Markov model and markers of small cell lung cancer: assessing the influence of reversible serum NSE, CYFRA 21-1 and TPS levels on prognosis

High serum NSE and advanced tumour stage are well-known negative prognostic determinants of small cell lung cancer (SCLC) when observed at presentation. However, such variables are reversible disease indicators as they can change during the course of therapy. The relationship between risk of death and marker level and disease state during treatment of SCLC chemotherapy is not known. A total of 52 patients with SCLC were followed during cisplatin-based chemotherapy (the median number of tumour status and marker level assessments was 4). The time-homogeneous Markov model was used in order to analyse separately the prognostic significance of change in the state of the serum marker level (NSE, CYFRA 21-1, TPS) or the change in tumour status. In this model, transition rate intensities were analysed according to three different states: alive with low marker level (state 0), alive with high marker level (state 1) and dead (absorbing state). The model analysing NSE levels showed that the mean time to move out of state ‘high marker level’ was short (123 days). There was a 44% probability of the opposite reversible state ‘low marker level’ being reached, which demonstrated the reversible property of the state ‘high marker level’. The relative risk of death from this state ‘high marker level’ was about 2.24 times greater in comparison with that of state 0 ‘low marker level’ (Wald's test; P < 0.01). For patients in state ‘high marker level’ at time of sampling, the probability of death increased dramatically, a transition explaining the rapid decrease in the probability of remaining stationary at this state. However, a non-nil probability to change from state 1 ‘high marker level’ to the opposite transient level, state 0 ‘low marker level’, was observed suggesting that, however infrequently, patients in state 1 ‘high marker level’ might still return to state 0 ‘low marker level’. Almost similar conclusions can be drawn regarding the three-state model constructed using the tumour response status. For the two cytokeratin markers, the Markov model suggests the lack of a true reversible property of these variables as there was only a very weak probability of a patient returning to state ‘low marker level’ once having entered state ‘high marker level’. In conclusion, The Markov model suggests that the observation of an increase in serum NSE level or a lack of response of the disease at any time during follow-up (according to the homogeneous assumption) was strongly associated with a worse prognosis but that the reversion to a low mortality risk state remains possible. © 1999 Cancer Research Campaig

Bacterial diversity and community composition from seasurface to subseafloor

© The International Society for Microbial Ecology, 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 10 (2016): 979–989, doi:10.1038/ismej.2015.175.We investigated compositional relationships between bacterial communities in the water column and those in deep-sea sediment at three environmentally distinct Pacific sites (two in the Equatorial Pacific and one in the North Pacific Gyre). Through pyrosequencing of the v4–v6 hypervariable regions of the 16S ribosomal RNA gene, we characterized 450 104 pyrotags representing 29 814 operational taxonomic units (OTUs, 97% similarity). Hierarchical clustering and non-metric multidimensional scaling partition the samples into four broad groups, regardless of geographic location: a photic-zone community, a subphotic community, a shallow sedimentary community and a subseafloor sedimentary community (greater than or equal to1.5 meters below seafloor). Abundance-weighted community compositions of water-column samples exhibit a similar trend with depth at all sites, with successive epipelagic, mesopelagic, bathypelagic and abyssopelagic communities. Taxonomic richness is generally highest in the water-column O2 minimum zone and lowest in the subseafloor sediment. OTUs represented by abundant tags in the subseafloor sediment are often present but represented by few tags in the water column, and represented by moderately abundant tags in the shallow sediment. In contrast, OTUs represented by abundant tags in the water are generally absent from the subseafloor sediment. These results are consistent with (i) dispersal of marine sedimentary bacteria via the ocean, and (ii) selection of the subseafloor sedimentary community from within the community present in shallow sediment.This study was funded by the Biological Oceanography Program of the US National Science Foundation (grant OCE-0752336) and by the NSF-funded Center for Dark Energy Biosphere Investigations (grant NSF-OCE-0939564)

Salt marsh sediment diversity : a test of the variability of the rare biosphere among environmental replicates

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 6 (2012): 2014–2023, doi:10.1038/ismej.2012.47.Much of the phylogenetic diversity in microbial systems arises from rare taxa that comprise the long tail of taxon rank distribution curves. This vast diversity presents a challenge to testing hypotheses about the effects of perturbations on microbial community composition because within site variability of the rare taxa may be sufficiently large that it would require a prohibitive degree of sequencing to discern differences among samples. In this study we used pyrosequencing of 16S rRNA tags to examine the diversity and local scale variability of salt marsh sediment bacteria. Our goal was to determine whether pyrosequencing could produce similar patterns in community composition among replicate environmental samples from the same location. We hypothesized that repeated sampling from the same location would produce different snapshots of the rare community due to incomplete sequencing of the taxonomically rich rare biosphere. The concern was that variation resulting from incomplete sequencing could mask subtle community shifts caused by environmental perturbations. Our data indicate that salt marsh sediments contain a remarkably diverse array of bacterial taxa and, in contrast to our hypothesis, repeated sampling from within the same site produces reliably similar patterns in bacterial community composition, even among rare organisms. These results demonstrate that deep sequencing of 16s tags is well suited to distinguish site-specific similarities and differences among rare taxa and is a valuable tool for hypothesis testing in microbial ecology.Funding for this research came from the National Science Foundation (DEB- 0717155 to JEH and HGM, and award DBI-0400819 to JLB).2012-12-2

Endospores of thermophilic bacteria as tracers of microbial dispersal by ocean currents

Microbial biogeography is influenced by the combined effects of passive dispersal and environmental selection, but the contribution of either factor can be difficult to discern. As thermophilic bacteria cannot grow in the cold seabed, their inactive spores are not subject to environmental selection. We therefore conducted a global experimental survey using thermophilic endospores that are passively deposited by sedimentation to the cold seafloor as tracers to study the effect of dispersal by ocean currents on the biogeography of marine microorganisms. Our analysis of 81 different marine sediments from around the world identified 146 species-level 16S rRNA phylotypes of endospore-forming, thermophilic Firmicutes. Phylotypes showed various patterns of spatial distribution in the world oceans and were dispersal-limited to different degrees. Co-occurrence of several phylotypes in locations separated by great distances (west of Svalbard, the Baltic Sea and the Gulf of California) demonstrated a widespread but not ubiquitous distribution. In contrast, Arctic regions with water masses that are relatively isolated from global ocean circulation (Baffin Bay and east of Svalbard) were characterized by low phylotype richness and different compositions of phylotypes. The observed distribution pattern of thermophilic endospores in marine sediments suggests that the impact of passive dispersal on marine microbial biogeography is controlled by the connectivity of local water masses to ocean circulation