Community assembly modeling of microbial evolution within Barrett's esophagus and esophageal adenocarcinoma.

Mathematical modeling of somatic evolution, a process impacting both host cells and microbial communities in the human body, can capture important dynamics driving carcinogenesis. Here we considered models for esophageal adenocarcinoma (EAC), a cancer that has dramatically increased in incidence over the past few decades in Western populations, with high case fatality rates due to late-stage diagnoses. Despite advancements in genomic analyses of the precursor Barrett's esophagus (BE), prevention of late-stage EAC remains a significant clinical challenge.

Significance of Crypt Atypia in Barrett's Esophagus: A Clinical, Molecular, and Outcome Study.

Background & Aims: The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett's esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).

Methods: The morphologic features of nondysplastic crypts in baseline biopsy specimens from 212 BE patients (2956 biopsy specimens) were graded histologically using a 4-point scale (crypt atypia levels, 0-3). DNA content abnormalities were detected using flow cytometry.

Extrachromosomal DNA in the cancerous transformation of Barrett's oesophagus.

Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett's oesophagus.

Somatic whole genome dynamics of precancer in Barrett's esophagus reveals features associated with disease progression.

While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett's esophagus compared to 40 Barrett's patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett's tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures.

Within-patient phylogenetic reconstruction reveals early events in Barrett's Esophagus.

Barrett's Esophagus is a neoplastic condition which progresses to esophageal adenocarcinoma in 5% of cases. Key events affecting the outcome likely occur before diagnosis of Barrett's and cannot be directly observed; we use phylogenetic analysis to infer such past events. We performed whole-genome sequencing on 4-6 samples from 40 cancer outcome and 40 noncancer outcome patients with Barrett's Esophagus, and inferred within-patient phylogenies of deconvoluted clonal lineages.

Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.

Correction to: NSAID use and somatic exomic mutations in Barrett's esophagus.

It was highlighted that in the original article [1] the Availability of data and materials section was incorrect.

Bilateral scapular kinematics, asymmetries and shoulder pain in wheelchair athletes.

Background: Shoulder pain is the most common complaint for wheelchair athletes. Scapular orientation and dyskinesia are thought to be associated with shoulder pathology, yet no previous studies have examined the bilateral scapula kinematics of wheelchair athletes during propulsion.

Research Question: To examine bilateral scapular kinematics of highly trained wheelchair rugby (WR) players and any associations with self-reported shoulder pain during everyday wheelchair propulsion.

NSAID use and somatic exomic mutations in Barrett's esophagus.

Background: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to protect against tetraploidy, aneuploidy, and chromosomal alterations in the metaplastic condition Barrett's esophagus (BE) and to lower the incidence and mortality of esophageal adenocarcinoma (EA). The esophagus is exposed to both intrinsic and extrinsic mutagens resulting from gastric reflux, chronic inflammation, and exposure to environmental carcinogens such as those found in cigarettes. Here we test the hypothesis that NSAID use inhibits accumulation of point mutations/indels during somatic genomic evolution in BE.

Evolution of Barrett's esophagus through space and time at single-crypt and whole-biopsy levels.

The low risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma can lead to over-diagnosis and over-treatment of BE patients. This may be addressed through a better understanding of the dynamics surrounding BE malignant progression. Although genetic diversity has been characterized as a marker of malignant development, it is still unclear how BE arises and develops.

Quantification of Multiple Tumor Clones Using Gene Array and Sequencing Data.

Cancer development is driven by genomic alterations, including copy number aberrations. The detection of copy number aberrations in tumor cells is often complicated by possible contamination of normal stromal cells in tumor samples and intratumor heterogeneity, namely the presence of multiple clones of tumor cells. In order to correctly quantify copy number aberrations, it is critical to successfully de-convolute the complex structure of the genetic information from tumor samples.

Reliability and Validity of Subjective Measures of Aerobic Intensity in Adults With Spinal Cord Injury: A Systematic Review.

Objective: To systematically synthesize and appraise research regarding test-retest reliability or criterion validity of subjective measures for assessing aerobic exercise intensity in adults with spinal cord injury (SCI).

Data Sources: Electronic databases (Pubmed, PsychINFO, SPORTDiscus, EMBASE, and CINAHL) were searched from inception to January 1, 2016.

Study Selection: Studies involving at least 50% of participants with SCI who performed an aerobic exercise test that included measurement of subjective and objective intensity based on test-retest reliability or criterion validity protocols.

Assessment of peak oxygen uptake during handcycling: Test-retest reliability and comparison of a ramp-incremented and perceptually-regulated exercise test.

Purpose: To examine the reliability of a perceptually-regulated maximal exercise test (PRETmax) to measure peak oxygen uptake ([Formula: see text]) during handcycle exercise and to compare peak responses to those derived from a ramp-incremented protocol (RAMP).

Methods: Twenty recreationally active individuals (14 male, 6 female) completed four trials across a 2-week period, using a randomised, counterbalanced design. Participants completed two RAMP protocols (20 W·min-1) in week 1, followed by two PRETmax in week 2, or vice versa.

Altering the Speed Profiles of Wheelchair Rugby Players With Game-Simulation Drill Design.

Purpose: To examine the speed profiles of elite wheelchair rugby (WCR) players during game-simulation training drills of differing player number and shot-clock regulations. A secondary aim was to determine whether the profiles were further influenced by player classification.

Methods: Eight elite WCR players (low-point n = 3, high-point n = 5) were monitored using a radio-frequency-based indoor tracking system during training sessions over a 5-mo period.

Effects of cooling before and during simulated match play on thermoregulatory responses of athletes with tetraplegia.

Objectives: Athletes with high level spinal cord injuries (tetraplegia) are under greater thermal strain during exercise than the able-bodied. The purpose of this study was to investigate the effectiveness of pre-cooling using an ice vest and the combination of pre-cooling and cooling during play using water sprays in athletes with tetraplegia.

Design: Counter-balanced, cross-over design.

Salivary alpha amylase not chromogranin A reflects sympathetic activity: exercise responses in elite male wheelchair athletes with or without cervical spinal cord injury.

Background: Salivary alpha amylase (sAA) and chromogranin A (sCgA) have both been suggested as non-invasive markers for sympathetic nervous system (SNS) activity. A complete cervical spinal cord injury leading to tetraplegia is accompanied with sympathetic dysfunction; the aim of this study was to establish the exercise response of these markers in this in vivo model.

Methods: Twenty-six elite male wheelchair athletes (C6-C7 tetraplegia: N = 8, T6-L1 paraplegia: N = 10 and non-spinal cord injured controls: N = 8) performed treadmill exercise to exhaustion.

A Comparison of Speed Profiles During Training and Competition in Elite Wheelchair Rugby Players.

Purpose: To investigate the speed profiles of individual training modes in comparison with wheelchair rugby (WCR) competition across player classifications.

Methods: Speed profiles of 15 international WCR players were determined using a radio-frequency-based indoor tracking system. Mean and peak speed (m/s), work:rest ratios, and the relative time spent in (%) and number of high-speed activities performed were measured across training sessions (n = 464) and international competition (n = 34).

Spinal Cord Injury Level Influences Acute Plasma Caffeine Responses.

Purpose: This study aimed to investigate the absorption curve and acute effects of caffeine at rest in individuals with no spinal cord injury (SCI), paraplegia (PARA), and tetraplegia (TETRA).

Methods: Twenty-four healthy males (eight able-bodied [AB], eight PARA, and eight TETRA) consumed 3 mg·kg caffeine anhydrous (CAF) in a fasted state. Plasma caffeine [CAF], glucose, lactate, free fatty acid, and catecholamine concentrations were measured during a 150-min rest period.

Studying Cancer Evolution in Barrett's Esophagus and Esophageal Adenocarcinoma.

Technological advances in genome sequencing and copy number analysis have allowed researchers to catalog the wide variety of genomic alterations that occur across diverse cancer types. For most cancer types, the lack of high-frequency alterations and the heterogeneity observed both within and between tumors suggest neoplastic progression proceeds through a branched evolutionary pathway as proposed by Nowell in 1976, as opposed to the linear pathway that has dominated medical science for the last century. To understand how cancer evolves over time and space in the body, new study designs are needed that can distinguish between alterations that develop in patients who progress to cancer from to those who don't.

Current Perspectives on Profiling and Enhancing Wheelchair Court Sport Performance.

Despite the growing interest in Paralympic sport, the evidence base for supporting elite wheelchair sport performance remains in its infancy when compared with able-bodied (AB) sport. Subsequently, current practice is often based on theory adapted from AB guidelines, with a heavy reliance on anecdotal evidence and practitioner experience. Many principles in training prescription and performance monitoring with wheelchair athletes are directly transferable from AB practice, including the periodization and tapering of athlete loads around competition, yet considerations for the physiological consequences of an athlete's impairment and the interface between athlete and equipment are vital when targeting interventions to optimize in-competition performance.

Arm and Intensity-Matched Leg Exercise Induce Similar Inflammatory Responses.

Introduction: The amount of active muscle mass can influence the acute inflammatory response to exercise, associated with reduced risk for chronic disease. This may affect those restricted to upper body exercise, for example, due to injury or disability. The purpose of this study was to compare the inflammatory responses for arm exercise and intensity-matched leg exercise.

Individualized Internal and External Training Load Relationships in Elite Wheelchair Rugby Players.

Aim: The quantification and longitudinal monitoring of athlete training load (TL) provides a scientific explanation for changes in performance and helps manage injury/illness risk. Therefore, accurate and reliable monitoring tools are essential for the optimization of athletic performance. The aim of the present study was to establish the relationship between measures of internal [heart rate (HR) and session RPE (sRPE)] and external TL specific to wheelchair rugby (WR).