609 research outputs found

    Phylogenetic analysis of human Chlamydia pneumoniae strains reveals a distinct Australian indigenous clade that predates European exploration of the continent

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    Š 2015 Roulis et al. Background: The obligate intracellular bacterium Chlamydia pneumoniae is a common respiratory pathogen, which has been found in a range of hosts including humans, marsupials and amphibians. Whole genome comparisons of human C. pneumoniae have previously highlighted a highly conserved nucleotide sequence, with minor but key polymorphisms and additional coding capacity when human and animal strains are compared. Results: In this study, we sequenced three Australian human C. pneumoniae strains, two of which were isolated from patients in remote indigenous communities, and compared them to all available C. pneumoniae genomes. Our study demonstrated a phylogenetically distinct human C. pneumoniae clade containing the two indigenous Australian strains, with estimates that the most recent common ancestor of these strains predates the arrival of European settlers to Australia. We describe several polymorphisms characteristic to these strains, some of which are similar in sequence to animal C. pneumoniae strains, as well as evidence to suggest that several recombination events have shaped these distinct strains. Conclusions: Our study reveals a greater sequence diversity amongst both human and animal C. pneumoniae strains, and suggests that a wider range of strains may be circulating in the human population than current sampling indicates

    Dynamic Bayesian belief network to model the development of walking and cycling schemes

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    This paper aims to describe a model which represents the formulation of decision-making processes (over a number of years) affecting the step-changes of walking and cycling (WaC) schemes. These processes can be seen as being driven by a number of causal factors, many of which are associated with the attitudes of a variety of factors, in terms of both determining whether any scheme will be implemented and, if it is implemented, the extent to which it is used. The outputs of the model are pathways as to how the future might unfold (in terms of a number of future time steps) with respect to specific pedestrian and cyclist schemes. The transitions of the decision making processes are formulated using a qualitative simulation method, which describes the step-changes of the WaC scheme development. In this article a Bayesian belief network (BBN) theory is extended to model the influence between and within factors in the dynamic decision making process

    Application of the pore water stable isotope method and hydrogeological approaches to characterise a wetland system

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    Three naturally intact wetland systems (swamps) were characterised based on sediment cores, analysis of surface water, swamp groundwater, regional groundwater and pore water stable isotopes. These swamps are classified as temperate highland peat swamps on sandstone (THPSS) and in Australia they are listed as threatened endangered ecological communities under state and federal legislation. This study applies the stable isotope direct vapour equilibration method in a wetland, aiming at quantification of the contributions of evaporation, rainfall and groundwater to swamp water balance. This technique potentially enables understanding of the depth of evaporative losses and the relative importance of groundwater flow within the swamp environment without the need for intrusive piezometer installation at multiple locations and depths. Additional advantages of the stable isotope direct vapour equilibration technique include detailed spatial and vertical depth profiles of δ18O and δ2H, with good accuracy comparable to other physical and chemical extraction methods. Depletion of δ18O and δ2H in pore water with increasing depth (to around 40–60&thinsp;cm depth) was observed in two swamps but remained uniform with depth in the third swamp. Within the upper surficial zone, the measurements respond to seasonal trends and are subject to evaporation in the capillary zone. Below this depth the pore water δ18O and δ2H signature approaches that of regional groundwater, indicating lateral groundwater contribution. Significant differences were found in stable pore water isotope samples collected after the dry weather period compared to wet periods where recharge of depleted rainfall (with low δ18O and δ2H values) was apparent. The organic-rich soil in the upper 40 to 60&thinsp;cm retains significant saturation following precipitation events and maintains moisture necessary for ecosystem functioning. An important finding for wetland and ecosystem response to changing swamp groundwater conditions (and potential ground movement) is that basal sands are observed to underlay these swamps, allowing relatively rapid drainage at the base of the swamp and lateral groundwater contribution. Based on the novel stable isotope direct vapour equilibration analysis of swamp sediment, our study identified the following important processes: rapid infiltration of rainfall to the water table with longer retention of moisture in the upper 40–60&thinsp;cm and lateral groundwater flow contribution at the base. This study also found that evaporation estimated using the stable isotope direct vapour equilibration method is more realistic compared to reference evapotranspiration (ET). Importantly, if swamp discharge data were available in combination with pore water isotope profiles, an appropriate transpiration rate could be determined for these swamps. Based on the results, the groundwater contribution to the swamp is a significant and perhaps dominant component of the water balance. Our methods could complement other monitoring studies and numerical water balance models to improve prediction of the hydrological response of the swamp to changes in water conditions due to natural or anthropogenic influences.</p

    Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes

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    BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK

    A Cognitive Model of an Epistemic Community: Mapping the Dynamics of Shallow Lake Ecosystems

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    We used fuzzy cognitive mapping (FCM) to develop a generic shallow lake ecosystem model by augmenting the individual cognitive maps drawn by 8 scientists working in the area of shallow lake ecology. We calculated graph theoretical indices of the individual cognitive maps and the collective cognitive map produced by augmentation. The graph theoretical indices revealed internal cycles showing non-linear dynamics in the shallow lake ecosystem. The ecological processes were organized democratically without a top-down hierarchical structure. The steady state condition of the generic model was a characteristic turbid shallow lake ecosystem since there were no dynamic environmental changes that could cause shifts between a turbid and a clearwater state, and the generic model indicated that only a dynamic disturbance regime could maintain the clearwater state. The model developed herein captured the empirical behavior of shallow lakes, and contained the basic model of the Alternative Stable States Theory. In addition, our model expanded the basic model by quantifying the relative effects of connections and by extending it. In our expanded model we ran 4 simulations: harvesting submerged plants, nutrient reduction, fish removal without nutrient reduction, and biomanipulation. Only biomanipulation, which included fish removal and nutrient reduction, had the potential to shift the turbid state into clearwater state. The structure and relationships in the generic model as well as the outcomes of the management simulations were supported by actual field studies in shallow lake ecosystems. Thus, fuzzy cognitive mapping methodology enabled us to understand the complex structure of shallow lake ecosystems as a whole and obtain a valid generic model based on tacit knowledge of experts in the field.Comment: 24 pages, 5 Figure

    Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

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    A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways

    Colorectal cancer ascertainment through cancer registries, hospital episode statistics, and self-reporting compared to confirmation by clinician: A cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

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    BACKGROUND: Electronic health records are frequently used for cancer epidemiology. We report on their quality for ascertaining colorectal cancer (CRC) in UK women. METHODS: Population-based, retrospective cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Postmenopausal women aged 50-74 who were diagnosed with CRC during 2001-11 following randomisation to the UKCTOCS were identified and their diagnosis confirmed with their treating clinician. The sensitivity and positive predictive value (PPV) of cancer and death registries, hospital episode statistics, and self-reporting were calculated by pairwise comparisons to the treating clinician's confirmation, while specificity and negative predictive value were estimated relative to expected cases. RESULTS: Notification of CRC events were received for 1,085 women as of 24 May 2011. Responses were received from 61% (660/1,085) of clinicians contacted. Nineteen women were excluded (18 no diagnosis date, one diagnosed after cut-off). Of the 641 eligible, 514 had CRC, 24 had a benign polyp, and 103 had neither diagnosis. The sensitivity of cancer registrations at one- and six-years post-diagnosis was 92 (95% CI 90-94) and 99% (97-100), respectively, with a PPV of 95% (95% CI 92/93-97). The sensitivity & PPV of cancer registrations (at one-year post-diagnosis) & hospital episode statistics combined were 98 (96-99) and 92% (89-94), respectively. CONCLUSIONS: Cancer and death registrations in the UK are a reliable resource for CRC ascertainment in women. Hospital episode statistics can supplement delays in cancer registration. Self-reporting seems less reliable
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