Design of the Endobronchial Valve for Emphysema Palliation Trial (VENT): a non-surgical method of lung volume reduction

Background

Lung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr^® endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema.

Methods

The trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV₁) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV₁ and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. George's Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV₁ and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined.

Conclusion

If endobronchial valves improve FEV₁ and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease.

Trial Registration

ClinicalTrials.gov: NCT00129584     

Phylogeographic and demographic effects of Pleistocene climatic fluctuations in a montane salamander, Plethodon fourchensis

Climatic changes associated with Pleistocene glacial cycles profoundly affected species distributions, patterns of interpopulation gene flow, and demography. In species restricted to montane habitats, ranges may expand and contract along an elevational gradients in response to environmental fluctuations and create high levels of genetic variation among populations on different mountains. The salamander Plethodon fourchensis is restricted to high-elevation, mesic forest on five montane isolates in the Ouachita Mountains. We used DNA sequence data along with ecological niche modelling and coalescent simulations to test several hypotheses related to the effects of Pleistocene climatic fluctuations on species in montane habitats. Our results revealed that P. fourchensis is composed of four well-supported, geographically structured lineages. Geographic breaks between lineages occurred in the vicinity of major valleys and a narrow high-elevation pass. Ecological niche modelling predicted that environmental conditions in valleys separating most mountains are suitable; however, interglacial periods like the present are predicted to be times of range expansion in P. fourchensis . Divergence dating and coalescent simulations indicated that lineage diversification occurred during the Middle Pleistocene via the fragmentation of a wide-ranging ancestor. Bayesian skyline plots showed gradual decreases in population size in three of four lineages over the most recent glacial period and a slight to moderate amount of population growth during the Holocene. Our results not only demonstrate that climatic changes during the Pleistocene had profound effects on species restricted to montane habitats, but comparison of our results for P. fourchensis with its parapatric, sister taxon, P. ouachitae , also emphasizes how responses can vary substantially even among closely related, similarly distributed taxa.     

Portable light transmission measuring system for preserved corneas

Background  

The authors have developed a small portable device for the objective measurement of the transparency of corneas stored in preservative medium, for use by eye banks in evaluation prior to transplantation.     

Microsatellite markers for the palaeotropic pioneer tree genus Macaranga (Euphorbiaceae) and their cross‐species transferability

We developed primer sequences for five polymorphic microsatellite loci in the tropical ant‐plant genus Macaranga (Euphorbiaceae). Population genetic parameters were determined on the basis of 30 individuals from each of two Macaranga species in Borneo. Allele numbers per locus ranged from three to 13. Expected and observed heterozygosities ranged from 0.160 to 0.850 and from 0.130 to 0.700, respectively. Four of the five primer pairs cross‐amplify polymorphic PCR products in a wide range of Macaranga species.     

Population demography influences climatic niche evolution: evidence from diploid American Hordeum species (Poaceae)

In this study, we explore the interplay of population demography with the evolution of ecological niches during or after speciation in Hordeum. While large populations maintain a high level of standing genetic diversity, gene flow and recombination buffers against fast alterations in ecological adaptation. Small populations harbour lower allele diversity but can more easily shift to new niches if they initially survive under changed conditions. Thus, large populations should be more conservative regarding niche changes in comparison to small populations. We used environmental niche modelling together with phylogenetic, phylogeographic and population genetic analyses to infer the correlation of population demography with changes in ecological niche dimensions in 12 diploid Hordeum species from the New World, forming four monophyletic groups. Our analyses found both shifts and conservatism in distinct niche dimensions within and among clades. Speciation due to vicariance resulted in three species with no pronounced climate niche differences, while species originating due to long‐distance dispersals or otherwise encountering genetic bottlenecks mostly revealed climate niche shifts. Niche convergence among clades indicates a niche‐filling pattern during the last 2 million years in South American Hordeum. We provide evidence that species, which did not encounter population reductions mainly showed ecoclimatic niche conservatism, while major niche shifts occurred in species which have undergone population bottlenecks. Our data allow the conclusion that population demography influences adaptation and niche shifts or conservatism in South American Hordeum species.