Zoning of mucosal phenotype, dysplasia, and telomerase activity measured by telomerase repeat assay protocol in Barrett's esophagus

Glandular dysplasia in Barrett's esophagus may regress spontaneously but can also progress to cancer. The human telomerase RNA template and the human telomerase reverse transcriptase enzyme which do not, of themselves, correlate strongly with telomerase activity, are too often overexpressed in Barrett's dysplasia to predict individual cancer risk. This study relates telomerase activity, mucosal phenotype, and dysplasia in Barrett's esophagus. Biopsies (n = 256) from squamous esophagus, columnar-lined esophagus every 2 cm, esophago-gastric junction, gastric body, and antrum from 32 patients with long-segment Barrett's esophagus were evaluated by telomerase repeat assay protocol (TRAP). Three biopsies for histology (n = 794) were simultaneously taken at each anatomical level. These and all prior and subsequent biopsies (n = 1917) were reviewed for mucosal phenotypes and dysplasia severity. Intestinal-type Barrett's mucosa was present at all levels in Barrett's esophagus. At least one Barrett's biopsy was TRAP(+) in 22 of 32 patients. TRAP positivity of intestinal-type Barrett's mucosa increased distally, possibly as a consequence of mucosal exposure to acid or bile reflux. Native gastric mucosa was rarely TRAP(+) (1/31 corpus, 2/32 antrum), whereas native squamous mucosa usually was TRAP(+) (31/32). Dysplasia almost always involved intestinal-type Barrett's mucosa (85/87; P</p

Active video games and health indicators in children and youth: a systematic review

BACKGROUND: Active video games (AVGs) have gained interest as a way to increase physical activity in children and youth. The effect of AVGs on acute energy expenditure (EE) has previously been reported; however, the influence of AVGs on other health-related lifestyle indicators remains unclear. OBJECTIVE: This systematic review aimed to explain the relationship between AVGs and nine health and behavioural indicators in the pediatric population (aged 0–17 years). DATA SOURCES: Online databases (MEDLINE, EMBASE, psycINFO, SPORTDiscus and Cochrane Central Database) and personal libraries were searched and content experts were consulted for additional material. DATA SELECTION: Included articles were required to have a measure of AVG and at least one relevant health or behaviour indicator: EE (both habitual and acute), adherence and appeal (i.e., participation and enjoyment), opportunity cost (both time and financial considerations, and adverse events), adiposity, cardiometabolic health, energy intake, adaptation (effects of continued play), learning and rehabilitation, and video game evolution (i.e., sustainability of AVG technology). RESULTS: 51 unique studies, represented in 52 articles were included in the review. Data were available from 1992 participants, aged 3–17 years, from 8 countries, and published from 2006–2012. Overall, AVGs are associated with acute increases in EE, but effects on habitual physical activity are not clear. Further, AVGs show promise when used for learning and rehabilitation within special populations. Evidence related to other indicators was limited and inconclusive. CONCLUSIONS: Controlled studies show that AVGs acutely increase light- to moderate-intensity physical activity; however, the findings about if or how AVG lead to increases in habitual physical activity or decreases in sedentary behaviour are less clear. Although AVGs may elicit some health benefits in special populations, there is not sufficient evidence to recommend AVGs as a means of increasing daily physical activity

A joint inversion of receiver function and Rayleigh wave phase velocity dispersion data to estimate crustal structure in West Antarctica

We determine crustal shear-wave velocity structure and crustal thickness at recently deployed seismic stations across West Antarctica, using a joint inversion of receiver functions and fundamental mode Rayleigh wave phase velocity dispersion. The stations are from both the UK Antarctic Network (UKANET) and Polar Earth Observing Network/Antarctic Network (POLENET/ANET). The former include, for the first time, 4 stations along the spine of the Antarctic Peninsula, 3 in the Ellsworth Land and 5 stations in the vicinity of the Pine Island Rift. Within the West Antarctic Rift System (WARS) we model a crustal thickness range of 18-28 km, and show that the thinnest crust (∼18 km) is in the vicinity of the Byrd Subglacial Basin and Bentley Subglacial Trench. In these regions we also find the highest ratio of fast (Vs = 4.0-4.3 km/s) (likely mafic) lower crust to felsic/intermediate upper crust. The thickest mafic lower crust we model is in Ellsworth Land, a critical area for constraining the eastern limits of the WARS. Although we find thinner crust in this region (∼30 km) than in the neighbouring Antarctic Peninsula and Haag-Ellsworth Whitmore block (HEW), the Ellsworth Land crust has not undergone as much extension as the central WARS. This suggests that the WARS does not link with the Weddell Sea Rift System through Ellsworth Land, and instead has progressed during its formation towards the Bellingshausen and Amundsen Sea Embayments. We also find that the thin WARS crust extends towards the Pine Island Rift, suggesting that the boundary between the WARS and the Thurston Island block lies in this region, ∼200 km north of its previously accepted position. The thickest crust (38-40 km) we model in this study is in the Ellsworth Mountain section of the HEW block. We find thinner crust (30-33 km) in the Whitmore Mountains and Haag Nunatak sectors of the HEW, consistent with the composite nature of the block. In the Antarctic Peninsula we find a crustal thickness range of 30-38 km and a likely dominantly felsic/intermediate crustal composition. By forward modelling high frequency receiver functions we also assess if any thick, low velocity subglacial sediment accumulations are present, and find a 0.1-0.8 km thick layer at 10 stations within the WARS, Thurston Island and Ellsworth Land. We suggest that these units of subglacial sediment could provide a source region for the soft basal till layers found beneath numerous outlet glaciers, and may act to accelerate ice flow

Cosmic Hydrogen Was Significantly Neutral a Billion Years After the Big Bang

The ionization fraction of cosmic hydrogen, left over from the big bang, provides crucial fossil evidence for when the first stars and quasar black holes formed in the infant universe. Spectra of the two most distant quasars known show nearly complete absorption of photons with wavelengths shorter than the Ly-alpha transition of neutral hydrogen, indicating that hydrogen in the intergalactic medium (IGM) had not been completely ionized at a redshift z~6.3, about a billion years after the big bang. Here we show that the radii of influence of ionizing radiation from these quasars imply that the surrounding IGM had a neutral hydrogen fraction of tens of percent prior to the quasar activity, much higher than previous lower limits of ~0.1%. When combined with the recent inference of a large cumulative optical depth to electron scattering after cosmological recombination from the WMAP data, our result suggests the existence of a second peak in the mean ionization history, potentially due to an early formation episode of the first stars.Comment: 14 Pages, 2 Figures. Accepted for publication in Nature. Press embargo until publishe

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Integrated method for quantitative morphometry and oxygen transport modelling in striated muscle

Identifying structural limitations in O2 transport is primarily restricted by current methods employed to characterise the nature of physiological remodelling. Inadequate resolution or breadth of available data has impaired development of routine diagnostic protocols and effective therapeutic strategies. Understanding O2 transport within striated muscle faces major challenges, most notably in quantifying how well individual fibres are supplied by the microcirculation, which has necessitated exploring tissue O2 supply using theoretical modelling of diffusive exchange. Having identified capillary domains as a suitable model for the description of local O2 supply, and requiring less computation than numerically calculating the trapping regions that are supplied by each capillary via biophysical transport models, we sought to design a high throughput method for histological analysis. We present an integrated package that identifies optimal protocols for identification of important input elements, processing of digitised images with semi-automated routines, and incorporation of these data into a mathematical modelling framework with computed output visualised as the tissue partial pressure of O2 (PO2) distribution across a biopsy sample. Worked examples are provided using muscle samples from experiments involving rats and humans