220 research outputs found

    Language, Indigenous Peoples, and the Right to Self-Determination

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    Language has always played a significant role in the colonization of peoples as an instrument of subjugation and homogenization. It has been used to control nondominant groups, including Indigenous peoples, often leading to their exclusion or assimilation. Many Indigenous groups, however, use language as a tool to connect the members of their community, to assert their group identity, and to preserve their culture. Thus, language has been used both as a means of oppression and as a mobilizer of Indigenous groups in their struggles for national recognition. Recognizing the significance of language in the identity and culture of Indigenous peoples, this article analyses how language rights can be viewed as an aspect of the right to self-determination of these groups

    The unacknowledged genocide: The Guatamalan Maya’s quest for justice

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    The era from the start of World War II through to the 1960s... was an era of unprecedented aggression in the occupation of indig-enous lands, and backed by the equally unprecedented wealth and power of the industrial world and the systematic dislocation of thousands of indigenous peoples around the world. [Coates, 2004. p. 226/7] The indigenous peoples of the Americas stood little chance of survival when faced with the strategic western military force they were met with and as a population, they share a sad collective history of exploitation and social condemnation. This paper aims to open up further discus-sion on the lack of justice achieved to date while assessing the true extent of damage caused to the indigenous society, how their customs and tra-ditions were upset, disjointed and in essence, erased. Drawing on the unquestionable relationship between indigenous peoples and land, this work will offer further insight into how the military-backed scorched earth policies not only destroyed important indigenous lands, but the forced removal of the indigenous population from these lands to the government designed ‘model villages’ completely upset indigenous custom, tradition and lineage, and hindered the transfer of said traditional practices and customs from one generation to the next. This paper will further hypoth-esise if the case would have been better suited to an international criminal tribunal like those instances of the International Criminal Tribunal for the Former Yugoslavia [ICTY], International Criminal Tribunal for Rwanda [ICTR], The Special Court of Sierra Leone [SCSL] and The Extraordinary Chambers in the Courts of Cambodia [ECCC].It has been over 20 years since the end of the civil war in Guatemala yet those responsible for some of the gravest crimes commited during the war have not been brought to justice. The crimes of Ríos Montt and his government remain unpunished and there is no closure for the indigenous peoples who were most affected by violence of the regime. The indigenous peoples of Guatemala still face uncertain hardships while enduring this perpetual quest for acknowledg-ment of the atrocities, recognition of victimhood and justice

    Process evaluation for OptiBIRTH, a randomised controlled trial of a complex intervention designed to increase rates of vaginal birth after caesarean section

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    Complex interventions encompassing several interconnecting and interacting components can be challenging to evaluate. Examining the underlying trial processes while an intervention is being tested can assist in explaining why an intervention was effective (or not). This paper describes a process evaluation of a pan-European cluster randomised controlled trial, OptiBIRTH (undertaken in Ireland, Italy and Germany), that successfully used both quantitative and qualitative methods to enhance understanding of the underlying trial mechanisms and their effect on the trial outcome

    Heritability of subcortical volumetric traits in mesial temporal lobe epilepsy.

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    OBJECTIVES: We aimed to 1) determine if subcortical volume deficits are common to mesial temporal lobe epilepsy (MTLE) patients and their unaffected siblings 2) assess the suitability of subcortical volumetric traits as endophenotypes for MTLE. METHODS: MRI-based volume measurements of the hippocampus, amygdala, thalamus, caudate, putamen and pallidium were generated using an automated brain reconstruction method (FreeSurfer) for 101 unrelated 'sporadic' MTLE patients [70 with hippocampal sclerosis (MTLE+HS), 31 with MRI-negative TLE], 83 unaffected full siblings of patients and 86 healthy control subjects. Changes in the volume of subcortical structures in patients and their unaffected siblings were determined by comparison with healthy controls. Narrow sense heritability was estimated ipsilateral and contralateral to the side of seizure activity. RESULTS: MTLE+HS patients displayed significant volume deficits across the hippocampus, amygdala and thalamus ipsilaterally. In addition, volume loss was detected in the putamen bilaterally. These volume deficits were not present in the unaffected siblings of MTLE+HS patients. Ipsilaterally, the heritability estimates were dramatically reduced for the volume of the hippocampus, thalamus and putamen but remained in the expected range for the amygdala. MRI-negative TLE patients and their unaffected siblings showed no significant volume changes across the same structures and heritability estimates were comparable with calculations from a healthy population. CONCLUSIONS: The findings indicate that volume deficits for many subcortical structures in 'sporadic' MTLE+HS are not heritable and likely related to acquired factors. Therefore, they do not represent suitable endophenotypes for MTLE+HS. The findings also support the view that, at a neuroanatomical level, MTLE+HS and MRI-negative TLE represent two distinct forms of MTLE

    Teaching emergency and disaster management in Australia: standards for higher education providers

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    The need for emergency and disaster professionals with multidisciplinary knowledge and holistic understanding is widely recognised. Despite this, there is currently no international nor an Australian consensus on a set of common standards for higher education that could ensure graduates possess knowledge and skills with sufficient commonality to facilitate interoperability in all facets of disaster management cycle. Thus, this research project aimed to develop a standards and an associated conceptual framework for higher education programs in emergency and disaster management. The Generic Emergency and Disaster Management Standards (GEDMS) were developed through a mixed qualitative research approach involving a systematic literature review, mapping of current course content offered in Australia and New Zealand, focus groups of experts and consultation with policy makers, industry representatives and other relevant stakeholders. The Standards consist of three main domains: knowledge, skills and application. Governance and policy frameworks, theoretical and conceptual basis for practice, and contemporary disaster management were identified as underlying themes for the knowledge domain. Leadership, communication, and collaboration were fitted under the skills domain. The professional practice, together with critical thinking, were considered the means by which knowledge and skills are applied

    Common coding variant in SERPINA1 increases the risk for large artery stroke

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    Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis

    Patterns and rates of exonic de novo mutations in autism spectrum disorders

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    Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there is significantly enriched connectivity among the proteins encoded by genes harboring de novo missense or nonsense mutations, and excess connectivity to prior ASD genes of major effect, suggesting a subset of observed events are relevant to ASD risk. The small increase in rate of de novo events, when taken together with the connections among the proteins themselves and to ASD, are consistent with an important but limited role for de novo point mutations, similar to that documented for de novo copy number variants. Genetic models incorporating these data suggest that the majority of observed de novo events are unconnected to ASD, those that do confer risk are distributed across many genes and are incompletely penetrant (i.e., not necessarily causal). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors

    Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

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    We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. © 2013 Liu et al

    THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

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    The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate
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