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  • Open Access English
    Authors: 
    Meixiu Yu; Daqing Yang; Xiaolong Liu; Qiongfang Li; Guoqing Wang;
    Publisher: MDPI AG
    Country: Netherlands

    Dam building and reservoir operations alter the downstream hydrological regime, and as a result, affect the health of the river aquatic ecosystem, particularly for large-scale cascade reservoirs. This study investigated the impact of the Gezhouba Reservoir (GR) and the Three Gorges Reservoir (TGR) on the spawning conditions of two critical taxa, i.e., the endemic four major carps and the endangered Chinese sturgeon in the Yangtze River. We analyzed the flow, sediment, and thermal regime in these two taxa spawning seasons and compared their features between the predam and postdam periods. Our results revealed that the GR and the TGR had altered the frequency distributions of flow, sediment, and water temperature to different degrees, with the impact by the GR on the carps and Chinese sturgeon ranked as water temperature > water temperature. For the GR, the satisfying degree of the suitable flow and water temperature of the carps increased, whilst the suitable flow, sediment, and water temperature for the Chinese sturgeon decreased. These changes in TGR showed a significant ascending (descending) trend in the suitable flow (water temperature) for the carps, and a clear decreasing trend in the flow, sediment, and temperature for Chinese sturgeon. Both the TGR and the GR had negative impacts on the spawning of these two taxa in terms of the rising/falling flow characteristics. flow, and the effect of the TGR on these two taxa were ordered as flow > water temperature, sediment > water temperature > flow, sediment > flow >

  • Publication . Article . 2020
    Open Access English
    Authors: 
    Tim Bayne; Anil K. Seth; Marcello Massimini;
    Countries: Italy, United Kingdom
    Project: EC | LUMINOUS (686764), EC | HBP SGA2 (785907), EC | HBP SGA3 (945539)

    Ordinary human experience is embedded in a web of causal relations that link the brain to the body and the wider environment. However, there might be conditions in which brain activity supports consciousness even when that activity is fully causally isolated from the body and its environment. Such cases would involve what we call islands of awareness: conscious states that are neither shaped by sensory input nor able to be expressed by motor output. This Opinion paper considers conditions in which such islands might occur, including ex cranio brains, hemispherotomy, and in cerebral organoids. We examine possible methods for detecting islands of awareness, and consider their implications for ethics and for the nature of consciousness.

  • Publication . Article . Other literature type . 2016
    Open Access
    Authors: 
    Trisha Greenhalgh; Ellen Annandale; Richard Ashcroft; James Barlow; Nick Black; Alan Bleakley; Ruth Boaden; Jeffrey Braithwaite; Nicky Britten; Franco A. Carnevale; +65 more
    Countries: Netherlands, Australia, United Kingdom, Netherlands

    Seventy six senior academics from 11 countries invite The BMJ ’s editors to reconsider their policy of rejecting qualitative research on the grounds of low priority. They challenge the journal to develop a proactive, scholarly, and pluralist approach to research that aligns with its stated mission

  • Open Access English
    Authors: 
    Jonkman, N.H.; Westland, H.; Trappenburg, J.C.A.; Groenwold, R.H.H.; Effing, T.W.; Troosters, T.; van der Palen, J.; Bourbeau, J.; Jaarsma, T.; Hoes, A.W.; +3 more
    Countries: Belgium, Sweden, Netherlands, Australia

    Introduction: Self-management interventions in patients with chronic conditions have received increasing attention over the past few years, yet the meta-analyses encountered considerable heterogeneity in results. This suggests that the effectiveness of self-management interventions must be assessed in the context of which components are responsible for eliciting the effect and in which subgroups of patients the intervention works best. The aim of the present study is to identify condition-transcending determinants of success of self-management interventions in two parallel individual patient data meta-analyses of self-management trials in patients with congestive heart failure (CHF) and in patients with chronic obstructive pulmonary disease (COPD). Methods and analysis: Investigators of 53 randomised trials (32 in CHF and 21 in COPD) will be requested to share their de-identified individual patient data. Data will be analysed using random effects models, taking clustering within studies into account. Effect modification by age, sex, disease severity, symptom status, comorbid conditions and level of education will be assessed. Sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination: The de-identified individual patient data are used only for the purpose for which they were originally collected and for which ethical approval has been obtained by the original investigators. Knowledge on the effective ingredients of self-management programmes and identification of subgroups of patients in which those interventions are most effective will guide the development of evidence-based personalised self-management interventions for patients with CHF and COPD as well as with other chronic diseases. Trial registration number: PROSPERO: CRD42013004698.

  • Open Access English
    Authors: 
    Ben Vandermeer; Ingeborg van der Tweel; Marijke C. Jansen-van der Weide; Stephanie S. Weinreich; Despina G. Contopoulos-Ioannidis; Dirk Bassler; Ricardo M. Fernandes; Lisa M. Askie; Haroon Saloojee; Paola Baiardi; +2 more
    Countries: Switzerland, Netherlands
    Project: NWO | Blue Action (32188), EC | GRIP (261060)

    Background: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former.Methods: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials.Results: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74).Conclusions: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

  • Open Access
    Authors: 
    Mansour Bechar; Abdeldjebar Hazzab; Mohamed Habbab; Pierre Sicard;
    Publisher: Institute of Advanced Engineering and Science

    In this paper, Reduced-Order Observer For Real-Time Implementation Speed Sensorless Control of Induction Using RT-LAB Softwareis presented. Speed estimation is performed through a reduced-order observer. The stability of the proposed observer is proved based on Lyapunov’s theorem. The model is initially built offline using Matlab/Simulink and implemented in real-time environment using RT-LAB package and an OP5600 digital simulator. RT-LAB configuration has two main subsystems master and console subsystems. These two subsystems were coordinated to achieve the real-time simulation. In order to verify the feasibility and effectiveness of proposed method, experimental results are presented over a wide speed range, including zero speed.

  • Closed Access
    Authors: 
    Stephen A. Marshall;
    Publisher: Magnolia Press

    The Micropezidae of Madagascar are reviewed, and the endemic genus Paramimegralla Hennig is revised. Twenty species are recognized including two Hybobata species and 18 Paramimegralla species, of which 12 are described as new (P. luteoscapus , brunnea , zinzala, zarpa, verticalis, taeniola, sulcata, campanula, anchivitta, quadrifasciata and longicephala ). Stiltissima Barraclough is synonymized with Paramimegralla Hennig and previous records of Rainieria Rondani from the island are shown to be incorrect. Paramimegralla steineri (Barraclough) and Paramimegralla volcanica (Barraclough) are given as new combinations, Paramimegralla stuckenbergi Barraclough is synonymized with P. nigra Barraclough, and Hybobata Enderlein is resurrected from synonymy with Mimegralla Rondani. All known Malagasy micropezid species are keyed and illustrated and all Paramimegralla species are described or redescribed.

  • Open Access English
    Authors: 
    Manish eSaggar; Brandon G King; Brandon G King; Anthony P Zanesco; Anthony P Zanesco; Katherine A MacLean; Stephen R Aichele; Stephen R Aichele; Tonya L Jacobs; David A Bridwell; +12 more
    Countries: United States, Australia
    Project: SSHRC

    The capacity to focus one's attention for an extended period of time can be increased through training in contemplative practices. However, the cognitive processes engaged during meditation that support trait changes in cognition are not well characterized. We conducted a longitudinal wait-list controlled study of intensive meditation training. Retreat participants practiced focused attention (FA) meditation techniques for three months during an initial retreat. Wait-list participants later undertook formally identical training during a second retreat. Dense-array scalp-recorded electroencephalogram (EEG) data were collected during 6 min of mindfulness of breathing meditation at three assessment points during each retreat. Second-order blind source separation, along with a novel semi-automatic artifact removal tool (SMART), was used for data preprocessing. We observed replicable reductions in meditative state-related beta-band power bilaterally over anteriocentral and posterior scalp regions. In addition, individual alpha frequency (IAF) decreased across both retreats and in direct relation to the amount of meditative practice. These findings provide evidence for replicable longitudinal changes in brain oscillatory activity during meditation and increase our understanding of the cortical processes engaged during meditation that may support long-term improvements in cognition.

  • Open Access
    Authors: 
    Heather L. Petrick; Henver Simionato Brunetta; Chris Pignanelli; Everson Araújo Nunes; Luc J. C. van Loon; Jamie F. Burr; Graham P. Holloway;
    Countries: Netherlands, Australia, Belgium
    Project: NSERC

    Key points Ketone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstratein vitrothat maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodiumdl-beta-hydroxybutyrate, beta-HB; lithium acetoacetate, AcAc) to stimulatein vitromitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (similar to 30-35% of pyruvate), RG (similar to 10-30%), and human vastus lateralis (similar to 2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 mu m beta-HB, 801 mu mAcAc; RG: 782 mu m beta-HB, 267 mu mAcAc) were greater than KB content representative of the muscle microenvironment (similar to 100 mu m). This would predict low rates (similar to 1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s(-1) mg(-1)) and RG (3-6 pmol s(-1) mg(-1)) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 mu m) reduced the ability of physiological beta-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

  • Open Access
    Authors: 
    Lars Kober; Manuel Martinez-Selles; Salim Yusuf; Antoni Bayes-Genis; Kim Krogsgaard; Olav Wendelboe Nielsen; Aldo Pietro Maggioni; Finlay McAlister; Carlos Fernandez-Palomeque; Albert Gabarrús; +10 more
    Country: Australia

    Aims Treatment of patients with heart failure (HF) relies on measurement of LVEF. However, the extent to which EF is recorded varies markedly. We sought to characterize the patient group that is missing a measure of EF, and to explore the association between missing EF and outcome. Methods and results Individual data on 30 445 patients from 28 observational studies in the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) project were used to compare the prevalence of co-morbidities and outcome across three groups of HF patients: those with missing EF (HF-mEF), reduced EF (HF-REF), and preserved EF (HF-PEF). A total of 29% had HF-mEF, 52% HF-REF, and 19% HF-PEF. Compared with patients in whom EF was known, patients with HF-mEF were older, had a greater prevalence of COPD and previous stroke, and were smokers. Patients with HF-mEF were less likely to receive evidence-based treatment than those with HF-REF. Adjusted mortality in HF-mEF was similar to that in HF-REF and greater than that in HF-PEF at 3 years [HF-REF, hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.95–1.12); HF-PEF, HR 0.78, 95% CI 0.71–0.86]. Conclusion Missing EF is common. The short- and long-term outcome of patients with HF-mEF is poor and they exhibit different co-morbidity profiles and treatment patterns compared with patients with known EF. HF patients with missing EF represent a high risk group.

Advanced search in
Research products
arrow_drop_down
Searching FieldsTerms
Any field
arrow_drop_down
includes
arrow_drop_down
Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
3,559 Research products, page 1 of 356
  • Open Access English
    Authors: 
    Meixiu Yu; Daqing Yang; Xiaolong Liu; Qiongfang Li; Guoqing Wang;
    Publisher: MDPI AG
    Country: Netherlands

    Dam building and reservoir operations alter the downstream hydrological regime, and as a result, affect the health of the river aquatic ecosystem, particularly for large-scale cascade reservoirs. This study investigated the impact of the Gezhouba Reservoir (GR) and the Three Gorges Reservoir (TGR) on the spawning conditions of two critical taxa, i.e., the endemic four major carps and the endangered Chinese sturgeon in the Yangtze River. We analyzed the flow, sediment, and thermal regime in these two taxa spawning seasons and compared their features between the predam and postdam periods. Our results revealed that the GR and the TGR had altered the frequency distributions of flow, sediment, and water temperature to different degrees, with the impact by the GR on the carps and Chinese sturgeon ranked as water temperature > water temperature. For the GR, the satisfying degree of the suitable flow and water temperature of the carps increased, whilst the suitable flow, sediment, and water temperature for the Chinese sturgeon decreased. These changes in TGR showed a significant ascending (descending) trend in the suitable flow (water temperature) for the carps, and a clear decreasing trend in the flow, sediment, and temperature for Chinese sturgeon. Both the TGR and the GR had negative impacts on the spawning of these two taxa in terms of the rising/falling flow characteristics. flow, and the effect of the TGR on these two taxa were ordered as flow > water temperature, sediment > water temperature > flow, sediment > flow >

  • Publication . Article . 2020
    Open Access English
    Authors: 
    Tim Bayne; Anil K. Seth; Marcello Massimini;
    Countries: Italy, United Kingdom
    Project: EC | LUMINOUS (686764), EC | HBP SGA2 (785907), EC | HBP SGA3 (945539)

    Ordinary human experience is embedded in a web of causal relations that link the brain to the body and the wider environment. However, there might be conditions in which brain activity supports consciousness even when that activity is fully causally isolated from the body and its environment. Such cases would involve what we call islands of awareness: conscious states that are neither shaped by sensory input nor able to be expressed by motor output. This Opinion paper considers conditions in which such islands might occur, including ex cranio brains, hemispherotomy, and in cerebral organoids. We examine possible methods for detecting islands of awareness, and consider their implications for ethics and for the nature of consciousness.

  • Publication . Article . Other literature type . 2016
    Open Access
    Authors: 
    Trisha Greenhalgh; Ellen Annandale; Richard Ashcroft; James Barlow; Nick Black; Alan Bleakley; Ruth Boaden; Jeffrey Braithwaite; Nicky Britten; Franco A. Carnevale; +65 more
    Countries: Netherlands, Australia, United Kingdom, Netherlands

    Seventy six senior academics from 11 countries invite The BMJ ’s editors to reconsider their policy of rejecting qualitative research on the grounds of low priority. They challenge the journal to develop a proactive, scholarly, and pluralist approach to research that aligns with its stated mission

  • Open Access English
    Authors: 
    Jonkman, N.H.; Westland, H.; Trappenburg, J.C.A.; Groenwold, R.H.H.; Effing, T.W.; Troosters, T.; van der Palen, J.; Bourbeau, J.; Jaarsma, T.; Hoes, A.W.; +3 more
    Countries: Belgium, Sweden, Netherlands, Australia

    Introduction: Self-management interventions in patients with chronic conditions have received increasing attention over the past few years, yet the meta-analyses encountered considerable heterogeneity in results. This suggests that the effectiveness of self-management interventions must be assessed in the context of which components are responsible for eliciting the effect and in which subgroups of patients the intervention works best. The aim of the present study is to identify condition-transcending determinants of success of self-management interventions in two parallel individual patient data meta-analyses of self-management trials in patients with congestive heart failure (CHF) and in patients with chronic obstructive pulmonary disease (COPD). Methods and analysis: Investigators of 53 randomised trials (32 in CHF and 21 in COPD) will be requested to share their de-identified individual patient data. Data will be analysed using random effects models, taking clustering within studies into account. Effect modification by age, sex, disease severity, symptom status, comorbid conditions and level of education will be assessed. Sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination: The de-identified individual patient data are used only for the purpose for which they were originally collected and for which ethical approval has been obtained by the original investigators. Knowledge on the effective ingredients of self-management programmes and identification of subgroups of patients in which those interventions are most effective will guide the development of evidence-based personalised self-management interventions for patients with CHF and COPD as well as with other chronic diseases. Trial registration number: PROSPERO: CRD42013004698.

  • Open Access English
    Authors: 
    Ben Vandermeer; Ingeborg van der Tweel; Marijke C. Jansen-van der Weide; Stephanie S. Weinreich; Despina G. Contopoulos-Ioannidis; Dirk Bassler; Ricardo M. Fernandes; Lisa M. Askie; Haroon Saloojee; Paola Baiardi; +2 more
    Countries: Switzerland, Netherlands
    Project: NWO | Blue Action (32188), EC | GRIP (261060)

    Background: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former.Methods: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials.Results: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74).Conclusions: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

  • Open Access
    Authors: 
    Mansour Bechar; Abdeldjebar Hazzab; Mohamed Habbab; Pierre Sicard;
    Publisher: Institute of Advanced Engineering and Science

    In this paper, Reduced-Order Observer For Real-Time Implementation Speed Sensorless Control of Induction Using RT-LAB Softwareis presented. Speed estimation is performed through a reduced-order observer. The stability of the proposed observer is proved based on Lyapunov’s theorem. The model is initially built offline using Matlab/Simulink and implemented in real-time environment using RT-LAB package and an OP5600 digital simulator. RT-LAB configuration has two main subsystems master and console subsystems. These two subsystems were coordinated to achieve the real-time simulation. In order to verify the feasibility and effectiveness of proposed method, experimental results are presented over a wide speed range, including zero speed.

  • Closed Access
    Authors: 
    Stephen A. Marshall;
    Publisher: Magnolia Press

    The Micropezidae of Madagascar are reviewed, and the endemic genus Paramimegralla Hennig is revised. Twenty species are recognized including two Hybobata species and 18 Paramimegralla species, of which 12 are described as new (P. luteoscapus , brunnea , zinzala, zarpa, verticalis, taeniola, sulcata, campanula, anchivitta, quadrifasciata and longicephala ). Stiltissima Barraclough is synonymized with Paramimegralla Hennig and previous records of Rainieria Rondani from the island are shown to be incorrect. Paramimegralla steineri (Barraclough) and Paramimegralla volcanica (Barraclough) are given as new combinations, Paramimegralla stuckenbergi Barraclough is synonymized with P. nigra Barraclough, and Hybobata Enderlein is resurrected from synonymy with Mimegralla Rondani. All known Malagasy micropezid species are keyed and illustrated and all Paramimegralla species are described or redescribed.

  • Open Access English
    Authors: 
    Manish eSaggar; Brandon G King; Brandon G King; Anthony P Zanesco; Anthony P Zanesco; Katherine A MacLean; Stephen R Aichele; Stephen R Aichele; Tonya L Jacobs; David A Bridwell; +12 more
    Countries: United States, Australia
    Project: SSHRC

    The capacity to focus one's attention for an extended period of time can be increased through training in contemplative practices. However, the cognitive processes engaged during meditation that support trait changes in cognition are not well characterized. We conducted a longitudinal wait-list controlled study of intensive meditation training. Retreat participants practiced focused attention (FA) meditation techniques for three months during an initial retreat. Wait-list participants later undertook formally identical training during a second retreat. Dense-array scalp-recorded electroencephalogram (EEG) data were collected during 6 min of mindfulness of breathing meditation at three assessment points during each retreat. Second-order blind source separation, along with a novel semi-automatic artifact removal tool (SMART), was used for data preprocessing. We observed replicable reductions in meditative state-related beta-band power bilaterally over anteriocentral and posterior scalp regions. In addition, individual alpha frequency (IAF) decreased across both retreats and in direct relation to the amount of meditative practice. These findings provide evidence for replicable longitudinal changes in brain oscillatory activity during meditation and increase our understanding of the cortical processes engaged during meditation that may support long-term improvements in cognition.

  • Open Access
    Authors: 
    Heather L. Petrick; Henver Simionato Brunetta; Chris Pignanelli; Everson Araújo Nunes; Luc J. C. van Loon; Jamie F. Burr; Graham P. Holloway;
    Countries: Netherlands, Australia, Belgium
    Project: NSERC

    Key points Ketone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstratein vitrothat maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodiumdl-beta-hydroxybutyrate, beta-HB; lithium acetoacetate, AcAc) to stimulatein vitromitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (similar to 30-35% of pyruvate), RG (similar to 10-30%), and human vastus lateralis (similar to 2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 mu m beta-HB, 801 mu mAcAc; RG: 782 mu m beta-HB, 267 mu mAcAc) were greater than KB content representative of the muscle microenvironment (similar to 100 mu m). This would predict low rates (similar to 1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s(-1) mg(-1)) and RG (3-6 pmol s(-1) mg(-1)) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 mu m) reduced the ability of physiological beta-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

  • Open Access
    Authors: 
    Lars Kober; Manuel Martinez-Selles; Salim Yusuf; Antoni Bayes-Genis; Kim Krogsgaard; Olav Wendelboe Nielsen; Aldo Pietro Maggioni; Finlay McAlister; Carlos Fernandez-Palomeque; Albert Gabarrús; +10 more
    Country: Australia

    Aims Treatment of patients with heart failure (HF) relies on measurement of LVEF. However, the extent to which EF is recorded varies markedly. We sought to characterize the patient group that is missing a measure of EF, and to explore the association between missing EF and outcome. Methods and results Individual data on 30 445 patients from 28 observational studies in the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) project were used to compare the prevalence of co-morbidities and outcome across three groups of HF patients: those with missing EF (HF-mEF), reduced EF (HF-REF), and preserved EF (HF-PEF). A total of 29% had HF-mEF, 52% HF-REF, and 19% HF-PEF. Compared with patients in whom EF was known, patients with HF-mEF were older, had a greater prevalence of COPD and previous stroke, and were smokers. Patients with HF-mEF were less likely to receive evidence-based treatment than those with HF-REF. Adjusted mortality in HF-mEF was similar to that in HF-REF and greater than that in HF-PEF at 3 years [HF-REF, hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.95–1.12); HF-PEF, HR 0.78, 95% CI 0.71–0.86]. Conclusion Missing EF is common. The short- and long-term outcome of patients with HF-mEF is poor and they exhibit different co-morbidity profiles and treatment patterns compared with patients with known EF. HF patients with missing EF represent a high risk group.