189 research outputs found

    The uncertainties associated with sediment fingerprinting suspended and recently deposited fluvial sediment in the Nene river basin

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    The use of tracers within a sediment fingerprinting framework has become a commonly used technique for investigating the sources of fine sediment. However, uncertainties associated with tracer behaviour have been cited as major potential limitations to sediment fingerprinting methodologies. This paper aims to determine the differences between fingerprinting results derived using different groups of tracer properties and to determine the role of organic matter content, particle size, and within-source variability in tracer concentrations on the observed differences. A mean difference of 24.1% between the predicted contributions of sediment originating from channel banks was found when using different tracer groups. Mean differences between tracer group predictions were lower, at between 8% and 11%, when fingerprinting contributions from urban street dusts. Organic matter content and / or particle size showed little indication that they caused differences between tracer group predictions. The within-source variability in tracer concentrations and small contrasts between the tracer concentrations of different source groups were identified as probable causes of inherent uncertainty in the fingerprinting predictions. We determined that the ratio of the percentage difference between median tracer concentrations in the source groups and the average within-source tracer concentration coefficient of variation could indicate the likely uncertainty in model predictions prior to tracer use

    Supplementation of porcin in vitro maturation medium with FGF2, LIF, and IGF1 enhances cytoplasmic maturation in prepubertal gilts oocytes and improves embryo quality

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    In porcine production (IVP) systems, the use of oocytes derived from prepubertal gilts, whilst being commercially attractive, remains challenging due to their poor developmental competence following maturation (IVM). Follicular fluid contains important growth factors and plays a key role during oocyte maturation; therefore, it is a common supplementation for porcine IVM medium. However, follicular fluid contains many poorly characterized components, is batch variable, and its use raises biosecurity concerns. In an effort to design a defined IVM system, growth factors such as cytokines have been previously tested. These include leukaemia inhibitory factor (LIF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF1), the combination of which is termed 'FLI'. Here, using abattoir-derived oocytes in a well established porcine IVP system, we compared follicular fluid and FLI supplementation during both IVM and embryo culture to test the hypothesis that FLI can substitute for follicular fluid without compromising oocyte nuclear and cytoplasmic maturation. We demonstrate that in oocytes derived from prepubertal gilts, FLI supplementation enhances oocyte meiotic maturation and has a positive effect on the quality and developmental competence of embryos. Moreover, for the first time, we studied the effects of follicular fluid and FLI combined showing no synergistic effects

    The impact of catchment source group classification on the accuracy of sediment fingerprinting outputs

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    The objective classification of sediment source groups is at present an under-investigated aspect of source tracing studies, which has the potential to statistically improve discrimination between sediment sources and reduce uncertainty. This paper investigates this potential using three different source group classification schemes. The first classification scheme was simple surface and subsurface groupings (Scheme 1). The tracer signatures were then used in a two-step cluster analysis to identify the sediment source groupings naturally defined by the tracer signatures (Scheme 2). The cluster source groups were then modified by splitting each one into a surface and subsurface component to suit catchment management goals (Scheme 3). The schemes were tested using artificial mixtures of sediment source samples. Controlled corruptions were made to some of the mixtures to mimic the potential causes of tracer non-conservatism present when using tracers in natural fluvial environments. It was determined how accurately the known proportions of sediment sources in the mixtures were identified after unmixing modelling using the three classification schemes. The cluster analysis derived source groups (2) significantly increased tracer variability ratios (inter-/ intra-source group variability) (up to 2122%, median 194%) compared to the surface and subsurface groupings (1). As a result, the composition of the artificial mixtures was identified an average of 9.8% more accurately on the 0e100% contribution scale. It was found that the cluster groups could be reclassified into a surface and subsurface component (3) with no significant increase in composite uncertainty(a 0.1% increase over Scheme 2). The far smaller effects of simulated tracer non-conservatism for the cluster analysis based schemes (2 and 3) was primarily attributed to the increased inter-group variability producing a far larger sediment source signal that the non-conservatism noise (1). Modified cluster analysis based classification methods have the potential to reduce composite uncertainty significantly in future source tracing studies

    Teaching for the transition: The Canadian PGY-1 neurosurgery \u27rookie camp\u27

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    Background: Transitioning from medical school to residency is difficult and stressful, necessitating innovation in easing this transition. In response, a Canadian neurosurgical Rookie Camp was designed and implemented to foster acquisition of technical, cognitive and behavioral skills among incoming Canadian post graduate year one (PGY-1) neurosurgery residents. Methods: The inaugural Rookie Camp was held in July 2012 in Halifax. The curriculum was developed based on a national needs-assessment and consisted of a pre-course manual, 7 case-based stations, 4 procedural skills stations and 2 group discussions. The content was clinically focused, used a variety of teaching methods, and addressed multiple CanMEDS competencies. Evaluation included participant and faculty surveys and a pre-course, post-course, and 3-month retention knowledge test. Results: 17 of 23 PGY-1 Canadian neurosurgical residents participated in the Camp. All agreed the course content was relevant for PGY-1 training and the experience prepared them for residency. All participants would recommend the course to future neurosurgical residents. A statistically significant improvement was observed in knowledge related to course content (F(2,32) = 7.572, p\u3c0.002). There were no significant differences between post-test and retention-test scores at three months. Conclusion: The inaugural Canadian Neurosurgery Rookie Camp for PGY-1 residents was successfully delivered, with engagement from participants, training programs, the Canadian Neurosurgical Society, and the Royal College. In addition to providing fundamental knowledge, which was shown to be retained, the course eased junior residents\u27 transition to residency by fostering camaraderie and socialization within the specialty

    Improving bank erosion modelling at catchment scale by incorporating temporal and spatial variability

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    Bank erosion can contribute a significant portion of the sediment budget within temperate catchments, yet few catchment scale models include an explicit representation of bank erosion processes. Furthermore, representation is often simplistic resulting in an inability to capture realistic spatial and temporal variability in simulated bank erosion. In this study, the sediment component of the catchment scale model SHETRAN is developed to incorporate key factors influencing the spatio-temporal rate of bank erosion, due to the effects of channel sinuosity and channel bank vegetation. The model is applied to the Eden catchment, north-west England, and validated using data derived from a GIS methodology. The developed model simulates magnitudes of total catchment annual bank erosion (617 - 4063 t yr-1) within the range of observed values (211 - 4426 t yr-1). Additionally the model provides both greater inter-annual and spatial variability of bank eroded sediment generation when compared with the basic model, and indicates a potential 61% increase of bank eroded sediment as a result of temporal flood clustering. The approach developed within this study can be used within a number of distributed hydrologic models and has general applicability to temperate catchments, yet further development of model representation of bank erosion processes is required

    Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

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    IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients

    A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

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    The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

    Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project.

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    Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests. All the data are now available through EuroPhenome database (www.europhenome.org) and the WTSI mouse portal (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are available through the European Mouse Mutant Archive (EMMA), the International Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP) Repository. Overall conclusions from both studies converged, with at least one phenotype scored in at least 80% of the mutant lines. In addition, 57% of the lines were viable, 13% subviable, 30% embryonic lethal, and 7% displayed fertility impairments. These efforts provide an important underpinning for a future global programme that will undertake the complete functional annotation of the mammalian genome in the mouse model
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