Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review

The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Thomas Jefferson and Great Britain in Peace and War

My subject is Thomas Jefferson’s attitude toward Great Britain in peace and war. And since I am now more practising novelist than scholar, let me begin by sketching a scene. In early March 1786 Jefferson, who was at that time the American Minister Plenipotentiary to France, was invited by John Adams, his counterpart in England, to come to London for a conference on certain matters of trade. They were to confer in London because Adams was a cranky man who disliked Paris very much, and also bec..

Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential

Immunotherapy approaches have advanced rapidly in recent years. While the greatest therapeutic advances so far have been achieved with T cell therapies such as immune checkpoint blockade and CAR-T, recent advances in NK cell therapy have highlighted the therapeutic potential of these cells. Chronic lymphocytic leukemia (CLL), the most prevalent form of leukemia in Western countries, is a very immunosuppressive disease but still shows significant potential as a target of immunotherapy, including NK-based therapies. In addition to their antileukemia potential, NK cells are important immune effectors in the response to infections, which represent a major clinical concern for CLL patients. Here, we review the interactions between NK cells and CLL, describing functional changes and mechanisms of CLL-induced NK suppression, interactions with current therapeutic options, and the potential for therapeutic benefit using NK cell therapies

Development of an abort gap monitor for high-energy proton rings

The fill pattern in proton synchrotrons usually features an empty gap, longer than the abort kicker raise time, for machine protection. This gap is referred to as the "abort gap" and any particles, which may accumulate in it due to injection errors and diffusion between RF buckets, would be lost inside the ring, rather than in the beam dump, during the kicker firing. In large proton rings, due to the high energies involved, it is vital to monitor the build up of charges in the abort gap with a high sensitivity. We present a study of an abort gap monitor based on a photomultiplier with a gated microchannel plate, which would allow for detecting low charge densities by monitoring the synchrotron radiation emitted. We show results of beam test experiments at the Advanced Light Source using a Hamamatsu 5916U MCP-PMT and compare them to the specifications for the Large Hadron Collide

Tailored terahertz pulses from a laser-modulated electron beam

Interaction of an electron beam with a femtosecond laser pulseco-propagating through a wiggler modulates the electronenergies within a short slice of the electron bunch comparable with the duration of the laser pulse (Figure 1). Propagating around an electron storage ring, this bunch develops a longitudinal density perturbation due to the dispersion of electron trajectories. Figure 1 shows how this creates femtosecond electron bunch wings which are used for femtosecond x-ray light. In addition, this density perturbation emits temporally and spatially coherent tera-hertz pulses whichare inherently synchronized to the modulating laser. This gives us a new way to study coherent synchrotron radaition, and creates an opportunity for tuning the THz emmission specifically for the needs of a given experiment

An Introduction to the Department of Energy\u27s Multispectral Thermal Imager (MTI) Project Emphasizing the Imaging and Calibration Subsystems

MTI is a comprehensive research and development project that includes up-front modeling and analysis, system design, fabrication, assembly and testing, on-orbit operations, and experimentation and data analysis. The satellite is designed to collect radiometrically calibrated, medium resolution imagery in 15 spectral bands ranging from 0.45 to 10.70 μm. The combination of spectral bands, very accurate radiometry and good spatial resolution make MTI unique among current and planned space-based imaging systems. The imaging system includes a three-mirror anastigmatic off-axis telescope, a single cryogenically cooled focal plane assembly, a mechanical cooler, and an onboard calibration system. The single focal plane sensor design alleviates the need for a beam splitter to separate spectral components, and it permits cold operation for ground test and alignment, while the telescope and electronics are at laboratory ambient temperature and pressure. Payload electronic subsystems include image digitizers, real-time image compressors and a solid state recorder. All payload components have been fabricated and tested, and the payload is integrated and currently undergoing environmental testing in preparation for calibration