Does Standing on a Cycle-ergometer, Towards the Conclusion of a Graded Exercise Test, Yield Cardiorespiratory Values Equivalent to Treadmill Testing?

Graded exercise testing (GXT), per a cycle-ergometer (CE), offers safety and monitoring advantages over treadmill (TM) GXT. Unfortunately, CE-VO2max and some other cardiorespiratory (CR) variables are frequently lower than TM-GXT values. It has been difficult to compare TM and CE-GXT values. However, it was hypothesized that standing towards the conclusion of the CE-GXT (Stand-CE) might increase CE values to those equal to TM-GXT. If Stand-CE and TM-GXT CR values were equal, Stand-CE-GXT could become the method of choice for GXT for the general population. The purpose of this investigation was to investigate the effect of Stand-CE on CR variables. An intentionally diverse sample (N = 34, 24 males and 10 females, aged 18-54 y, with VO2max values 25-76 ml/kg/min) representing the general population participated. Volunteers completed two GXT trials, one per TM (Bruce protocol) and the other per a MET-TM-matched CE-GXT where initially-seated participants stood and pedaled after their respiratory exchange ratio (RER) reached 1.0. Eighteen participants underwent a third MET-TM-matched trial where they remained seated throughout GXT (Sit-CE). Trials were counter-balanced with at least 48 h between GXT. There were significant statistical differences (p \u3c 0.05) between TM and Stand-CE per matched-samples T-test (N = 34) on the following variables: VEmax (TM = 115 + 24.4 l/min, Stand-CE = 99.4 + 28.1), VCO2max (TM = 4.26 + 0.9 l/min, Stand-CE = 3.56 + 0.84), VO2max (TM = 44.9 + 9.1 ml/kg/min, Stand-CE = 39.3 + 9.0), METSmax (TM = 12.8 + 2.6 METS, Stand-CE = 11.2 + 2.5), and HRmax (TM = 175 + 13 bpm, Stand-CE = 166 + 12). One-way repeated measures ANOVA (N = 18) demonstrated no statistical differences between all trials: VEmax (TM = 112.8 + 25.3 l/min, Stand-CE = 102.3 + 25.2, Sit-CE = 107.3 + 33.1), VCO2max (TM = 4.17 + 0.99 l/min, Stand-CE = 3.62 + 0.80, Sit-CE = 3.55 + 0.83), VO2max (TM = 47.1 + 9.8 ml/kg/min, Stand-CE = 42.0 + 9.0, Sit-CE = 43.3 + 8.9), METSmax (TM = 13.5 + 2.8 METS, Stand-CE = 12.0 + 2.6, Sit-CE = 12.4 + 2.5), and HRmax (TM = 176 + 13 bpm, Stand-CE = 171 + 12, Sit-CE = 173 + 11). Results of this investigation suggest that TM-GXT CR values are larger than Stand-CE, and Stand-CE values are not different from Sit-CE. Future studies will test validity of these findings per gender, aerobic training status, in populations that are highly-skilled with TM and CE (tri-athletes), children, the elderly, and diseased populations

Development of a new SonovueTM contrast-enhanced ultrasound approach reveals temporal and age-related features of muscle microvascular responses to feeding

Compromised limb blood flow in aging may contribute to the development of sarcopenia, frailty, and the metabolic syndrome. We developed a novel contrast-enhanced ultrasound technique using Sonovue™ to characterize muscle microvasculature responses to an oral feeding stimulus (15 g essential amino acids) in young (~20 years) and older (~70 years) men. Intensity-time replenishment curves were made via an ultrasound probe “fixed” over the quadriceps, with intermittent high mechanical index destruction of microbubbles within muscle vasculature. This permitted real-time measures of microvascular blood volume (MBV), microvascular flow velocity (MFV) and their product, microvascular blood flow (MBF). Leg blood flow (LBF) was measured by Doppler and insulin by enzyme-linked immunosorbent assay. Steady-state contrast concentrations needed for comparison between different physiological states were achieved <150 sec from commencing Sonovue™ infusion, and MFV and MBV measurements were completed <120 sec thereafter. Interindividual coefficients of variation in MBV and MFV were 35–40%, (N = 36). Younger men (N = 6) exhibited biphasic vascular responses to feeding with early increases in MBV (+36%, P < 0.008 45 min post feed) reflecting capillary recruitment, and late increases in MFV (+77%, P < 0.008) and MBF (+130%, P < 0.007 195 min post feed) reflecting more proximal vessel dilatation. Early MBV responses were synchronized with peak insulin but not increased LBF, while later changes in MFV and MBF occurred with insulin at post absorptive values but alongside increased LBF. All circulatory responses were absent in old men (N = 7). Thus, impaired postprandial circulation could impact age-related declines in muscle glucose disposal, protein anabolism, and muscle mass

Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans

Ageing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of ‘anabolic resistance’ in older humans. Twenty healthy male individuals, 10 younger (Y; 23 ± 1 years) and 10 older (O; 69 ± 3 years), performed 6 weeks unilateral RET (6 × 8 repetitions, 75% of one repetition maximum (1-RM), 3 times per week). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom%; thereafter 50 ml week−1), further bilateral VL muscle biopsies were taken at 3 and 6 weeks to quantify muscle protein synthesis (MPS) via gas chromatography–pyrolysis–isotope ratio mass spectrometry. After RET, 1-RM increased in Y (+35 ± 4%) and O (+25 ± 3%; P < 0.01), while MVC increased in Y (+21 ± 5%; P < 0.01) but not O (+6 ± 3%; not significant (NS)). In comparison to Y, O displayed blunted RET-induced increases in muscle thickness (at 3 and 6 weeks, respectively, Y: +8 ± 1% and +11 ± 2%, P < 0.01; O: +2.6 ± 1% and +3.5 ± 2%, NS). While ‘basal’ longer term MPS was identical between Y and O (∼1.35 ± 0.1% day−1), MPS increased in response to RET only in Y (3 weeks, Y: 1.61 ± 0.1% day−1; O: 1.49 ± 0.1% day−1). Consistent with this, O exhibited inferior ribosomal biogenesis (RNA:DNA ratio and c-MYC induction: Y: +4 ± 2 fold change; O: +1.9 ± 1 fold change), translational efficiency (S6K1 phosphorylation, Y: +10 ± 4 fold change; O: +4 ± 2 fold change) and anabolic hormone milieu (testosterone, Y: 367 ± 19; O: 274 ± 19 ng dl−1 (all P < 0.05). Anabolic resistance is thus multifactorial

The UbiI (VisC) aerobic ubiquinone synthase is required for expression of type 1 pili, biofilm formation, and pathogenesis in uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC), which causes the majority of urinary tract infections (UTI), uses pilus-mediated adherence to initiate biofilm formation in the urinary tract. Oxygen gradients within E. coli biofilms regulate expression and localization of adhesive type 1 pili. A transposon mutant screen for strains defective in biofilm formation identified the ubiI (formerly visC) aerobic ubiquinone synthase gene as critical for UPEC biofilm formation. In this study, we characterized a nonpolar ubiI deletion mutant and compared its behavior to that of wild-type bacteria grown under aerobic and anoxic conditions. Consistent with its function as an aerobic ubiquinone-8 synthase, deletion of ubiI in UPEC resulted in reduced membrane potential, diminished motility, and reduced expression of chaperone-usher pathway pili. Loss of aerobic respiration was previously shown to negatively impact expression of type 1 pili. To determine whether this reduction in type 1 pili was due to an energy deficit, wild-type UPEC and the ubiI mutant were compared for energy-dependent phenotypes under anoxic conditions, in which quinone synthesis is undertaken by anaerobic quinone synthases. Under anoxic conditions, the two strains exhibited wild-type levels of motility but produced diminished numbers of type 1 pili, suggesting that the reduction of type 1 pilus expression in the absence of oxygen is not due to a cellular energy deficit. Acute- and chronic-infection studies in a mouse model of UTI revealed a significant virulence deficit in the ubiI mutant, indicating that UPEC encounters enough oxygen in the bladder to induce aerobic ubiquinone synthesis during infection. IMPORTANCE The majority of urinary tract infections are caused by uropathogenic E. coli, a bacterium that can respire in the presence and absence of oxygen. The bladder environment is hypoxic, with oxygen concentrations ranging from 4% to 7%, compared to 21% atmospheric oxygen. This work provides evidence that aerobic ubiquinone synthesis must be engaged during bladder infection, indicating that UPEC bacteria sense and use oxygen as a terminal electron acceptor in the bladder and that this ability drives infection potential despite the fact that UPEC is a facultative anaerobe

The Local, the ‘Indigenous’ and the Limits of Rethinking Peacebuilding

© 2021 Informa UK Limited, trading as Taylor & Francis Group. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1080/17502977.2021.1882755Recent critical perspectives on peacebuilding have sought to shed light on experiences so far marginalized by mainstream approaches. In particular, critics have pushed peacebuilding towards radically different ways of thinking about governance, conflict and peace, by engaging with narratives, experiences and knowledge coming from societies perceived as not invested in modernity or liberalism, such as Indigenous communities. Whilst this may force theory to confront questions of human-centrism, colonial erasure, and structural violence, turning to Indigeneity without questioning the impact of liberal peace ‘thinking', might further elicit marginalization and appropriation, and simply ‘save’ liberal peacebuilding through the back door.Peer reviewe

Implementation of AI/Deep Learning Disruption Predictor into a Plasma Control System

This paper reports on advances to the state-of-the-art deep-learning disruption prediction models based on the Fusion Recurrent Neural Network (FRNN) originally introduced a 2019 Nature publication. In particular, the predictor now features not only the disruption score, as an indicator of the probability of an imminent disruption, but also a sensitivity score in real-time to indicate the underlying reasons for the imminent disruption. This adds valuable physics-interpretability for the deep-learning model and can provide helpful guidance for control actuators now that it is fully implemented into a modern Plasma Control System (PCS). The advance is a significant step forward in moving from modern deep-learning disruption prediction to real-time control and brings novel AI-enabled capabilities relevant for application to the future burning plasma ITER system. Our analyses use large amounts of data from JET and DIII-D vetted in the earlier NATURE publication. In addition to when a shot is predicted to disrupt, this paper addresses reasons why by carrying out sensitivity studies. FRNN is accordingly extended to use many more channels of information, including measured DIII-D signals such as (i) the n1rms signal that is correlated with the n =1 modes with finite frequency, including neoclassical tearing mode and sawtooth dynamics, (ii) the bolometer data indicative of plasma impurity content, and (iii) q-min, the minimum value of the safety factor relevant to the key physics of kink modes. The additional channels and interpretability features expand the ability of the deep learning FRNN software to provide information about disruption subcategories as well as more precise and direct guidance for the actuators in a plasma control system

Radiation dosimetry in digital breast tomosynthesis: Report of AAPM Tomosynthesis Subcommittee Task Group 223

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134828/1/mp2600.pd

Bridge to the stars: A mission concept to an interstellar object

Exoplanet discoveries since the mid-1990’s have revealed an astounding diversity of planetary systems. Studying these systems is essential to understanding planetary formation processes, as well as the development of life in the universe. Unfortunately, humanity can only observe limited aspects of exoplanetary systems by telescope, and the significant distances between stars presents a barrier to in situ exploration. In this study, we propose an alternative path to gain insight into exoplanetary systems: Bridge, a mission concept design to fly by an interstellar object as it passes through our solar system. Designed as a New Frontiers-class mission during the National Aeronautics and Space Administration (NASA) Planetary Science Summer School, Bridge would provide a unique opportunity to gain insight into potential physical, chemical, and biological differences between solar systems as well as the possible exchange of planetary materials between them. Bridge employs ultraviolet/visible, near-infrared, and mid-infrared point spectrometers, a visible camera, and a guided impactor. We also provide a quantitative Monte Carlo analysis that estimates wait times for a suitable target, and examines key trades between ground storage and a parking orbit, power sources, inner versus outer solar system encounters, and launch criteria. Due to the fleeting nature of interstellar objects, reaching an interstellar object may require an extended ground storage phase for the spacecraft until a suitable ISO is discovered, followed by a rapid response launch strategy. To enable rapid response missions designed to intercept such unique targets, language would need to be added to future NASA announcements of opportunity such that ground storage and rapid response would be allowable components of a proposed mission

Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations

Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA sequencing (&gt;100 million reads) of peripheral blood as a diagnostic tool for predicting the severity of the disease and as a means to pinpoint specific compensatory NAb treatments. Clinical data were prospectively collected at multiple time points during ICU admission, and amino acid sequences for the NAb CDR3 segments were identified. Patients who survived severe COVID-19 had significantly more of a Class 3 antibody (C135) to SARS-CoV-2 compared to non-survivors (15059.4 vs. 1412.7, p = 0.016). In addition to highlighting the utility of RNA sequencing in revealing unique NAb profiles in COVID-19 patients with different outcomes, we provided a physical basis for our findings via atomistic modeling combined with molecular dynamics simulations. We established the interactions of the Class 3 NAb C135 with the SARS-CoV-2 spike protein, proposing a mechanistic basis for inhibition via multiple conformations that can effectively prevent ACE2 from binding to the spike protein, despite C135 not directly blocking the ACE2 binding motif. Overall, we demonstrate that deep RNA sequencing combined with structural modeling offers the new potential to identify and understand novel therapeutic(s) NAbs in individuals lacking certain immune responses due to their poor endogenous production. Our results suggest a possible window of opportunity for administration of such NAbs when their full sequence becomes available. A method involving rapid deep RNA sequencing of patients infected with SARS-CoV-2 or its variants at the earliest infection time could help to develop personalized treatments using the identified specific NAbs