Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans: A study protocol

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide and aging is the primary risk factor for the development of CVD. The increased risk of CVD with aging is largely mediated by the development of vascular dysfunction. Excessive production of mitochondrial reactive oxygen species (mtROS) is a key mechanism of age-related vascular dysfunction. Therefore, establishing the efficacy of therapies to reduce mtROS to improve vascular function with aging is of high biomedical importance. Previously, in a small, randomized, crossover-design pilot clinical trial, our laboratory obtained initial evidence that chronic oral supplementation with the mitochondrial-targeted antioxidant MitoQ improves vascular function in healthy older adults. Here, we describe the protocol for an ongoing R01-funded phase IIa clinical trial to establish the efficacy of MitoQ as a therapy to improve vascular function in older adults (ClinicalTrials.gov Identifier: NCT04851288). Outcomes: The primary outcome of the study is nitric oxide (NO)-mediated endothelium-dependent dilation (EDD) as assessed by brachial artery flow-mediated dilation (FMDBA). Secondary outcomes include mtROS-mediated suppression of EDD, aortic stiffness as measured by carotid-femoral pulse wave velocity, carotid compliance and &beta;-stiffness index, and intima media thickness. Other outcomes include the assessment of endothelial mitochondrial health and oxidative stress in endothelial cells obtained by endovascular biopsy; the effect of altered circulating factors following MitoQ treatment on endothelial cell NO bioavailability and whole cell and mitochondrial reactive oxygen species production ex vivo; and circulating markers of oxidative stress, antioxidant status, and inflammation. Methods: We are conducting a randomized, placebo-controlled, double-blind, parallel group, phase IIa clinical trial in 90 (45/group) healthy older men and women 60&nbsp;years of age or older. Participants complete baseline testing and are then randomized to either 3&nbsp;months of oral MitoQ (20&nbsp;mg; once daily) or placebo supplementation. Outcome measures are assessed at the midpoint of treatment, i.e., 6&nbsp;weeks, and again at the conclusion of treatment. Discussion: This study is designed to establish the efficacy of chronic supplementation with the mitochondrial-targeted antioxidant MitoQ for improving vascular endothelial function and reducing large elastic artery stiffness in older adults, and to investigate the mechanisms by which MitoQ supplementation improves endothelial function. &nbsp;</p

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies

Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed

6th International Conference on the Philosophy of Computer Games: The Nature of Player Experience

We hereby invite scholars in any field of studies who take a professional interest in the philosophy of computer games to submit papers to the 6th International Conference on the Philosophy of Computer Games, to be held in Madrid, Spain, on January 29th-31st 2012. Accepted papers will have a clear focus on philosophy and philosophical issues in relation to computer games. They will refer to specific examples from computer games rather than merely invoke them in general terms. The over-arching theme of the conference is The Nature of Player Experience. Over the past decade, the topic of player experience has attracted attention from a multitude of disciplines and practices focusing on computer games. For this conference, we are soliciting proposals that examine the philosophical underpinnings of player experience from a variety of perspectives, including but not limited to those mentioned below. Imagination and interpretation. World, space and experience. Technology, process, and experience. Experience of time in computer game play. Embodiment and player experience. Emotions and player experience. Perspectives on aesthetics and player experience. Perspectives on ethics and player experience. Methodological and epistemological considerations on studying player experience. We invite abstracts of maximum 1000 words including bibliography. If your submission falls under one or more headings, please indicate which ones. The extended deadline for submissions is 17:00 GMT, October 15th, 2011. Please submit your abstract in PDF format throughhttp://review.gamephilosophy.org/. All submitted abstracts will be subject to double blind peer review, and the program committee will make a final selection of papers for the conference on the basis of this. Some papers may be accepted for alternative forms of presentation, such as poster sessions, workshops, or demonstrations. A full paper draft must then be submitted by January 1st, 2012 and will be made available on the conference website. There will be an opportunity to revise the paper after the conference. Notification of accepted submissions will be sent out by November 15th, 2011. Olav Asheim. Euridice Cabanes. Gordon Calleja. Patrick Coppock. Olli Tapio Leino, program committee chair. Anita Leirfall. Daniel Parente. John Richard Sageng. This conference will be organised in conjunction with Madrid Game Conference. This site will be updated with more details during September, please do check back. In the meantime, if you have any questions, please contact the program committee at [email protected].