301 research outputs found

    Multi-element association and regional geochemistry of protoliths in tashan jatau area, northwestern nigeria: implications for gold exploration

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    Soil geochemical surveys are widely used in the early stages of gold exploration, especially in areas with poor outcrops and thick overburden. Fifty-one (51) soil samples were collected in duplicate with the aim of analyzing them geochemically and determining the gold grade through panning and weighing methods. The geochemical results were subjected to multivariate statistical treatment through Factor analysis and Pearson correlation matrix. Four factors were generated from the PCA. These are Factor 1: Cu-Sr-Nb-Ba-La-W-Pb-Zr, suggesting sulfide mineralization that is related to granitic rock while Factor 2 has Au with a low to negative correlation with Mo and Nb suggesting a second phase of intrusion-related activity which must have emplaced gold in this area. Factor 3 is made up of W-Pb suggesting a second sulfide mineralization distinct from the first. While Factor 4 gives a single element factor, Hg. Single-elementt maps were constructed to show the element dispersion in the catchment. In general gold concentrations in this study is erratic and attain a high of 0.67ppm and 0.90g/t. The study delineates the northwestern part of the catchment to be the most prolific in terms of gold potential and shows that the granitic batholiths are the most primary gold-hosting lithology. &nbsp

    Are symptoms of insomnia in primary care associated with subsequent onset of dementia? A matched retrospective case-control study

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    Objective: There is evidence from neuroimaging studies of an association between insomnia and early dementia biomarkers, but observational studies have so far failed to show a clear association between insomnia and the later development of dementia. We investigated the association between dementia diagnosis and recording of insomnia symptoms 5-10 years earlier in primary care. Method: A case-control study using data from the Clinical Practice Research Datalink. 15,209 cases with dementia (either Alzheimer's, vascular, mixed or non-specific subtypes) at least 65 years old at time of diagnosis, were matched with the same number of controls on year of birth and gender. We ascertained the presence of insomnia symptoms during a five-year period starting 10 years before the index date. Odds ratios for developing dementia were estimated using logistic regression after controlling for hypnotic exposure and physical and mental health comorbidities. Results: The adjusted odds ratio for dementia in those with previous insomnia was 1.34 (95% CI = 1.20-1.50). Conclusion: There is an association between dementia and previous insomnia. It may be possible to incorporate insomnia into predictive tools for dementia

    Biopolitics meets Terrapolitics: Political Ontologies and Governance in Settler-Colonial Australia

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    Crises persist in Australian Indigenous affairs because current policy approaches do not address the intersection of Indigenous and European political worlds. This paper responds to this challenge by providing a heuristic device for delineating Settler and Indigenous Australian political ontologies and considering their interaction. It first evokes Settler and Aboriginal ontologies as respectively biopolitical (focused through life) and terrapolitical (focused through land). These ideal types help to identify important differences that inform current governance challenges. The paper discusses the entwinement of these traditions as a story of biopolitical dominance wherein Aboriginal people are governed as an “included-exclusion” within the Australian political community. Despite the overall pattern of dominance, this same entwinement offers possibilities for exchange between biopolitics and terrapolitics, and hence for breaking the recurrent crises of Indigenous affairs

    Spatial chemical distance based on atomic property fields

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    Similarity of compound chemical structures often leads to close pharmacological profiles, including binding to the same protein targets. The opposite, however, is not always true, as distinct chemical scaffolds can exhibit similar pharmacology as well. Therefore, relying on chemical similarity to known binders in search for novel chemicals targeting the same protein artificially narrows down the results and makes lead hopping impossible. In this study we attempt to design a compound similarity/distance measure that better captures structural aspects of their pharmacology and molecular interactions. The measure is based on our recently published method for compound spatial alignment with atomic property fields as a generalized 3D pharmacophoric potential. We optimized contributions of different atomic properties for better discrimination of compound pairs with the same pharmacology from those with different pharmacology using Partial Least Squares regression. Our proposed similarity measure was then tested for its ability to discriminate pharmacologically similar pairs from decoys on a large diverse dataset of 115 protein–ligand complexes. Compared to 2D Tanimoto and Shape Tanimoto approaches, our new approach led to improvement in the area under the receiver operating characteristic curve values in 66 and 58% of domains respectively. The improvement was particularly high for the previously problematic cases (weak performance of the 2D Tanimoto and Shape Tanimoto measures) with original AUC values below 0.8. In fact for these cases we obtained improvement in 86% of domains compare to 2D Tanimoto measure and 85% compare to Shape Tanimoto measure. The proposed spatial chemical distance measure can be used in virtual ligand screening

    Epigenetic polypharmacology: from combination therapy to multitargeted drugs

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    The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed

    Skin infection, housing and social circumstances in children living in remote Indigenous communities: testing conceptual and methodological approaches

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    BACKGROUND: Poor housing conditions in remote Indigenous communities in Australia are a major underlying factor in poor child health, including high rates of skin infections. The aim of this study is to test approaches to data collection, analysis and feedback for a follow-up study of the impact of housing conditions on child health. METHODS: Participation was negotiated in three communities with community councils and individual participants. Data were collected by survey of dwelling condition, interviews, and audit health centre records of children aged under seven years. Community feedback comprised immediate report of items requiring urgent repair followed by a summary descriptive report. Multivariate models were developed to calculate adjusted incidence rate ratios (IRR) for skin infections and their association with aspects of household infrastructure. RESULTS: There was a high level of participation in all communities. Health centre records were inadequate for audit in one community. The records of 138 children were available for development of multivariate analytic models. Rates of skin infection in dwellings that lacked functioning facilities for removing faeces or which had concrete floors may be up to twice as high as for other dwellings, and the latter association appears to be exacerbated by crowding. Younger children living in older dwellings may also be at approximately two-fold higher risk. A number of socioeconomic and socio-demographic variables also appear to be directly associated with high rates of skin infections. CONCLUSION: The methods used in the pilot study were generally feasible, and the analytic approach provides meaningful results. The study provides some evidence that new and modern housing is contributing to a reduction in skin infections in Aboriginal children in remote communities, particularly when this housing leads to a reduction in crowding and the effective removal of human waste

    On the Matter of Time

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    Drawing on several disciplinary areas, this article considers diverse cultural concepts of time, space, and materiality. It explores historical shifts in ideas about time, observing that these have gone full circle, from visions in which time and space were conflated, through increasingly divergent linear understandings of the relationship between them, to their reunion in contemporary notions of space-time. Making use of long-term ethnographic research and explorations of the topic of Time at Durham University’s Institute of Advanced Study (2012–13), the article considers Aboriginal Australian ideas about relationality and the movement of matter through space and time. It asks why these earliest explanations of the cosmos, though couched in a wholly different idiom, seem to have more in common with the theories proposed by contemporary physicists than with the ideas that dominated the period between the Holocene and the Anthropocene. The analysis suggests that such unexpected resonance between these oldest and newest ideas about time and space may spring from the fact that they share an intense observational focus on material events. Comparing these vastly different but intriguingly compatible worldviews meets interdisciplinary aims in providing a fresh perspective on both of them

    Ethnoontology: Ways of world‐building across cultures

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    This article outlines a program of ethnoontology that brings together empirical research in the ethnosciences with ontological debates in philosophy. First, we survey empirical evidence from heterogeneous cultural contexts and disciplines. Second, we propose a model of cross‐cultural relations between ontologies beyond a simple divide between universalist and relativist models. Third, we argue for an integrative model of ontology building that synthesizes insights from different fields such as biological taxonomy, cognitive science, cultural anthropology, and political ecology. We conclude by arguing that a program of ethnoontology provides philosophers both with insights about traditional issues such as debates about natural kinds and with novel strategies for connecting philosophy with pressing global issues such as the conservation of local environments and the self‐determination of Indigenous communities

    Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

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    Exposure to environmental chemicals and drugs may have a negative effect on human health. A better understanding of the molecular mechanism of such compounds is needed to determine the risk. We present a high confidence human protein-protein association network built upon the integration of chemical toxicology and systems biology. This computational systems chemical biology model reveals uncharacterized connections between compounds and diseases, thus predicting which compounds may be risk factors for human health. Additionally, the network can be used to identify unexpected potential associations between chemicals and proteins. Examples are shown for chemicals associated with breast cancer, lung cancer and necrosis, and potential protein targets for di-ethylhexyl-phthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxin, pirinixic acid and permethrine. The chemical-protein associations are supported through recent published studies, which illustrate the power of our approach that integrates toxicogenomics data with other data types
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