Regionalization of Flood Data Using Probability Distributions and Their Parameters

The U. S. Geological survey recently used the method of residuals to delineate seven flood regions for the State of Kentucky. As an alternative approach, the FASTCLUS clustering procedure of the Statistical Analysis system (SAS) is used in this study to delineate five to six cluster regions in conjunction with statistical properties of the AMF series, like the coefficient of variation as estimated using method of L-moments, LCV, the parameters of the EVl and GEV flood frequency distributions, and the specific mean annual flood, QSP. For both cluster and USGS flood regions, regionalized flood frequency growth curves are developed and their performance evaluated using Monte Carlo simulation techniques. Flood regions are.then evaluated and compared ·using trends in the hydrological characteristics of important.variables, performance of the regionalized flood frequency growth curves, discriminant analysis and regression equations relating flood quantiles to watershed physical characteristics. Results show that the cluster regions are more distinguishable in terms of their flood characteristics than the USGS regions. The.regionalized flood frequency growth curves of the EVl and GEV model are more distinct for the cluster regions than the USGS regions, although their performance in terms of bias and RMSE are comparable. The standard errors associated with the regression equations, developed for predicting the EVl and GEV flood quantiles, are similar for cluster and USGS regions

TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSB mutations in predicting diabetes

<p>Abstract</p> <p>Background</p> <p>Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to developing countries in tropical regions and one of its important features is invariable progression to diabetes, a condition called fibro-calculous pancreatic diabetes (FCPD), but the nature of diabetes in TCP is controversial. We analysed the recently reported type 2 diabetes (T2D) associated polymorphisms in the <it>TCF7L2 </it>gene using a case-control approach, under the hypothesis that <it>TCF7L2 </it>variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the <it>TCF7L2 </it>variants and N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations, since they are strong predictors of risk for TCP.</p> <p>Methods</p> <p>Two polymorphisms rs7903146 and rs12255372 in the <it>TCF7L2 </it>gene were analyzed by direct sequencing in 478 well-characterized TCP patients and 661 healthy controls of Dravidian and Indo-European ethnicities. Their association with TCP with diabetes (FCPD) and without diabetes was tested in both populations independently using chi-square test. Finally, a meta analysis was performed on all the cases and controls for assessing the overall significance irrespective of ethnicity. We dichotomized the whole cohort based on the presence or absence of N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations and further subdivided them into TCP and FCPD patients and compared the distribution of <it>TCF7L2 </it>variants between them.</p> <p>Results</p> <p>The allelic and genotypic frequencies for both <it>TCF7L2 </it>polymorphisms, did not differ significantly between TCP patients and controls belonging to either of the ethnic groups or taken together. No statistically significant association of the SNPs was observed with TCP or FCPD or between carriers and non-carriers of N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S <it>SPINK1 </it>variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93–2.70, P = 0.09), while, <it>TCF7L2</it><it/>variant showed a statistically significant association between TCP and FCPD patients carrying the 26V allele (OR = 1.69, 95% CI = 1.11–2.56, P = 0.013).</p> <p>Conclusion</p> <p>Type 2 diabetes associated <it>TCF7L2 </it>variants are not associated with diabetes in TCP. Since, <it>TCF7L2 </it>is a major susceptibility gene for T2D, it may be hypothesized that the diabetes in TCP patients may not be similar to T2D. Our data also suggests that co-existence of <it>TCF7L2 </it>variants and the <it>SPINK1 </it>and <it>CTSB </it>mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.</p

The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis

Background PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. Methods We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. Results We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52–0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77–0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. Conclusions The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection

Pancreatology

BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection