Increasing prevalence of advanced colonic polyps in young patients undergoing colonoscopy in a referral academic hospital in Hong Kong

Aim: To investigate the distribution and frequency of advanced polyps over eight years. Methods: 6424 colonoscopies were reviewed during the study period 1998 to 2005. The study period was subdivided into period I: 1998 to 2001 and period II: 2002-2005. Results: 1856 polyps (33% advanced polyps) and 328 CRCs were detected. The mean ages of the patients with advanced polyps and cancer were 69.2 ± 12.0 and 71.6 ± 13.8 years, respectively. Advanced polyps were mainly left sided (59.5%). Advanced polyps were found in patients ≤ 60 years from 17.7% in period I to 26.3% in period II (P 0.05). Conclusion: Advanced polyps increased significantly in the younger male group in the most recent period and there seems to be a shift towards a proximal location. © 2007 WJG. All rights reserved.published_or_final_versio

Selection for environmental variance of litter size in rabbits

[EN] Background: In recent years, there has been an increasing interest in the genetic determination of environmental variance. In the case of litter size, environmental variance can be related to the capacity of animals to adapt to new environmental conditions, which can improve animal welfare. Results: We developed a ten-generation divergent selection experiment on environmental variance. We selected one line of rabbits for litter size homogeneity and one line for litter size heterogeneity by measuring intra-doe phenotypic variance. We proved that environmental variance of litter size is genetically determined and can be modified by selection. Response to selection was 4.5% of the original environmental variance per generation. Litter size was consistently higher in the Low line than in the High line during the entire experiment. Conclusions: We conclude that environmental variance of litter size is genetically determined based on the results of our divergent selection experiment. This has implications for animal welfare, since animals that cope better with their environment have better welfare than more sensitive animals. We also conclude that selection for reduced environmental variance of litter size does not depress litter size.This research was funded by the Ministerio de Economía y Competitividad (Spain), Projects AGL2014-55921, C2-1-P and C2-2-P. Marina Martínez-Alvaro has a Grant from the same funding source, BES-2012-052655.Blasco Mateu, A.; Martínez Álvaro, M.; García Pardo, MDLL.; Ibáñez Escriche, N.; Argente, MJ. (2017). Selection for environmental variance of litter size in rabbits. Genetics Selection Evolution. 49(48):1-8. https://doi.org/10.1186/s12711-017-0323-4S184948Morgante F, Sørensen P, Sorensen DA, Maltecca C, Mackay TFC. Genetic architecture of micro-environmental plasticity in Drosophila melanogaster. Sci Rep. 2015;5:9785.Sørensen P, de los Campos G, Morgante F, Mackay TFC, Sorensen D. 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Effect of selection for residual variance of litter size on hematology parameters as immunology indicators in rabbits. In: Proceedings of the 10th World Congress on genetics applied to livestock production. Vancouver; 2014.García ML, Zbynovska K, Petruska P, Bovdisová I, Kalafová A, Capcarova M, et al. Effect of selection for residual variance of litter size on biochemical parameters in rabbits. In: Proceedings of the 67th annual meeting of the European Federation of Animal Science. Belfast; 2016.Broom DM. Welfare assessment and relevant ethical decisions: key concepts. Annu Rev Biomed Sci. 2008;20:79–90.SanCristobal-Gaudy M, Bodin L, Elsen JM, Chevalet C. Genetic components of litter size variability in sheep. Genet Sel Evol. 2001;33:249–71.Sorensen D, Waagepetersen R. Normal linear models with genetically structured residual variance heterogeneity: a case study. Genet Res. 2003;82:207–22.Mulder HA, Hill WG, Knol EF. Heritable environmental variance causes nonlinear relationships between traits: application to birth weight and stillbirth of pigs. Genetics. 2015;199:1255–69.Ros M, Sorensen D, Waagepetersen R, Dupont-Nivet M, San Cristobal M, Bonnet JC. Evidence for genetic control of adult weight plasticity in the snail Helix aspersa. Genetics. 2004;168:2089–97.Gutiérrez JP, Nieto B, Piqueras P, Ibáñez N, Salgado C. Genetic parameters for components analysis of litter size and litter weight traits at birth in mice. Genet Sel Evol. 2006;38:445–62.Ibáñez-Escriche N, Sorensen D, Waagepetersen R, Blasco A. Selection for environmental variation: a statistical analysis and power calculations to detect response. Genetics. 2008;180:2209–26.Wolc A, White IM, Avendano S, Hill WG. Genetic variability in residual variation of body weight and conformation scores in broiler chickens. Poult Sci. 2009;88:1156–61.Fina M, Ibáñez-Escriche N, Piedrafita J, Casellas J. Canalization analysis of birth weight in Bruna dels Pirineus beef cattle. J Anim Sci. 2013;91:3070–8.Mulder HA, Rönnegård L, Fikse WF, Veerkamp RF, Strandberg E. Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models. Genet Sel Evol. 2013;45:23.Janhunen M, Kause A, Vehviläinen H, Järvisalom O. Genetics of microenvironmental sensitivity of body weight in rainbow trout (Oncorhynchus mykiss) selected for improved growth. PLoS One. 2012;7:e38766.Sonesson AK, Ødegård J, Rönnegård L. Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar). Genet Sel Evol. 2013;45:41.Garreau H, Bolet G, Larzul C, Robert-Granie C, Saleil G, SanCristobal M, et al. Results of four generations of a canalising selection for rabbit birth weight. Livest Sci. 2008;119:55–62.Pun A, Cervantes I, Nieto B, Salgado C, Pérez-Cabal MA, Ibáñez-Escriche N, et al. Genetic parameters for birth weight environmental variability in mice. J Anim Breed Genet. 2012;130:404–14.Hill WG, Mulder HA. Genetic analysis of environmental variation. Genet Res (Camb). 2010;92:381–95.Yang Y, Christensen OF, Sorensen D. Analysis of a genetically structured variance heterogeneity model using the Box–Cox transformation. Genet Res (Camb). 2011;93:33–46.Piles M, Garcia ML, Rafel O, Ramon J, Baselga M. Genetics of litter size in three maternal lines of rabbits: repeatability versus multiple-trait models. J Anim Sci. 2006;84:2309–15.Estany J, Baselga M, Blasco A, Camacho J. Mixed model methodology for the estimation of genetic response to selection in litter size of rabbits. Livest Prod Sci. 1989;21:67–75.Box GEP, Tiao GC. Bayesian inference in statistical analysis. New York: Wiley; 1973.Searle SR. Matrix algebra useful for statistics. Toronto: Wiley; 1982.Sorensen D, Gianola D. Likelihood, Bayesian and MCMC methods in quantitative genetics. New York: Springer; 2002.Geyer CM. Practical Markov chain Monte Carlo (with discussion). Stat Sci. 1992;7:467–511.Legarra A. TM threshold model. 2008. http://genoweb.toulouse.inra.fr/~alegarra/tm_folder/ . Accessed 02 May 2017.Blasco A. Bayesian data analysis for animal scientists. New York: Springer; 2017.Rönnegård L, Felleki M, Fikse F, Mulder HA, Strandberg E. Genetic heterogeneity of residual variance—estimation of variance components using double hierarchical generalized linear models. Genet Sel Evol. 2010;42:8.Felleki M, Lee D, Lee Y, Gilmour AR, Rönnegård L. Estimation of breeding values for mean and dispersion, their variance and correlation using double hierarchical generalized linear models. Genet Res (Camb). 2012;94:307–17.Thompson R. Estimation of realized heritability in a selected population using mixed model methods. Genet Sel Evol. 1986;18:475–84.Sorensen DA, Johansson K. Estimation of direct and correlated responses to selection using univariate animal models. 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Th Inducing POZ-Kruppel Factor (ThPOK) Is a Key Regulator of the Immune Response since the Early Steps of Colorectal Carcinogenesis

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells

Identification of Mendelian inconsistencies between SNP and pedigree information of sibs

Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype information are not in agreement. Methods Straightforward tests to detect Mendelian inconsistencies exist that count the number of opposing homozygous marker (e.g. SNP) genotypes between parent and offspring (PAR-OFF). Here, we develop two tests to identify Mendelian inconsistencies between sibs. The first test counts SNP with opposing homozygous genotypes between sib pairs (SIBCOUNT). The second test compares pedigree and SNP-based relationships (SIBREL). All tests iteratively remove animals based on decreasing numbers of inconsistent parents and offspring or sibs. The PAR-OFF test, followed by either SIB test, was applied to a dataset comprising 2,078 genotyped cows and 211 genotyped sires. Theoretical expectations for distributions of test statistics of all three tests were calculated and compared to empirically derived values. Type I and II error rates were calculated after applying the tests to the edited data, while Mendelian inconsistencies were introduced by permuting pedigree against genotype data for various proportions of animals. Results Both SIB tests identified animal pairs for which pedigree and genomic relationships could be considered as inconsistent by visual inspection of a scatter plot of pairwise pedigree and SNP-based relationships. After removal of 235 animals with the PAR-OFF test, SIBCOUNT (SIBREL) identified 18 (22) additional inconsistent animals. Seventeen animals were identified by both methods. The numbers of incorrectly deleted animals (Type I error), were equally low for both methods, while the numbers of incorrectly non-deleted animals (Type II error), were considerably higher for SIBREL compared to SIBCOUNT. Conclusions Tests to remove Mendelian inconsistencies between sibs should be preceded by a test for parent-offspring inconsistencies. This parent-offspring test should not only consider parent-offspring pairs based on pedigree data, but also those based on SNP information. Both SIB tests could identify pairs of sibs with Mendelian inconsistencies. Based on type I and II error rates, counting opposing homozygotes between sibs (SIBCOUNT) appears slightly more precise than comparing genomic and pedigree relationships (SIBREL) to detect Mendelian inconsistencies between sib

Discordance in diagnosis of osteoporosis using spine and hip bone densitometry

BACKGROUND: Diagnostic discordance for osteoporosis is the observation that the T-score of an individual patient varies from one key measurement site to another, falling into two different diagnostic categories identified by the World Health Organization (WHO) classification system. This study was conducted to evaluate the presence and risk factors for this phenomenon in a large sample of Iranian population. METHODS: Demographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database on 4229 patients referred to a community-based outpatient osteoporosis testing center from 2000 to 2003. Dual-energy X-ray absorptiometry (DXA) was performed on L1–L4 lumbar spine and total hip for all cases. Minor discordance was defined as present when the difference between two sites was no more than one WHO diagnostic class. Major discordance was present when one site is osteoporotic and the other is normal. Subjects with incomplete data were excluded. RESULTS: In 4188 participants (3848 female, mean age 53.4 ± 11.8 years), major discordance, minor discordance, and concordance of T-scores were seen in 2.7%, 38.9% and 58.3%, respectively. In multivariate logistic regression analysis, older age, menopause, obesity, and belated menopause were recognized as risk factors and hormone replacement therapy as a protective factor against T-score discordance. CONCLUSION: The high prevalence of T-score discordance may lead to problems in interpretation of the densitometry results for some patients. This phenomenon should be regarded as a real and prevalent finding and physicians should develop a particular strategy approaching to these patients

Entrepreneurs, Chance, and the Deterministic Concentration of Wealth

In many economies, wealth is strikingly concentrated. Entrepreneurs–individuals with ownership in for-profit enterprises–comprise a large portion of the wealthiest individuals, and their behavior may help explain patterns in the national distribution of wealth. Entrepreneurs are less diversified and more heavily invested in their own companies than is commonly assumed in economic models. We present an intentionally simplified individual-based model of wealth generation among entrepreneurs to assess the role of chance and determinism in the distribution of wealth. We demonstrate that chance alone, combined with the deterministic effects of compounding returns, can lead to unlimited concentration of wealth, such that the percentage of all wealth owned by a few entrepreneurs eventually approaches 100%. Specifically, concentration of wealth results when the rate of return on investment varies by entrepreneur and by time. This result is robust to inclusion of realities such as differing skill among entrepreneurs. The most likely overall growth rate of the economy decreases as businesses become less diverse, suggesting that high concentrations of wealth may adversely affect a country's economic growth. We show that a tax on large inherited fortunes, applied to a small portion of the most fortunate in the population, can efficiently arrest the concentration of wealth at intermediate levels

Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils

Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.Tis study was supported by Sao Paulo Research foundation: grants 2008/57889-1, 2010/20010-4, 2014/19326-6, by the Brazilian National Counsel of Technological and Scientifc Development: grant 573799/2008-3. KLFA and RAMR had PhD fellowships by Sao Paulo Research Foundation, CRSF has a Coordination for the Improvement of Higher Education Personnel PhD fellowship. We thank the Pathology Department of the School of Medicine, coordinated by Prof. Venâncio Avancini Ferreira Alves, Universidade de São Paulo for the slides containing histological samples from the biopsies used in this study. We thank Sandra Alexandre Alves for her technical support.info:eu-repo/semantics/publishedVersio

Fecal Tests: From Blood to Molecular Markers

Detection of molecular markers for colorectal neoplasia in feces has the potential to improve performance of simple noninvasive screening tests for colorectal cancer. Most research has explored the value of DNA-based, RNA-based, and protein-based markers. In all cases there has been a trend to move from a single marker to a panel of markers to improve sensitivity. Unfortunately, no type of molecular marker has proved specific for neoplasia. DNA tests have been improved by combining mutation detection with assessment of DNA integrity plus epigenetic markers of neoplasia. RNA-based approaches are just beginning to explore the full power of transcriptomics. So far, no protein-based fecal test has proved better than fecal immunochemical tests for hemoglobin. Finally, no marker or panel of markers has yet been developed to the point where it has been evaluated in large unbiased population studies to assess performance across all stages of neoplasia and in all practical environments