Mortality from cutaneous melanoma: evidence for contrasting trends between populations

In recent years several reports have been published concerning trends in melanoma mortality in different countries, some of which have indicated that rates are beginning to fall. Many of these reports, however, have been based on small populations and have used different forms of statistical analysis. Our objective was to analyse systematically to what degree the epidemic of melanoma mortality had evolved similarly in different populations and whether there were any divergent trends that might increase our understanding. Instead of using all available data, we focused on countries with a minimum time series of 30 years and a minimum of 100 deaths annually in at least one sex from melanoma. We first inspected sex-specific age-standardized mortality rates and then performed age-period-cohort modelling. We found that the increase in mortality observed after 1950 was more pronounced in the age group 60–79. Statistical modelling showed a general increase in mortality rates in generations born after the turn of the century. Downturns in mortality, essentially in women and starting with generations born just before World War II, were found in Australia (where the earliest decreases were noted), the Nordic countries and the USA. Small decreases in rates in more recent generations were found in the UK and Canada. However, in France, Italy and Czechoslovakia, mortality rates were seen to be still increasing in recent cohorts. Our analysis suggests that populations are at different places on the melanoma mortality epidemic curve. The three trend patterns we observed are in agreement with time differences between populations with respect to the promotion of sun protection and the surveillance of pigmented skin lesions. © 2000 Cancer Research Campaig

Homoplasy corrected estimation of genetic similarity from AFLP bands, and the effect of the number of bands on the precision of estimation

AFLP is a DNA fingerprinting technique, resulting in binary band presence–absence patterns, called profiles, with known or unknown band positions. We model AFLP as a sampling procedure of fragments, with lengths sampled from a distribution. Bands represent fragments of specific lengths. We focus on estimation of pairwise genetic similarity, defined as average fraction of common fragments, by AFLP. Usual estimators are Dice (D) or Jaccard coefficients. D overestimates genetic similarity, since identical bands in profile pairs may correspond to different fragments (homoplasy). Another complicating factor is the occurrence of different fragments of equal length within a profile, appearing as a single band, which we call collision. The bias of D increases with larger numbers of bands, and lower genetic similarity. We propose two homoplasy- and collision-corrected estimators of genetic similarity. The first is a modification of D, replacing band counts by estimated fragment counts. The second is a maximum likelihood estimator, only applicable if band positions are available. Properties of the estimators are studied by simulation. Standard errors and confidence intervals for the first are obtained by bootstrapping, and for the second by likelihood theory. The estimators are nearly unbiased, and have for most practical cases smaller standard error than D. The likelihood-based estimator generally gives the highest precision. The relationship between fragment counts and precision is studied using simulation. The usual range of band counts (50–100) appears nearly optimal. The methodology is illustrated using data from a phylogenetic study on lettuce

Evaluation of Spatially Targeted Strategies to Control Non-Domiciliated Triatoma dimidiata Vector of Chagas Disease

Chagas disease is one of the most important parasitic diseases in Latin America. Since the 1980's, many national and international initiatives have contributed to eliminate vectors developing inside human domiciles. Today's challenge is to control vectors that are non-adapted to the human domicile, but still able to transmit the parasite through regular short stay in the houses. Here, we assess the potential of different control strategies applied in specific spatial patterns using a mathematical model that reproduces the dynamic of dispersion of such ‘non-domiciliated’ vectors within a village of the Yucatan Peninsula, Mexico. We show that no single strategy applied in the periphery of the village, where the insects are more abundant, provides satisfying protection to the whole village. However, combining the use of insect screens in houses at the periphery of the village (to simultaneously fight insects dispersing from the garden and the forest), and the cleaning of the peri-domicile areas of the centre of the village (where sylvatic insects are absent), would provide a cost-effective control. This type of spatially mixed strategy offers a promising way to reduce the cost associated with the repeated interventions required to control non-domiciliated vectors that permanently attempt to infest houses

フィリピンの小児デングウイルス感染症の重症化に、HLA-A*33:01アレルは防御的に働く

Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A*33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection.長崎大学学位論文 学位記番号:博(医歯薬)乙第39号 学位授与年月日:平成27年6月3日Author: Edelwisa Segubre Mercado, Fe Esperanza Espino, Ma. Lucila M. Perez, Josie M. Bilar, Jemimah Dawn P. Bajaro, Nguyen Tien Huy, Benilda Q Baello, Mihoko Kikuchi, Kenji HirayamaCitation: PLOS ONE, 10(2), e0115619; 2015Nagasaki University (長崎大学)論文博

Inference for stochastic chemical kinetics using moment equations and system size expansion

Quantitative mechanistic models are valuable tools for disentangling biochemical pathways and for achieving a comprehensive understanding of biological systems. However, to be quantitative the parameters of these models have to be estimated from experimental data. In the presence of significant stochastic fluctuations this is a challenging task as stochastic simulations are usually too time-consuming and a macroscopic description using reaction rate equations (RREs) is no longer accurate. In this manuscript, we therefore consider moment-closure approximation (MA) and the system size expansion (SSE), which approximate the statistical moments of stochastic processes and tend to be more precise than macroscopic descriptions. We introduce gradient-based parameter optimization methods and uncertainty analysis methods for MA and SSE. Efficiency and reliability of the methods are assessed using simulation examples as well as by an application to data for Epo-induced JAK/STAT signaling. The application revealed that even if merely population-average data are available, MA and SSE improve parameter identifiability in comparison to RRE. Furthermore, the simulation examples revealed that the resulting estimates are more reliable for an intermediate volume regime. In this regime the estimation error is reduced and we propose methods to determine the regime boundaries. These results illustrate that inference using MA and SSE is feasible and possesses a high sensitivity