Effect of MTU length on child-adult difference in neuromuscular fatigue

Purpose The purpose of this study was to compare the development and etiology of neuromuscular fatigue of the knee extensor muscles (KE) at different muscle-tendon unit (MTU) lengths during repeated maximal voluntary isometric contractions (MVIC) between boys and men.Methods Twenty-two pre-pubertal boys (9-11 years) and 22 men (18-30 years) performed three KE fatigue protocols at short (SHORT), optimal (OPT) and long (LONG) MTU lengths, consisting of repeating 5-s MVIC interspersed with 5-s passive recovery periods until torque reached 60% of the initial MVIC torque. The etiology of neuromuscular fatigue was identified using non-invasive methods such as surface electromyography, near-infrared spectroscopy, magnetic nerve stimulation and twitch interpolation technique.Results The number of repetitions was significantly lower in men at OPT (14.8$\pm$3.2) and LONG (15.8$\pm$5.8) than boys (39.7$\pm$18.4 and 29.5 $\pm$10.2, respectively; p<0.001), while no difference was found at SHORT between both age groups (boys: 33.7$\pm$15.4, men: 40.9$\pm$14.2). At OPT and LONG boys showed a lower reduction in the single potentiated twitch (Qtwpot) and a greater decrease in the voluntary activation level (VA) than men. At SHORT, both populations displayed a moderate Qtwpot decrement and a significant VA reduction (p<0.001). The differences in maximal torque between boys and men were almost twice greater at OPT (223.9 N.m) than at SHORT (123.3 N.m) and LONG (136.5 N.m).Conclusion The differences in neuromuscular fatigue between children and adults are dependent on MTU length. Differences in maximal torque could underpin differences in neuromuscular fatigue between children and adults at OPT and SHORT. However, at LONG these differences do not seem to be explained by differences in maximal torque. The origins of this specific effect of MTU length remain to be determined

Cancer risk management strategies and perceptions of unaffected women 5 years after predictive genetic testing for BRCA1/2 mutations

In a French national cohort of unaffected females carriers/non-carriers of a BRCA1/2 mutation, long-term preventive strategies and breast/ovarian cancer risk perceptions were followed up to 5 years after test result disclosure, using self-administered questionnaires. Response rate was 74%. Carriers (N=101) were younger (average age±SD=37±10) than non-carriers (N=145; 42±12). There were four management strategies that comprised 88% of the decisions made by the unaffected carriers: 50% opted for breast surveillance alone, based on either magnetic resonance imaging (MRI) and other imaging (31%) or mammography alone (19%); 38% opted for either risk reducing salpingo-oophorectomy (RRSO) and breast surveillance, based on MRI and other imaging (28%) or mammography alone (10%). The other three strategies were: risk reducing mastectomy (RRM) and RRSO (5%), RRM alone (2%) and neither RRM/RRSO nor surveillance (6%). The results obtained for various age groups are presented here. Non-carriers often opted for screening despite their low cancer risk. Result disclosure increased carriers' short-term high breast/ovarian cancer risk perceptions (P⩽0.02) and decreased non-carriers' short- and long-term perceptions (P<0.001). During follow-up, high breast cancer risk perceptions increased with time among those who had no RRM and decreased in the opposite case; high ovarian cancer risk perceptions increased further with time among those who had no RRSO and decreased in the opposite case; RRSO did not affect breast cancer risk perceptions. Informed decision-making involves letting women know whether opting for RRSO and breast MRI surveillance is as effective in terms of survival as RRM and RRSO

Children Exhibit a More Comparable Neuromuscular Fatigue Profile to Endurance Athletes Than Untrained Adults

The present study compared neuromuscular fatigue profiles between children, untrained adults and adult endurance athletes during repeated maximal muscle contractions. Eighteen prepubertal boys, 19 untrained men and 13 endurance male athletes performed 5-s maximal voluntary isometric knee extensor contractions (MVICs) interspersed with 5-s recovery until MVIC reached 60% of its initial value. Single and doublet magnetic stimulations were delivered to the femoral nerve to quantify the time course of potentiated twitch amplitude (Ttw,pot), high-frequency torque (T100Hz) and the low-to-high frequency torque ratio (T10Hz/T100Hz), i.e., indicators of peripheral fatigue. M-wave-normalized EMG amplitudes (EMG/M) and the maximal voluntary activation level (VA) were calculated to quantify central fatigue. Adults (15.9 ± 3.9 repetitions) performed fewer MVICs than children (40.4 ± 19.7) and endurance athletes (51.7 ± 19.6), however, no difference was observed between children and athletes (P = 0.13). Ttw,pot (∼52%, P &lt; 0.001), T100Hz (∼39%, P &lt; 0.001) and T10Hz/T100Hz (∼23%, P &lt; 0.001) decreased only in adults. Similar decrements in vastus medialis and vastus lateralis EMG/M were observed in children and endurance athletes (range: 40–50%), and these were greater than in adults (∼15%). Whilst VA decreased more in children (-38.4 ± 22.5%, P &lt; 0.001) than endurance athletes (-20.3 ± 10.1%, P &lt; 0.001), it did not change in adults. Thus, children fatigued more slowly than adults and as much as endurance athletes. They developed less peripheral and more central fatigue than adults and, although central fatigue appeared somewhat higher in children than endurance athletes, both children and endurance athletes experienced greater decrements than adults. Therefore, children exhibit a more comparable neuromuscular fatigue profile to endurance athletes than adults

There Is a Clinical Need to Consider the Physical Activity: Sedentary Pattern in Children with Obesity – Position Paper of the European Childhood Obesity Group

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; While international prevention guidelines recently advocated, in addition to moderate and vigorous physical activity (MVPA) guidelines, for a minimization of sedentary (SED) time, recommendations remain to be developed for youths with obesity. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A literature search was conducted in PubMed, the Cochrane Library, plus the reference lists of selected articles for relevant publications in English, including original papers, systematic reviews, and meta-analyses, with search terms “sedentary behaviors” or “sedentary time” or “screen time” AND “children” or “adolescents” AND “obesity” or “adiposity” or “cardiometabolic risk” or “cardiometabolic disease.” The results were summarized as a narrative review and presented to the scientific board of the European Childhood Obesity Group (ECOG), who then discussed their implication in clinical practice and proposed the position outlined in this paper. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; SED and screen times are associated with adiposity and cardiometabolic risks, independently of youths’ physical activity (PA) level. Besides considering MVPA and SED times as separate variables, comprehensive studies have questioned the impact of different patterns of MVPA and SED levels. Although lower body adiposity and better cardiometabolic health are achieved among those with desirable movement behavior patterns (i.e., more MVPA/less SED or active/not SED), youths with intermediate patterns (i.e., high MVPA/high SED and low MVPA/low SED, or active/SED and inactive/not SED) have been found to be associated with intermediate risks. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; There is a need to decrease SED behaviors irrespective of MVPA and to consider PA-SED patterns in youth with obesity. The ECOG encourages anti-obesity strategies targeting both PA and SED behaviors to support the shift from long periods of SED time, especially screen time, to daily routines incorporating bouts of PA. Stepwise or sequential approaches to movement behavior counseling might start with targeting SED at first to decrease cardiometabolic risks when implementing MVPA is not yet possible. </jats:p

European Language Grid: A Joint Platform for the European Language Technology Community

Europe is a multilingual society, in which dozens of languages are spoken. The only option to enable and to benefit from multilingualism is through Language Technologies (LT), i.e., Natural Language Processing and Speech Technologies. We describe the European Language Grid (ELG), which is targeted to evolve into the primary platform and marketplace for LT in Europe by providing one umbrella platform for the European LT landscape, including research and industry, enabling all stakeholders to upload, share and distribute their services, products and resources. At the end of our EU project, which will establish a legal entity in 2022, the ELG will provide access to approx. 1300 services for all European languages as well as thousands of data sets

The relationship between glucose and the liver-alpha cell axis – A systematic review

Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Funder: CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Italian Association for Cancer Research (AIRC; grant no.16933) to L. Ottini. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. Jacopo Azzollini is supported by funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5x1000’). DEMOKRITOS: European Union (European Social Fund – ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. FPGMX: FISPI05/2275 and Mutua Madrileña Foundation (FMMA). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HRBCP: Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health1R 03CA130065, and North California Cancer Center. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5x1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MODSQUAD: MH CZ - DRO (MMCI, 00209805), MEYS - NPS I - LO1413 to LF and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NAROD: 1R01 CA149429-01. NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC: Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-12007). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032, P20CA233307, American Cancer Society (MRSG-13-063-01-TBG, CRP-10-119-01-CCE), Breast Cancer Research Foundation, Susan G. Komen Foundation (SAC110026), and Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance. Mr. Qian was supported by the Alpha Omega Alpha Carolyn L. Cuckein Student Research Fellowship. UCLA: Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Research UK. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.Abstract: Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as