Does ursodeoxycholic acid change the proliferation of the colorectal mucosa? A randomized, placebo-controlled study

Background: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans. Methods: Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography. Results: The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 mumol/l, 0.9-1.8) than in group B (0.7 mumol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups. Conclusions: In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation. Copyright (C) 2003 S. Karger AG, Basel

Rapid turnover of the recirculating lymphocyte pool in vivo

Lymphocytes are unique among blood cells in their capacity to continually recirculate between blood and the tissues via the lymph. Previous estimates of lymphocyte lifespan in vivo and the turnover of the recirculating lymphocyte pool have been deduced from indirect labeling techniques. Using the fluorescent dye PKH-26, individual labeled cells have been tracked in sheep for periods >2 months. By direct measurement their lifespan was calculated. This label was found to be stable in vivo, allowing long-term analysis of the characteristics of the recirculating lymphocyte pool. It Is possible to calculate the rate of turnover of cells of the recirculating pool based on the rate at which labeled cells disappear from the lymphatic circulation. The recirculating lymphocyte pool was found to repopulate itself every 16.5 ± 3.0 days. Using this label, it was estimated that recirculating lymphocytes divide on average once every 29.8 ± 6.8 days. Labeled erythrocytes were also examined and found to have an average lifespan of 153 days, demonstrating no dye loss over the 2 month period of observation. These data suggest that the recirculating lymphocyte pool is a highly dynamic compartment, with a high rate of turnover and peripheral cell division in vivo. This is the first report of the direct measurement of the in vivo turnover of recirculating lymphocyte pools, and this method may now be used to further analyze the lifespan of individual lymphocyte subsets and the in vivo lifespan of other cell types in viv

Inverse Medea as a Novel Gene Drive System for Local Population Replacement: A Theoretical Analysis

One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components—a zygotic toxin and maternal antidote—which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes

Facilitating children's self-concept: A rationale and evaluative study

This study reports on the design and effectiveness of the Exploring Self-Concept program for primary school children using self-concept as the outcome measure. The program aims to provide a procedure that incorporates organisation, elaboration, thinking, and problem-solving strategies and links these to children's multidimensional self-concept. The results of this research support the notion that teachers and guidance counsellors need to establish a nonthreatening framework that allows them to discuss with children a range of relevant issues related to peer pressure, parent relations, self-image, body image, gender bias, media pressure, values and life goals, in a systematic, objective and cooperative manner. Within the paper, notions associated with self-concept maturation, 'crystallisation' of self-concept beliefs, cognitive differentiation and self-concept segmentation are reviewed

Late Miocene to early Pliocene stratigraphic record in northern Taranaki Basin: Condensed sedimentation ahead of Northern Graben extension and progradation of the modern continental margin

The middle Pliocene-Pleistocene progradation of the Giant Foresets Formation in Taranaki Basin built up the modern continental margin offshore from western North Island. The late Miocene to early Pliocene interval preceding this progradation was characterised in northern Taranaki Basin by the accumulation of hemipelagic mudstone (Manganui Formation), volcaniclastic sediments (Mohakatino Formation), and marl (Ariki Formation), all at bathyal depths. The Manganui Formation has generally featureless wireline log signatures and moderate to low amplitude seismic reflection characteristics. Mohakatino Formation is characterised by a sharp decrease in the GR log value at its base, a blocky GR log motif reflecting sandstone packets, and erratic resistivity logs. Seismic profiles show bold laterally continuous reflectors. The Ariki Formation has a distinctive barrel-shaped to blocky GR log motif. This signature is mirrored by the SP log and often by an increase in resistivity values through this interval. The Ariki Formation comprises (calcareous) marl made up of abundant planktic foraminifera, is 109 m thick in Ariki-1, and accumulated over parts of the Western Stable Platform and beneath the fill of the Northern Graben. It indicates condensed sedimentation reflecting the distance of the northern region from the contemporary continental margin to the south

Morphogenetic Theory and the Constructivist Institutionalist Challenge

This article engages with two meta-theoretical approaches to social analysis, ‘morphogenetic theory’ and ‘constructivist institutionalism’, and specifically explores how the former fares under the critical scrutiny of the latter. The key proponent of constructivist institutionalism, Colin Hay, has offered two detailed critiques of morphogenesis that criticise its position on the foundational sociological issues of structure-agency and material-ideational. Although Hay’s critiques are largely rejected in an overall defence of the morphogenetic approach, the process of engagement is seen to be particularly useful for morphogenetic theory because it allows a number of important clarifications to be made and it also opens up space for theoretical development. In the course of this debate, accessible introductions are given to both theories, and the similarities and differences between them are outlined, providing clarity to both. Therefore, although this article ultimately operates as a defence of morphogenetic theory, especially in the form proposed by Margaret Archer and Douglas Porpora, it finds a great deal of fruitful discussion in the constructivist institutionalist challenge

An Information Theoretic perspective on perceptual structure: cross-accent vowel perception

Analytical tools from Information Theory were used to quantify behaviour in cross-accent vowel perception by Australian, London, New Zealand, Yorkshire and Newcastle UK listeners. Results show that Australian listeners impose expected patterns of perceptual similarity from their own accent experience on unfamiliar accents, regardless of the actual phonetic distance between accents

Neuroimaging in bulimia nervosa and binge eating disorder: a systematic review.

OBJECTIVE: In recent decades there has been growing interest in the use of neuroimaging techniques to explore the structural and functional brain changes that take place in those with eating disorders. However, to date, the majority of research has focused on patients with anorexia nervosa. This systematic review addresses a gap in the literature by providing an examination of the published literature on the neurobiology of individuals who binge eat; specifically, individuals with bulimia nervosa (BN) and binge eating disorder (BED). METHODS: A systematic review was conducted in accordance with PRISMA guidelines using PubMed, PsycInfo, Medline and Web of Science, and additional hand searches through reference lists. 1,003 papers were identified in the database search. Published studies were included if they were an original research paper written in English; studied humans only; used samples of participants with a diagnosed eating disorder characterised by recurrent binge eating; included a healthy control sample; and reported group comparisons between clinical groups and healthy control groups. RESULTS: Thirty-two papers were included in the systematic review. Significant heterogeneity in the methods used in the included papers coupled with small sample sizes impeded the interpretation of results. Twenty-one papers utilised functional Magnetic Resonance Imaging (fMRI); seven papers utilized Magnetic Resonance Imaging (MRI) with one of these using both MRI and Positron Emission Technology (PET); three studies used Single-Photon Emission Computed Tomography (SPECT) and one study used PET only. A small number of consistent findings emerged in individuals in the acute phase of illness with BN or BED including: volume reduction and increases across a range of areas; hypoactivity in the frontostriatal circuits; and aberrant responses in the insula, amygdala, middle frontal gyrus and occipital cortex to a range of different stimuli or tasks; a link between illness severity in BN and neural changes; diminished attentional capacity and early learning; and in SPECT studies, increased rCBF in relation to disorder-related stimuli. CONCLUSIONS: Studies included in this review are heterogenous, preventing many robust conclusions from being drawn. The precise neurobiology of BN and BED remains unclear and ongoing, large-scale investigations are required. One clear finding is that illness severity, exclusively defined as the frequency of binge eating or bulimic episodes, is related to greater neural changes. The results of this review indicate additional research is required, particularly extending findings of reduced cortical volumes and diminished activity in regions associated with self-regulation (frontostriatal circuits) and further exploring responses to disorder-related stimuli in people with BN and BED

Testing the recovery of stellar rotation signals from Kepler light curves using a blind hare-and-hounds exercise

We present the results of a blind exercise to test the recoverability of stellar rotation and differential rotation in Kepler light curves. The simulated light curves lasted 1000 days and included activity cycles, Sun-like butterfly patterns, differential rotation and spot evolution. The range of rotation periods, activity levels and spot lifetime were chosen to be representative of the Kepler data of solar like stars. Of the 1000 simulated light curves, 770 were injected into actual quiescent Kepler light curves to simulate Kepler noise. The test also included five 1000-day segments of the Sun's total irradiance variations at different points in the Sun's activity cycle. Five teams took part in the blind exercise, plus two teams who participated after the content of the light curves had been released. The methods used included Lomb-Scargle periodograms and variants thereof, auto-correlation function, and wavelet-based analyses, plus spot modelling to search for differential rotation. The results show that the `overall' period is well recovered for stars exhibiting low and moderate activity levels. Most teams reported values within 10% of the true value in 70% of the cases. There was, however, little correlation between the reported and simulated values of the differential rotation shear, suggesting that differential rotation studies based on full-disk light curves alone need to be treated with caution, at least for solar-type stars. The simulated light curves and associated parameters are available online for the community to test their own methods.Comment: Accepted for publication in MNRAS. Accepted, 13 April 2015. Received, 26 March 2015; in original form, 9 November 201