Past, present and future of Barrett's oesophagus

Barrett's oesophagus is a condition which predisposes towards development of oesophageal adenocarcinoma, a highly lethal tumour which has been increasing in incidence in the Western world over the past three decades. There have been tremendous advances in the field of Barrett's oesophagus, not only in diagnostic modalities, but also in therapeutic strategies available to treat this premalignant disease. In this review, we discuss the past, present and future of Barrett's oesophagus. We describe the historical and new evolving diagnostic criteria of Barrett's oesophagus, while also comparing and contrasting the British Society of Gastroenterology guidelines, American College of Gastroenterology guidelines and International Benign Barrett's and CAncer Taskforce (BOBCAT) for Barrett's oesophagus. Advances in endoscopic modalities such as confocal and volumetric laser endomicroscopy, and a non-endoscopic sampling device, the Cytosponge, are described which could aid in identification of Barrett's oesophagus. With regards to therapy we review the evidence for the utility of endoscopic mucosal resection and radiofrequency ablation when coupled with better characterization of dysplasia. These endoscopic advances have transformed the management of Barrett's oesophagus from a primarily surgical disease into an endoscopically managed condition.The BEST-1 study was funded by the Medical Research Council gap fund. The BEST-2 study was funded by Cancer Research UK

Diffractive Higgs Production by AdS Pomeron Fusion

The double diffractive Higgs production at central rapidity is formulated in terms of the fusion of two AdS gravitons/Pomerons first introduced by Brower, Polchinski, Strassler and Tan in elastic scattering. Here we propose a simple self-consistent holographic framework capable of providing phenomenologically compelling estimates of diffractive cross sections at the LHC. As in the traditional weak coupling approach, we anticipate that several phenomenological parameters must be tested and calibrated through factorization for a self-consistent description of other diffractive process such as total cross sections, deep inelastic scattering and heavy quark production in the central region.Comment: 53 pages, 8 figure

A Randomized Waitlist-Controlled Trial of an Intergenerational Arts and Heritage-Based Intervention in Singapore: Project ARTISAN

Loneliness has become a global major public health concern, with detrimental effects to the young and old. ARTISAN (Aspiration and Resilience Through Intergenerational Storytelling and Art-based Narratives) is a 5-week, 15-h participatory art and group-based intervention that focuses on resilience building and loneliness alleviation among the young and old through a structured multimodal framework held at a museum space. Developed with a Participatory Action Research (PAR) approach, this intervention is evaluated using an open-label waitlist randomized controlled trial design (RCT) comprised of community-dwelling youth and older adults randomized into an intervention group (n = 35) or a waitlist-control group (n = 33). Participants were assessed on standardized self-reported psychometric measures including loneliness, resilience, quality of life, social support, life satisfaction and national identity at three time points. Qualitative data generated during each intervention session as well as acceptability focus groups were recorded and transcribed. Linear mixed modeling analyses revealed that participants in the intervention group experienced improvements in life satisfaction compared to participants in the waitlist-control group (95% CI: 0.22 to 0.77, p &amp;lt; 0.001, Cohen's d = 0.53) immediately after the completion of ARTISAN. Subgroup analyses for youth participants indicated improvements in quality of life (95% CI: 0.16 to 0.52, p &amp;lt; 0.001, d = 1.31) and national identity (95% CI: 0.18 to 0.80, p = 0.002, d = 0.43) in comparison to the waitlist-control group. At 5-weeks follow-up, the intervention group participants continued to experience high levels of life satisfaction (95% CI: 0.04 to 0.42, p = 0.017, d = 0.47), enhancements in resilience (95% CI: 0.07 to 0.55, p = 0.011, d = 0.46), as well as a significant reduction in loneliness (95% CI: −0.34 to −0.08, p = 0.001, d = 0.61) compared to baseline, reflecting the effectiveness and positive residual effects of the ARTISAN intervention. Similarly, the qualitative findings provided support for the intervention and additional insights to the quantitative findings. This holistic intervention framework that integrates stories, arts and heritage for bridging and empowering lives fills a critical gap in knowledge and practice between the arts, health and citizenship, paving the way for further research in creating a more caring and inclusive society with the arts.Clinical Trials Registration:www.ClinicalTrials.gov, identifier: NCT03048708.</jats:p

In vivo impact of presynaptic calcium channel dysfunction on motor axons in episodic ataxia type 2

Ion channel dysfunction causes a range of neurological disorders by altering transmembrane ion fluxes, neuronal or muscle excitability, and neurotransmitter release. Genetic neuronal channelopathies affecting peripheral axons provide a unique opportunity to examine the impact of dysfunction of a single channel subtype in detail in vivo. Episodic ataxia type 2 is caused by mutations in CACNA1A, which encodes the pore-forming subunit of the neuronal voltage-gated calcium channel Cav2.1. In peripheral motor axons, this channel is highly expressed at the presynaptic neuromuscular junction where it contributes to action potential-evoked neurotransmitter release, but it is not expressed mid-axon or thought to contribute to action potential generation. Eight patients from five families with genetically confirmed episodic ataxia type 2 underwent neurophysiological assessment to determine whether axonal excitability was normal and, if not, whether changes could be explained by Cav2.1 dysfunction. New mutations in the CACNA1A gene were identified in two families. Nerve conduction studies were normal, but increased jitter in single-fibre EMG studies indicated unstable neuromuscular transmission in two patients. Excitability properties of median motor axons were compared with those in 30 age-matched healthy control subjects. All patients had similar excitability abnormalities, including a high electrical threshold and increased responses to hyperpolarizing (P < 0.00007) and depolarizing currents (P < 0.001) in threshold electrotonus. In the recovery cycle, refractoriness (P < 0.0002) and superexcitability (P < 0.006) were increased. Cav2.1 dysfunction in episodic ataxia type 2 thus has unexpected effects on axon excitability, which may reflect an indirect effect of abnormal calcium current fluxes during development

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study

BACKGROUND: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Evaluation of stability of directly standardized rates for sparse data using simulation methods.

Background Directly standardized rates (DSRs) adjust for different age distributions in different populations and enable, say, the rates of disease between the populations to be directly compared. They are routinely published but there is concern that a DSR is not valid when it is based on a “small” number of events. The aim of this study was to determine the value at which a DSR should not be published when analyzing real data in England. Methods Standard Monte Carlo simulation techniques were used assuming the number of events in 19 age groups (i.e., 0–4, 5–9, ... 90+ years) follow independent Poisson distributions. The total number of events, age specific risks, and the population sizes in each age group were varied. For each of 10,000 simulations the DSR (using the 2013 European Standard Population weights), together with the coverage of three different methods (normal approximation, Dobson, and Tiwari modified gamma) of estimating the 95% confidence intervals (CIs), were calculated. Results The normal approximation was, as expected, not suitable for use when fewer than 100 events occurred. The Tiwari method and the Dobson method of calculating confidence intervals produced similar estimates and either was suitable when the expected or observed numbers of events were 10 or greater. The accuracy of the CIs was not influenced by the distribution of the events across categories (i.e., the degree of clustering, the age distributions of the sampling populations, and the number of categories with no events occurring in them). Conclusions DSRs should not be given when the total observed number of events is less than 10. The Dobson method might be considered the preferred method due to the formulae being simpler than that of the Tiwari method and the coverage being slightly more accurate

Interpopulation crosses, inheritance study, and genetic variability in the brown planthopper complex, Nilaparvata lugens (Homoptera: Delphacidae)

Studies on hybridization, inheritance, and population genetics of brown planthoppers that infest rice and weeds were undertaken using starch gel electrophoresis to determine whether the weed-infesting population represents a biological race or a species. F(1) and F(2) generations were produced by crosses between parental insects from the two populations with little indication of hybrid sterility. Gpi, Mdh, and Idh loci were inherited in a simple Mendelian fashion in families of two sympatric populations. Sixteen populations of Nilaparvata spp. from eight locations were collected. The Mdh, Idh, Pgm, Gpi, 6Pgd, and Acp loci were polymorphic. The N. lugens of rice with high esterase activity were clustered into a group and characterized by the presence of alleles Gpi (110) and Gpi (120), whereas N. lugens from weeds with low esterase activity were clustered into another group and characterized by Gpi (100) and Gpi (90) . There was a lack of heterozygotes between the common alleles of the two populations. This means that the two groups of individuals belong to different gene pools

New generalized nonspherical black hole solutions

We present numerical evidence for the existence of several types of static black hole solutions with a nonspherical event horizon topology in $d\geq 6$ spacetime dimensions. These asymptotically flat configurations are found for a specific metric ansatz and can be viewed as higher dimensional counterparts of the $d=5$ static black rings, dirings and black Saturn. Similar to that case, they are supported against collapse by conical singularities. The issue of rotating generalizations of these solutions is also considered.Comment: 47 pages, 11 figures, some comments adde

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Copy number variation analysis based on AluScan sequences

BACKGROUND: AluScan combines inter-Alu PCR using multiple Alu-based primers with opposite orientations and next-generation sequencing to capture a huge number of Alu-proximal genomic sequences for investigation. Its requirement of only sub-microgram quantities of DNA facilitates the examination of large numbers of samples. However, the special features of AluScan data rendered difficult the calling of copy number variation (CNV) directly using the calling algorithms designed for whole genome sequencing (WGS) or exome sequencing. RESULTS: In this study, an AluScanCNV package has been assembled for efficient CNV calling from AluScan sequencing data employing a Geary-Hinkley transformation (GHT) of read-depth ratios between either paired test-control samples, or between test samples and a reference template constructed from reference samples, to call the localized CNVs, followed by use of a GISTIC-like algorithm to identify recurrent CNVs and circular binary segmentation (CBS) to reveal large extended CNVs. To evaluate the utility of CNVs called from AluScan data, the AluScans from 23 non-cancer and 38 cancer genomes were analyzed in this study. The glioma samples analyzed yielded the familiar extended copy-number losses on chromosomes 1p and 9. Also, the recurrent somatic CNVs identified from liver cancer samples were similar to those reported for liver cancer WGS with respect to a striking enrichment of copy-number gains in chromosomes 1q and 8q. When localized or recurrent CNV-features capable of distinguishing between liver and non-liver cancer samples were selected by correlation-based machine learning, a highly accurate separation of the liver and non-liver cancer classes was attained. CONCLUSIONS: The results obtained from non-cancer and cancerous tissues indicated that the AluScanCNV package can be employed to call localized, recurrent and extended CNVs from AluScan sequences. Moreover, both the localized and recurrent CNVs identified by this method could be subjected to machine-learning selection to yield distinguishing CNV-features that were capable of separating between liver cancers and other types of cancers. Since the method is applicable to any human DNA sample with or without the availability of a paired control, it can also be employed to analyze the constitutional CNVs of individuals.published_or_final_versio