RELIABILITY OF THE LONG-RANGE CORRELATIONS OBTAINED FROM DETRENDED FLUCTUATION ANALYSIS OF RUNNING STRIDE INTERVALS

Monitoring stride interval long-range correlations has been suggested as a method for coaches and clinicians to track changes in fatigue and injury risk. This study investigated the between-day reliability of stride interval long-range correlations during treadmill running. Stride interval long-range correlations were assessed on two occasions 1-week apart using detrended fluctuation analysis during 6 minutes of running at 11, 13 and 15 km·h-1. Stride interval long-range correlations demonstrated good absolute reliability (95% limits of agreement: 0.11-0.14 arbitrary units) and relative reliability (intraclass correlation coefficient: 0.74-0.87) at each running speed. The absolute reliability values reported in this study can be used by athletes, coaches and clinicians to determine real changes in stride interval long-range correlations

THE SYMMETRY ANGLE IDENTIFIES LESS CLINICALLY RELEVANT INTER-LIMB ASYMMETRIES THAN THE SYMMETRY INDEX IN HEALTHY ADULTS

There are several methods for calculating inter-limb symmetry, an inter-limb difference ≥15% has been suggested as an indicator of sporting injury risk. The purpose of this study was to compare three common methods for determining symmetry: the Symmetry Index (percentage difference; SI) when referenced to the left limb (SILeft) or the average of both limbs (SIAverage), and the Symmetry Angle (vector difference; SA). 15 recreationally active participants completed a sprint protocol on a non-motorised treadmill. Accelerometers were positioned on both tibias to measure peak resultant acceleration (PRA). The SA identified less clinically relevant PRA inter-limb asymmetries than the SI in healthy adults. Once an appropriate level of asymmetry as measured by the SA is determined, this may help to more correctly identify asymmetry in athletes and patients than the SI

A Systematic Review and Meta-Analysis of Crossover Studies Comparing Physiological, Perceptual and Performance Measures Between Treadmill and Overground Running

Background Treadmills are routinely used to assess running performance and training parameters related to physiological or perceived effort. These measurements are presumed to replicate overground running but there has been no systematic review comparing performance, physiology and perceived effort between treadmill and overground running. Objective The objective of this systematic review was to compare physiological, perceptual and performance measures between treadmill and overground running in healthy adults.MethodsAMED (Allied and Contemporary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, SCOPUS, SPORTDiscus and Web of Science databases were searched from inception until May 2018. Included studies used a crossover study design to compare physiological (oxygen uptake [VO-2], heart rate [HR], blood lactate concentration [La]), perceptual (rating of perceived exertion [RPE] and preferred speed) or running endurance and sprint performance (i.e. time trial duration or sprint speed) outcomes between treadmill (motorised or non-motorised) and overground running. Physiological outcomes were considered across submaximal, near-maximal and maximal running intensity subgroups. Meta-analyses were used to determine mean difference (MD) or standardised MD (SMD) 95% confidence intervals. Results Thirty-four studies were included. Twelve studies used a 1% grade for the treadmill condition and three used grades >1%. Similar (V) over dotO(2) but lower La occurred during submaximal motorised treadmill running at 0% ((V) over dot O-2 MD: -0.55 0.93mL/kg/min; La MD: -1.26 +/- 0.71mmol/L) and 1% ((V) over dotO(2) MD: 0.37 +/- 1.12mL/kg/min; La MD: -0.52 +/- 0.50mmol/L) grade than during overground running. HR and RPE during motorised treadmill running were higher at faster submaximal speeds and lower at slower submaximal speeds than during overground running. (V) over dotO(2) (MD: -1.25 +/- 2.09mL/kg/min) and La (MD: -0.54 +/- 0.63mmol/L) tended to be lower, but HR (MD: 0 +/- 1bpm), and RPE (MD: -0.4 +/- 2.0units [6-20 scale]) were similar during near-maximal motorised treadmill running to during overground running. Maximal motorised treadmill running caused similar (V) over dotO(2) (MD: 0.78 +/- 1.55mL/kg/min) and HR (MD: -1 +/- 2bpm) to overground running. Endurance performance was poorer (SMD: -0.50 +/- 0.36) on a motorised treadmill than overground but sprint performance varied considerably and was not significantly different (MD: -1.4 +/- 5.8km/h). Conclusions Some, but not all, variables differ between treadmill and overground running, and may be dependent on the running speed at which they are assessed. Protocol registration (PROSPERO International Prospective Register of Systematic Reviews)

The Demands of Professional Rugby League Match-Play: a Meta-analysis

Background Rugby league is a collision sport, where players are expected to be physically competent in a range of areas, including aerobic fitness, strength, speed and power. Several studies have attempted to characterise the physical demands of rugby league match-play, but these studies often have relatively small sample sizes based on one or two clubs, which makes generalisation of the findings difficult. Therefore, the aim of this review was to synthesise studies that investigated the physical demands of professional rugby league match-play. Methods SPORTDiscus, CINAHL, MEDLINE (EBSCO) and Embase (EBSCO) databases were systematically searched from inception until October 2018. Articles were included if they (1) recruited professional rugby league athletes aged ≥ 18 years and (2) provided at least one match-play relevant variable (including playing time, total and relative distance, repeat high-intensity efforts (RHIE), efforts per RHIE, accelerations and decelerations, total and relative collisions). Meta-analyses were used to provide pooled estimates ± 95% confidence intervals. Results A total of 30 studies were included. Pooled estimates indicated that, compared to adjustables and backs, forwards have less playing time (− 17.2 ± 5.6 and − 25.6 ± 5.8 min, respectively), cover less ‘slow-speed’ (− 2230 ± 735 and − 1348 ± 655 m, respectively) and ‘high-speed’ distance (− 139 ± 108 and − 229 ± 101 m, respectively), but complete more relative RHIEs (+ 0.05 ± 0.05 and + 0.08 ± 0.04 per minute, respectively), and total (+ 12.0 ± 8.1 and + 12.8 ± 7.2 collisions, respectively) and relative collisions (+ 0.32 ± 0.22 and + 0.41 ± 0.22 collisions per minute, respectively). Notably, when the distance was expressed relative to playing time, forwards were not different from adjustables and backs in slow-speed (P ≥ 0.295) and high-speed (P ≥ 0.889) relative distance. The adjustables and backs subgroups were similar in most variables, except playing time (shorter for adjustables, − 8.5 ± 6.2 min), slow-speed distance (greater for adjustables, + 882 ± 763 m) and total relative distance (greater for adjustables, + 11.3 ± 5.2 m·min−1). There were no significant differences between positional groups for efforts per RHIE, accelerations and decelerations (P ≥ 0.745). Conclusions These results indicate the unique physical demands of each playing position and should be considered by strength and conditioning and tactical coaches when planning for professional rugby league performance

Is Motorized Treadmill Running Biomechanically Comparable to Overground Running? A Systematic Review and Meta-Analysis of Cross-Over Studies

Background Treadmills are often used in research, clinical practice, and training. Biomechanical investigations comparing treadmill and overground running report inconsistent findings. Objective This study aimed at comparing biomechanical outcomes between motorized treadmill and overground running. Methods Four databases were searched until June 2019. Crossover design studies comparing lower limb biomechanics during non-inclined, non-cushioned, quasi-constant-velocity motorized treadmill running with overground running in healthy humans (18-65 years) and written in English were included. Meta-analyses and meta-regressions were performed where possible. Results 33 studies (n = 494 participants) were included. Most outcomes did not differ between running conditions. However, during treadmill running, sagittal foot-ground angle at footstrike (mean difference (MD) − 9.8° [95% confidence interval: − 13.1 to − 6.6]; low GRADE evidence), knee flexion range of motion from footstrike to peak during stance (MD 6.3° [4.5 to 8.2]; low), vertical displacement center of mass/pelvis (MD − 1.5 cm [− 2.7 to − 0.8]; low), and peak propulsive force (MD − 0.04 body weights [− 0.06 to − 0.02]; very low) were lower, while contact time (MD 5.0 ms [0.5 to 9.5]; low), knee flexion at footstrike (MD − 2.3° [− 3.6 to − 1.1]; low), and ankle sagittal plane internal joint moment (MD − 0.4 Nm/kg [− 0.7 to − 0.2]; low) were longer/higher, when pooled across overground surfaces. Conflicting findings were reported for amplitude of muscle activity. Conclusions Spatiotemporal, kinematic, kinetic, muscle activity, and muscle-tendon outcome measures are largely comparable between motorized treadmill and overground running. Considerations should, however, particularly be given to sagittal plane kinematic differences at footstrike when extrapolating treadmill running biomechanics to overground running

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued

AbstractDNA immunization in conjunction with antiretroviral therapy was evaluated in SIV-infected rhesus macaques treated with [R]-9-[2-phosphonylmethoxypropyl]adenine (PMPA). Macaques were immunized monthly with DNA vaccines expressing either SIV gag/tat or SIV gag/tat and 19 CD8+ T cell epitopes during 7 months of therapy. Half the animals from each group were additionally immunized before infection. Only 60% of the animals (4 controls, 20 vaccinated) responded to PMPA (ART responders). All 4 ART responder controls demonstrated viral rebound or CD4 decline after PMPA was withdrawn. In contrast, 17 of 20 vaccinated ART responders contained viral rebound for over 7 months after PMPA was withdrawn. Viral control correlated with stable CD4 counts, higher lymphoproliferation and an increase in the magnitude and breadth of the CD8+ T cell response. Immunizing before infection or with multi-epitopes enhanced these effects. These results demonstrate that DNA immunization during antiretroviral therapy may be an effective strategy to treat HIV infection

Increased Throughput by Parallelization of Library Preparation for Massive Sequencing

Background: Massively parallel sequencing systems continue to improve on data output, while leaving labor-intensive library preparations a potential bottleneck. Efforts are currently under way to relieve the crucial and time-consuming work to prepare DNA for high-throughput sequencing. Methodology/Principal Findings: In this study, we demonstrate an automated parallel library preparation protocol using generic carboxylic acid-coated superparamagnetic beads and polyethylene glycol precipitation as a reproducible and flexible method for DNA fragment length separation. With this approach the library preparation for DNA sequencing can easily be adjusted to a desired fragment length. The automated protocol, here demonstrated using the GS FLX Titanium instrument, was compared to the standard manual library preparation, showing higher yield, throughput and great reproducibility. In addition, 12 libraries were prepared and uniquely tagged in parallel, and the distribution of sequence reads between these indexed samples could be improved using quantitative PCR-assisted pooling. Conclusions/Significance: We present a novel automated procedure that makes it possible to prepare 36 indexed libraries per person and day, which can be increased to up to 96 libraries processed simultaneously. The yield, speed and robust performance of the protocol constitute a substantial improvement to present manual methods, without the need of extensive equipment investments. The described procedure enables a considerable efficiency increase for small to midsiz

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, nonrandomised dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10–150 mg ml−1 in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml−1. Urinary VEGF was affected by Suramin at doses above 50 mg ml−1, corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml−1 intravesically