Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Development of Social Vocalizations in Mice

Adult mice are highly vocal animals, with both males and females vocalizing in same sex and cross sex social encounters. Mouse pups are also highly vocal, producing isolation vocalizations when they are cold or removed from the nest. This study examined patterns in the development of pup isolation vocalizations, and compared these to adult vocalizations. In three litters of CBA/CaJ mice, we recorded isolation vocalizations at ages postnatal day 5 (p5), p7, p9, p11, and p13. Adult vocalizations were obtained in a variety of social situations. Altogether, 28,384 discrete vocal signals were recorded using high-frequency-sensitive equipment and analyzed for syllable type, spectral and temporal features, and the temporal sequencing within bouts. We found that pups produced all but one of the 11 syllable types recorded from adults. The proportions of syllable types changed developmentally, but even the youngest pups produced complex syllables with frequency-time variations. When all syllable types were pooled together for analysis, changes in the peak frequency or the duration of syllables were small, although significant, from p5 through p13. However, individual syllable types showed different, large patterns of change over development, requiring analysis of each syllable type separately. Most adult syllables were substantially lower in frequency and shorter in duration. As pups aged, the complexity of vocal bouts increased, with a greater tendency to switch between syllable types. Vocal bouts from older animals, p13 and adult, had significantly more sequential structure than those from younger mice. Overall, these results demonstrate substantial changes in social vocalizations with age. Future studies are required to identify whether these changes result from developmental processes affecting the vocal tract or control of vocalization, or from vocal learning. To provide a tool for further research, we developed a MATLAB program that generates bouts of vocalizations that correspond to mice of different ages

Comparison of the protein-coding genomes of three deep-sea, sulfur-oxidising bacteria: “Candidatus Ruthia magnifica”, “Candidatus Vesicomyosocius okutanii” and Thiomicrospira crunogena

Abstract Objective “ Candidatus Ruthia magnifica”, “Candidatus Vesicomyosocius okutanii” and Thiomicrospira crunogena are all sulfur-oxidising bacteria found in deep-sea vent environments. Recent research suggests that the two symbiotic organisms, “Candidatus R. magnifica” and “Candidatus V. okutanii”, may share common ancestry with the autonomously living species T. crunogena. We used comparative genomics to examine the genome-wide protein-coding content of all three species to explore their similarities. In particular, we used the OrthoMCL algorithm to sort proteins into groups of putative orthologs on the basis of sequence similarity. Results The OrthoMCL inflation parameter was tuned using biological criteria. Using the tuned value, OrthoMCL delimited 1070 protein groups. 63.5% of these groups contained one protein from each species. Two groups contained duplicate protein copies from all three species. 123 groups were unique to T. crunogena and ten groups included multiple copies of T. crunogena proteins but only single copies from the other species. “Candidatus R. magnifica” had one unique group, and had multiple copies in one group where the other species had a single copy. There were no groups unique to “Candidatus V. okutanii”, and no groups in which there were multiple “Candidatus V. okutanii” proteins but only single proteins from the other species. Results align with previous suggestions that all three species share a common ancestor. However this is not definitive evidence to make taxonomic conclusions and the possibility of horizontal gene transfer was not investigated. Methodologically, the tuning of the OrthoMCL inflation parameter using biological criteria provides further methods to refine the OrthoMCL procedure

Atypical birdsong and artificial languages provide insights into how communication systems are shaped by learning, use and transmission

In this article, I argue that a comparative approach focusing on the cognitive capacities and behavioral mechanisms that underlie vocal learning in songbirds and humans can provide valuable insights into the evolutionary origins of language. The experimental approaches I discuss use abnormal song and atypical linguistic input to study the processes of individual learning, social interaction, and cultural transmission. Atypical input places increased learning and communicative pressure on learners, so exploring how they respond to this type of input provides a particularly clear picture of the biases and constraints at work during learning and use. Furthermore, simulating the cultural transmission of these unnatural communication systems in the laboratory informs us about how learning and social biases influence the structure of communication systems in the long run. Findings based on these methods suggest fundamental similarities in the basic social–cognitive mechanisms underlying vocal learning in birds and humans, and continuing research promises insights into the uniquely human mechanisms and into how human cognition and social behavior interact, and ultimately impact on the evolution of language

Research in progress: report on the ICAIL 2017 doctoral consortium

This paper arose out of the 2017 international conference on AI and law doctoral consortium. There were five students who presented their Ph.D. work, and each of them has contributed a section to this paper. The paper offers a view of what topics are currently engaging students, and shows the diversity of their interests and influences

A single evolutionary innovation drives the deep evolution of symbiotic N₂-fixation in angiosperms

Symbiotic associations occur in every habitat on earth, but we know very little about their evolutionary histories. Current models of trait evolution cannot adequately reconstruct the deep history of symbiotic innovation, because they assume homogenous evolutionary processes across millions of years. Here we use a recently developed, heterogeneous and quantitative phylogenetic framework to study the origin of the symbiosis between angiosperms and nitrogen-fixing (N2) bacterial symbionts housed in nodules. We compile the largest database of global nodulating plant species and reconstruct the symbiosis’ evolution. We identify a single, cryptic evolutionary innovation driving symbiotic N2-fixation evolution, followed by multiple gains and losses of the symbiosis, and the subsequent emergence of ‘stable fixers’ (clades extremely unlikely to lose the symbiosis). Originating over 100 MYA, this innovation suggests deep homology in symbiotic N2-fixation. Identifying cryptic innovations on the tree of life is key to understanding the evolution of complex traits, including symbiotic partnerships

Characterizing Ligand-Gated Ion Channel Receptors with Genetically Encoded Ca++ Sensors

We present a cell based system and experimental approach to characterize agonist and antagonist selectivity for ligand-gated ion channels (LGIC) by developing sensor cells stably expressing a Ca2+ permeable LGIC and a genetically encoded Förster (or fluorescence) resonance energy transfer (FRET)-based calcium sensor. In particular, we describe separate lines with human α7 and human α4β2 nicotinic acetylcholine receptors, mouse 5-HT3A serotonin receptors and a chimera of human α7/mouse 5-HT3A receptors. Complete concentration-response curves for agonists and Schild plots of antagonists were generated from these sensors and the results validate known pharmacology of the receptors tested. Concentration-response relations can be generated from either the initial rate or maximal amplitudes of FRET-signal. Although assaying at a medium throughput level, this pharmacological fluorescence detection technique employs a clonal line for stability and has versatility for screening laboratory generated congeners as agonists or antagonists on multiple subtypes of ligand-gated ion channels. The clonal sensor lines are also compatible with in vivo usage to measure indirectly receptor activation by endogenous neurotransmitters

Green Sturgeon Physical Habitat Use in the Coastal Pacific Ocean

The green sturgeon (Acipenser medirostris) is a highly migratory, oceanic, anadromous species with a complex life history that makes it vulnerable to species-wide threats in both freshwater and at sea. Green sturgeon population declines have preceded legal protection and curtailment of activities in marine environments deemed to increase its extinction risk. Yet, its marine habitat is poorly understood. We built a statistical model to characterize green sturgeon marine habitat using data from a coastal tracking array located along the Siletz Reef near Newport, Oregon, USA that recorded the passage of 37 acoustically tagged green sturgeon. We classified seafloor physical habitat features with high-resolution bathymetric and backscatter data. We then described the distribution of habitat components and their relationship to green sturgeon presence using ordination and subsequently used generalized linear model selection to identify important habitat components. Finally, we summarized depth and temperature recordings from seven green sturgeon present off the Oregon coast that were fitted with pop-off archival geolocation tags. Our analyses indicated that green sturgeon, on average, spent a longer duration in areas with high seafloor complexity, especially where a greater proportion of the substrate consists of boulders. Green sturgeon in marine habitats are primarily found at depths of 20–60 meters and from 9.5–16.0°C. Many sturgeon in this study were likely migrating in a northward direction, moving deeper, and may have been using complex seafloor habitat because it coincides with the distribution of benthic prey taxa or provides refuge from predators. Identifying important green sturgeon marine habitat is an essential step towards accurately defining the conditions that are necessary for its survival and will eventually yield range-wide, spatially explicit predictions of green sturgeon distribution

Solution Structure and Phylogenetics of Prod1, a Member of the Three-Finger Protein Superfamily Implicated in Salamander Limb Regeneration

Prod1 is a cell-surface molecule of the three-finger protein (TFP) superfamily involved in the specification of newt limb PD identity. The TFP superfamily is a highly diverse group of metazoan proteins that includes snake venom toxins, mammalian transmembrane receptors and miscellaneous signaling molecules..The available data suggest that Prod1, and thereby its role in encoding PD identity, is restricted to salamanders. The lack of comparable limb-regenerative capability in other adult vertebrates could be correlated with the absence of the Prod1 gene