and health-related quality of life after Roux-en-Y gastric bypass. Method. Forty severely obese patients undergoing Roux-en-Y gastric bypass were included in the GASMITO study. Information about physiological and psychological factors was prospectively assessed at four time points, two times prior to surgery and two times after surgery. Measures included oral and intravenous glucose tolerance tests, VO2max test, Symptoms Checklist (SCL-90), Short Form Health Survey 36 (SF-36), Body Image Questionnaire, and a questionnaire assessing sociodemographic factors and medical status. Results. Mean % excess weight loss was 65% (±12) at 18-month follow-up and 50% of the participants with diabetes experienced total remission. Also, significant improvements were observed with regard to physical fitness, mental distress, health-related quality of life, and weight-related body image (p < 0.05). The interaction between follow-up time and type 2 diabetes at baseline significantly predicted six of the thirteen psychological subscales (p < 0.05) and, across the follow-ups, physical fitness level made modest contributions to variations in mental symptoms and HRQOL but not weight-related body image. Conclusion. The results suggest that baseline difference in mental symptoms and physical HRQOL between diabetic and nondiabetic patients declines across follow-ups and resolves around the time of surgery.

Objective: To study adipose tissue mitochondrial respiration and lipolysis following a massive weight loss., Methods: High resolution respirometry of adipose tissue biopsies and tracer determined whole body lipolysis. Sixteen obese patients with type 2 diabetes (T2DM) and 27 without (OB) were studied following a massive weight loss by diet and Roux-en-Y gastric bypass (RYGB)., Results: The mitochondrial respiratory rates were similar in OB and T2DM, and the mass-specific oxygen flux increased significantly 4 and 18 months post-surgery (P < 0.05). With normalization to mitochondrial content, no differences in oxidative capacity after RYGB were seen. The ratio between the oxidative phosphorylation system capacity (P) and the capacity of the electron transfer system (E) increased 18 months after RYGB in both groups (P < 0.05). Lipolysis per fat mass was similar in the two groups and was increased (P < 0.05) and lipid oxidation during hyperinsulinemia decreased 4 months post-surgery. In T2DM, visceral fat mass was always higher relative to the body fat mass (%) compared to OB., Conclusions: Adipose tissue mitochondrial respiratory capacity increases with RYGB. Adipocytes adapt to massive weight loss by increasing the phosphorylation system ratio (P/E), suggesting an increased ability to oxidize substrates after RYGB. Lipolysis increases in the short term post-surgery, and insulin sensitivity for suppression of lipolysis increases with RYGB., (© 2015 The Obesity Society.)

The present study utilized a novel method aiming to investigate mitochondrial function in human skeletal muscle at submaximal levels and at a predefined membrane potential. The effect of age and training status was investigated using a cross-sectional design. Ageing was found to be related to decreased leak regardless of training status. Increased training status was associated with increased mitochondrial hydrogen peroxide emission. Despite numerous studies, there is no consensus about whether mitochondrial function is altered with increased age. The novelty of the present study is the determination of mitochondrial function at submaximal activity rates, which is more physiologically relevant than the ex vivo functionality protocols used previously. Muscle biopsies were taken from 64 old or young male subjects (aged 60-70 or 20-30 years). Aged subjects were recruited as trained or untrained. Muscle biopsies were used for the isolation of mitochondria and subsequent measurements of DNA repair, anti-oxidant capacity and mitochondrial protein levels (complexes I-V). Mitochondrial function was determined by simultaneous measurement of oxygen consumption, membrane potential and hydrogen peroxide emission using pyruvate + malate (PM) or succinate + rotenone (SR) as substrates. Proton leak was lower in aged subjects when determined at the same membrane potential and was unaffected by training status. State 3 respiration was lower in aged untrained subjects. This effect, however, was alleviated in aged trained subjects. H2 O2 emission with PM was higher in aged subjects, and was exacerbated by training, although it was not changed when using SR. However, with a higher manganese superoxide dismuthase content, the trained aged subjects may actually have lower or similar mitochondrial superoxide emission compared to the untrained subjects. We conclude that ageing and the physical activity level in aged subjects are both related to changes in the intrinsic functionality of the mitochondrion in skeletal muscle. Both of these changes could be important factors in determining the metabolic health of the aged skeletal muscle cell., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

The majority of the patients with type 2 diabetes (T2DM) show remission after Roux-en-Y gastric bypass (RYGB). This is the result of increased postoperative insulin sensitivity and β-cell secretion. The aim of the present study was to elucidate the importance of the preoperative β-cell function in T2DM for the chance of remission after RYGB. Fifteen patients with and 18 without T2DM had 25 g oral (OGTT) and intravenous (IVGTT) glucose tolerance tests performed at inclusion, after a diet-induced weight loss, and 4 and 18 months after RYGB. Postoperative first phase insulin secretion rate (ISR) during the IVGTT and β-cell glucose sensitivity during the OGTT increased in T2DM. Postoperative insulin sensitivity and the disposition index (DI) markedly increased in both groups. By stratifying the T2DM into two groups according to highest (T2DMhigh ) and lowest (T2DMlow ) baseline DI, a restoration of first phase ISR and β-cell glucose sensitivity were seen only in T2DMhigh . Remission of type 2 diabetes was 71 and 38% in T2DMhigh and T2DMlow , respectively. Postoperative postprandial GLP-1 concentrations increased markedly, but did not differ between the groups. Our findings emphasize the importance of the preoperative of β-cell function for remission of diabetes after RYGB., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Background: Some bariatric patients are referred for surgery with a diagnosis of type 2 diabetes while others are referred without co-morbid diabetes, but psychological differences between patients with and without type 2 diabetes undergoing bariatric surgery have not yet been investigated. The objective of this study was to present the baseline results of the longitudinal GASMITO-PSYC study, and to evaluate the psychological differences between bariatric patients with and without type 2 diabetes., Methods: A total of 129 Roux-en- Y gastric bypass patients were recruited from the bariatric clinic at a hospital in the suburban Copenhagen area. Participants answered questionnaires concerning personality, mental symptoms, health-related quality of life (HRQOL), body image, lifestyle, and physical health including diabetes status on average 11 weeks before surgery. Questionnaires were either sent to the participant's home address or administered at the University of Copenhagen., Results: Patients with type 2 diabetes scored higher on 'physical function' (P = .001), 'physical role' (P = .014), 'physical pain' (P = .021), and 'vitality' (P = .007) than nondiabetic patients after controlling for sex and age. The total study sample differed significantly from Danish test norms reporting higher neuroticism (P = .000), more mental symptoms (P = .000), lower HRQOL (P = .000), and less positive weight-related body image (P = .000)., Conclusion: Patients with type 2 diabetes had better physical HRQOL than nondiabetic patients. This study highlights the importance of investigating whether these differences affect surgical outcomes., (Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Biofuels are proposed to play an important role in several mitigation strategies to meet future CO2 emission targets for the transport sector but remain controversial due to significant uncertainties in net impacts on environment, society, and climate. A switch to biofuels can also affect short-lived climate forcers (SLCFs), which provide significant contributions to the net climate impact of transportation. We quantify the radiative forcing (RF) and global-mean temperature response over time to EU on-road fossil diesel SLCFs and the impact of 20% (B20) and 100% (B100) replacement of fossil diesel by biodiesel. SLCFs are compared to impacts of on-road CO2 using different approaches from existing literature to account for biodiesel CO2. Given the best estimates for changes in emissions when replacing fossil diesel with biodiesel, the net positive RF from EU on-road fossil diesel SLCFs of 3.4 mW/m(2) is reduced by 15% and 80% in B20 and B100, respectively. Over time the warming of SLCFs is likely small compared to biodiesel CO2 impacts. However, SLCFs may be relatively more important for the total warming than in the fossil fuel case if biodiesel from feedstock with very short rotation periods and low land-use-change impacts replaces a high fraction of fossil diesel.

Aim: After both oral and intravenous glucose administration, peripheral insulin concentrations are lower in trained compared with untrained humans. Part of this is explained by an adaptation within the β-cell. The insulin secretion rate is higher after oral compared with intravenous glucose administration due to the release of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) enhancing the glucose-induced insulin secretion (the incretin effect). Our aim was to investigate whether GIP or GLP-1 release or the incretin effect was different in trained compared with untrained humans after oral and intravenous glucose administration., Methods: A 3½-h oral glucose tolerance test was performed in eleven trained and ten untrained, young, healthy men. On a separate day, an isoglycaemic intravenous glucose infusion was performed matching the individual glucose concentrations obtained during the oral glucose tolerance test. Blood samples for insulin, C-peptide, GIP and GLP-1 analyses were obtained frequently during both tests, and the insulin secretion rate, incretin effect and insulin clearance were calculated., Results: Plasma GIP and GLP-1 concentrations, the incretin effect and the insulin clearance did not differ, and plasma glucose, insulin and C-peptide concentrations and the insulin secretion rate were lower in trained compared with untrained subjects during both tests., Conclusion: With no difference in incretin effect and insulin clearance between the two groups, the lower plasma insulin concentrations found in trained compared with untrained, young, healthy men are most likely explained by lower β-cell sensitivity to glucose and enhanced glucose uptake in skeletal muscle in the former group., (© 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Postprandial insulin release is lower in healthy aerobically trained (T) compared to untrained (UT) individuals. This may be mediated by a lower release of the two incretin hormones [glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] in T. The aim of this study was to assess and compare gut hormone response and satiety changes after a liquid meal intake in young, healthy T and UT males. Postprandial gut hormone release and subjective feelings of hunger, satiety, fullness and prospective food consumption were assessed before and frequently for the following 3 h after a 200 ml liquid meal (1,260 kJ and 27, 41 and 32 energy % as protein, carbohydrates and fat, respectively) in ten T and ten UT young, healthy male subjects. The insulin and GIP responses were markedly lower in T than UT and correlated during the first 30 min after the liquid meal. Baseline GLP-1 concentration was higher in T versus UT, but the response in the following 3 h after a liquid meal was similar in T and UT. Satiety measures did not differ between groups throughout the test. It is possible that in aerobically T subjects, a lower GIP release is partly responsible for a lower postprandial incretin stimulated insulin secretion.

Data on interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-α release during exercise. We have now studied the temporal relationship of leg IL-6 and TNF-α release before and during isolated two-legged exercise after 14 days of one-leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.6 ± 0.7 kg m(-2); and maximal oxygen uptake, 46.8 ± 1.4 ml kg(-1) min(-1)) performed 45 min of two-legged dynamic knee-extensor exercise at 19.6 ± 0.8 W. Arterial and femoral venous blood samples from the CON and the IM leg were collected every 15 min during exercise, and leg blood flow was measured with Doppler ultrasound. The arterial plasma IL-6 concentration increased (P < 0.05) with exercise (rest, 1.3 ± 0.1 pg ml(-1); 15 min, 1.9 ± 0.2 pg ml(-1); 30 min, 2.4 ± 0.2 pg ml(-1); and 45 min, 3.1 ± 0.3 pg ml(-1)). Interleukin-6 release occurred after 15 min of exercise, and the release from the IM leg was significantly greater compared with the CON leg after 45 min (1114 ± 152 versus 606 ± 14 pg min(-1), respectively, P < 0.05). Tumour necrosis factor-α release did not differ between the CON and the IM leg, and arterial concentrations remained unchanged during exercise (P > 0.05). In conclusion, prior immobilization enhances release of IL-6 from the leg during exercise at a moderate workload, and the release is already present in the early phase of exercise. Neither immobilization nor exercise had an effect on TNF-α release in the working legs.

We utilize a range of emission scenarios for shipping to determine the induced global-mean radiative forcing and temperature change. Ship emission scenarios consistent with the new regulations on nitrogen oxides (NO(x)) and sulfur dioxide (SO(2)) from the International Maritime Organization and two of the Representative Concentration Pathways are used as input to a simple climate model (SCM). Based on a complex aerosol-climate model we develop and test new parametrizations of the indirect aerosol effect (IAE) in the SCM that account for nonlinearities in radiative forcing of ship-induced IAE. We find that shipping causes a net global cooling impact throughout the period 1900-2050 across all parametrizations and scenarios. However, calculated total net global-mean temperature change in 2050 ranges from -0.03[-0.07,-0.002]°C to -0.3[-0.6,-0.2]°C in the A1B scenario. This wide range across parametrizations emphasizes the importance of properly representing the IAE in SCMs and to reflect the uncertainties from complex global models. Furthermore, our calculations show that the future ship-induced temperature response is likely a continued cooling if SO(2) and NO(x) emissions continue to increase due to a strong increase in activity, despite current emission regulations. However, such cooling does not negate the need for continued efforts to reduce CO(2) emissions, since residual warming from CO(2) is long-lived.

A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on the shapes of all other vertebrae in the image. The difference between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality. In contrast with the current (semi-)quantitative grading strategies this method takes the full shape into account, it develops a patient-specific reference by combining population-based information on biological variation in vertebral shape and vertebra interrelations, and it provides a continuous measure of deformity. The method is demonstrated on 282 lateral spine radiographs with in total 93 fractures. Vertebral fracture detection is shown to be in good agreement with semi-quantitative scoring by experienced radiologists and is superior to the performance of shape models alone.

A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on all other vertebrae in the image. The differences between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality. In contrast with the current (semi-)quantitative grading strategies this method takes the full shape into account, it uses a patient-specific reference by combining population-based information on biological variation in vertebra shape and vertebra interrelations, and it provides a continuous measure of deformity. The method is demonstrated on 212 lateral spine radiographs with in total 78 fractures. The distance between prediction and true shape is 1.0 mm for unfractured vertebrae and 3.7 mm for fractures, which makes it possible to diagnose and assess the severity of a fracture.