Valjanost mjerenja razine mišićne aktivacije izokinetičkim testiranjem

The study aimed at testing the possibility of using an isokinetic dynamometer to measure muscle activation level (AL). The AL measured with an isokinetic dynamometer and calculated as a ratio between the maximum isometric and eccentric torques was compared against the AL obtained by the double interpolated twitch method. Eighteen male students with different levels of training participated in the study. The average ALs measured by the isokinetic dynamometer (AL_ISOK) at knee angles of 55° and 60°, as well as the average AL calculated from the maximum eccentric torque independently of a knee angle at angular velocities of 60°/s (100.10±13.25%, 92.43±11.82% and 84.33±9.29%, respectively) and 120°/s (99.93±11.93%, 94.61±13.79% and 88.52±14.07%, respectively) did not differ significantly from the average ALs measured by the double interpolated twitch method (AL_TW=89.50±7.42%). Significant correlations were found between AL_TW and several AL_ISOK at the angular velocity of 120°/s. However, the correlations were negative and low to medium (from –.478 to –.609). It was concluded that the AL_ISOK were not comparable to the AL_TW and therefore seemed not suitable for the activation level measurement, although the negative correlations between the two methods still leave this possibility.Cilj je ovoga istraživanja bilo testiranje mogućnosti korištenja izokinetičkoga dinamometra za mjerenje razine mišićne aktivacije (AL). Razina mišićne aktivacije mjerena pomoću izokinetičkoga dinamometra i izračunata kao omjer između maksimalne izometričke i ekscentrične zakretne sile uspoređena je s razinom mišićne aktivacije, dobivenom pomoću metode superponirane stimulacije mišića (interpolated twitch method). Osamnaest studenata različitih razina treniranosti sudjelovalo je u ovom istraživanju. Prosječna vrijednost mišićne aktivacije mjerene pomoću izokinetičkoga dinamometra (AL_ISOK) pri kutovima koljenoga zgloba od 55° i 60°, kao i prosječna vrijednost mišićne aktivacije izračunate iz maksimalne ekscentrične zakretne sile neovisno o kutu u koljenom zglobu pri kutnoj brzini od 60°/s (100.10±13.25%, 92.43±11.82% i 84.33±9.29%) te pri kutnoj brzini od 120°/s (99.93±11.93%, 94.61±13.79% i 88.52±14.07%) nije bila značajno različita od prosječne vrijednosti razine mišićne aktivacije izmjerene pomoću metode superponirane stimulacije mišića (AL_TW=89.50±7.42%). Značajne korelacije utvrđene su između razine mišićne aktivacije AL_ TW i nekoliko vrijednosti izmjerenih izokinetičkim dinamometrom (AL_ISOK) pri kutnim brzinama od 120°/s. Ipak, korelacije su bile negativne i niske do umjerene (od –.478 do –.609). Zaključeno je da razine mišićne aktivacije izmjerene dinamometrom (AL_ISOK) nisu usporedive s razinama izmjerenima metodom superponirane stimulacije mišića (AL_TW) te se zbog toga čini da izokinetički dinamometar nije prikladan za mjerenje razine mišićne aktivacije, premda negativne korelacije između tih dviju metoda još uvijek ostavljaju tu mogućnost

Multiscale characterisation of chimneys/pipes: Fluid escape structures within sedimentary basins

Evaluation of seismic reflection data has identified the presence of fluid escape structures cross-cutting overburden stratigraphy within sedimentary basins globally. Seismically-imaged chimneys/pipes are considered to be possible pathways for fluid flow, which may hydraulically connect deeper strata to the seabed. The properties of fluid migration pathways through the overburden must be constrained to enable secure, long-term subsurface carbon dioxide (CO2) storage. We have investigated a site of natural active fluid escape in the North Sea, the Scanner pockmark complex, to determine the physical characteristics of focused fluid conduits, and how they control fluid flow. Here we show that a multi-scale, multi-disciplinary experimental approach is required for complete characterisation of fluid escape structures. Geophysical techniques are necessary to resolve fracture geometry and subsurface structure (e.g., multi-frequency seismics) and physical parameters of sediments (e.g., controlled source electromagnetics) across a wide range of length scales (m to km). At smaller (mm to cm) scales, sediment cores were sampled directly and their physical and chemical properties assessed using laboratory-based methods. Numerical modelling approaches bridge the resolution gap, though their validity is dependent on calibration and constraint from field and laboratory experimental data. Further, time-lapse seismic and acoustic methods capable of resolving temporal changes are key for determining fluid flux. Future optimisation of experiment resource use may be facilitated by the installation of permanent seabed infrastructure, and replacement of manual data processing with automated workflows. This study can be used to inform measurement, monitoring and verification workflows that will assist policymaking, regulation, and best practice for CO2 subsurface storage operations

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Measurement of muscle activation level with comparing the maximum torques during isometric and eccentric contraction

Cilj naloge je bil preveriti uporabnost meritve nivoja mišične aktivacije (NA) s primerjavo največjega izometričnega in ekscentričnega navora (metoda razmerij navorov – MRN), izmerjenega s pomočjo enostavnega hidravličnega sistema domače izdelave, vgrajenega v trenažer za izteg kolen. Rezultate, dobljene z MRN, smo primerjali s tistimi, dobljenimi z že uveljavljeno metodo dvojnega vrinjenega skrčka (MDS). V ta namen smo želeli ugotoviti zanesljivost in občutljivost meritev ter njihovo veljavnost v pogojih akutnih (utrujanje) in kroničnih (vadba za moč) vplivov na NA. V raziskavi je prostovoljno sodelovalo 28 rekreativno treniranih merjencev moškega spola (povprečna starost in standardni odklon 30,3 ± 10,6 let, telesna višina 181,6 ± 8,0 cm, telesna masa 83,6 ± 9,7 kg). Raziskava je potekala v dveh delih. V prvem delu je 9 merjencev znotraj merilnega dneva opravilo 2 meritvi NA z obema metodama (2 ponovitvi za vsako metodo, vrstni red je bil naključno izbran), nato je sledil protokol utrujanja, ki je vseboval 2-min zadrževanje največjega hotenega izometričnega naprezanja. Takoj zatem so merjenci ponovno opravili po 2 meritvi NA z vsako metodo (isti vrstni red). V drugem delu je bilo vključenih 6 merjencev eksperimentalne skupine (ES) in 6 kontrolne skupine (KS), ki so znotraj merilnega dneva po naključnem vrstnem redu izvedli po 2 meritvi NA z MRN in 1 meritev z MDS. Opravili so začetne (ZM) in končne (KM) meritve. Med merilnima dnevoma je ES izvajala 4-tedenski program vadbe za razvoj mišične aktivacije, medtem ko je KS opravljala običajne aktivnosti. Pri posamezni meritvi z MRN sta bila izmerjena največji hoteni izometrični navor v kotu v kolenu 60° in v isti gibalni akciji največji hoteni ekscentrični navor v amplitudi od 55° do 70° iztega kolena, ki ga je omogočil hidravlični sistem med potiskom vzvoda trenažerja s konstantno hitrostjo 35°/s do 65°/s. NA, izmerjen z MRN (NA_MRN), je bil izračunan kot razmerje med največjim hotenim izometričnim in ekscentričnim navorom. Meritev z MDS je bila opravljena na izometričnem dinamometru za izteg kolen, kjer smo s pomočjo tokovno konstantnega električnega stimulatorja preko površine kože na trebuhu mišice stimulirali štiriglavo stegensko mišico z dvojnim supramaksimalnim električnim dražljajem (dvofazni impulz trajanja 0,3 ms, interval med impulzoma 10 ms). NA, izmerjen z MDS (NA_MDS), je bil izračunan na osnovi primerjave velikosti skrčka med največjim hotenim izometričnim naprezanjem in takoj po njem, ob sproščeni mišici, v kotu 60° iztega kolena. Rezultati meritev z MRN v izhodiščnem stanju (spočitost merjencev, meritve, izvedene pred obema intervencijama) so pokazali odlično ponovljivost za vse obravnavane spremenljivke (ICC > 0,90p r > 0,94p > 0,05). Vadba za moč ni prinesla pričakovanih rezultatov, saj med ZM in KM nismo ugotovili razlik v izmerjenih vrednostih največjih hotenih izometričnih navorov za obe skupini kot tudi ne med skupinama (p > 0,05). Kljub visokim korelacijam med metodama v največjih hotenih izometričnih navorih primerjava povprečnih vrednostih NA, izmerjenih v vseh treh stanjih (i – spočito, ii – po protokolu utrujanja ter iii – po vadbi), ni pokazala značilnega ujemanja med metodama, saj so se vrednosti med seboj razlikovale (p 0,90p r > 0,94p > 0,05). Strength training did not produce the expected results, as we did not find differences between the IM and FM in measured values of maximum voluntary isometric torques for the two groups, as well as between the groups (p > 0,05). Despite the high correlations between the methods in the maximum torque isometric torques, the comparison of the average NA values measured in all three conditions (i - restful, ii - after fatigue protocol and iii - after exercise) did not show significant match between the methods, since the values differed (p ICC < 0,20). We found that the use of a hydraulic system for measuring AL with TRM does not provide comparable results with the DTW

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts