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607 Research products, page 1 of 61

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  • Publication . Article . Other literature type . 2012
    Open Access English
    Authors: 
    Martin J. Gibala; Jonathan P. Little; Maureen J. MacDonald; John A. Hawley;
    Publisher: Blackwell Science Inc
    Country: Australia

    Thank you for the opportunity to respond to the letter submitted by Gayda and colleagues in response to our recent review published in The Journal of Physiology (Gibala et al. 2012). With regards to their first comment regarding our new ‘practical’ high-intensity interval exercise (HIIE) protocol, we disagree with the assertion that ‘exercise intensity at 60% of peak power cannot be considered high intensity.’ In our efforts to develop a low-volume HIIE protocol that can be applied across different cohorts including clinical populations, we devised a model comprising 10 × 60 s work bouts at an intensity eliciting ∼85–90% of maximal heart rate (HRmax; averaged over the 10 intervals), interspersed by 60 s of recovery. We have found that the percentage of peak power output (PPO; determined using a standard ramp test to volitional fatigue which does not always elicit peak O2 uptake) that approximates the desired target heart rate (i.e. the % of HRmax) varies considerably between subjects and is exercise-mode specific. For example, in the study by Hood et al. (2011) which was conducted on sedentary healthy adults, a workload equivalent to 60% of PPO during upright cycling was sufficient to elicit a training intensity of ∼90% HRmax. However, in our recent study conducted on patients with type 2 diabetes, the intensity required to elicit ∼90% HRmax was ∼95% of PPO determined during recumbent cycling (Little et al. 2011). We agree with the assertion by Gayda and colleagues that ‘acute physiological responses during different HIIE protocols as well as patient's safety, tolerance and comfort should be tested before their implementation into training programs’. Ongoing protocol optimization work in our laboratory reveal that when interval exercise was prescribed as 80% of PPO in coronary artery disease (CAD) patients – most of whom were taking beta-blocker medication – the 10 × 60 s protocol resulted in peak heart rates during the exercise that averaged ∼85% of age-predicted HRmax. Further, the 10 × 60 s protocol was best tolerated and rated as most preferred by CAD patients in comparison with a modified Wingate protocol (repeated 30 s efforts at 100% PPO with 4 min unloaded cycling for recovery), the standard aerobic interval training protocol used by Wisloff and colleagues (2007), or a moderate-intensity continuous exercise (MICE) protocol. It is likely that high-intensity interval training (HIT) does not conform to a ‘one size fits all’ approach and the interval training stimulus needs to be tailored to individuals depending on their initial level of fitness, exercise tolerance, use of prescription medications and other factors. We also concur with the other main comment by Gayda and colleagues that ‘the superiority of this HIIE protocol [our 10 × 60 s ‘hard’/60 s ‘easy’ model]… needs to be demonstrated.’ Indeed, our review concluded ‘One aspect that is unclear from the present literature is the precise intensity and minimal volume of training that is needed to potentiate the effect of the stimulus-adaptation on outcomes such as mitochondrial biogenesis and relevant health markers. To answer such questions, a complex series of studies needs to be undertaken that systematically ‘titrate’ levels of the ‘training impulse’ and determine subsequent cellular, performance and clinical responses after divergent training interventions.’ Specifically with respect to the use of HIIE in patients with cardiovascular risk or cardiovascular disease, the letter by Gayda and colleagues highlights four references from their laboratory that were not cited in our review. Given the relatively broad scope of our review and the fact that Journal guidelines restricted the number of references to 50, it was obviously not possible to cite all relevant work. Moreover, two of the citations listed by Gayda et al. were acute exercise studies (whereas the focus of our review was training adaptations) and the other two citations were a journal abstract and a recent paper published in February 2012 (neither of which we had access to at the time of submission of our original manuscript). We are also aware of the pioneering research conducted by Meyer and colleagues (e.g. Meyer et al. 1998) and have acknowledged this work in a previous commentary (MacDonald & Currie, 2009). We apologize to all authors whose work on interval training we could not cite due to the broad focus of our review and referencing limitations imposed by The Journal.

  • 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: United Kingdom, United Kingdom, Australia, Netherlands, United Kingdom, United Kingdom, United Kingdom, United Kingdom, United Kingdom

    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
    Authors: 
    Heather L. Petrick; Henver Simionato Brunetta; Chris Pignanelli; Everson Araújo Nunes; Luc J. C. van Loon; Jamie F. Burr; Graham P. Holloway;
    Publisher: Wiley
    Countries: Netherlands, Belgium, Australia
    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: 
    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
    Publisher: Zenodo
    Countries: Netherlands, Switzerland
    Project: EC | GRIP (261060), NWO | Blue Action (32188)

    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.

  • Publication . Other literature type . Article . 2018
    Open Access English
    Authors: 
    Atherton, Christopher John; Barton, Thomas; Basney, Jim; Broeder, Daan; Costa, Alessandro; Daalen, Mirjam Van; Dyke, Stephanie; Elbers, Willem; Enell, Carl-Fredrik; Fasanelli, Enrico Maria Vincenzo; +30 more
    Country: Germany
    Project: EC | GN4-2 (731122), EC | IS-ENES2 (312979), EC | IS-ENES (228203), EC | CALIPSOplus (730872), EC | CORBEL (654248), EC | AARC2 (730941), EC | EOSC-hub (777536), EC | ELIXIR-EXCELERATE (676559), NSF | Data Handling and Analysi... (1700765)

    The authors also acknowledge the support and collaboration of many other colleagues in their respective institutes, research communities and IT Infrastructures, together with the funding received by these from many different sources. These include but are not limited to the following: (i) The Worldwide LHC Computing Grid (WLCG) project is a global collaboration of more than 170 computing centres in 43 countries, linking up national and international grid infrastructures. Funding is acknowledged from many national funding bodies and we acknowledge the support of several operational infrastructures including EGI, OSG and NDGF/NeIC. (ii) EGI acknowledges the funding and support received from the European Commission and the many National Grid Initiatives and other members. EOSC-hub receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 777536. (iii) The work leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 730941 (AARC2). (iv) Work on the development of ESGF's identity management system has been supported by The UK Natural Environment Research Council and funding from the European Union's Seventh Framework Programme for research, technological development and demonstration through projects IS-ENES (grant agreement no 228203) and IS-ENES2 (grant agreement no 312979). (v) Ludek Matyska and Michal Prochazka acknowledge funding from the RI ELIXIR CZ project funded by MEYS Czech Republic No. LM2015047. (vi) Scott Koranda acknowledges support provided by the United States National Science Foundation under Grant No. PHY-1700765. (vii) GÉANT Association on behalf of the GN4 Phase 2 project (GN4-2).The research leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 731122(GN4-2). (viii) ELIXIR acknowledges support from Research Infrastructure programme of Horizon 2020 grant No 676559 EXCELERATE. (ix) CORBEL life science cluster acknowledges support from Horizon 2020 research and innovation programme under grant agreement No 654248. (x) Mirjam van Daalen acknowledges that the research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. (xi) EISCAT is an international association supported by research organisations in China (CRIRP), Finland (SA), Japan (NIPR), Norway (NFR), Sweden (VR), and the United Kingdom (NERC). This white-paper expresses common requirements of Research Communities seeking to leverage Identity Federation for Authentication and Authorisation. Recommendations are made to Stakeholders to guide the future evolution of Federated Identity Management in a direction that better satisfies research use cases. The authors represent research communities, Research Services, Infrastructures, Identity Federations and Interfederations, with a joint motivation to ease collaboration for distributed researchers. The content has been edited collaboratively by the Federated Identity Management for Research (FIM4R) Community, with input sought at conferences and meetings in Europe, Asia and North America.

  • Open Access English
    Authors: 
    Adam L. Bujak; Justin D. Crane; James S. V. Lally; Rebecca J. Ford; Sally J. Kang; Irena A. Rebalka; Alex E. Green; Bruce E. Kemp; Thomas J. Hawke; Jonathan D. Schertzer; +1 more
    Publisher: Cell Press
    Country: Australia
    Project: NSERC , CIHR

    SummaryThe AMP-activated protein kinase (AMPK) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK (AMPK-MKO) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging.

  • Open Access
    Authors: 
    Margo Mountjoy; Jorunn Sundgot-Borgen; Louise M. Burke; Susan D. Carter; Naama Constantini; Constance M. Lebrun; Nanna L. Meyer; Roberta Sherman; Kathrin Steffen; Richard Budgett; +1 more
    Country: Australia

    In April 2014, the International Olympic Committee (IOC) published a Consensus Statement in this journal entitled “Beyond the Female Athlete Triad: Relative Energy Deficiency in Sport (RED-S)”.1 In reference to that Consensus Statement, Professor Mary Jane De Souza and colleagues published an editorial (July 2014).2 The editorial below expands on the original Consensus Statement and comments on the 2014 Editorial by Professor Mary Jane De Souza and colleagues. Albert Einstein said: “The important thing is to never stop questioning.” A group of 11 IOC authors have called attention, as others in the past,3 ,4 to a problem that is wider and more complex than originally identified when the term ‘Female Athlete Triad’ (Triad or FAT) was first coined in 1992. Just as knowledge evolves, so too should ideas and constructs on how to address it. Given the evolution of science since 1992, and to more accurately describe the clinical syndrome originally known as the Female Athlete Triad, the IOC introduced a more comprehensive, broader term: Relative Energy Deficiency in Sport. The syndrome of RED-S refers to impaired physiological functioning caused by relative energy deficiency, and includes but is not limited to impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular health. Our April 2014 Consensus statement identifies the aetiological factor underpinning the syndrome as: an energy deficiency relative to the balance between dietary energy intake and the energy expenditure required to support homeostasis, health and the activities of daily living, growth and sporting activities. We reaffirm the principle that the IOC Consensus Statement highlights about energy deficiency/low energy availability among exercising people. De Souza and colleagues’ editorial criticises the use of the word ‘balance,’ suggesting that the IOC authors have confused the terms energy availability and energy balance. We used the term …

  • Open Access English
    Authors: 
    Maxime Lobry; Médéric Loyez; Karima Chah; Eman M. Hassan; Erik Goormaghtigh; Maria C. DeRosa; Ruddy Wattiez; Christophe Caucheteur;
    Publisher: Optical Society of America
    Countries: Canada, Belgium

    In the biomedical detection context, plasmonic tilted fiber Bragg gratings (TFBGs) have been demonstrated to be a very accurate and sensitive sensing tool, especially well-adapted for biochemical detection. In this work, we have developed an aptasensor following a triple strategy to improve the overall sensing performances and robustness. Single polarization fiber (SPF) is used as biosensor substrate while the demodulation is based on tracking a peculiar feature of the lower envelope of the cladding mode resonances spectrum. This method is highly sensitive and yields wavelength shifts several tens of times higher than the ones reported so far based on the tracking of individual modes of the spectrum. An amplification of the response is further performed through a sandwich assay by the use of specific antibodies. These improvements have been achieved on a biosensor developed for the detection of the HER2 (Human Epidermal Growth Factor Receptor-2) protein, a relevant breast cancer biomarker. These advanced developments can be very interesting for point-of-care biomedical measurements in a convenient practical way.

  • Publication . Other literature type . Article . 2016
    Open Access
    Authors: 
    Edeline Gagnon; Anne Bruneau; Colin E. Hughes; Luciano Paganucci de Queiroz; Gwilym P. Lewis;
    Publisher: Zenodo
    Country: Switzerland
    Project: NSERC

    Abstract The Caesalpinia group is a large pantropical clade of ca. 205 species in subfamily Caesalpinioideae (Leguminosae) in which generic delimitation has been in a state of considerable flux. Here we present new phylogenetic analyses based on five plastid and one nuclear ribosomal marker, with dense taxon sampling including 172 (84%) of the species and representatives of all previously described genera in the Caesalpinia group. These analyses show that the current classification of the Caesalpinia group into 21 genera needs to be revised. Several genera (Poincianella, Erythrostemon, Cenostigma and Caesalpinia sensu Lewis, 2005) are non-monophyletic and several previously unclassified Asian species segregate into clades that merit recognition at generic rank. In addition, the near-completeness of our taxon sampling identifies three species that do not belong in any of the main clades and these are recognised as new monospecific genera. A new generic classification of the Caesalpinia group is presented including a key for the identification of genera, full generic descriptions, illustrations (drawings and photo plates of all genera), and (for most genera) the nomenclatural transfer of species to their correct genus. We recognise 26 genera, with reinstatement of two previously described genera (Biancaea Tod., Denisophytum R. Vig.), re-delimitation and expansion of several others (Moullava, Cenostigma, Libidibia and Erythrostemon), contraction of Caesalpinia s.s. and description of four new ones (Gelrebia, Paubrasilia, Hererolandia and Hultholia), and make 75 new nomenclatural combinations in this new generic system.

  • Open Access English
    Authors: 
    Szabolcs David; Anneriet M. Heemskerk; Francesco Corrivetti; Michel Thiebaut de Schotten; Silvio Sarubbo; Francesco Corsini; Alessandro De Benedictis; Laurent Petit; Max A. Viergever; Derek K. Jones; +5 more
    Publisher: HAL CCSD
    Countries: France, France, Netherlands, Australia
    Project: WT , NWO | Diffusion MRI analysis be... (25096), NIH | Axon, Testosterone and Me... (5R01MH085772-02)

    International audience; Fiber tractography (FT) using diffusion magnetic resonance imaging (dMRI) is widely used for investigating microstructural properties of white matter (WM) fiber-bundles and for mapping structural connections of the human brain. While studying the architectural configuration of the brain's circuitry with FT is not without controversy, recent progress in acquisition, processing, modeling, analysis, and visualization of dMRI data pushes forward the reliability in reconstructing WM pathways. Despite being aware of the well-known pitfalls in analyzing dMRI data and several other limitations of FT discussed in recent literature, we present the superoanterior fasciculus (SAF), a novel bilateral fiber tract in the frontal region of the human brain that-to the best of our knowledge-has not been documented. The SAF has a similar shape to the anterior part of the cingulum bundle, but it is located more frontally. To minimize the possibility that these FT findings are based on acquisition or processing artifacts, different dMRI data sets and processing pipelines have been used to describe the SAF. Furthermore, we evaluated the configuration of the SAF with complementary methods, such as polarized light imaging (PLI) and human brain dissections. The FT results of the SAF demonstrate a long pathway, consistent across individuals, while the human dissections indicate fiber pathways connecting the postero-dorsal with the antero-dorsal cortices of the frontal lobe.

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The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
607 Research products, page 1 of 61
  • Publication . Article . Other literature type . 2012
    Open Access English
    Authors: 
    Martin J. Gibala; Jonathan P. Little; Maureen J. MacDonald; John A. Hawley;
    Publisher: Blackwell Science Inc
    Country: Australia

    Thank you for the opportunity to respond to the letter submitted by Gayda and colleagues in response to our recent review published in The Journal of Physiology (Gibala et al. 2012). With regards to their first comment regarding our new ‘practical’ high-intensity interval exercise (HIIE) protocol, we disagree with the assertion that ‘exercise intensity at 60% of peak power cannot be considered high intensity.’ In our efforts to develop a low-volume HIIE protocol that can be applied across different cohorts including clinical populations, we devised a model comprising 10 × 60 s work bouts at an intensity eliciting ∼85–90% of maximal heart rate (HRmax; averaged over the 10 intervals), interspersed by 60 s of recovery. We have found that the percentage of peak power output (PPO; determined using a standard ramp test to volitional fatigue which does not always elicit peak O2 uptake) that approximates the desired target heart rate (i.e. the % of HRmax) varies considerably between subjects and is exercise-mode specific. For example, in the study by Hood et al. (2011) which was conducted on sedentary healthy adults, a workload equivalent to 60% of PPO during upright cycling was sufficient to elicit a training intensity of ∼90% HRmax. However, in our recent study conducted on patients with type 2 diabetes, the intensity required to elicit ∼90% HRmax was ∼95% of PPO determined during recumbent cycling (Little et al. 2011). We agree with the assertion by Gayda and colleagues that ‘acute physiological responses during different HIIE protocols as well as patient's safety, tolerance and comfort should be tested before their implementation into training programs’. Ongoing protocol optimization work in our laboratory reveal that when interval exercise was prescribed as 80% of PPO in coronary artery disease (CAD) patients – most of whom were taking beta-blocker medication – the 10 × 60 s protocol resulted in peak heart rates during the exercise that averaged ∼85% of age-predicted HRmax. Further, the 10 × 60 s protocol was best tolerated and rated as most preferred by CAD patients in comparison with a modified Wingate protocol (repeated 30 s efforts at 100% PPO with 4 min unloaded cycling for recovery), the standard aerobic interval training protocol used by Wisloff and colleagues (2007), or a moderate-intensity continuous exercise (MICE) protocol. It is likely that high-intensity interval training (HIT) does not conform to a ‘one size fits all’ approach and the interval training stimulus needs to be tailored to individuals depending on their initial level of fitness, exercise tolerance, use of prescription medications and other factors. We also concur with the other main comment by Gayda and colleagues that ‘the superiority of this HIIE protocol [our 10 × 60 s ‘hard’/60 s ‘easy’ model]… needs to be demonstrated.’ Indeed, our review concluded ‘One aspect that is unclear from the present literature is the precise intensity and minimal volume of training that is needed to potentiate the effect of the stimulus-adaptation on outcomes such as mitochondrial biogenesis and relevant health markers. To answer such questions, a complex series of studies needs to be undertaken that systematically ‘titrate’ levels of the ‘training impulse’ and determine subsequent cellular, performance and clinical responses after divergent training interventions.’ Specifically with respect to the use of HIIE in patients with cardiovascular risk or cardiovascular disease, the letter by Gayda and colleagues highlights four references from their laboratory that were not cited in our review. Given the relatively broad scope of our review and the fact that Journal guidelines restricted the number of references to 50, it was obviously not possible to cite all relevant work. Moreover, two of the citations listed by Gayda et al. were acute exercise studies (whereas the focus of our review was training adaptations) and the other two citations were a journal abstract and a recent paper published in February 2012 (neither of which we had access to at the time of submission of our original manuscript). We are also aware of the pioneering research conducted by Meyer and colleagues (e.g. Meyer et al. 1998) and have acknowledged this work in a previous commentary (MacDonald & Currie, 2009). We apologize to all authors whose work on interval training we could not cite due to the broad focus of our review and referencing limitations imposed by The Journal.

  • 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: United Kingdom, United Kingdom, Australia, Netherlands, United Kingdom, United Kingdom, United Kingdom, United Kingdom, United Kingdom

    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
    Authors: 
    Heather L. Petrick; Henver Simionato Brunetta; Chris Pignanelli; Everson Araújo Nunes; Luc J. C. van Loon; Jamie F. Burr; Graham P. Holloway;
    Publisher: Wiley
    Countries: Netherlands, Belgium, Australia
    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: 
    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
    Publisher: Zenodo
    Countries: Netherlands, Switzerland
    Project: EC | GRIP (261060), NWO | Blue Action (32188)

    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.

  • Publication . Other literature type . Article . 2018
    Open Access English
    Authors: 
    Atherton, Christopher John; Barton, Thomas; Basney, Jim; Broeder, Daan; Costa, Alessandro; Daalen, Mirjam Van; Dyke, Stephanie; Elbers, Willem; Enell, Carl-Fredrik; Fasanelli, Enrico Maria Vincenzo; +30 more
    Country: Germany
    Project: EC | GN4-2 (731122), EC | IS-ENES2 (312979), EC | IS-ENES (228203), EC | CALIPSOplus (730872), EC | CORBEL (654248), EC | AARC2 (730941), EC | EOSC-hub (777536), EC | ELIXIR-EXCELERATE (676559), NSF | Data Handling and Analysi... (1700765)

    The authors also acknowledge the support and collaboration of many other colleagues in their respective institutes, research communities and IT Infrastructures, together with the funding received by these from many different sources. These include but are not limited to the following: (i) The Worldwide LHC Computing Grid (WLCG) project is a global collaboration of more than 170 computing centres in 43 countries, linking up national and international grid infrastructures. Funding is acknowledged from many national funding bodies and we acknowledge the support of several operational infrastructures including EGI, OSG and NDGF/NeIC. (ii) EGI acknowledges the funding and support received from the European Commission and the many National Grid Initiatives and other members. EOSC-hub receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 777536. (iii) The work leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 730941 (AARC2). (iv) Work on the development of ESGF's identity management system has been supported by The UK Natural Environment Research Council and funding from the European Union's Seventh Framework Programme for research, technological development and demonstration through projects IS-ENES (grant agreement no 228203) and IS-ENES2 (grant agreement no 312979). (v) Ludek Matyska and Michal Prochazka acknowledge funding from the RI ELIXIR CZ project funded by MEYS Czech Republic No. LM2015047. (vi) Scott Koranda acknowledges support provided by the United States National Science Foundation under Grant No. PHY-1700765. (vii) GÉANT Association on behalf of the GN4 Phase 2 project (GN4-2).The research leading to these results has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 731122(GN4-2). (viii) ELIXIR acknowledges support from Research Infrastructure programme of Horizon 2020 grant No 676559 EXCELERATE. (ix) CORBEL life science cluster acknowledges support from Horizon 2020 research and innovation programme under grant agreement No 654248. (x) Mirjam van Daalen acknowledges that the research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. (xi) EISCAT is an international association supported by research organisations in China (CRIRP), Finland (SA), Japan (NIPR), Norway (NFR), Sweden (VR), and the United Kingdom (NERC). This white-paper expresses common requirements of Research Communities seeking to leverage Identity Federation for Authentication and Authorisation. Recommendations are made to Stakeholders to guide the future evolution of Federated Identity Management in a direction that better satisfies research use cases. The authors represent research communities, Research Services, Infrastructures, Identity Federations and Interfederations, with a joint motivation to ease collaboration for distributed researchers. The content has been edited collaboratively by the Federated Identity Management for Research (FIM4R) Community, with input sought at conferences and meetings in Europe, Asia and North America.

  • Open Access English
    Authors: 
    Adam L. Bujak; Justin D. Crane; James S. V. Lally; Rebecca J. Ford; Sally J. Kang; Irena A. Rebalka; Alex E. Green; Bruce E. Kemp; Thomas J. Hawke; Jonathan D. Schertzer; +1 more
    Publisher: Cell Press
    Country: Australia
    Project: NSERC , CIHR

    SummaryThe AMP-activated protein kinase (AMPK) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK (AMPK-MKO) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging.

  • Open Access
    Authors: 
    Margo Mountjoy; Jorunn Sundgot-Borgen; Louise M. Burke; Susan D. Carter; Naama Constantini; Constance M. Lebrun; Nanna L. Meyer; Roberta Sherman; Kathrin Steffen; Richard Budgett; +1 more
    Country: Australia

    In April 2014, the International Olympic Committee (IOC) published a Consensus Statement in this journal entitled “Beyond the Female Athlete Triad: Relative Energy Deficiency in Sport (RED-S)”.1 In reference to that Consensus Statement, Professor Mary Jane De Souza and colleagues published an editorial (July 2014).2 The editorial below expands on the original Consensus Statement and comments on the 2014 Editorial by Professor Mary Jane De Souza and colleagues. Albert Einstein said: “The important thing is to never stop questioning.” A group of 11 IOC authors have called attention, as others in the past,3 ,4 to a problem that is wider and more complex than originally identified when the term ‘Female Athlete Triad’ (Triad or FAT) was first coined in 1992. Just as knowledge evolves, so too should ideas and constructs on how to address it. Given the evolution of science since 1992, and to more accurately describe the clinical syndrome originally known as the Female Athlete Triad, the IOC introduced a more comprehensive, broader term: Relative Energy Deficiency in Sport. The syndrome of RED-S refers to impaired physiological functioning caused by relative energy deficiency, and includes but is not limited to impairments of metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular health. Our April 2014 Consensus statement identifies the aetiological factor underpinning the syndrome as: an energy deficiency relative to the balance between dietary energy intake and the energy expenditure required to support homeostasis, health and the activities of daily living, growth and sporting activities. We reaffirm the principle that the IOC Consensus Statement highlights about energy deficiency/low energy availability among exercising people. De Souza and colleagues’ editorial criticises the use of the word ‘balance,’ suggesting that the IOC authors have confused the terms energy availability and energy balance. We used the term …

  • Open Access English
    Authors: 
    Maxime Lobry; Médéric Loyez; Karima Chah; Eman M. Hassan; Erik Goormaghtigh; Maria C. DeRosa; Ruddy Wattiez; Christophe Caucheteur;
    Publisher: Optical Society of America
    Countries: Canada, Belgium

    In the biomedical detection context, plasmonic tilted fiber Bragg gratings (TFBGs) have been demonstrated to be a very accurate and sensitive sensing tool, especially well-adapted for biochemical detection. In this work, we have developed an aptasensor following a triple strategy to improve the overall sensing performances and robustness. Single polarization fiber (SPF) is used as biosensor substrate while the demodulation is based on tracking a peculiar feature of the lower envelope of the cladding mode resonances spectrum. This method is highly sensitive and yields wavelength shifts several tens of times higher than the ones reported so far based on the tracking of individual modes of the spectrum. An amplification of the response is further performed through a sandwich assay by the use of specific antibodies. These improvements have been achieved on a biosensor developed for the detection of the HER2 (Human Epidermal Growth Factor Receptor-2) protein, a relevant breast cancer biomarker. These advanced developments can be very interesting for point-of-care biomedical measurements in a convenient practical way.

  • Publication . Other literature type . Article . 2016
    Open Access
    Authors: 
    Edeline Gagnon; Anne Bruneau; Colin E. Hughes; Luciano Paganucci de Queiroz; Gwilym P. Lewis;
    Publisher: Zenodo
    Country: Switzerland
    Project: NSERC

    Abstract The Caesalpinia group is a large pantropical clade of ca. 205 species in subfamily Caesalpinioideae (Leguminosae) in which generic delimitation has been in a state of considerable flux. Here we present new phylogenetic analyses based on five plastid and one nuclear ribosomal marker, with dense taxon sampling including 172 (84%) of the species and representatives of all previously described genera in the Caesalpinia group. These analyses show that the current classification of the Caesalpinia group into 21 genera needs to be revised. Several genera (Poincianella, Erythrostemon, Cenostigma and Caesalpinia sensu Lewis, 2005) are non-monophyletic and several previously unclassified Asian species segregate into clades that merit recognition at generic rank. In addition, the near-completeness of our taxon sampling identifies three species that do not belong in any of the main clades and these are recognised as new monospecific genera. A new generic classification of the Caesalpinia group is presented including a key for the identification of genera, full generic descriptions, illustrations (drawings and photo plates of all genera), and (for most genera) the nomenclatural transfer of species to their correct genus. We recognise 26 genera, with reinstatement of two previously described genera (Biancaea Tod., Denisophytum R. Vig.), re-delimitation and expansion of several others (Moullava, Cenostigma, Libidibia and Erythrostemon), contraction of Caesalpinia s.s. and description of four new ones (Gelrebia, Paubrasilia, Hererolandia and Hultholia), and make 75 new nomenclatural combinations in this new generic system.

  • Open Access English
    Authors: 
    Szabolcs David; Anneriet M. Heemskerk; Francesco Corrivetti; Michel Thiebaut de Schotten; Silvio Sarubbo; Francesco Corsini; Alessandro De Benedictis; Laurent Petit; Max A. Viergever; Derek K. Jones; +5 more
    Publisher: HAL CCSD
    Countries: France, France, Netherlands, Australia
    Project: WT , NWO | Diffusion MRI analysis be... (25096), NIH | Axon, Testosterone and Me... (5R01MH085772-02)

    International audience; Fiber tractography (FT) using diffusion magnetic resonance imaging (dMRI) is widely used for investigating microstructural properties of white matter (WM) fiber-bundles and for mapping structural connections of the human brain. While studying the architectural configuration of the brain's circuitry with FT is not without controversy, recent progress in acquisition, processing, modeling, analysis, and visualization of dMRI data pushes forward the reliability in reconstructing WM pathways. Despite being aware of the well-known pitfalls in analyzing dMRI data and several other limitations of FT discussed in recent literature, we present the superoanterior fasciculus (SAF), a novel bilateral fiber tract in the frontal region of the human brain that-to the best of our knowledge-has not been documented. The SAF has a similar shape to the anterior part of the cingulum bundle, but it is located more frontally. To minimize the possibility that these FT findings are based on acquisition or processing artifacts, different dMRI data sets and processing pipelines have been used to describe the SAF. Furthermore, we evaluated the configuration of the SAF with complementary methods, such as polarized light imaging (PLI) and human brain dissections. The FT results of the SAF demonstrate a long pathway, consistent across individuals, while the human dissections indicate fiber pathways connecting the postero-dorsal with the antero-dorsal cortices of the frontal lobe.