Chemotherapy-induced peripheral neuropathy after neoadjuvant or adjuvant treatment of breast cancer: a prospective cohort study

PURPOSE:The purposes of this study were to estimate the incidence of chemotherapy-induced peripheral neuropathy (CIPN) and to identify its main determinants and impact in patient-reported outcomes. METHODS:We performed a prospective cohort study including 296 patients with incident breast cancer submitted to chemotherapy, followed for 1 year. Patients with incident CIPN were reevaluated 6 months after this diagnosis. Relative risks (RR) with 95 % confidence intervals (95 % CI) were computed to quantify the relation between different clinical characteristics and the occurrence of CIPN, using Poisson regression. The variation of patient-reported outcomes between baseline and 1-year follow-up assessments was compared between patients with and without CIPN. RESULTS:The cumulative incidence of CIPN in the first year after diagnosis was 28.7 % (95 % CI 23.8-34.1), and more than 80 % of the patients were still symptomatic after 6 months. Among the latter, there was a significant decrease in the median total neuropathy score, clinical version (7 versus 4) between the two periods. In multivariable analysis, the risk of CIPN was higher for treatment with docetaxel (cumulative doses ≤300 mg/m(2), RR = 6.96, 95 % CI 2.53-19.10; >300 mg/m(2), RR = 13.32; 95 % CI 4.11-43.14). Alcohol consumption and diabetes were not significantly associated with CIPN. There were no significant differences in the variation of patient-reported outcomes between the baseline and 1-year follow-up evaluations. CONCLUSIONS:CIPN was frequent in this contemporary cohort of early-stage breast cancer patients and was strongly associated with docetaxel-based regimens. Symptoms persisted for at least 6 months in most patients, but severity was low and CIPN had no impact on patient-reported outcomes

Retention Time Variability as a Mechanism for Animal Mediated Long-Distance Dispersal

Long-distance dispersal (LDD) events, although rare for most plant species, can strongly influence population and community dynamics. Animals function as a key biotic vector of seeds and thus, a mechanistic and quantitative understanding of how individual animal behaviors scale to dispersal patterns at different spatial scales is a question of critical importance from both basic and applied perspectives. Using a diffusion-theory based analytical approach for a wide range of animal movement and seed transportation patterns, we show that the scale (a measure of local dispersal) of the seed dispersal kernel increases with the organisms' rate of movement and mean seed retention time. We reveal that variations in seed retention time is a key determinant of various measures of LDD such as kurtosis (or shape) of the kernel, thinkness of tails and the absolute number of seeds falling beyond a threshold distance. Using empirical data sets of frugivores, we illustrate the importance of variability in retention times for predicting the key disperser species that influence LDD. Our study makes testable predictions linking animal movement behaviors and gut retention times to dispersal patterns and, more generally, highlights the potential importance of animal behavioral variability for the LDD of seeds

Measuring local depletion of terrestrial game vertebrates by central-place hunters in rural Amazonia

The degree to which terrestrial vertebrate populations are depleted in tropical forests occupied by human communities has been the subject of an intense polarising debate that has important conservation implications. Conservation ecologists and practitioners are divided over the extent to which community-based subsistence offtake is compatible with ecologically functional populations of tropical forest game species. To quantify depletion envelopes of forest vertebrates around human communities, we deployed a total of 383 camera trap stations and 78 quantitative interviews to survey the peri-community areas controlled by 60 semi-subsistence communities over a combined area of over 3.2 million hectares in the Médio Juruá and Uatumã regions of Central-Western Brazilian Amazonia. Our results largely conform with prior evidence that hunting large-bodied vertebrates reduces wildlife populations near settlements, such that they are only found at a distance to settlements where they are hunted less frequently. Camera trap data suggest that a select few harvest-sensitive species, including lowland tapir, are either repelled or depleted by human communities. Nocturnal and cathemeral species were detected relatively more frequently in disturbed areas close to communities, but individual species did not necessarily shift their activity patterns. Group biomass of all species was depressed in the wider neighbourhood of urban areas rather than communities. Interview data suggest that species traits, especially group size and body mass, mediate these relationships. Large-bodied, large-group-living species are detected farther from communities as reported by experienced informants. Long-established communities in our study regions have not “emptied” the surrounding forest. Low human population density and low hunting offtake due to abundant sources of alternative aquatic protein, suggest that these communities represent a best-case scenario for sustainable hunting of wildlife for food, thereby providing a conservative assessment of game depletion. Given this ‘best-case’ camera trap and interview-based evidence for hunting depletion, regions with higher human population densities, external trade in wildlife and limited access to alternative protein will likely exhibit more severe depletion

Marsh macrophyte responses to inundation anticipate impacts of sea-level rise and indicate ongoing drowning of North Carolina marshes

In situ persistence of coastal marsh habitat as sea level rises depends on whether macrophytes induce compensatory accretion of the marsh surface. Experimental planters in two North Carolina marshes served to expose two dominant macrophyte species to six different elevations spanning 0.75 m (inundation durations 0.4–99 %). Spartina alterniflora and Juncus roemerianus exhibited similar responses—with production in planters suggesting initial increases and then demonstrating subsequent steep declines with increasing inundation, conforming to a segment of the ecophysiological parabola. Projecting inundation levels experienced by macrophytes in the planters onto adjacent marsh platforms revealed that neither species occupied elevations associated with increasing production. Declining macrophyte production with rising seas reduces both bioaccumulation of roots below-ground and baffle-induced sedimentation above-ground. By occupying only descending portions of the parabola, macrophytes in central North Carolina marshes are responding to rising water levels by progressive declines in production, ultimately leading to marsh drowning

Mosaic Origins of a Complex Chimeric Mitochondrial Gene in Silene vulgaris

Chimeric genes are significant sources of evolutionary innovation that are normally created when portions of two or more protein coding regions fuse to form a new open reading frame. In plant mitochondria astonishingly high numbers of different novel chimeric genes have been reported, where they are generated through processes of rearrangement and recombination. Nonetheless, because most studies do not find or report nucleotide variation within the same chimeric gene, evolution after the origination of these chimeric genes remains unstudied. Here we identify two alleles of a complex chimera in Silene vulgaris that are divergent in nucleotide sequence, genomic position relative to other mitochondrial genes, and expression patterns. Structural patterns suggest a history partially influenced by gene conversion between the chimeric gene and functional copies of subunit 1 of the mitochondrial ATP synthase gene (atp1). We identified small repeat structures within the chimeras that are likely recombination sites allowing generation of the chimera. These results establish the potential for chimeric gene divergence in different plant mitochondrial lineages within the same species. This result contrasts with the absence of diversity within mitochondrial chimeras found in crop species

Reconstructing the reproductive mode of an Ediacaran macro-organism.

Enigmatic macrofossils of late Ediacaran age (580-541 million years ago) provide the oldest known record of diverse complex organisms on Earth, lying between the microbially dominated ecosystems of the Proterozoic and the Cambrian emergence of the modern biosphere. Among the oldest and most enigmatic of these macrofossils are the Rangeomorpha, a group characterized by modular, self-similar branching and a sessile benthic habit. Localized occurrences of large in situ fossilized rangeomorph populations allow fundamental aspects of their biology to be resolved using spatial point process techniques. Here we use such techniques to identify recurrent clustering patterns in the rangeomorph Fractofusus, revealing a complex life history of multigenerational, stolon-like asexual reproduction, interspersed with dispersal by waterborne propagules. Ecologically, such a habit would have allowed both for the rapid colonization of a localized area and for transport to new, previously uncolonized areas. The capacity of Fractofusus to derive adult morphology by two distinct reproductive modes documents the sophistication of its underlying developmental biology.This work has been supported by the Natural Environment Research Council [grant numbers NE/I005927/1 to C.G.K., NE/J5000045/1 to J.J.M., NE/L011409/1 to A.G.L. and NE/G523539/1 to E.G.M.], and a Henslow Junior Research Fellowship from Cambridge Philosophical Society to A.G.L.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nature1464

Changes in grassland management and linear infrastructures associated to the decline of an endangered bird population

European grassland birds are experiencing major population declines, mainly due to changes in farmland management. We analyzed the role of habitat availability, grazing management and linear infrastructures (roads and power lines) in explaining spatial and temporal variation in the population density of little bustards (Tetrax tetrax) in Portugal, during a decade in which the species population size halved. We used data from 51 areas (totaling ca. 1,50,000 ha) that were sampled in two different periods (2003–2006 and 2016). In 2003–2006, when the species occurred at high densities, habitat availability was the only factor affecting spatial variation in bustard density. In the 2016 survey, variation in density was explained by habitat availability and livestock management, with reduced bird numbers in areas with higher proportions of cattle. Population declines across the study period were steeper in areas that initially held higher densities of bustards and in areas with a higher proportion of cattle in the total stocking rate. Areas with higher densities of power lines also registered greater density declines, probably due to avoidance behavior and to increased mortality. Overall, our results show little bustards are currently lacking high quality grassland habitat, whose persistence depends on extensive grazing regimes and low linear infrastructure densitiesinfo:eu-repo/semantics/publishedVersio

Identification and characterization of Rhipicephalus (Boophilus) microplus candidate protective antigens for the control of cattle tick infestations

The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world. Tick vaccines constitute a cost-effective and environmentally friendly alternative to tick control. The recombinant Rhipicephalus microplus Bm86 antigen has been shown to protect cattle against tick infestations. However, variable efficacy of Bm86-based vaccines against geographic tick strains has encouraged the research for additional tick-protective antigens. Herein, we describe the analysis of R. microplus glutathione-S transferase, ubiquitin (UBQ), selenoprotein W, elongation factor-1 alpha, and subolesin (SUB) complementary DNAs (cDNAs) by RNA interference (RNAi) in R. microplus and Rhipicephalus annulatus. Candidate protective antigens were selected for vaccination experiments based on the effect of gene knockdown on tick mortality, feeding, and fertility. Two cDNA clones encoding for UBQ and SUB were used for cattle vaccination and infestation with R. microplus and R. annulatus. Control groups were immunized with recombinant Bm86 or adjuvant/saline. The highest vaccine efficacy for the control of tick infestations was obtained for Bm86. Although with low immunogenic response, the results with the SUB vaccine encourage further investigations on the use of recombinant subolesin alone or in combination with other antigens for the control of cattle tick infestations. The UBQ peptide showed low immunogenicity, and the results of the vaccination trial were inconclusive to assess the protective efficacy of this antigen. These experiments showed that RNAi could be used for the selection of candidate tick-protective antigens. However, vaccination trials are necessary to evaluate the effect of recombinant antigens in the control of tick infestations, a process that requires efficient recombinant protein production and formulation systems