Breath-by-breath measurement of the volume displaced by diaphragm motion.

To develop an accurate method to measure the volume displaced by diaphragm motion (DeltaVdi) breath by breath, we compared DeltaVdi measured by a previously evaluated biplanar radiographic method (Singh B, Eastwood PR, and Finucane KE. J Appl Physiol 91: 1913-1923, 2001) at several lung volumes during vital capacity inspirations in 10 healthy and nine hyperinflated subjects with 1) DeltaVdi measured from the same chest X-rays by two previously described uniplanar methods (Petroll WM, Knight H, and Rochester DF. J Appl Physiol 69: 2175-2182, 1990; Verschakelen JA, Deschepper K, and Demendts M. J Appl Physiol 72: 1536-1540, 1992) and a proposed method that considered actual cross-sectional shape of the rib cage and spinal volume (DeltaVdi(S)); and 2) DeltaVdi(S) measured by lateral fluoroscopy in the same 10 healthy subjects. Relative to biplanar DeltaVdi, DeltaVdi(S) values from lateral chest X-rays and fluoroscopy were not different, whereas DeltaVdi values of Petroll et al. and Verschakelen et al. were increased by (means +/- SD) 1.98 +/- 1.59 and 1.16 +/- 0.82 liters, respectively (both P < 0.001). During quiet breathing, DeltaVdi(S) by lateral fluoroscopy was 66 +/- 16% of tidal volume and similar to that between functional residual capacity and one-half inspiratory capacity by the biplanar radiographic method. We conclude that accurate breath-by-breath measurements of DeltaVdi can be made by using lateral fluoroscopy.     

Analysis of gene origin in the first adult returns to the Cultus sockeye salmon captive breeding program

Rigorous evaluation of the utility of captive breeding for the restoration of depleted wild salmonid fish populations has not been undertaken. In particular, little is known about the reproductive success of captively-bred individuals that are released back into an extant population and their capacity to assist in long-term population persistence. For the endangered Cultus Lake sockeye salmon population, we examined the potential genetic contribution of the first juvenile fish released from a captive breeding program upon their maturity in the natural Cultus Lake environment. Genetic analysis of 792 Cultus sockeye salmon that were spawned in captivity in 2004 and their adult progeny of 2007 and 2008 revealed a genetic bottleneck originating from 20 wild sockeye salmon hatchery-spawned at Cultus Lake in the previous generation. Pedigree analysis revealed that six of the 20 sockeye salmon spawned in 2001 (grandparents) gave rise to a majority of the hatchery spawners in 2004 (parents) and provided more than 30% of the genes in the progeny that survived to maturity in the wild. Allele frequencies and genetic diversity of the age three progeny that returned to Cultus Lake from their marine migration in 2007 reflected the bottleneck, but its genetic signature was faint among the more genetically diverse age four fish that returned in 2008. Two-generation analysis of gene origin among fish resulting from 2004 hatchery production indicated that they contained the genetic diversity expected from 36 effective ancestors.     

Regulation of mucosal dendritic cell function by receptor activator of NF-kappa B (RANK)/RANK ligand interactions: impact on tolerance induction

The mucosal immune system is uniquely equipped to discriminate between potentially invasive pathogens and innocuous food proteins. While the mechanisms responsible for induction of mucosal immunity vs tolerance are not yet fully delineated, recent studies have highlighted mucosal dendritic cells (DC) as being important in determining the fate of orally administered Ag. To further investigate the DC:T cell signals involved in regulating the homeostatic balance between mucosal immunity and tolerance, we have examined the expression and function of the TNFR family member receptor activator of NF-kappaB (RANK) and its cognate ligand, RANKL, in vitro and in vivo. Our data show that although DC isolated from mucosal lymphoid tissues expressed similar levels of surface RANK compared with DC isolated from peripheral lymphoid tissues, DC from the distinct anatomical sites displayed differential responsiveness to RANK engagement with soluble RANKL. Whereas splenic DC responded to RANKL stimulation with elevated IL-12 p40 mRNA expression, Peyer's patch DC instead preferentially displayed increased IL-10 mRNA expression. Our data also show that the in vivo functional capacity of mucosal DC can be modulated by RANKL. Treatment with RANKL in vivo at the time of oral administration of soluble OVA enhanced the induction of tolerance in two different mouse models. These studies underscore the functional differences between mucosal and peripheral DC and highlight a novel role for RANK/RANKL interactions during the induction of mucosal immune responses.     

Host specificity of adult versus larval cestodes of the elasmobranch tapeworm order Trypanorhyncha

Host specificity between the adult and final larval stages (plerocercus, plerocercoid, or merocercoid) of a diversity of trypanorhynch species was compared using the host specificity index (HS s). Index values were generated for a total of 63 species representing all five trypanorhynch superfamilies and 11 families. Host specificity of both adults and final larvae was found to be widely variable among species, ranging from very high (oioxenous) to very low (euryxenous) for both stages. However, in general, host specificity was highest for the adult stage in the definitive host (mean HS s=3.86) and lowest for the final larval stage in the second intermediate host (mean HS s=6.29). This difference was found to be significant using the Wilcoxon signed-rank test. Limited data available for procercoids in the first intermediate host suggest that this stage exhibits a degree of specificity intermediate between that of the former two stages (mean HS s=4.23). No taxonomic trend was seen. Species with a plerocercoid final larval stage (mean HS s=8.62) were significantly less host-specific than those with plerocerci or merocercoids (mean HS s=5.56). This result may reflect the use of paratenic hosts by species possessing the relatively more resilient plerocercoid as their final larval stage. These results provide an example of how HS s can be used to compare levels of host specificity, in this instance, among stages of polyxenous life cycles. They also emphasise the importance of articulating the life cycle stage under consideration when general statements are made about host specificity.     

Association between the Fatty Liver Index and Risk of Type 2 Diabetes in the EPIC-Potsdam Study

The fatty liver index (FLI) predicts fatty liver by using BMI, waist circumference, γ-glutamyltransferase and triglycerides. We investigated the association between the FLI and the risk of type 2 diabetes and evaluated to what extent single FLI components contribute to the diabetes risk. We analysed a case-cohort study (random sub-cohort: 1922; incident cases: 563) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. The proportion of exposure effect (PEE) explained by single FLI components was evaluated and effect decomposition using inverse probability weighting (IPW) was applied. Women and men with a FLI ≥60 compared to those with a FLI <30 had a multivariable-adjusted Hazard Ratio (HR) of 17.6; 95% confidence interval (CI) 11.1-28.0 and HR: 10.9; 95% CI 6.22-19.2, respectively. Adjustment for BMI or waist circumference attenuated this association in men [PEE_BMI (95% CI) = 53.8% (43.9%-65.8%); PEE_waist (95% CI) = 54.8% (44.2%-68.8%)]. In women, adjustment for waist circumference attenuated the association to a lesser degree than in men [PEE_waist (95% CI) = 31.1%; (21.9%-43.1%)] while BMI had no appreciable effect [PEE_BMI (95% CI) = 11.0% (2.68%-21.0%)]. γ-glutamyltransferase and triglycerides showed only a small attenuation in women [PEE_GGT(95% CI) = 3.11% (-0.72%-4.48%); PEE_TG (95% CI) = 6.36% (3.81%-9.92%)] and in men [PEE_GGT = 0%; PEE_TG (95% CI) = 6.23% (2.03%-11.8%)]. In women, the total effect was decomposed into a direct effect and 4 indirect effects (HR_BMI = 1.10; HR_waist = 1.28; HR_GGT = 0.97 and HR_TG = 1.03). In men, the 4 indirect effects were HR_BMI = 1.25; HR_waist = 1.29; HR_GGT = 0.97 and HR_TG = 0.99. These data suggest that the FLI, as a proxy for fatty liver, is associated with risk of type 2 diabetes. This association is only partly explained by standard estimates of overall and abdominal body fatness, particularly among women.     

Covariate selection strategies for causal inference: Classification and comparison

When causal effects are to be estimated from observational data, we have to adjust for confounding. A central aim of covariate selection for causal inference is therefore to determine a set that is sufficient for confounding adjustment, but other aims such as efficiency or robustness can be important as well. In this paper, we review six general approaches to covariate selection that differ in the targeted type of adjustment set. We discuss and illustrate their advantages and disadvantages using causal diagrams. Moreover, the approaches and different ways of implementing them are compared empirically in an extensive simulation study. We conclude that there are considerable differences between the approaches but none of them is uniformly best, with performance depending on the chosen adjustment method as well as the true confounding structure. Any prior structural knowledge on the causal relations is helpful to choose the most appropriate method.     

Localisation génétique et caractérisation biochimique de mutations affectant le gène de structure de l'hydrolyase altronique chez Escherichia coli K 12

Molecular Genetics and Genomics - Mutants of E. coli specifically deficient for the enzyme altronic hydrolyase have been isolated. These strains are unable to metabolize galacturonate but still...