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Increased rates of deformation and seismicity are well-established precursors to volcanic eruptions, and their interpretation forms the basis for eruption warnings worldwide. Rates of ground displacement and the number of earthquakes escalate before many eruptions1-3, as magma forces its way towards the surface. However, the pre-eruptive patterns of deformation and seismicity vary widely. Here we show how an eruption beginning on 19 March 2021 at Fagradalsfjall, Iceland, was preceded by a period of tectonic stress release ending with a decline in deformation and seismicity over several days preceding the eruption onset. High rates of deformation and seismicity occurred from 24 February to mid-March in relation to gradual emplacement of an approximately 9-km-long magma-filled dyke, between the surface and 8 km depth (volume approximately 34 × 106 m3), as well as the triggering of strike-slip earthquakes up to magnitude MW 5.64. As stored tectonic stress was systematically released, there was less lateral migration of magma and a reduction in both the deformation rates and seismicity. Weaker crust near the surface may also have contributed to reduced seismicity, as the depth of active magma emplacement progressively shallowed. This demonstrates that the interaction between volcanoes and tectonic stress as well as crustal layering need to be fully considered when forecasting eruptions.
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OBJECTIVES: To examine the severity of coronary artery disease (CAD) in people from rural or remote Western Australia referred for invasive coronary angiography (ICA) in Perth and their subsequent management; to estimate the cost savings were computed tomography coronary angiography (CTCA) offered in rural centres as a first line investigation for people with suspected CAD. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Adults with stable symptoms in rural and remote WA referred to Perth public tertiary hospitals for ICA evaluation during the 2019 calendar year. MAIN OUTCOME MEASURES: Severity and management of CAD (medical management or revascularisation); health care costs by care model (standard care or a proposed alternative model with local CTCA assessment). RESULTS: The mean age of the 1017 people from rural and remote WA who underwent ICA in Perth was 62 years (standard deviation, 13 years); 680 were men (66.9%), 245 were Indigenous people (24.1%). Indications for referral were non-ST elevation myocardial infarction (438, 43.1%), chest pain with normal troponin level (394, 38.7%), and other (185, 18.2%). After ICA assessment, 619 people were medically managed (60.9%) and 398 underwent revascularisation (39.1%). None of the 365 patients (35.9%) without obstructed coronaries (< 50% stenosis) underwent revascularisation; nine patients with moderate CAD (50-69% stenosis; 7%) and 389 with severe CAD (≥ 70% stenosis or occluded vessel; 75.5%) underwent revascularisation. Were CTCA used locally to determine the need for referral, 527 referrals could have been averted (53%), the ICA:revascularisation ratio would have improved from 2.6 to 1.6, and 1757 metropolitan hospital bed-days (43% reduction) and $7.3 million in health care costs (36% reduction) would have been saved. CONCLUSION: Many rural and remote Western Australians transferred for ICA in Perth have non-obstructive CAD and are medically managed. Providing CTCA as a first line investigation in rural centres could avert half of these transfers and be a cost-effective strategy for risk stratification of people with suspected CAD.
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Doença da Artéria Coronariana , Atenção à Saúde , Custos de Cuidados de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Austrália , Angiografia por Tomografia Computadorizada/economia , Constrição Patológica , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Análise Custo-Benefício , Estudos Transversais , Valor Preditivo dos Testes , Estudos Retrospectivos , Atenção à Saúde/economia , Atenção à Saúde/métodos , Atenção à Saúde/normas , Austrália Ocidental , População Rural , Transferência de Pacientes/economia , Transferência de Pacientes/estatística & dados numéricos , Idoso , Povos Aborígenes Australianos e Ilhéus do Estreito de TorresRESUMO
Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long. Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens, or magma flowing vertically into dykes from an underlying source, with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bárðarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System (GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bárðarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bárðarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
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BACKGROUND: Little is known on the trends of aeromedical retrieval (AR) during social isolation. AIM: To compare the pre, lockdown, and post-lockdown AR patient characteristics during a period of Coronavirus 2019 (COVID-19) social isolation. METHODS: An observational study with retrospective data collection, consisting of AR between 26 January and 23 June 2020. RESULTS: There were 16 981 AR consisting of 1983 (11.7%) primary evacuations and 14 998 (88.3%) inter-hospital transfers, with a population median age of 52 years (interquartile range 29.0-69.0), with 49.0% (n = 8283) of the cohort being male and 38.0% (n = 6399) being female. There were six confirmed and 230 suspected cases of COVID-19, with the majority of cases (n = 134; 58.3%) in the social isolation period. As compared to pre-restriction, the odds of retrieval for the restriction and post-restriction period differed across time between the major diagnostic groups. This included, an increase in cardiovascular retrieval for both restriction and post-restriction periods (odds ratio (OR) 1.12, 95% confidence interval (CI) 1.02-1.24 and OR 1.18 95%, CI 1.08-1.30 respectively), increases in neoplasm in the post restriction period (OR 1.31, 95% CI 1.04-1.64) and increases for congenital conditions in the restriction period (OR 2.56, 95% CI 1.39-4.71). Cardiovascular and congenital conditions had increased rates of priority 1 patients in the restriction and post restriction periods. There was a decrease in endocrine and metabolic disease retrievals in the restriction period (OR 0.72, 95% CI 0.53-0.98). There were lower odds during the post-restriction period for retrievals of the respiratory system (OR 0.78, 95% CI 0.67-0.93), and disease of the skin (OR 0.78, 95% CI 0.6-1.0). Distribution between the 2019 and 2020 time periods differed (P < 0.05), with the lockdown period resulting in a significant reduction in activity. CONCLUSION: The lockdown period resulted in increased AR rates of circulatory and congenital conditions.
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Resgate Aéreo , COVID-19/epidemiologia , Controle de Doenças Transmissíveis/tendências , Transferência de Pacientes/tendências , Quarentena/tendências , Adulto , Idoso , Austrália/epidemiologia , Controle de Doenças Transmissíveis/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Our laboratory recently demonstrated that seizures activate the hypothalamic-pituitary-adrenal (HPA) axis, increasing circulating levels of corticosterone (O'Toole et al., 2013). Given the well-established proconvulsant actions of corticosterone, we hypothesized that seizure-induced activation of the HPA axis may contribute to future seizure susceptibility. Further, since hypercortisolism is associated with depression, we propose that seizure-induced activation of the HPA axis may contribute to comorbid depression and epilepsy. To test this hypothesis, we generated mice lacking the GABAA receptor (GABAAR) δ subunit specifically in corticotropin-releasing hormone (CRH) neurons (Gabrd/Crh mice), which exhibit hyporeactivity of the HPA axis (Lee et al., 2014). Gabrd/Crh mice exhibit blunted seizure-induced elevations in corticosterone, establishing a useful tool to investigate the contribution of HPA axis dysfunction on epilepsy and associated comorbidities. Interestingly, Gabrd/Crh mice exhibit decreased acute seizure susceptibility following kainic acid (KA) administration. Furthermore, chronically epileptic Gabrd/Crh mice exhibit a decrease in both spontaneous seizure frequency and depression-like behaviors compared with chronically epileptic Cre-/- littermates. Seizure susceptibility and associated depression-like behaviors can be restored to wild type levels by treating Gabrd/Crh mice with exogenous corticosterone. Similarly, chemogenetic activation of CRH neurons in the paraventricular nucleus (PVN) is sufficient to increase seizure susceptibility; whereas, chemogenetic inhibition of CRH neurons in the PVN of the hypothalamus is sufficient to decrease seizure susceptibility and depression-like behaviors in chronically epileptic mice. These data suggest that seizure-induced activation of the HPA axis promotes seizure susceptibility and comorbid depression-like behaviors, suggesting that the HPA axis may be a novel target for seizure control.
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Corticosterona/farmacologia , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de GABA-A/metabolismo , Convulsões/epidemiologia , Animais , Hormônio Liberador da Corticotropina/sangue , Hormônio Liberador da Corticotropina/metabolismo , Transtorno Depressivo/fisiopatologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular , Sistema Hipófise-Suprarrenal/fisiopatologia , Convulsões/sangue , Convulsões/fisiopatologiaRESUMO
A subset of corticotropin-releasing hormone (CRH) neurons was previously identified in the hippocampus with unknown function. Here we demonstrate that hippocampal CRH neurons represent a novel subtype of interneurons in the hippocampus, exhibiting unique morphology, electrophysiological properties, molecular markers, and connectivity. This subset of hippocampal CRH neurons in the mouse reside in the CA1 pyramidal cell layer and tract tracing studies using AAV-Flex-ChR2-tdTomato reveal dense back-projections of these neurons onto principal neurons in the CA3 region of the hippocampus. These hippocampal CRH neurons express both GABA and GAD67 and using in vitro optogenetic techniques, we demonstrate that these neurons make functional connections and release GABA onto CA3 principal neurons. The location, morphology, and importantly the functional connectivity of these neurons demonstrate that hippocampal CRH neurons represent a unique subtype of hippocampal interneurons. The connectivity of these neurons has significant implications for hippocampal function.
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Hormônio Liberador da Corticotropina/metabolismo , Hipocampo/citologia , Hipocampo/fisiologia , Interneurônios/citologia , Interneurônios/fisiologia , Animais , Hormônio Liberador da Corticotropina/genética , Glutamato Descarboxilase/metabolismo , Imuno-Histoquímica , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Potenciais da Membrana , Camundongos Transgênicos , Inibição Neural/fisiologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Técnicas de Rastreamento Neuroanatômico , Optogenética , Técnicas de Patch-Clamp , Reação em Cadeia da Polimerase , Análise de Célula Única , Técnicas de Cultura de Tecidos , Ácido gama-Aminobutírico/metabolismoRESUMO
It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition in dentate gyrus granule cells contributes, at least in part, to deficits in learning and memory associated with chronic stress. These findings have significant implications regarding the pathophysiological mechanisms underlying impairments in learning and memory associated with stress and suggest a role for GABAA R δ subunit containing receptors in dentate gyrus granule cells. © 2016 Wiley Periodicals, Inc.
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Giro Denteado/metabolismo , Deficiências da Aprendizagem/metabolismo , Transtornos da Memória/metabolismo , Inibição Neural/fisiologia , Estresse Psicológico/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Doença Crônica , Feminino , Aprendizagem/fisiologia , Deficiências da Aprendizagem/etiologia , Masculino , Memória/fisiologia , Transtornos da Memória/etiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de GABA-A/deficiência , Receptores de GABA-A/genética , Restrição Física , Estresse Psicológico/complicações , Técnicas de Cultura de TecidosRESUMO
Gradual inflation of magma chambers often precedes eruptions at highly active volcanoes. During such eruptions, rapid deflation occurs as magma flows out and pressure is reduced. Less is known about the deformation style at moderately active volcanoes, such as Eyjafjallajökull, Iceland, where an explosive summit eruption of trachyandesite beginning on 14 April 2010 caused exceptional disruption to air traffic, closing airspace over much of Europe for days. This eruption was preceded by an effusive flank eruption of basalt from 20 March to 12 April 2010. The 2010 eruptions are the culmination of 18 years of intermittent volcanic unrest. Here we show that deformation associated with the eruptions was unusual because it did not relate to pressure changes within a single magma chamber. Deformation was rapid before the first eruption (>5 mm per day after 4 March), but negligible during it. Lack of distinct co-eruptive deflation indicates that the net volume of magma drained from shallow depth during this eruption was small; rather, magma flowed from considerable depth. Before the eruption, a â¼0.05 km(3) magmatic intrusion grew over a period of three months, in a temporally and spatially complex manner, as revealed by GPS (Global Positioning System) geodetic measurements and interferometric analysis of satellite radar images. The second eruption occurred within the ice-capped caldera of the volcano, with explosivity amplified by magma-ice interaction. Gradual contraction of a source, distinct from the pre-eruptive inflation sources, is evident from geodetic data. Eyjafjallajökull's behaviour can be attributed to its off-rift setting with a 'cold' subsurface structure and limited magma at shallow depth, as may be typical for moderately active volcanoes. Clear signs of volcanic unrest signals over years to weeks may indicate reawakening of such volcanoes, whereas immediate short-term eruption precursors may be subtle and difficult to detect.
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Major strike-slip faults that develop between strong and weaker regions are thought to focus along narrow shear zones at the rheological boundary. Here we present the InSAR-derived velocity field spanning almost the entire length of one such fault, the 1600 km-long Altyn Tagh Fault (ATF), and analyse the strain distribution. We find that localisation of strain is actually variable, in contrast to other major strike-slip faults that show little variation, with strain concentrated at the fault for some sections and distributed over broad (>100 km) shear zones for others. Slip rate along the ATF is also variable, decreasing along the fault from 11.6 ± 1.6 mm/yr in the west to 7.2 ± 1.4 mm/yr in the central portion, before increasing again to 11.7 ± 0.9 mm/yr over the eastern portion. We show that the variable shear zone width may be linked to geological variability and the influence of heat flow, and the results imply that sub-parallel faults play an important role in the overall deformation field. This demonstrates the significance of accurately characterising strain rates over a broad region when assessing seismic hazard.
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Human papillomavirus (HPV)-related cervical and nasopharyngeal cancers differ in molecular mechanisms underlying the oncogenic processes. The disparity may be attributed to differential expression of oncoproteins. The current study investigated the host oncogenes expression pattern in HPV-associated cervical and nasopharyngeal cancer. Formalin-fixed paraffin-embedded tissues originating from the nasopharyngeal and cervical regions were screened using Hematoxylin and Eosin staining. Genomic DNA and total RNA were extracted from confirmed cancer biopsies and non-cancer tissues (NC). HPV was detected by PCR using MY09/GP5+/6+ primers. Protein expression levels of AKT, IQGAP1, and MMP16 in HPV-infected cancers and controls were determined by immunohistochemistry. RT-qPCR was used to profile mRNAs of the oncogenes. AKT and IQGAP1 proteins were highly expressed in the epithelial cancers compared with the non-cancer tissues (p < 0.05). IQGAP1 and MMP16 mRNAs level was significantly higher in the cancers than in the NC (p < 0.05), but not AKT mRNA levels. MMP16 protein was ubiquitously expressed in all tissues. AKT mRNA level was significantly elevated in CC compared with NPC (p < 0.001). However, the difference in AKT, IQGAP1 and MMP16 proteins level between CC and NPC was not significant (p > 0.05). The oncoproteins expression level between the HPV-positive and HPV-negative cancer biopsies showed no significant difference (p < 0.05). Current study reports AKT but not IQGAP1 and MMP16 mRNAs differentially expression in cervical and nasopharyngeal cancers, independent of HPV infection status.
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Many examples of exposed giant dike swarms can be found where lateral magma flow has exceeded hundreds of kilometers. We show that massive magma flow into dikes can be established with only modest overpressure in a magma body if a large enough pathway opens at its boundary and gradual buildup of high tensile stress has occurred along the dike pathway prior to the onset of diking. This explains rapid initial magma flow rates, modeled up to about 7400 cubic meters per second into a dike ~15-kilometers long, which propagated under the town of Grindavík, Southwest Iceland, in November 2023. Such high flow rates provide insight into the formation of major dikes and imply a serious hazard potential for high-flow rate intrusions that propagate to the surface and transition into eruptions.
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AIM: To describe clinical characteristics, assessment and treatment of patients diagnosed in an emergency department (ED) with acute pericarditis. METHODS: A medical record review of patients with an ED diagnosis of pericarditis conducted in an adult tertiary hospital over a 5-year period. Variables collected included pain characteristics, associated symptoms, physical examination findings, investigation results, ED treatment and disposition. RESULTS: 179 presentations were included, with 73.9% men and a mean age of 38.8 years. The majority of patients described pleuritic chest pain worse with inspiration with half characterising the pain as sharp or stabbing, with others describing tightness, dullness or cramping. Radiation to the left shoulder occurred in 2.8% and change of pain with posture occurred in 46.4%. A pericardial rub was documented in 19 presentations. All patients had an ECG recorded with ST segment elevation present in 69.3% and PR segment depression in 49.2%. Nearly 90% of patients had troponin testing but only 6.4% of these were positive. Only 8.1% of cases were treated with colchicine. No patients required pericardiocentesis. Patients with high-risk factors were more likely to have previous pericarditis, dyspnoea, nausea, abnormal investigation results, treatment with colchicine and admission to hospital. However, 16.9% of patients without risk factors were admitted, and 46.9% of patients with at least one risk factor were discharged. CONCLUSIONS: Pericarditis may not follow the classical clinical description. Admission and discharge decisions appear to relate to individual clinical characteristics rather than known risk factors. Use of colchicine for treatment in ED is infrequent.
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Serviço Hospitalar de Emergência/estatística & dados numéricos , Pericardite/diagnóstico , Doença Aguda , Adulto , Distribuição por Idade , Dor no Peito/diagnóstico , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericardite/etiologia , Pericardite/terapia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Anxiety disorders are the most prevalent mental health disorder worldwide, with a lifetime prevalence of 5-7 % of the human population. Although the etiology of anxiety disorders is incompletely understood, one aspect of host health that affects anxiety disorders is the gut-brain axis. Adolescence is a key developmental window in which stress and anxiety disorders are a major health concern. We used adolescent female mice in a gastrointestinal (GI) colonization model to demonstrate that the commensal fungus Candida albicans affects host health via the gut-brain axis. In mice, bacterial members of the gut microbiota can influence the host gut-brain axis, affecting anxiety-like behavior and the hypothalamus-pituitary-adrenal (HPA) axis which produces the stress hormone corticosterone (CORT). Here we showed that mice colonized with C. albicans demonstrated increased anxiety-like behavior and increased basal production of CORT as well as dysregulation of CORT production following acute stress. The HPA axis and anxiety-like behavior are negatively regulated by the endocannabinoid N-arachidonoylethanolamide (AEA). We demonstrated that C. albicans-colonized mice exhibited changes in the endocannabinoidome. Further, increasing AEA levels using the well-characterized fatty acid amide hydrolase (FAAH) inhibitor URB597 was sufficient to reverse both neuroendocrine phenotypes in C. albicans-colonized mice. Thus, a commensal fungus that is a common colonizer of humans had widespread effects on the physiology of its host. To our knowledge, this is the first report of microbial manipulation of the endocannabinoid (eCB) system that resulted in neuroendocrine changes contributing to anxiety-like behavior.
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Candida albicans/patogenicidade , Endocanabinoides/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Ansiedade/metabolismo , Ansiedade/microbiologia , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/microbiologia , Ácidos Araquidônicos/metabolismo , Encéfalo/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Corticosterona/análise , Corticosterona/sangue , Endocanabinoides/farmacologia , Feminino , Sistema Hipotálamo-Hipofisário/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Sistemas Neurossecretores/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiologia , Alcamidas Poli-Insaturadas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/microbiologiaRESUMO
Large volume effusive eruptions with relatively minor observed precursory signals are at odds with widely used models to interpret volcano deformation. Here we propose a new modelling framework that resolves this discrepancy by accounting for magma buoyancy, viscoelastic crustal properties, and sustained magma channels. At low magma accumulation rates, the stability of deep magma bodies is governed by the magma-host rock density contrast and the magma body thickness. During eruptions, inelastic processes including magma mush erosion and thermal effects, can form a sustained channel that supports magma flow, driven by the pressure difference between the magma body and surface vents. At failure onset, it may be difficult to forecast the final eruption volume; pressure in a magma body may drop well below the lithostatic load, create under-pressure and initiate a caldera collapse, despite only modest precursors.
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BACKGROUND: Providing thrombectomy services to rural or remote regions with small, dispersed populations presents a particular challenge. Sustaining local thrombectomy services is not viable given the low throughput of cases, therefore large vessel occlusion (LVO) stroke patients require emergent transfer, often by air, to the closest high volume urban thrombectomy unit. The aim of this paper is to present logistical, time-metric data and outcome data on LVO stroke patients that have been aeromedically retrieved for thrombectomy from the vast, 2,500,000-km2 rural catchment of the Western Australian state thrombectomy unit. METHODS: The prospectively collected state thrombectomy registry was reviewed and all patients that underwent thrombectomy for LVO strokes following aeromedical retrieval from remote or rural catchments were identified. Multiple logistic and time-metric data points were recorded and outcomes were compared to a cohort of urban patients treated over the same period. RESULTS: Over a 2-year period 30 patients underwent thrombectomy following aeromedical retrieval, either by helicopter or fixed wing aircraft, from rural and remote regions of Western Australia. The mean aeromedical retrieval distance was 393â¯km while the maximum retrieval distance was over 2600â¯km. The mean ictus to recanalization time was 657â¯min, an mTICI 2b-3 recanalization was achieved in 93% of cases and 62% of anterior circulation, and 50% of posterior circulation LVO stroke patients achieved functional independence at 90-days. Outcome data for rural patients compared favourably to urban patients treated over the same time period. CONCLUSION: With the availability of an efficient aeromedical retrieval service, LVO stroke patients in rural and remote regions can achieve excellent outcomes following transfer to a high volume thrombectomy unit, even if distances involved are very large.
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Transferência de Pacientes/métodos , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Transporte de Pacientes/métodos , Idoso , Viagem Aérea , Austrália , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , População Rural , Resultado do TratamentoRESUMO
Neonatal stroke presents with seizures and results in neurologic morbidity, including epilepsy, hemiparesis, and cognitive deficits. Stem cell-based therapy offers a possible therapeutic strategy for neonatal stroke. We developed an immature mouse model of stroke with acute seizures and ischemic brain injury. Postnatal day 12 CD1 mice received right-sided carotid ligation. Two or 7 days after ligation, mice received an intrastriatal injection of B5 embryonic stem cell-derived neural stem cells. Four weeks after ligation, hemispheric brain atrophy was measured. Pups receiving stem cells 2 days after ligation had less severe hemispheric brain atrophy compared with either noninjected or vehicle-injected ligated controls. Transplanted cells survived, but 3 out of 10 pups injected with stem cells developed local tumors. No difference in hemispheric brain atrophy was seen in mice injected with stem cells 7 days after ligation. Neural stem cells have the potential to ameliorate ischemic injury in the immature brain, although tumor development is a serious concern.
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Isquemia Encefálica/terapia , Artérias Carótidas/fisiologia , Neurônios/transplante , Transplante de Células-Tronco , Acidente Vascular Cerebral/terapia , Animais , Atrofia , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Neoplasias Encefálicas/patologia , Sobrevivência Celular , Ligadura , Camundongos , Neurônios/efeitos dos fármacos , Convulsões/etiologia , Transplante de Células-Tronco/efeitos adversos , Células-Tronco/efeitos dos fármacos , Técnicas Estereotáxicas , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Teratoma/patologia , Tretinoína/farmacologiaRESUMO
Corticotropin-releasing hormone (CRH) signaling in the hippocampus has been established to be important for mediating the effects of stress on learning and memory. Given our laboratory's recent characterization of a subset of hippocampal CRH neurons as a novel class of GABAergic interneurons, we hypothesized that these local GABAergic hippocampal CRH neurons may influence hippocampal function. Here we applied an array of molecular tools to selectively label and manipulate hippocampal CRH neurons in mice, in order to assess this interneuron population's impact on hippocampus-dependent behaviors and hippocampal network excitability. Genetically-targeted ablation of hippocampal CRH neurons in vivo impaired object recognition memory and substantially enhanced the severity of kainic acid-induced seizures. Conversely, selective activation of CRH neurons in vitro suppressed the excitability of the mossy fiber-CA3 pathway. Additional experiments are needed to reconcile the functions of GABA and CRH signaling of hippocampal CRH neurons on hippocampal function. However, our results indicate that this interneuron population plays an important role in maintaining adaptive network excitability, and provide a specific circuit-level mechanism for this role.
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Região CA3 Hipocampal/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Neurônios GABAérgicos/metabolismo , Memória , Animais , Região CA3 Hipocampal/citologia , Eletroencefalografia , Locomoção , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismoRESUMO
The stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is normally suppressed during pregnancy. Dysregulation of the HPA axis has been proposed to play a role in postpartum depression. However, direct investigation into the relationship between the HPA axis and postpartum depression has been hindered by the lack of useful animal models. Building on our discovery of a role for the K+/Cl-co-transporter, KCC2, in the GABAergic regulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN), critical for mounting the body's physiological response to stress, we assessed the role of KCC2 in the regulation of the HPA axis during pregnancy and the postpartum period. Here we demonstrate that the normal suppression of the stress-induced activation of the HPA axis during the peripartum period involves maintenance of KCC2 in the PVN. Mice lacking KCC2 specifically in corticosterone-releasing hormone (CRH) neurons, which govern the activity of the HPA axis (KCC2/Crh mice), exhibit dysregulation of the HPA axis and abnormal postpartum behaviors. Loss of KCC2 specifically in CRH neurons in the PVN is sufficient to reproduce the depression-like phenotype and deficits in maternal behaviors during the postpartum period. Similarly, chemogenetic activation of CRH neurons in the PVN is sufficient to induce abnormal postpartum behaviors and chemogenetic silencing of CRH neurons in the PVN can ameliorate abnormal postpartum behaviors observed in KCC2/Crh mice. This study demonstrates that dysregulation of the HPA axis is sufficient to induce abnormal postpartum behaviors and deficits in maternal behaviors in mice, providing empirical support for a role of HPA axis dysfunction in the pathophysiology of postpartum depression.
Assuntos
Período Periparto/metabolismo , Período Pós-Parto/metabolismo , Simportadores/metabolismo , Animais , Comportamento Animal/fisiologia , Corticosterona/farmacologia , Hormônio Liberador da Corticotropina/metabolismo , Depressão/metabolismo , Depressão Pós-Parto/metabolismo , Feminino , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/metabolismo , Camundongos , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Período Periparto/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiopatologia , Período Pós-Parto/efeitos dos fármacos , Período Pós-Parto/psicologia , Cotransportadores de K e Cl-RESUMO
Earthquakes are caused by the release of tectonic strain accumulated between events. Recent advances in satellite geodesy mean we can now measure this interseismic strain accumulation with a high degree of accuracy. But it remains unclear how to interpret short-term geodetic observations, measured over decades, when estimating the seismic hazard of faults accumulating strain over centuries. Here, we show that strain accumulation rates calculated from geodetic measurements around a major transform fault are constant for its entire 250-year interseismic period, except in the ~10 years following an earthquake. The shear strain rate history requires a weak fault zone embedded within a strong lower crust with viscosity greater than ~1020 Pa s. The results support the notion that short-term geodetic observations can directly contribute to long-term seismic hazard assessment and suggest that lower-crustal viscosities derived from postseismic studies are not representative of the lower crust at all spatial and temporal scales.
RESUMO
BACKGROUND: Intellectual disability (ID) is the most prevalent disability in the world. People with intellectual disability (PWID) frequently experience extreme violations of numerous human rights. Despite greater prevalence in South Africa than in high-income countries, most ID research currently comes from the Global North. This leaves us with few contextually sensitive studies to draw from to advance inclusive citizenship. OBJECTIVES: Our scoping review aims to investigate pertinent ID rights issues in South Africa, synthesise quantitative and qualitative studies, and provide a synopsis of available evidence on which to base future work. We aim to clarify key concepts, address gaps in the literature and identify opportunities for further research. METHOD: We followed strict eligibility criteria. Medical subject heading terms were entered into seven databases. Seven reviewers worked independently, two per paper. Quantitative and qualitative data extraction forms were designed. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and registered a protocol. An inductive approach enabled a thematic analysis of selected studies. RESULTS: By following PRISMA guidelines, 82 studies were assessed for eligibility of which 59 were included. Ten sub-themes were integrated into four main themes: the right not to be discriminated against, the right to psychological and bodily integrity, the right to accommodating services and challenges to rights implementation. CONCLUSION: People with intellectual disability face compound difficulties when trying to assert their constitutionally entitled rights. This ongoing project requires serious commitment and action. Statutory obligations to nurture every South African's human rights naturally extend to PWID and their supporters who forge ahead in a disabling environment.