211 research outputs found

    Submarine landslides on the upper southeast Australian passive continental margin – preliminary findings

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    The southeast Australian passive continental margin is narrow, steep and sediment-deficient, and characterized by relatively low rates of modern sedimentation. Upper slope (\u3c1200m) sediments comprise mixtures of calcareous and terrigenous sand and mud. Three of twelve sediment cores recovered from geologically-recent, submarine landslides located offshore New South Wales/Queensland (NSW/QLD) are interpreted to have sampled failure surfaces at depths of between 85 cm and 220 cm below the present-day seabed. Differences in sediment physical properties are recorded above and below the three slide-plane boundaries. Sediment taken directly above the inferred submarine landslide failure surfaces and presumed to be post-landslide, returned radiocarbon ages of 15.8 ka, 20.7 ka and 20.1 ka. The last two ages correspond to adjacent slide features, which are inferred to be consistent with their being triggered by a single event such as an earthquake. Slope stability models based on classical soil mechanics and measured sediment shearstrengths indicate that the upper slope sediments should be stable. However, multibeam sonar data reveal that many upper slope landslides occur across the margin and that submarine landsliding is a common process. We infer from these results that: a) an unidentified mechanism regularly acts to reduce the shear resistance of these sediments to the very low values required to enable slope failure, and/or b) the margin experiences seismic events that act to destabilise the slope sediments

    The BCD Triage Sieve outperforms all existing major incident triage tools:comparative analysis using the UK national trauma registry population

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    BACKGROUND: Natural disasters, conflict, and terrorism are major global causes of death and disability. Central to the healthcare response is triage, vital to ensure the right care is provided to the right patient at the right time. The ideal triage tool has high sensitivity for the highest priority (P1) patients with acceptably low over-triage. This study compared the performance of major incident triage tools in predicting P1 casualty status in adults in the prospective UK Trauma Audit and Research Network (TARN) registry. METHODS: TARN patients aged 16+ years (January 2008-December 2017) were included. Ten existing triage tools were applied using patients’ first recorded pre-hospital physiology. Patients were subsequently assigned triage categories (P1, P2, P3, Expectant or Dead) based on pre-defined, intervention-based criteria. Tool performance was assessed by comparing tool-predicted and intervention-based priority status. FINDINGS: 195,709 patients were included; mortality was 7·0% (n=13,601); median Injury Severity Score (ISS) was 9 (IQR 9–17); 97·1% sustained blunt injuries. 22,144 (11·3%) patients fulfilled intervention-based criteria for P1 status, exhibiting higher mortality (12·8% vs. 5·0%, p<0.001), increased intensive care requirement (52·4% vs 5·0%, p<0.001), and more severe injuries (median ISS 21 vs 9, p<0.001) compared with P2 patients. In 16–64 year olds, the highest performing tool was the Battlefield Casualty Drills (BCD) Triage Sieve (Prediction of P1 status: 70·4% sensitivity, over-triage 70·9%, area under the receiver operating curve (AUC) 0·068 [95%CI 0·676–0·684]). The UK National Ambulance Resilience Unit (NARU) Triage Sieve had sensitivity of 44·9%; over-triage 56·4%; AUC 0·666 (95%CI 0·662–0·670). All tools performed poorly amongst the elderly (65+ years). INTERPRETATION: The BCD Triage Sieve performed best in this nationally representative population; we recommend it supersede the NARU Triage Sieve as the UK primary major incident triage tool. Validated triage category definitions are recommended for appraising future major incidents. FUNDING: This study is funded by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. GVG also acknowledges support from the MRC Heath Data Research UK (HDRUK/CFC/01). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the Ministry of Defence

    Observation- and model-based estimates of particulate dry nitrogen deposition to the oceans

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    Anthropogenic nitrogen (N) emissions to the atmosphere have increased significantly the deposition of nitrate (NO3-) and ammonium (NH4+) to the surface waters of the open ocean, with potential impacts on marine productivity and the global carbon cycle. Global-scale understanding of the impacts of N deposition to the oceans is reliant on our ability to produce and validate models of nitrogen emission, atmospheric chemistry, transport and deposition. In this work, ~2900 observations of aerosol NO3- and NH4+ concentrations, acquired from sampling aboard ships in the period 1995 - 2012, are used to assess the performance of modelled N concentration and deposition fields over the remote ocean. Three ocean regions (the eastern tropical North Atlantic, the northern Indian Ocean and northwest Pacific) were selected, in which the density and distribution of observational data were considered sufficient to provide effective comparison to model products. All of these study regions are affected by transport and deposition of mineral dust, which alters the deposition of N, due to uptake of nitrogen oxides (NOx) on mineral surfaces. Assessment of the impacts of atmospheric N deposition on the ocean requires atmospheric chemical transport models to report deposition fluxes, however these fluxes cannot be measured over the ocean. Modelling studies such as the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), which only report deposition flux are therefore very difficult to validate for dry deposition. Here the available observational data were averaged over a 5° x 5° grid and compared to ACCMIP dry deposition fluxes (ModDep) of oxidised N (NOy) and reduced N (NHx) and to the following parameters from the TM4-ECPL (TM4) model: ModDep for NOy, NHx and particulate NO3- and NH4+, and surface-level particulate NO3- and NH4+ concentrations. As a model ensemble, ACCMIP can be expected to be more robust than TM4, while TM4 gives access to speciated parameters (NO3- and NH4+) that are more relevant to the observed parameters and which are not available in ACCMIP. Dry deposition fluxes (CalDep) were calculated from the observed concentrations using estimates of dry deposition velocities. Model – observation ratios, weighted by grid-cell area and numbers of observations, (RA,n) were used to assess the performance of the models. Comparison in the three study regions suggests that TM4 over-estimates NO3- concentrations (RA,n = 1.4 – 2.9) and under-estimates NH4+ concentrations (RA,n = 0.5 – 0.7), with spatial distributions in the tropical Atlantic and northern Indian Ocean not being reproduced by the model. In the case of NH4+ in the Indian Ocean, this discrepancy was probably due to seasonal biases in the sampling. Similar patterns were observed in the various comparisons of CalDep to ModDep (RA,n = 0.6 – 2.6 for NO3-, 0.6 – 3.1 for NH4+). Values of RA,n for NHx CalDep - ModDep comparisons were approximately double the corresponding values for NH4+ CalDep - ModDep comparisons due to the significant fraction of gas-phase NH3 deposition incorporated in the TM4 and ACCMIP NHx model products. All of the comparisons suffered due to the scarcity of observational data and the large uncertainty in dry deposition velocities used to derive deposition fluxes from concentrations. These uncertainties have been a major limitation on estimates of the flux of material to the oceans for several decades. Recommendations are made for improvements in N deposition estimation through changes in observations, modelling and model – observation comparison procedures. Validation of modelled dry deposition requires effective comparisons to observable aerosol-phase species concentrations and this cannot be achieved if model products only report dry deposition flux over the ocean

    Heterochromatin Protein 1 (HP1a) Positively Regulates Euchromatic Gene Expression through RNA Transcript Association and Interaction with hnRNPs in Drosophila

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    Heterochromatin Protein 1 (HP1a) is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1a. According to the model, histone methyltransferase enzymes (HMTases) methylate the histone H3 at lysine 9 (H3K9me), creating selective binding sites for itself and the chromodomain of HP1a. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1a plays a role in telomere capping. Surprisingly, recent studies have shown that HP1a is present at many euchromatic sites along polytene chromosomes of Drosophila melanogaster, including the developmental and heat-shock-induced puffs, and that this protein can be removed from these sites by in vivo RNase treatment, thus suggesting an association of HP1a with the transcripts of many active genes. To test this suggestion, we performed an extensive screening by RIP-chip assay (RNA–immunoprecipitation on microarrays), and we found that HP1a is associated with transcripts of more than one hundred euchromatic genes. An expression analysis in HP1a mutants shows that HP1a is required for positive regulation of these genes. Cytogenetic and molecular assays show that HP1a also interacts with the well known proteins DDP1, HRB87F, and PEP, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs) involved in RNA processing. Surprisingly, we found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Together, our data show novel and unexpected functions for HP1a and hnRNPs proteins. All these proteins are in fact involved both in RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms have a significant role on both RNA and heterochromatin metabolisms

    Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit through Trophic Support in Huntington's Disease Mouse Models

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    We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy

    LATE-NC staging in routine neuropathologic diagnosis : an update

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    An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.Peer reviewe
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