Efficacy and cost-effectiveness of a community-based smoke-free-home intervention with or without indoor-air-quality feedback in Bangladesh (MCLASS II): a three-arm, cluster-randomised, controlled trial

Background Exposure to second-hand smoke from tobacco is a major contributor to global morbidity and mortality. We aimed to evaluate the efficacy and cost-effectiveness of a community-based smoke-free-home intervention, with or without indoor-air-quality feedback, in reducing second-hand-smoke exposure in homes in Bangladesh. Methods We did a three-arm, cluster-randomised, controlled trial in Dhaka, Bangladesh, and randomly assigned (1:1:1) mosques and consenting households from their congregations to a smoke-free-home intervention plus indoor-air-quality feedback, smoke-free-home intervention only, or usual services. Households were eligible if they had at least one resident attending one of the participating mosques, at least one adult resident (age 18 years or older) who smoked cigarettes or other forms of smoked tobacco (eg, bidi, waterpipe) regularly (on at least 25 days per month), and at least one non-smoking resident of any age. The smoke-free-home intervention consisted of weekly health messages delivered within an Islamic discourse by religious leaders at mosques over 12 weeks. Indoor-air-quality feedback comprised providing households with feedback on their indoor air quality measured over 24 h. Households in the usual services group received no intervention. Masking of participants and mosque leaders was not possible. The primary outcome was the 24-h mean household airborne fine particulate matter (<2·5 microns in diameter [PM2·5]) concentration (a marker of second-hand smoke) at 12 months after randomisation. Cost-effectiveness was estimated using incremental cost-effectiveness ratios (ICERs). This trial is registered with ISRCTN, 49975452. Findings Between April 11 and Aug 2, 2018, we enrolled 1801 households from 45 mosques. 640 households (35·5%) were assigned to the smoke-free-home intervention plus indoor-air-quality feedback group, 560 (31·1%) to the smoke-free-home intervention only group, and 601 (33·4%) to the usual services group. At 12 months, the adjusted mean difference in household mean 24-h PM2·5 concentration was −1·0 μg/m3 (95% CI −12·8 to 10·9, p=0·88) for the smoke-free-home intervention plus indoor-air-quality feedback group versus the usual services group, 5·0 μg/m3 (–7·9 to 18·0, p=0·45) for the smoke-free-home intervention only group versus the usual services group, and −6·0 μg/m3 (–18·3 to 6·3, p=0·34) for the smoke-free-home intervention plus indoor-air-quality feedback group versus the smoke-free-home intervention only group. The ICER for the smoke-free-home intervention plus indoor-air-quality feedback versus usual services was US$653 per quality-adjusted life-year (QALY) gained, which was more than the upper limit of the Bangladesh willingness-to-pay threshold of$427 per QALY. Interpretation The smoke-free-home intervention, with or without indoor-air-quality feedback, was neither effective nor cost-effective in reducing household second-hand-smoke exposure compared with usual services. These interventions are therefore not recommended for Bangladesh

The role of historical and contemporary processes on phylogeographic structure and genetic diversity in the Northern Cardinal, Cardinalis cardinalis

Background Earth history events such as climate change are believed to have played a major role in shaping patterns of genetic structure and diversity in species. However, there is a lag between the time of historical events and the collection of present-day samples that are used to infer contemporary population structure. During this lag phase contemporary processes such as dispersal or non-random mating can erase or reinforce population differences generated by historical events. In this study we evaluate the role of both historical and contemporary processes on the phylogeography of a widespread North American songbird, the Northern Cardinal, Cardinalis cardinalis. Results Phylogenetic analysis revealed deep mtDNA structure with six lineages across the species\u27 range. Ecological niche models supported the same geographic breaks revealed by the mtDNA. A paleoecological niche model for the Last Glacial Maximum indicated that cardinals underwent a dramatic range reduction in eastern North America, whereas their ranges were more stable in México. In eastern North America cardinals expanded out of glacial refugia, but we found no signature of decreased genetic diversity in areas colonized after the Last Glacial Maximum. Present-day demographic data suggested that population growth across the expansion cline is positively correlated with latitude. We propose that there was no loss of genetic diversity in areas colonized after the Last Glacial Maximum because recent high-levels of gene flow across the region have homogenized genetic diversity in eastern North America. Conclusion We show that both deep historical events as well as demographic processes that occurred following these events are critical in shaping genetic pattern and diversity in C. cardinalis. The general implication of our results is that patterns of genetic diversity are best understood when information on species history, ecology, and demography are considered simultaneously

The role of historical and contemporary processes on phylogeographic structure and genetic diversity in the Northern Cardinal, Cardinalis cardinalis

<p>Abstract</p> <p>Background</p> <p>Earth history events such as climate change are believed to have played a major role in shaping patterns of genetic structure and diversity in species. However, there is a lag between the time of historical events and the collection of present-day samples that are used to infer contemporary population structure. During this lag phase contemporary processes such as dispersal or non-random mating can erase or reinforce population differences generated by historical events. In this study we evaluate the role of both historical and contemporary processes on the phylogeography of a widespread North American songbird, the Northern Cardinal, <it>Cardinalis cardinalis</it>.</p> <p>Results</p> <p>Phylogenetic analysis revealed deep mtDNA structure with six lineages across the species' range. Ecological niche models supported the same geographic breaks revealed by the mtDNA. A paleoecological niche model for the Last Glacial Maximum indicated that cardinals underwent a dramatic range reduction in eastern North America, whereas their ranges were more stable in México. In eastern North America cardinals expanded out of glacial refugia, but we found no signature of decreased genetic diversity in areas colonized after the Last Glacial Maximum. Present-day demographic data suggested that population growth across the expansion cline is positively correlated with latitude. We propose that there was no loss of genetic diversity in areas colonized after the Last Glacial Maximum because recent high-levels of gene flow across the region have homogenized genetic diversity in eastern North America.</p> <p>Conclusion</p> <p>We show that both deep historical events as well as demographic processes that occurred following these events are critical in shaping genetic pattern and diversity in <it>C. cardinalis</it>. The general implication of our results is that patterns of genetic diversity are best understood when information on species history, ecology, and demography are considered simultaneously.</p

Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns

Derivation of Xeno-Free and GMP-Grade Human Embryonic Stem Cells – Platforms for Future Clinical Applications

Clinically compliant human embryonic stem cells (hESCs) should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP)-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs

Genetic differentiation and admixture between sibling allopolyploids in the Dactylorhiza majalis complex

Allopolyploidization often happens recurrently, but the evolutionary significance of its iterative nature is not yet fully understood. Of particular interest are the gene flow dynamics and the mechanisms that allow young sibling polyploids to remain distinct while sharing the same ploidy, heritage and overlapping distribution areas. By using eight highly variable nuclear microsatellites, newly reported here, we investigate the patterns of divergence and gene flow between 386 polyploid and 42 diploid individuals, representing the sibling allopolyploids Dactylorhiza majalis s.s. and D. traunsteineri s.l. and their parents at localities across Europe. We make use in our inference of the distinct distribution ranges of the polyploids, including areas in which they are sympatric (that is, the Alps) or allopatric (for example, Pyrenees with D. majalis only and Britain with D. traunsteineri only). Our results show a phylogeographic signal, but no clear genetic differentiation between the allopolyploids, despite the visible phenotypic divergence between them. The results indicate that gene flow between sibling Dactylorhiza allopolyploids is frequent in sympatry, with potential implications for the genetic patterns across their entire distribution range. Limited interploidal introgression is also evidenced, in particular between D. incarnata and D. traunsteineri. Altogether the allopolyploid genomes appear to be porous for introgression from related diploids and polyploids. We conclude that the observed phenotypic divergence between D. majalis and D. traunsteineri is maintained by strong divergent selection on specific genomic areas with strong penetrance, but which are short enough to remain undetected by genotyping dispersed neutral markers.UE FWF; P22260UE: Y66

From Late Miocene to Holocene: Processes of Differentiation within the Telestes Genus (Actinopterygii: Cyprinidae)

Investigating processes and timing of differentiation of organisms is critical in the understanding of the evolutionary mechanisms involved in microevolution, speciation, and macroevolution that generated the extant biodiversity. From this perspective, the Telestes genus is of special interest: the Telestes species have a wide distribution range across Europe (from the Danubian district to Mediterranean districts) and have not been prone to translocation. Molecular data (mtDNA: 1,232 bp including the entire Cyt b gene; nuclear genome: 11 microsatellites) were gathered from 34 populations of the Telestes genus, almost encompassing the entire geographic range. Using several phylogenetic and molecular dating methods interpreted in conjunction with paleoclimatic and geomorphologic evidence, we investigated the processes and timing of differentiation of the Telestes lineages. The observed genetic structure and diversity were largely congruent between mtDNA and microsatellites. The Messinian Salinity Crisis (Late Miocene) seems to have played a major role in the speciation processes of the genus. Focusing on T. souffia, a species occurring in the Danube and Rhone drainages, we were able to point out several specific events from the Pleistocene to the Holocene that have likely driven the differentiation and the historical demography of this taxon. This study provides support for an evolutionary history of dispersal and vicariance with unprecedented resolution for any freshwater fish in this region

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration

Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD