Helicobacter pylori and Gastric Cancer: What Are the Benefits of Screening Only for the CagA Phenotype of H. pylori?

Background. Strains of Helicobacter pylori that express the CagA protein are associated with a threefold increased gastric cancer risk as compared to H. pylori strains that do not express CagA. Screening and treatment only for CagA antibodies should target those individuals at highest gastric cancer risk while reducing the number of patients requiring antibiotics. We compared the costs and benefits of screening asymptomatic 50-year-old individuals for CagA, screening for all H. pylori strains, and no screening, both in the United States and abroad.
Materials and Methods. We employed Markov cost-effectiveness analysis using data from randomized, case-control, and cohort studies.
Results. In the United States, CagA screening would result in 1.5 million fewer antibiotic treatments but would prevent 1,400 fewer gastric cancers than would screening for all H. pylori. The incremental cost-effectiveness of CagA screening is $23,900 per life-year gained; for H. pylori screening, it is $25,100. Screening in countries with epidemiological characteristics similar to those of Colombia, Finland, and Japan costs less than $5,000 per life-year gained, and the difference between CagA and H. pylori screening is smaller than that in the United States.
Conclusions. Screening only for CagA-positive H. pylori is not substantially better than is screening for all H. pylori , either in the United States nor abroad. Screening is substantially more cost-effective outside the United States. Whether population screening is justified, however, is uncertain pending conclusive data regarding the reduction in gastric cancer risk from antibiotics.     

From Duty to Desire: Remaking Families in a Spanish Village

From Duty to Desire: Remaking Families in. Spanish Village. Jane Fishburne Collier. Princeton, NJ: Princeton University Press, 1997.264 pp.     

Statistical methods for analyzing microarray feature data with replications.

Expression levels in oligonucleotide microarray experiments depend on a potentially large number of factors, for example, treatment conditions, different probes, different arrays, and so on. To dissect the effects of these factors on expression levels, fixed-effects ANOVA methods have previously been proposed. Because we are not necessarily interested in estimating the specific effects of different probes and arrays, we propose to treat these as random effects. Then we only need to estimate their means and variances but not the effect of each of their levels; that is, we can work with a much reduced number of parameters and, consequently, higher precision for estimating expression levels. Thus, we developed a mixed-effects ANOVA model with some random and some fixed effects. It automatically accounts for local normalization between different arrays and for background correction. The method was applied to each of the 6,584 genes investigated in a microarray experiment on two mouse cell lines, PA6/S and PA6/8, where PA6/S enhances proliferation of Pre B cells in vitro but PA6/8 does not. To detect a set of differentially expressed genes (multiple testing problem), we applied the method of controlling the false discovery rate (FDR), which successfully identified 207 genes with significantly different expression levels.     

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.     

DEFINING THE MAJOR LINEAGES OF RED ALGAE (RHODOPHYTA)1

Previous phylogenetic studies of the Rhodophyta have provided a framework for understanding red algal phylogeny, but there still exists the need for a comprehensive analysis using a broad sampling of taxa and sufficient phylogenetic information to clearly define the major lineages. In this study, we determined 48 sequences of the PSI P700 chl a apoprotein A1 (psaA) and rbcL coding regions and established a robust red algal phylogeny to identify the major clades. The tree included most of the lineages of the Bangiophyceae (25 genera, 48 taxa). Seven well‐supported lineages were identified with this analysis with the Cyanidiales having the earliest divergence and being distinct from the remaining taxa; i.e. the Porphyridiales 1–3, Bangiales, Florideophyceae, and Compsopogonales. We also analyzed data sets with fewer taxa but using seven proteins or the DNA sequence from nine genes to resolve inter‐clade relationships. Based on all of these analyses, we propose that the Rhodophyta contains two new subphyla, the Cyanidiophytina with a single class, the Cyanidiophyceae, and the Rhodophytina with six classes, the Bangiophyceae, Compsopogonophyceae, Florideophyceae, Porphyridiophyceae classis nov. (which contains Porphyridium, Flintiella, and Erythrolobus), Rhodellophyceae, and Stylonematophyceae classis nov. (which contains Stylonema, Bangiopsis, Chroodactylon, Chroothece, Purpureofilum, Rhodosorus, Rhodospora, and Rufusia). We also describe a new order, Rhodellales, and a new family, Rhodellaceae (with Rhodella, Dixoniella, and Glaucosphaera).     

Laboratory studies of predator-prey encounters in turbulent environments: effects of changes in orientation and field of view

Small polystyrene particles were used to represent aquatic micro-organismson millimeter scales, assuming small or negligible self-inducedmotions. A large number of such particles were released in turbulentflows that were generated in a controlled laboratory experiment,where the turbulence parameters were reproducible and couldbe kept constant over extended times. These polystyrene particlesare tracked by video techniques. The available database allowsestimates of the equivalents of planktonic contact rates inthe turbulent flow. The results are expressed in terms of averageprey fluxes. Scaling laws for the average contact rates fordifferent turbulence intensities and for varying ranges of interceptionof the predators and also for different forms of the fieldsof view were analyzed, using two models for the orientationwith respect to the flow. Irrespective of orientation and shapeof the volume of interception, the scaling with the turbulenceintensity is weak, while the variations with the range of perceptionare significant. The scaling laws obtained by this procedurehave universal validity, and they are applicable also for conditionsin nature. The sole restriction is that the range of predatorperception is within the universal subrange.     

Effect of Canavanine from Alfalfa Seeds on the Population Biology of Bacillus cereus

Bacillus cereus UW85 suppresses diseases of alfalfa seedlings, although alfalfa seed exudate inhibits the growth of UW85 in culture (J. L. Milner, S. J. Raffel, B. J. Lethbridge, and J. Handelsman, Appl. Microbiol. Biotechnol. 43:685–691, 1995). In this study, we determined the chemical basis for and biological role of the inhibitory activity. All of the alfalfa germ plasm tested included seeds that released inhibitory material. We purified the inhibitory material from one alfalfa cultivar and identified it as canavanine, which was present in the cultivar Iroquois seed exudate at a concentration of 2 mg/g of seeds. Multiple lines of evidence suggested that canavanine activity accounted for all of the inhibitory activity. Both canavanine and seed exudate inhibited the growth of UW85 on minimal medium; growth inhibition by either canavanine or seed exudate was prevented by arginine, histidine, or lysine; and canavanine and crude seed exudate had the same spectrum of activity against B. cereus, Bacillus thuringiensis, and Vibrio cholerae. The B. cereus UW85 populations surrounding canavanine-exuding seeds were up to 100-fold smaller than the populations surrounding non-canavanine-exuding seeds, but canavanine did not affect the growth of UW85 on seed surfaces. The spermosphere populations of canavanine-resistant mutants of UW85 were larger than the spermosphere populations of UW85, but the mutants and UW85 were similar in spermoplane colonization. These results indicate that canavanine exuded from alfalfa seeds affects the population biology of B. cereus.     

Detection of Genetic Interference: Simulation Studies and Mouse Data

Genetic chiasma interference occurs when the occurrence of one crossover (or chiasma) influences the probability of another crossover occurring nearby. We investigated, by simulation studies, the power of three statistical methods to detect interference. Neither the traditional three-locus method nor a multiplicative model approach are very powerful, while a multilocus-feasible map function approach is more powerful, particularly as the number of loci increases. We show that the power to detect interference is quite sensitive to the underlying type of interference. When we tested for interference in two mouse data sets (from chromosomes 1 and 12), we found significant evidence of positive interference.     

Current and future distribution of a parasite with complex life cycle under global change scenarios: Echinococcus multilocularis in Europe

Global change is expected to have complex effects on the distribution and transmission patterns of zoonotic parasites. Modelling habitat suitability for parasites with complex life cycles is essential to further our understanding of how disease systems respond to environmental changes, and to make spatial predictions of their future distributions. However, the limited availability of high quality occurrence data with high spatial resolution often constrains these investigations. Using 449 reliable occurrence records for Echinococcus multilocularis from across Europe published over the last 35 years, we modelled habitat suitability for this parasite, the aetiological agent of alveolar echinococcosis, in order to describe its environmental niche, predict its current and future distribution under three global change scenarios, and quantify the probability of occurrence for each European country. Using a machine learning approach, we developed large-scale (25 × 25 km) species distribution models based on seven sets of predictors, each set representing a distinct biological hypothesis supported by current knowledge of the autecology of the parasite. The best-supported hypothesis included climatic, orographic and land-use/land-cover variables such as the temperature of the coldest quarter, forest cover, urban cover and the precipitation seasonality. Future projections suggested the appearance of highly suitable areas for E. multilocularis towards northern latitudes and in the whole Alpine region under all scenarios, while decreases in habitat suitability were predicted for central Europe. Our spatially explicit predictions of habitat suitability shed light on the complex responses of parasites to ongoing global changes.