| 1. |
- Massaro, Giulia, et al.
(author)
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Fetal gene therapy for neurodegenerative disease of infants
- 2018
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:9, s. 1317-1323
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Journal article (peer-reviewed)abstract
- For inherited genetic diseases, fetal gene therapy offers the potential of prophylaxis against early, irreversible and lethal pathological change. To explore this, we studied neuronopathic Gaucher disease (nGD), caused by mutations in GBA. In adult patients, the milder form presents with hepatomegaly, splenomegaly and occasional lung and bone disease; this is managed, symptomatically, by enzyme replacement therapy. The acute childhood lethal form of nGD is untreatable since enzyme cannot cross the blood–brain barrier. Patients with nGD exhibit signs consistent with hindbrain neurodegeneration, including neck hyperextension, strabismus and, often, fatal apnea1. We selected a mouse model of nGD carrying a loxP-flanked neomycin disruption of Gba plus Cre recombinase regulated by the keratinocyte-specific K14 promoter. Exclusive skin expression of Gba prevents fatal neonatal dehydration. Instead, mice develop fatal neurodegeneration within 15 days2. Using this model, fetal intracranial injection of adeno-associated virus (AAV) vector reconstituted neuronal glucocerebrosidase expression. Mice lived for up to at least 18 weeks, were fertile and fully mobile. Neurodegeneration was abolished and neuroinflammation ameliorated. Neonatal intervention also rescued mice but less effectively. As the next step to clinical translation, we also demonstrated the feasibility of ultrasound-guided global AAV gene transfer to fetal macaque brains.
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| 2. |
- Valente, André, et al.
(author)
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A compilation of global bio-optical in situ data for ocean-colour satellite applications - version two
- 2019
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 11:3, s. 1037-1068
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Journal article (peer-reviewed)abstract
- A global compilation of in situ data is useful to evaluate the quality of ocean-colour satellite data records. Here we describe the data compiled for the validation of the ocean-colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI). The data were acquired from several sources (including, inter alia, MOBY, BOUSSOLE, AERONET-OC, SeaBASS, NOMAD, MERMAID, AMT, ICES, HOT and GeP&CO) and span the period from 1997 to 2018. Observations of the following variables were compiled: spectral remote-sensing reflectances, concentrations of chlorophyll a, spectral inherent optical properties, spectral diffuse attenuation coefficients and total suspended matter. The data were from multi-project archives acquired via open internet services or from individual projects, acquired directly from data providers. Methodologies were implemented for homogenization, quality control and merging of all data. No changes were made to the original data, other than averaging of observations that were close in time and space, elimination of some points after quality control and conversion to a standard format. The final result is a merged table designed for validation of satellite-derived ocean-colour products and available in text format. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) was propagated throughout the work and made available in the final table. By making the metadata available, provenance is better documented, and it is also possible to analyse each set of data separately. This paper also describes the changes that were made to the compilation in relation to the previous version (Valente et al., 2016). The compiled data are available at https://doi.org/10.1594/PANGAEA.898188 (Valente et al., 2019).
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| 3. |
- Aamodt, K., et al.
(author)
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The ALICE experiment at the CERN LHC
- 2008
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In: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Research review (peer-reviewed)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 6. |
- Dinger, Florian, et al.
(author)
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Periodicity in the BrO/SO2 molar ratios in the volcanic gas plume of Cotopaxi and its correlation with the Earth tides during the eruption in 2015
- 2018
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In: Solid Earth. - : Copernicus GmbH. - 1869-9510 .- 1869-9529. ; 9:2, s. 247-266
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Journal article (peer-reviewed)abstract
- We evaluated NOVAC (Network for Observation of Volcanic and Atmospheric Change) gas emission data from the 2015 eruption of the Cotopaxi volcano (Ecuador) for BrO/SO2 molar ratios. The BrO=SO2 molar ratios were very small prior to the phreatomagmatic explosions in August 2015, significantly higher after the explosions, and continuously increasing until the end of the unrest period in December 2015. These observations together with similar findings in previous studies at other volcanoes (Mt. Etna, Nevado del Ruiz, Tungurahua) suggest a possible link between a drop in BrO/SO2 and a future explosion. In addition, the observed relatively high BrO/SO2 molar ratios after December 2015 imply that bromine degassed predominately after sulfur from the magmatic melt. Furthermore, statistical analysis of the data revealed a conspicuous periodic pattern with a periodicity of about 2 weeks in a 3-month time series. While the time series is too short to rule out a chance recurrence of transient geological or meteorological events as a possible origin for the periodic signal, we nevertheless took this observation as a motivation to examine the influence of natural forcings with periodicities of around 2 weeks on volcanic gas emissions. One strong aspirant with such a periodicity are the Earth tides, which are thus central in this study. We present the BrO=SO2 data, analyse the reliability of the periodic signal, discuss a possible meteorological or eruption-induced origin of this signal, and compare the signal with the theoretical ground surface displacement pattern caused by the Earth tides. Our central result is the observation of a significant correlation between the BrO=SO2 molar ratios with the north–south and vertical components of the calculated tideinduced surface displacement with correlation coefficients of 47 and 36 %, respectively. From all other investigated parameters, only the correlation between the BrO=SO2 molar ratios and the relative humidity in the local atmosphere resulted in a comparable correlation coefficient of about 33 %.
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| 7. |
- Hebert-Losier, Kim, 1985-, et al.
(author)
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Factors that Influence the Performance of Elite Sprint Cross-Country Skiers
- 2017
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In: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 47:2, s. 319-342
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Journal article (peer-reviewed)abstract
- Background: Sprint events in cross-country skiing are unique not only with respect to their length (0.8–1.8 km), but also in involving four high-intensity heats of ~3 min in duration, separated by a relatively short recovery period (15–60 min). Objective: Our aim was to systematically review the scientific literature to identify factors related to the performance of elite sprint cross-country skiers. Methods: Four electronic databases were searched using relevant medical subject headings and keywords, as were reference lists, relevant journals, and key authors in the field. Only original research articles addressing physiology, biomechanics, anthropometry, or neuromuscular characteristics and elite sprint cross-country skiers and performance outcomes were included. All articles meeting inclusion criteria were quality assessed. Data were extracted from each article using a standardized form and subsequently summarized. Results: Thirty-one articles met the criteria for inclusion, were reviewed, and scored an average of 66 ± 7 % (range 56–78 %) upon quality assessment. All articles except for two were quasi-experimental, and only one had a fully-experimental research design. In total, articles comprised 567 subjects (74 % male), with only nine articles explicitly reporting their skiers’ sprint International Skiing Federation points (weighted mean 116 ± 78). A similar number of articles addressed skating and classical techniques, with more than half of the investigations involving roller-skiing assessments under laboratory conditions. A range of physiological, biomechanical, anthropometric, and neuromuscular characteristics was reported to relate to sprint skiing performance. Both aerobic and anaerobic capacities are important qualities, with the anaerobic system suggested to contribute more to the performance during the first of repeated heats; and the aerobic system during subsequent heats. A capacity for high speed in all the following instances is important for the performance of sprint cross-country skiers: at the start of the race, at any given point when required (e.g., when being challenged by a competitor), and in the final section of each heat. Although high skiing speed is suggested to rely primarily on high cycle rates, longer cycle lengths are commonly observed in faster skiers. In addition, faster skiers rely on different technical strategies when approaching peak speeds, employ more effective techniques, and use better coordinated movements to optimize generation of propulsive force from the resultant ski and pole forces. Strong uphill technique is critical to race performance since uphill segments are the most influential on race outcomes. A certain strength level is required, although more does not necessarily translate to superior sprint skiing performance, and sufficient strength-endurance capacities are also of importance to minimize the impact and accumulation of fatigue during repeated heats. Lastly, higher lean mass does appear to benefit sprint skiers’ performance, with no clear advantage conferred via body height and mass. Limitations: Generalization of findings from one study to the next is challenging considering the array of experimental tasks, variables defining performance, fundamental differences between skiing techniques, and evolution of sprint skiing competitions. Although laboratory-based measures can effectively assess on-snow skiing performance, conclusions drawn from roller-skiing investigations might not fully apply to on-snow skiing performance. A low number of subjects were females (only 17 %), warranting further studies to better understand this population. Lastly, more training studies involving high-level elite sprint skiers and investigations pertaining to the ability of skiers to maintain high-sprint speeds at the end of races are recommended to assist in understanding and improving high-level sprint skiing performance, and resilience to fatigue. Conclusions: Successful sprint cross-country skiing involves well-developed aerobic and anaerobic capacities, high speed abilities, effective biomechanical techniques, and the ability to develop high forces rapidly. A certain level of strength is required, particularly ski-specific strength, as well as the ability to withstand fatigue across the repeated heats of sprint races. Cross-country sprint skiing is demonstrably a demanding and complex sport, where high-performance skiers need to simultaneously address physiological, biomechanical, anthropometric, and neuromuscular aspects to ensure success.
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| 8. |
- Hébert-Losier, Kim, et al.
(author)
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Sources of Variability in Performance Times at the World Orienteering Championships
- 2015
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In: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 47:7, s. 1523-1530
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Journal article (peer-reviewed)abstract
- Purpose An improvement equal to 0.3 of the typical variation in an elite athlete's race-to-race performance estimates the smallest worthwhile enhancement, which has not yet been determined for orienteers. Moreover, much of the research in high-performance orienteering has focused on physical and cognitive aspects, although course characteristics might influence race performance. Analysis of race data provides insights into environmental effects and other aspects of competitive performance. Our aim was to examine such factors in relation to World Orienteering Championships performances. Methods We used mixed linear modelling to analyze finishing times from the three qualification rounds and final round of the sprint, middle-distance, and long-distance disciplines of World Orienteering Championships from 2006 to 2013. Models accounted for race length, distance climbed, number of controls, home advantage, venue identity, round (qualification final), athlete identity, and athlete age. Results Within-athlete variability (coefficient of variation, mean SD) was lower in the final (4.9% +/- 1.4%) than in the qualification (7.3% +/- 2.4%) rounds and provided estimates of smallest worthwhile enhancements of 1.0%-3.5%. The home advantage was clear in most disciplines, with distance climbed particularly impacting sprint performances. Small to very large between-venue differences were apparent. Performance predictability expressed as intraclass correlation coefficients was extremely high within years and was high to very high between years. Age of peak performance ranged from 27 to 31 yr. Conclusions Our results suggest that elite orienteers should focus on training and strategies that enhance performance by at least 1.0%-3.5% for smallest worthwhile enhancement. Moreover, as greater familiarity with the terrain likely mediated the home advantage, foreign athletes would benefit from training in nations hosting the World Orienteering Championships for familiarization.
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| 10. |
- McGawley, Kerry, 1978-, et al.
(author)
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The validity and reliability of a four-minute running time trial in assessing VO2max and performance
- 2015
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Conference paper (peer-reviewed)abstract
- INTRODUCTION: Incremental tests to volitional exhaustion are widely used to assess VO2max. However, the need to establish starting workloads, stage durations, and step increments make administration problematic. Moreover, the validity of such tests has been questioned (Beltrami et al., 2012, Br J Sports Med, 46:23-29; Mauger & Sculthorpe, 2012, Br J Sports Med, 46:59-63). Short time trials represent a simpler and more ecologically valid alternative to assess VO2max and performance across exercise modes (Crouter et al., 2001, Med Sci Sports Exerc, 33:644-647; Ansley et al., 2004, Med Sci Sports Exerc, 36:1819-1825; McGawley & Holmberg, 2014, Int J Sports Physiol Perform 9:32-40). The aim of the current study was to assess the reliability and validity of a treadmill running time trial (RunTT) for the assessment of VO2max and performance. METHODS: Ten recreational athletes (5 males, 5 females; 32 ± 7 y) completed five incremental tests to exhaustion (INC) including a verification phase (VER) on a treadmill and five, 4-min RunTTs. The order of INC+VER and RunTT trials was alternated and counter-balanced. The INC and VER protocols were externally controlled, with incline increasing by 1% every minute during the INC. By contrast, the RunTT protocol was athlete controlled, with running speed self-adjusted via a laser system fitted to the treadmill (and incline fixed at 1%). Performance was measured as time to exhaustion for INC and VER and distance covered for RunTT. Heart rate (HR) was monitored continuously throughout each protocol. RPE and lactate were assessed immediately post-exercise and at 1-min intervals for four minutes post-exercise, respectively. RESULTS: The CV for VO2max was not significantly different between INC, VER and RunTT (1.9, 2.2 and 1.7%, respectively) but for performance was significantly different between all types of test (4.5, 9.7 and 1.8% for INC, VER and RunTT, respectively; P<0.005). VO2max was significantly higher for INC compared with VER and RunTT (59.2 versus 58.0 and 57.6 mL/kg/min, respectively; P<0.001) and Bland-Altman limits of agreement showed a bias ± 95% of 1.5 ± 3.1 mL/kg/min for INC versus RunTT. Peak HR was also significantly higher for INC compared with RunTT (181 versus 177 beats/min; P<0.001), while peak RER and RPE were not different. Peak lactate was higher after RunTT compared with INC (10.13 versus 9.22 mmol/L; P<0.001). CONCLUSION: A RunTT appears to provide more reliable performance data in comparison to INC; however, VO2max values were ~ 1.5 mL/kg/min lower and peak lactate was significantly higher.
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