Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Skill Variety, Innovation and New Business Formation

We extend Lazear's theory of skills variety and entrepreneurship in three directions. First, we provide a theoretical framework linking new business creation with an entrepreneur's skill variety. Second, in this model we allow for both generalists and specialists to possess skill variety. Third, we test our model empirically using data from Germany and the Netherlands. Individuals with more varied work experience seems indeed more likely to successfully start up a new business and that being a generalist does not seem to be important in this regard. Finally, we find that innovation positively moderates the relationship between having varied experiences, and being successful in starting up a new business. Our conclusion is that entrepreneurs with more varied work experience are more likely to introduce innovations that have not only technical, but also commercial value. Our findings support the notion that entrepreneurship can be learned

Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand

BACKGROUND: No data currently exist about use of antibiotics to prevent surgical site infections (SSI) among patients undergoing appendectomy in Thailand. We therefore examined risk factors, use, and efficacy of prophylactic antibiotics for surgical site infection SSI among patients with uncomplicated open appendectomy. METHODS: From July 1, 2003 to June 30, 2004 we conducted a prospective cohort study in eight hospitals in Thailand. We used the National Nosocomial Infection Surveillance (NNIS) system criteria to identify SSI associated with appendectomy. We used logistic regression analysis to obtain relative risk estimates for predictors of SSI. RESULTS: Among 2139 appendectomy patients, we identified 26 SSIs, yielding a SSI rate of 1.2 infections/100 operations. Ninety-two percent of all patients (95% CI, 91.0–93.3) received antibiotic prophylaxis. Metronidazole and gentamicin were the two most common antibiotic agents, with a combined single dose administered in 39% of cases. In 54% of cases, antibiotic prophylaxis was administered for one day. We found that a prolonged duration of operation was significantly associated with an increased SSI risk. Antibiotic prophylaxis was significantly associated with a decreased risk of SSI regardless of whether the antibiotic was administered preoperatively or intraoperatively. Compared with no antibiotic prophylaxis, SSI relative risks for combined single-dose of metronidazole and gentamicin, one-day prophylaxis, and multiple-day antibiotic prophylaxis were 0.28 (0.09–0.90), 0.30 (0.11–0.88) and 0.32 (0.10–0.98), respectively. CONCLUSION: Single-dose combination of metronidazole and gentamicin seems sufficient to reduce SSIs in uncomplicated appendicitis patients despite whether the antibiotic was administered preoperatively or intraoperatively

Euclid preparation: XVII. Cosmic Dawn Survey: Spitzer Space Telescope observations of the Euclid deep fields and calibration fields

We present a new infrared survey covering the three Euclid deep fields and four other Euclid calibration fields using Spitzer Space Telescope's Infrared Array Camera (IRAC). We combined these new observations with all relevant IRAC archival data of these fields in order to produce the deepest possible mosaics of these regions. In total, these observations represent nearly 11 % of the total Spitzer Space Telescope mission time. The resulting mosaics cover a total of approximately 71.5 deg^{2} in the 3.6 and 4.5 μm bands, and approximately 21.8 deg^{2} in the 5.8 and 8 μm bands. They reach at least 24 AB magnitude (measured to 5σ, in a 2″​​.5 aperture) in the 3.6 μm band and up to ∼5 mag deeper in the deepest regions. The astrometry is tied to the Gaia astrometric reference system, and the typical astrometric uncertainty for sources with 16 "< "[3.6]< 19 is ≲ 0″​​.15. The photometric calibration is in excellent agreement with previous WISE measurements. We extracted source number counts from the 3.6 μm band mosaics, and they are in excellent agreement with previous measurements. Given that the Spitzer Space Telescope has now been decommissioned, these mosaics are likely to be the definitive reduction of these IRAC data. This survey therefore represents an essential first step in assembling multi-wavelength data on the Euclid deep fields, which are set to become some of the premier fields for extragalactic astronomy in the 2020s

<em>Euclid</em> preparation: XLVII. Improving cosmological constraints using a new multi-tracer method with the spectroscopic and photometric samples

\ua9 2024 The Authors. Future data provided by the Euclid mission will allow us to better understand the cosmic history of the Universe. A metric of its performance is the figure-of-merit (FoM) of dark energy, usually estimated with Fisher forecasts. The expected FoM has previously been estimated taking into account the two main probes of Euclid, namely the three-dimensional clustering of the spectroscopic galaxy sample, and the so-called 3 72pt signal from the photometric sample (i.e., the weak lensing signal, the galaxy clustering, and their cross-correlation). So far, these two probes have been treated as independent. In this paper, we introduce a new observable given by the ratio of the (angular) two-point correlation function of galaxies from the two surveys. For identical (normalised) selection functions, this observable is unaffected by sampling noise, and its variance is solely controlled by Poisson noise. We present forecasts for Euclid where this multi-tracer method is applied and is particularly relevant because the two surveys will cover the same area of the sky. This method allows for the exploitation of the combination of the spectroscopic and photometric samples. When the correlation between this new observable and the other probes is not taken into account, a significant gain is obtained in the FoM, as well as in the constraints on other cosmological parameters. The benefit is more pronounced for a commonly investigated modified gravity model, namely the γ parametrisation of the growth factor. However, the correlation between the different probes is found to be significant and hence the actual gain is uncertain. We present various strategies for circumventing this issue and still extract useful information from the new observable

Euclid preparation XLI. Galaxy power spectrum modelling in real space

We investigate the accuracy of the perturbative galaxy bias expansion in view of the forthcoming analysis of the Euclid spectroscopic galaxy samples. We compare the performance of a Eulerian galaxy bias expansion using state-of-the-art prescriptions from the effective field theory of large-scale structure (EFTofLSS) with a hybrid approach based on Lagrangian perturbation theory and high-resolution simulations. These models are benchmarked against comoving snapshots of the flagship I N-body simulation at z = (0.9, 1.2, 1.5, 1.8), which have been populated with Hα galaxies leading to catalogues of millions of objects within a volume of about 58 h−3 Gpc3. Our analysis suggests that both models can be used to provide a robust inference of the parameters (h, ωc) in the redshift range under consideration, with comparable constraining power. We additionally determine the range of validity of the EFTofLSS model in terms of scale cuts and model degrees of freedom. From these tests, it emerges that the standard third-order Eulerian bias expansion – which includes local and non-local bias parameters, a matter counter term, and a correction to the shot-noise contribution – can accurately describe the full shape of the real-space galaxy power spectrum up to the maximum wavenumber of kmax = 0.45 h Mpc−1, and with a measurement precision of well below the percentage level. Fixing either of the tidal bias parameters to physically motivated relations still leads to unbiased cosmological constraints, and helps in reducing the severity of projection effects due to the large dimensionality of the model. We finally show how we repeated our analysis assuming a volume that matches the expected footprint of Euclid, but without considering observational effects, such as purity and completeness, showing that we can get constraints on the combination (h, ωc) that are consistent with the fiducial values to better than the 68% confidence interval over this range of scales and redshifts

Euclid II. The VIS instrument

This paper presents the specification, design, and development of the Visible Camera (VIS) on the European Space Agency's mission. VIS is a large optical-band imager with a field of view of 0.54 deg$^2$ sampled at with an array of 609 Megapixels and a spatial resolution of . It will be used to survey approximately 14 000 deg$^2$ of extragalactic sky to measure the distortion of galaxies in the redshift range $z=0.1$--1.5 resulting from weak gravitational lensing, one of the two principal cosmology probes leveraged by With photometric redshifts, the distribution of dark matter can be mapped in three dimensions, and the extent to which this has changed with look-back time can be used to constrain the nature of dark energy and theories of gravity. The entire VIS focal plane will be transmitted to provide the largest images of the Universe from space to date, specified to reach AB with a signal-to-noise ratio S/N in a single broad E (r+i+z)$band over a six-year survey. The particularly challenging aspects of the instrument are the control and calibration of observational biases, which lead to stringent performance requirements and calibration regimes. With its combination of spatial resolution, calibration knowledge, depth, and area covering most of the extra-Galactic sky, VIS will also provide a legacy data set for many other fields. This paper discusses the rationale behind the conception of VIS and describes the instrument design and development, before reporting the prelaunch performance derived from ground calibrations and brief results from the in-orbit commissioning. VIS should reach fainter than AB =25$ with $S/N 10$ for galaxies with a full width at half maximum of in a diameter aperture over the Wide Survey, and $m_ AB for a Deep Survey that will cover more than 50 deg$^2$. The paper also describes how the instrument works with the telescope and survey, and with the science data processing, to extract the cosmological information

Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats

Dopamine related disorders usually respond to dopaminergic drugs, but not all symptoms are equally responsive. In Parkinson’s disease (PD) in particular, axial symptoms resulting in impaired gait and postural control are difficult to treat. Stochastic vestibular stimulation (SVS) has been put forward as a method to improve CNS function in dopamine related disorders, but the mechanisms of action are not well understood. This thesis aimed to investigate the effects of SVS on neuronal brain activity and to evaluate the possible enhancing effect of SVS on motor control in PD and on cognitive functions and motor learning in Attention deficit hyperactivity disorder (ADHD). Behavioural tests were conducted in the 6-OHDA rat model of PD using the accelerating Rotarod and the Montoya skilled reach test to evaluate the effect of SVS on motor control. The effect of SVS on brain activity was assessed using in vivo microdialysis and immunohistochemistry. We evaluated the effect of SVS on postural control and Parkinsonism in patients with PD and the effect of SVS on cognitive function in people with ADHD. The behavioural animal studies indicate that SVS may have an enhancing effect on locomotion, but not skilled forepaw function. SVS increased GABA transmission in the ipsilesional substantia nigra (SN) and may have a rebalancing effect on dysfunctional brain activity. SVS increased c-Fos activity more than levodopa and saline in the vestibular nucleus of all animals. c-Fos expression was also higher in this region in the 6-OHDA lesioned than in shamlesioned animals, supporting the theory that SVS may have larger effects in the dopamine depleted brain. SVS increased c-Fos expression in the habenula nucleus substantially more than levodopa did. Furthermore, SVS and levodopa had similar effects on many brain regions, including the striatum, where saline had no effect. The clinical studies revealed improvement of postural control in PD during SVS. There was a trend towards reduced Parkinsonism during SVS when off levodopa. No substantial effects were found on cognitive performance in ADHD. In PD, SVS may improve motor control by inhibiting the overactive SN, possibly through a non-dopaminergic modulatory pathway involving increased neurotransmission in the habenula nucleus. SVS could be trialled in larger studies to evaluate long-term effects on treatment resistant axial symptoms associated with PD

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA

<em>Euclid</em>: the potential of slitless infrared spectroscopy: a z = 5.4 quasar and new ultracool dwarfs

\ua9 2025 The Author(s). We demonstrate the potential of Euclid \u27s slitless spectroscopy to discover high-redshift (5$]]&gt;) quasars and their main photometric contaminant, ultracool dwarfs. Sensitive infrared spectroscopy from space is able to efficiently identify both populations, as demonstrated by Euclid Near-Infrared Spectrometer and Photometer Red Grism (NISP) spectra of the newly discovered quasar EUCL J181530.01652054.0, as well as several ultracool dwarfs in the Euclid Deep Field North and the Euclid Early Release Observation field Abell 2764. The ultracool dwarfs were identified by cross-correlating their spectra with templates. The quasar was identified by its strong and broad and emission lines in the NISP 1206-1892 nm spectrum, and confirmed through optical spectroscopy from the Large Binocular Telescope. The NISP Blue Grism (NISP) 926-1366 nm spectrum confirms and emission. NISP can find bright quasars at and, redshift ranges that are challenging for photometric selection due to contamination from ultracool dwarfs. EUCL J181530.01652054.0 is a high-excitation, broad absorption line quasar detected at 144 MHz by the LOw-Frequency Array (W Hz). The quasar has a bolometric luminosity of and is powered by a black hole. The discovery of this bright quasar is noteworthy as fewer than one such object was expected in the 20 deg surveyed. This finding highlights the potential and effectiveness of NISP spectroscopy in identifying rare, luminous high-redshift quasars, previewing the census of these sources that Euclid\u27s slitless spectroscopy will deliver over about deg of the sky