Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment

BACKGROUND: In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. METHODS: Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. RESULTS: The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0–2% at 1 year, 0–12% at 3 years, and 0–1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10–12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1–6% at 1 year, 15–26% at 3 years, and 0–12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. CONCLUSION: Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the statistical methods of assessment. This would be clinically relevant in the development or improvement of clinical management strategies

Population genetics of Oncomelania hupensis snails, intermediate hosts of Schistosoma japonium, from emerging, re-emerging or established habitats within China

Schistosomiasis remains one of the world’s most significant neglected tropical diseases, second only to malaria in terms of socioeconomic impact. In 2014, China proposed the goal of schistosomiasis japonicum elimination by 2025. However, one major challenge is the widely distributed, and in certain cases potentially increasing, habitats of Oncomelania hupensis, the snail intermediate hosts of S. japonicum. Therefore, an understanding of population genetics of O. hupensis in new or re-emerged habitats, together with that of the established habitats with snail persistence, would be valuable in controlling and predicting the future transmission dynamics of schistosomiasis in China. Using nine microsatellite loci, we conducted population genetic analyses of snails sampled from one habitat where snails were detected for the first time, one (previously eliminated) habitat with re-emerged snails, and one habitat with established snail persistence. Results showed lower diversities, in terms of number of observed alleles per locus (Na), number of effective alleles per locus (NeA), observed (Ho) and expected heterozygosity (He), in snails from new or re-emerged snail habitats than from the habitat with snail persistence. The smallest effective population size was inferred in the re-emerged snail habitat, but the largest was in the new habitat rather than in the habitat with snail persistence. No bottleneck effects were detected in new or re-merged habitats. No or low sub-structure was inferred in new and persistent snail habitats. Snails from the three sites were clearly separated and low gene flow was estimated between sites. We propose that snails at the new habitat may have been introduced through immigration, whereas snails at the re-emerged habitat may be the consequence of those few snails remaining subsequently expanding through reproduction. We discuss our results in terms of their theoretical and applied implications

Phylogeography of a Land Snail Suggests Trans-Mediterranean Neolithic Transport

Background: Fragmented distribution ranges of species with little active dispersal capacity raise the question about their place of origin and the processes and timing of either range fragmentation or dispersal. The peculiar distribution of the land snail Tudorella sulcata s. str. in Southern France, Sardinia and Algeria is such a challenging case. Methodology: Statistical phylogeographic analyses with mitochondrial COI and nuclear hsp70 haplotypes were used to answer the questions of the species' origin, sequence and timing of dispersal. The origin of the species was on Sardinia. Starting from there, a first expansion to Algeria and then to France took place. Abiotic and zoochorous dispersal could be excluded by considering the species' life style, leaving only anthropogenic translocation as parsimonious explanation. The geographic expansion could be dated to approximately 8,000 years before present with a 95% confidence interval of 10,000 to 3,000 years before present. Conclusions: This period coincides with the Neolithic expansion in the Western Mediterranean, suggesting a role of these settlers as vectors. Our findings thus propose that non-domesticated animals and plants may give hints on the direction and timing of early human expansion routes

Gender-Associated Genes in Filarial Nematodes Are Important for Reproduction and Potential Intervention Targets

Lymphatic filariasis is a neglected tropical disease that is caused by thread-like parasitic worms that live and reproduce in lymphatic vessels of the human host. There are no vaccines to prevent filariasis, and available drugs are not effective against all stages of the parasite. In addition, recent reports suggest that the filarial nematodes may be developing resistance to key medications. Therefore, there is an urgent need to identify new drug targets in filarial worms. The purpose of this study was to perform a genome-wide analysis of gender-associated gene transcription to improve understanding of key reproductive processes in filarial nematodes. Our results indicate that thousands of genes are differentially expressed in male and female adult worms. Many of those genes are involved in specific reproductive processes such as embryogenesis and spermatogenesis. In addition, expression of some of those genes is suppressed by tetracycline, a drug that leads to sterilization of adult female worms in many filarial species. Thus, gender-associated genes represent priority targets for design of vaccines and drugs that interfere with reproduction of filarial nematodes. Additional work with this type of integrated systems biology approach should lead to important new tools for controlling filarial diseases

Experimental Demonstration of the Fitness Consequences of an Introduced Parasite of Darwin's Finches

Introduced parasites are a particular threat to small populations of hosts living on islands because extinction can occur before hosts have a chance to evolve effective defenses. An experimental approach in which parasite abundance is manipulated in the field can be the most informative means of assessing a parasite's impact on the host. The parasitic fly Philornis downsi, recently introduced to the Galápagos Islands, feeds on nestling Darwin's finches and other land birds. Several correlational studies, and one experimental study of mixed species over several years, reported that the flies reduce host fitness. Here we report the results of a larger scale experimental study of a single species at a single site over a single breeding season.We manipulated the abundance of flies in the nests of medium ground finches (Geospiza fortis) and quantified the impact of the parasites on nestling growth and fledging success. We used nylon nest liners to reduce the number of parasites in 24 nests, leaving another 24 nests as controls. A significant reduction in mean parasite abundance led to a significant increase in the number of nests that successfully fledged young. Nestlings in parasite-reduced nests also tended to be larger prior to fledging.Our results confirm that P. downsi has significant negative effects on the fitness of medium ground finches, and they may pose a serious threat to other species of Darwin's finches. These data can help in the design of management plans for controlling P. downsi in Darwin's finch breeding populations

Prediction of uncomplicated pregnancies in obese women: A prospective multicentre study

BACKGROUND: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. METHODS: Data form obese women (BMI ≥ 30 kg/m 2 ) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15 +0 to 18 +6 weeks' gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. RESULTS: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m 2 ), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68-0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65-0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. CONCLUSION: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth

Factors and processes shaping the population structure and distribution of genetic variation across the species range of the freshwater snail radix balthica (Pulmonata, Basommatophora)

Background: Factors and processes shaping the population structure and spatial distribution of genetic diversity across a species' distribution range are important in determining the range limits. We comprehensively analysed the influence of recurrent and historic factors and processes on the population genetic structure, mating system and the distribution of genetic variability of the pulmonate freshwater snail Radix balthica. This analysis was based on microsatellite variation and mitochondrial haplotypes using Generalised Linear Statistical Modelling in a Model Selection framework. Results: Populations of R. balthica were found throughout North-Western Europe with range margins marked either by dispersal barriers or the presence of other Radix taxa. Overall, the population structure was characterised by distance independent passive dispersal mainly along a Southwest-Northeast axis, the absence of isolation-by-distance together with rather isolated and genetically depauperated populations compared to the variation present in the entire species due to strong local drift. A recent, climate driven range expansion explained most of the variance in genetic variation, reducing at least temporarily the genetic variability in this area. Other factors such as geographic marginality and dispersal barriers play only a minor role. Conclusions: To our knowledge, such a population structure has rarely been reported before. It might nevertheless be typical for passively dispersed, patchily distributed taxa (e.g. freshwater invertebrates). The strong local drift implied in such a structure is expected to erode genetic variation at both neutral and coding loci and thus probably diminish evolutionary potential. This study shows that the analysis of multiple factors is crucial for the inference of the processes shaping the distribution of genetic variation throughout species ranges. Additional files Additional file 1: Distribution of Radix taxa. Spatial distribution of the Radix MOTU as defined in Pfenninger et al. 2006 plus an additional, newly discovered taxon. This map is the basis for the inference of the species range of R. balthica. Additional file 2: Sampling site table and spatial distribution of diversity indices, selfing estimates and inferred population bottlenecks for R. balthica. Table of sampling site code, geographical position in decimal degrees latitude and longitude, number of individuals analysed with microsatellites (Nnuc), expected heterozygosity (HE) and standard deviation across loci, mean rarefied number of alleles per microsatellite locus (A) and their standard deviation, number of individuals analysed for mitochondrial variation (Nmt), rarefied number of mitochondrial COI haplotypes (Hmt), number of individuals measured for body size (Nsize). Figures A1 - A3 show a graphical representation of the spatial distribution of He, Hmt and, s, respectively. Additional file 3: Assessment of environmental marginality. PCA (principle component analysis) on 35 climatic parameters for the period from 1960 - 2000 from publicly availableWorldClim data. Additional file 4: Inference of a recent climate driven range expansion in R. balthica. Analysis of the freshwater benthos long term monitoring data of the Swedish national monitoring databases at the Swedish University of Agricultural Sciences SLU with canonical correspondence analysis

Optimal foraging and fitness in Columbian ground squirrels

Optimal diets were determined for each of 109 individual Columbian ground squirrels ( Spermophilus columbianus ) at two sites in northwestern Montana. Body mass, daily activity time, and vegetation consumption rates for individuals were measured in the field, along with the average water content of vegetation at each ground squirrel colony. I also measured stomach and caecal capacity and turnover rate of plant food through the digestive tract for individuals in the laboratory to construct regressions of digestive capacity as a function of individual body mass. Finally, I obtained literature estimates of average daily energy requirements as a function of body mass and digestible energy content of vegetation. These data were used to construct a linear programming diet model for each individual. The model for each individual was used to predict the proportion of two food types (monocots and dicots) that maximized daily energy intake, given time and digestive constraints on foraging. Individuals were classified as “optimal” or “deviating”, depending on whether their observed diet was significantly different from their predicted optimal diet. I determined the consequences of selecting an optimal diet for energy intake and fitness. As expected, daily energy intake calculated for deviators (based on their observed diet proportion) was less than that for optimal foragers. Deviating foragers do not appear to compensate for their lower calculated energy intake through other factors such as body size or physiological efficiency of processing food. Growth rate, yearly survivorship, and litter size increase with calculated energy intake, and optimal foragers have six times the reproductive success of deviators by age three. Optimal foraging behavior, therefore, appears to confer a considerable fitness advantage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47783/1/442_2004_Article_BF00318534.pd