Commentaries on viewpoint : managing the power grid : how myoglobin can regulate PO2 and energy distribution in skeletal muscle

Q2Q1To the editor: a recent article by Clanton (1) highlights an insightful Viewpoint regarding the emerging role of myoglobin (Mb) as an interstitial Po2 (PiO2) regulator during exercise by switching from a nitric oxide (NO) consumer to an NO producer.Revista Nacional - Indexad

Raw and Count Data Comparability of Hip-Worn ActiGraph GT3X+ and Link Accelerometers

To enable inter- and intrastudy comparisons it is important to ascertain comparability among accelerometer models. Purpose: The purpose of this study was to compare raw and count data between hip-worn ActiGraph GT3X+ and GT9X Link accelerometers. Methods: Adults (n = 26 (n = 15 women); age, 49.1 T 20.0 yr) wore GT3X+ and Link accelerometers over the right hip for an 80-min protocol involving 12–21 sedentary, household, and ambulatory/exercise activities lasting 2–15 min each. For each accelerometer, mean and variance of the raw (60 Hz) data for each axis and vector magnitude (VM) were extracted in 30-s epochs. A machine learning model (Montoye 2015) was used to predict energy expenditure in METs from the raw data. Raw data were also processed into activity counts in 30-s epochs for each axis and VM, with Freedson 1998 and 2011 count-based regression models used to predictMETs. Time spent in sedentary, light, moderate, and vigorous intensities was derived from predicted METs from each model. Correlations were calculated to compare raw and count data between accelerometers, and percent agreement was used to compare epoch-by-epoch activity intensity. Results: For raw data, correlations for mean acceleration were 0.96 T 0.05, 0.89 T 0.16, 0.71 T 0.33, and 0.80 T 0.28, and those for variance were 0.98 T 0.02, 0.98 T 0.03, 0.91 T 0.06, and 1.00 T 0.00 in the X, Y, and Z axes and VM, respectively. For count data, corresponding correlations were 1.00 T 0.01, 0.98 T 0.02, 0.96 T 0.04, and 1.00 T 0.00, respectively. Freedson 1998 and 2011 count-based models had significantly higher percent agreement for activity intensity (95.1% T 5.6% and 95.5% T 4.0%) compared with theMontoye 2015 raw data model (61.5% T 27.6%; P G 0.001). Conclusions: Count data were more highly comparable than raw data between accelerometers. Data filtering and/or more robust raw data models are needed to improve raw data comparability between ActiGraph GT3X+ and Link accelerometers

Statistical Learning Methods to Predict Activity Intensity from Body-Worn Accelerometers

 Physical activity, especially when performed at moderate or vigorous intensity, has short- and long-term health benefits, but measurement of free-living physical activity is challenging. Accelerometers are popular tools to assess physical activity, although accuracy of conventional accelerometer analysis methods is suboptimal. This study developed and tested statistical learning models for assessing activity intensity from body-worn accelerometers. Twenty-eight adults performed 10-21 activities of daily living in two visits while wearing four accelerometers (right hip, right ankle, both wrists). Accelerometer placement is of crucial practical concern and this paper addresses this issue. Boosting, bagging, random forest and decision tree models were created for each accelerometer and for two-, three-, and four-accelerometer combinations to predict activity intensity. Research staff observations of activity intensity served as the criterion. Point estimates of error for the ankle accelerometer were 2.2-4.7 percentage points lower than other single-accelerometer placements, and the left wrist-ankle combination had errors 0.8-5.8 percentage points lower than other two-accelerometer combinations. Decision trees had poorer accuracy than the other models. Using an accelerometer worn on the lower limb, by itself or in combination with an upper-limb accelerometer, appears to offer optimal accuracy for activity intensity measurement

Development of Cut-points for Determining Activity Intensity From a Wrist-worn ActiGraph Accelerometer in Free-living Adults

Despite recent popularity of wrist-worn accelerometers for assessing free-living physical behaviours, there is a lack of user-friendly methods to characterize physical activity from a wrist-worn ActiGraph accelerometer. Participants in this study completed a laboratory protocol and/or 3–8 hours of directly observed free-living (criterion measure of activity intensity) while wearing ActiGraph GT9X Link accel- erometers on the right hip and non-dominant wrist. All laboratory data (n = 36) and 11 participants’ free- living data were used to develop vector magnitude count cut-points (counts/min) for activity intensity for the wrist-worn accelerometer, and 12 participants’ free-living data were used to cross-validate cut-point accuracy. The cut-points were: \u3c2,860 counts/min (sedentary); 2,860–3,940 counts/min (light); and ≥3,941counts/min (moderate-to-vigorous (MVPA)). These cut-points had an accuracy of 70.8% for asses- sing free-living activity intensity, whereas Sasaki/Freedson cut-points for the hip accelerometer had an accuracy of 77.1%, and Hildebrand Euclidean Norm Minus One (ENMO) cut-points for the wrist accel- erometer had an accuracy of 75.2%. While accuracy was higher for a hip-worn accelerometer and for ENMO wrist cut-points, the high wear compliance of wrist accelerometers shown in past work and the ease of use of count-based analysis methods may justify use of these developed cut-points until more accurate, equally usable methods can be developed

A Consensus Method for Estimating Physical Activity Levels in Adults Using Accelerometry

Identifying the best analytical approach for capturing moderate-to-vigorous physical activity (MVPA) using accelerometry is complex but inconsistent approaches employed in research and surveillance limits comparability. We illustrate the use of a consensus method that pools estimates from multiple approaches for characterising MVPA using accelerometry. Participants (n = 30) wore an accelerometer on their right hip during two laboratory visits. Ten individual classification methods estimated minutes of MVPA, including cut-point, two-regression, and machine learning approaches, using open-source count and raw inputs and several epoch lengths. Results were averaged to derive the consensus estimate. Mean MVPA ranged from 33.9–50.4 min across individual methods, but only one (38.9 min) was statistically equivalent to the criterion of direct observation (38.2 min). The consensus estimate (39.2 min) was equivalent to the criterion (even after removal of the one individual method that was equivalent to the criterion), had a smaller mean absolute error (4.2 min) compared to individual methods (4.9–12.3 min), and enabled the estimation of participant-level variance (mean standard deviation: 7.7 min). The consensus method allows for addition/removal of methods depending on data availability or field progression and may improve accuracy and comparability of device-based MVPA estimates while limiting variability due to convergence between estimate

Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine

Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients

Deconvolution of Images from BLAST 2005: Insight into the K3-50 and IC 5146 Star-Forming Regions

We present an implementation of the iterative flux-conserving Lucy-Richardson (L-R) deconvolution method of image restoration for maps produced by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). We have analyzed its performance and convergence extensively through simulations and cross-correlations of the deconvolved images with available highresolution maps. We present new science results from two BLAST surveys, in the Galactic regions K3-50 and IC 5146, further demonstrating the benefits of performing this deconvolution. We have resolved three clumps within a radius of 4.'5 inside the star-forming molecular cloud containing K3-50. Combining the well-resolved dust emission map with available multi-wavelength data, we have constrained the Spectral Energy Distributions (SEDs) of five clumps to obtain masses (M), bolometric luminosities (L), and dust temperatures (T). The L-M diagram has been used as a diagnostic tool to estimate the evolutionary stages of the clumps. There are close relationships between dust continuum emission and both 21-cm radio continuum and 12CO molecular line emission. The restored extended large scale structures in the Northern Streamer of IC 5146 have a strong spatial correlation with both SCUBA and high resolution extinction images. A dust temperature of 12 K has been obtained for the central filament. We report physical properties of ten compact sources, including six associated protostars, by fitting SEDs to multi-wavelength data. All of these compact sources are still quite cold (typical temperature below ~ 16 K) and are above the critical Bonner-Ebert mass. They have associated low-power Young Stellar Objects (YSOs). Further evidence for starless clumps has also been found in the IC 5146 region.Comment: 13 pages, 12 Figures, 3 Table

Do Behavioral Foraging Responses of Prey to Predators Function Similarly in Restored and Pristine Foodwebs?

Efforts to restore top predators in human-altered systems raise the question of whether rebounds in predator populations are sufficient to restore pristine foodweb dynamics. Ocean ecosystems provide an ideal system to test this question. Removal of fishing in marine reserves often reverses declines in predator densities and size. However, whether this leads to restoration of key functional characteristics of foodwebs, especially prey foraging behavior, is unclear. The question of whether restored and pristine foodwebs function similarly is nonetheless critically important for management and restoration efforts. We explored this question in light of one important determinant of ecosystem function and structure – herbivorous prey foraging behavior. We compared these responses for two functionally distinct herbivorous prey fishes (the damselfish Plectroglyphidodon dickii and the parrotfish Chlorurus sordidus) within pairs of coral reefs in pristine and restored ecosystems in two regions of these species' biogeographic ranges, allowing us to quantify the magnitude and temporal scale of this key ecosystem variable's recovery. We demonstrate that restoration of top predator abundances also restored prey foraging excursion behaviors to a condition closely resembling those of a pristine ecosystem. Increased understanding of behavioral aspects of ecosystem change will greatly improve our ability to predict the cascading consequences of conservation tools aimed at ecological restoration, such as marine reserves