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Understanding the connection between aquifers, aquitards, and groundwater-dependant ecosystems remains a key challenge when developing a conceptual hydrogeological model. The aim of this study was to develop a systematic strontium isotope (87Sr/86Sr) fingerprinting framework of rocks and water within the sedimentary Surat and Clarence-Moreton basins (SCM basins) in eastern Australia - an area of extensive coal seam gas development and high potential for aquifer and groundwater-surface water connectivity. To do this, new groundwater samples (nâ¯=â¯298) were collected, analyzed and integrated with published data (nâ¯=â¯154) from the basins' major sedimentary, volcanic and alluvial aquifers, including the major coal seam gas target, the Walloon Coal Measures. Samples were also analyzed from rainfall (nâ¯=â¯2) and surface water (nâ¯=â¯40). In addition, rock core samples (nâ¯=â¯39) from exploration and stratigraphic wells were analyzed to determine the range of Sr isotope composition from host rocks. The analyses of cores demonstrate a distinct and systematic contrast in 87Sr/86Sr between different hydrogeological units. The analyses confirm that all major hydrogeological units have a narrow range with unique 87Sr/86Sr population characteristics that are useful for guiding conceptual model development. Comparison with selected hydrochemical and groundwater age tracers (14C and 36Cl) suggests only limited changes of 87Sr/86Sr from recharge beds to the deeper parts of the basins or with a decrease in natural 14C and 36Cl tracer content along flow paths. Stream sampling during baseflow conditions confirms that 87Sr/86Sr in surface waters are similar to those of the underlying bedrock formations. We demonstrated that 87Sr/86Sr analyses of rocks and water provide a powerful hydrostratigraphic and chemostratigraphic fingerprinting framework in the SCM basins, enabling reliable assessments of plausible aquifer and groundwater-surface water interconnectivity pathways. Applied in other complex multi-aquifer sedimentary basins in Australia, and globally, a similar approach can help to constrain conceptual hydrogeological models and facilitate improved water resource management.
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The detection and attribution of methane in aquifers overlying oil and gas reservoirs has recently gained increasing attention internationally. The Surat Basin, in the Great Artesian Basin (GAB), Australia, hosts a coal seam gas (CSG) reservoir, with feedlots, town water supply, mines and agriculture that extract groundwater from aquifers that underly and overly the gas reservoir. This study aimed to use a multi-isotopic approach to differentiate biogenic methane generated in situ in GAB aquifers and the Condamine Alluvium, from the biogenic CSG produced from the underlying Walloon Coal Measures reservoir, to understand if gas had migrated or not. Dissolved methane (0.001 to 160 mg/l) and total methane concentrations (up to 91,818 ppmv) were measured using closed sampling methods and were higher than from open direct fill sampling (<0.001 to 25.4 mg/l), especially in gassy bores that contain dissolved methane above 10 to 13 mg/l. The CSG production waters and a gassy overlying aquifer bore had the most depleted water isotopes, and also the most enriched δ13C-DIC indicating strong methanogenesis. The majority of aquifers have isotopic signatures (δ13C-DIC, CH4 and CO2) indicating in situ methane production by primary CO2 reduction or fermentation, distinct from secondary microbial CO2 reduction in the CSG reservoir. Fractionation factors support methane production mainly via CO2 reduction, with fermentation in a subset of aquifer samples. The gas wetness parameters (636 to 20,000) are consistent with mainly microbial gases, with low dissolved ethane (max 0.04 mg/l). The majority of aquifer and alluvium samples in this study are consistent with in situ methane production, not migration, however in several gassy bores the methane source could not be clearly identified. This study is broadly applicable to understanding methane sources in aquifers overlying CSG reservoirs.
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Agua Subterránea , Contaminantes Químicos del Agua , Metano/análisis , Dióxido de Carbono , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Gases , Yacimiento de Petróleo y Gas , Carbón MineralRESUMEN
Seismicity associated with subsurface operations is a major societal concern. It is therefore critical to improve predictions of the induced seismic hazard. Current statistical approaches account for the physics of pore pressure increase only. Here, we present a novel mathematical model that generalises adopted statistics for use in arbitrary injection/production protocols and applies to arbitrary physical processes. In our model, seismicity is driven by a normalised integral over the spatial reservoir volume of induced variations in frictional Coulomb stress, which-combined with the seismogenic index-provides a dimensionless proxy of the induced seismic hazard. Our model incorporates the classical pressure diffusion based and poroelastic seismogenic index models as special cases. Applying our approach to modeling geothermal systems, we find that seismicity rates are sensitive to imposed fluid-pressure rates, temperature variations, and tectonic conditions. We further demonstrate that a controlled injection protocol can decrease the induced seismic risk and that thermo-poroelastic stress transfer results in a larger spatial seismic footprint and in higher-magnitude events than does direct pore pressure impact for the same amount of injected volume and hydraulic energy. Our results, validated against field observations, showcase the relevance of the novel approach to forecast seismic hazards induced by subsurface activities.
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Various vasodilator medications are used in the treatment of pulmonary arterial hypertension (PAH), such as endothelin receptor antagonists (ERA) or phosphodiesterase-5-(PDE-5-)inhibitors. In a human ex vivo model, we investigated whether the combination of two substance classes could achieve a higher effect or - without loss of vasodilatation - a lower dosage of the individual substances might be sufficient. We established an ex vivo organ bath model to evaluate the dose-dependent effects of ERA and PDE-5-inhibitors on pulmonary vessels harvested from patients who underwent surgery (lung resection/transplantation). We compared the combined use of both substance classes with administration of one class of drugs alone. Due to the limitations of the experimental design, it is not possible to extrapolate our results to the conditions in vivo. Nevertheless, organ bath proved to be helpful in evaluating the dose-dependent effects of ERA and PDE-5 inhibitors, which is not practical in everyday clinical practice. In this setting, the effectiveness of the combination therapy and the potential for dose reduction depended on the concentrations used and on the influence of previous illnesses on blood vessel function. This article describes the most important results of our experimental investigations and suggestions for future projects.
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Hipertensión Pulmonar , Preparaciones Farmacéuticas , Hipertensión Arterial Pulmonar , Antihipertensivos , Quimioterapia Combinada , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéuticoRESUMEN
PURPOSE: Medical combination therapy of pulmonary arterial hypertension (PAH) may alleviate the drawbacks of monotherapy by avoiding drug tolerance and by increasing effectiveness, as shown by the combination of ambrisentan and tadalafil (AMBITION trial). The present ex-vivo study evaluated the combination of the endothelin receptor antagonists (ERA) macitentan and bosentan with the phosphodiesterase-5 (PDE-5) inhibitor vardenafil in pulmonary arteries from patients suffering from terminal lung disease as a model of PAH. METHODS: Segments of the pulmonary vessels were excised from resected lungs of patients requiring lung transplantation (LTX). Contraction of pulmonary arteries (PA) was elicited by consecutive dose-response curves of endothelin-1 (ET-1) followed by norepinephrine (NE) to allow inhibition by different pathways. Forces were measured isometrically in an organ bath in the presence and absence of ERA and PDE-5 inhibitors and their combination. RESULTS: PA of 38 patients were examined between October 2016 and November 2019. Bosentan (1E-7 M) and macitentan (1E-8 M, 3E-8 M, 1E-7 M) inhibited ET-1 induced contractions, whereas vardenafil (1E-6 M, 3E-6 M, 1E-5 M) inhibited only the NE induced part of the contractions. Vardenafil enhanced bosentan-induced inhibition of vasoconstriction in a dose-dependent fashion. Combination effects exceeded single bosentan at 3E-6 M and 1E-5 M vardenafil, and they exceeded single vardenafil at the lower vardenafil concentrations. Macitentan showed a more pronounced inhibition than bosentan regardless of the lower concentrations. Accordingly, combination effects with vardenafil resembled those of macitentan alone. CONCLUSIONS: Macitentan and bosentan were potent antagonists of vasoconstriction in PA of LTX patients. The benefit of drug combinations was demonstrated at selected concentrations only owing to a narrow therapeutic range of vardenafil in this ex-vivo model. These results suggest the utility of drug combinations other than the established pair of ambrisentan and tadalafil in PAH treatment but also make a case for a further assessment of vasodilator properties of drugs complementing ERA.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Antagonistas de los Receptores de Endotelina/farmacología , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/farmacología , Arteria PulmonarRESUMEN
We propose a likely contribution to severe COVID-19 morbidity by extracellular DNA in neutrophil extracellular traps (NETs). Dornase alfa degrades extracellular DNA to reduce mucus rigidity and accumulation, and was associated with respiratory improvement in a first patient. Dornase alfa should be considered for clinical trials in treatment of severe COVID-19.
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In regional chemotherapy of the pleural space a differentiation is made between intrapleural hyperthermic perfusion (IHP) and hyperthermic intrathoracic chemotherapy (HITOC). The HITOC in particular is carried out as an additive procedure after surgical cytoreduction of the pleural tumor manifestation. The main indications are for malignant pleural mesothelioma and thymoma with pleural spread (stage IVa), whereas treatment of secondary pleural carcinomatosis is indicated only in selected patients suitable for resection followed by HITOC. Cisplatin is the standard chemotherapeutic agent and a concentration of 150-175â¯mg/m2 body surface area is recommended. Postoperative, HITOC-related complications (e.g. renal insufficiency) can be minimized by an adapted perioperative management. Safety measures should be accomplished adhered to for the protection of personnel. The aim of HITOC is to achieve a better local tumor control with a corresponding longer recurrence-free and overall survival.
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Hipertermia Inducida , Mesotelioma , Neoplasias Pleurales , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia del Cáncer por Perfusión Regional , Cisplatino , Terapia Combinada , Humanos , Recurrencia Local de Neoplasia , Neoplasias Pleurales/terapia , Cirugía Torácica/tendenciasRESUMEN
BACKGROUND: A tracheoarterial fistula (TAF) is an uncommon but life-threatening complication after tracheostomy. Only an immediate and targeted treatment provides a chance to survive. OBJECTIVE: Surgical treatment of TAF. METHODS: Selective review of the literature and case description. RESULTS: A TAF leads to an acute bleeding complication with displacement of the respiratory tract. The mortality rate is nearly 100% without a surgical intervention. In the literature various interventional and surgical treatment procedures are described. Rapid control of bleeding via manual compression and overinflation of the tracheal cuff are the most important steps of treatment. Subsequent emergency surgery with ligation or resection of the TAF and covering of the tracheal lesion should be performed. Extracorporeal membrane oxygenation (ECMO) and a heart-lung machine can sometimes be necessary. CONCLUSION: Despite all treatment options the mortality rate of TAF remains high. The critical steps are a quick diagnosis of TAF, securing the airway and immediate bleeding control.
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Oxigenación por Membrana Extracorpórea , Fístula del Sistema Respiratorio , Enfermedades de la Tráquea , Humanos , Fístula del Sistema Respiratorio/cirugía , Tráquea , Enfermedades de la Tráquea/cirugía , TraqueostomíaRESUMEN
Transient storage zones (TSZs) are located at the interface of rivers and their abutting aquifers and play an important role in hydrological and biogeochemical functioning of rivers. The natural radioactive tracer 222 Rn is a particularly well-suited tracer for studying TSZ water exchange and age. Although 222 Rn measurement techniques have developed rapidly, there has been less progress in modeling 222 Rn activities. Here, we combine field measurements with the numerical model HydroGeoSphere (HGS) to simulate 222 Rn emanation, decay and transport during steady state (riffle-pool sequence) and transient (bank storage) conditions. Comparing the HGS mean water ages with the conventional 222 Rn apparent ages during steady state showed a systemic underestimation of apparent age with increasing dispersion and especially where large concentration gradients exist within the subsurface. A large underestimation of apparent water age was also observed at the advective front during bank storage where regional high 222 Rn groundwater mixes with newly infiltrated surface water. The explicit modeling of radiogenic tracers such as 222 Rn offers a physical interpretation of this data as well as a useful way to test simplified apparent age models.
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Agua Subterránea , Radón , Hidrología , RíosRESUMEN
BACKGROUND: The lungs are the second most common organ site for metastases in patients with colorectal cancer (CRC). Lymph node metastasis of CRC represents a prognostic factor for survival. OBJECTIVE: The present study investigated the influence of CRC lymph node metastasis on lung metastasis, in particular thoracic lymph node metastasis. MATERIAL AND METHODS: A retrospective analysis of 88 patients (nâ¯= 56 male) with curative resection of lung metastases of CRC was performed. Primary endpoint: influence of lymph node status of CRC on lung metastases. Secondary endpoints: disease-free survival and overall survival. Statistical evaluation was carried out with SPSS. RESULTS: In 48 patients a positive lymph node status of CRC and in 9 patients an N+ status of lung metastases were determined. The lymph node status of the CRC significantly affected the incidence of synchronous metastases (pâ¯= 0.03), disease-free interval until formation of metachronous lung metastases (pâ¯= 0.012) and the overall survival of patients with CRC (pâ¯= 0.048). The 5year survival rate for CRC patients with lung metastases was 48.7% after pulmonary metastasectomy. Thoracic lymph node involvement also significantly affected survival (pâ¯= 0.001). CONCLUSION: Screening for pulmonary metastases should be included in the staging and follow-up of all patients with CRC, especially in patients with a positive lymph node status of the CRC.
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Neoplasias Colorrectales , Neoplasias Pulmonares , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos , Masculino , Neumonectomía , Pronóstico , Estudios RetrospectivosRESUMEN
Nanoparticles with smaller diameters have larger surface areas. Unfortunately, this fact is often neglected in their biomedical characterization, e.g. in the evaluation of their toxicity with cell viability tests. We here point out the different scientific conclusions drawn in such tests when considering the traditional mass or concentration of nanoparticles, or their surface areas.
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Nanopartículas del Metal/toxicidad , Supervivencia Celular , Compuestos Férricos , Células HeLa , Humanos , Pruebas de ToxicidadRESUMEN
OBJECTIVE: We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34+0 weeks of gestation. DESIGN: Population-based prospective cohort study. SETTING: Ten public hospitals in the Austrian province of Styria. SAMPLE: A total of 87 065 neonates delivered in the period 2004-2015. METHODS: Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. MAIN OUTCOME MEASURES: Neonatal composite adverse and severely adverse outcome measures. RESULTS: The odds ratio for severely adverse events during the night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500-1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. CONCLUSIONS: Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. TWEETABLE ABSTRACT: Deliveries during night time lead to a greater number of neonates experiencing severely adverse events.
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Salas de Parto/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Personal de Hospital/estadística & datos numéricos , Adulto , Austria/epidemiología , Femenino , Edad Gestacional , Hospitales de Alto Volumen/estadística & datos numéricos , Hospitales de Bajo Volumen/estadística & datos numéricos , Hospitales Públicos/estadística & datos numéricos , Humanos , Recién Nacido , Modelos Lineales , Complicaciones del Trabajo de Parto/epidemiología , Oportunidad Relativa , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Factores de TiempoRESUMEN
Despite advances in neuroscience cancer research during the past decades, the survival of cancer patients has only marginally improved and the cure remains unlikely. The blood-brain barrier (BBB) is a major obstacle protecting the entry of therapeutic agents to central nervous system, especially for primary central nervous system lymphoma (PCNSL). Thus, the use of small nanoparticle as a drug carrier may be new strategies to overcome this problem. In this study, we fabricated liposome consisting of superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with anti-CD20 (Rituximab; RTX). The designed nanoparticles have a theranostic property which is not only to improve drug delivery, but also to offer diagnostic and monitoring capabilities. TEM images revealed the spherical shape of liposome with the approximately average diameters about 140-190nm with slightly negatively charge surfaces. Superparamagnetic property of SPIONs-loaded liposomes was confirmed by VSM. Liposome colloidal could be prolonged at 4°C and 25°C storages. RTX conjugated liposome induced cell internalization and apoptosis effect in B-lymphoma cells. Drug targeting and therapeutic effect was investigated in BBB model. The result confirmed that liposome nanocarrier is required as a drug carrier for effectively RTX across the BBB.
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Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Compuestos Férricos/química , Linfoma/tratamiento farmacológico , Nanopartículas de Magnetita/química , Rituximab/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/química , Antineoplásicos Inmunológicos/farmacocinética , Barrera Hematoencefálica/metabolismo , Línea Celular Tumoral , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/patología , Portadores de Fármacos/química , Humanos , Liposomas/química , Liposomas/ultraestructura , Linfoma/metabolismo , Linfoma/patología , Fenómenos Magnéticos , Nanopartículas de Magnetita/ultraestructura , Ratones Desnudos , Rituximab/química , Rituximab/farmacocinética , Nanomedicina Teranóstica/métodosAsunto(s)
Borrelia burgdorferi , Enfermedad de Lyme , ADN Bacteriano , Humanos , Inflamación , NeoplasiasRESUMEN
A young patient presented himself to the emergency department with sudden-onset, breathing-dependent right-sided thoracic pain. The auscultation revealed diminished breath sounds on the right. The radiograph showed a pneumothorax which was immediately dealt with chest tube drainage. The CT scan of the thorax showed minuscule subpleural bullae. Video-assisted thoracoscopic surgery (VATS) was performed due to persistent fistulae formation through the drain. The subpleural, bullous and emphysematous changes were histologically confirmed. Investigations into the cause showed evidence of alpha-1-antitrypsin deficiency (AATD). The patient is a Pi MZ type. Few cases of spontaneous pneumothorax as the first manifestation of alpha-1-antitrypsin deficiency have been described. Conclusion: When diagnosing primary spontaneous pneumothorax, alpha-1-antitrypsin deficiency should be considered.
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Neumotórax/etiología , Enfisema Pulmonar/diagnóstico , Deficiencia de alfa 1-Antitripsina/diagnóstico , Diagnóstico Diferencial , Drenaje , Estudios de Seguimiento , Humanos , Pulmón/patología , Masculino , Neumonectomía , Neumotórax/diagnóstico , Neumotórax/patología , Neumotórax/cirugía , Enfisema Pulmonar/patología , Enfisema Pulmonar/cirugía , Toracoscopía , Tomografía Computarizada por Rayos X , Adulto Joven , Deficiencia de alfa 1-Antitripsina/patología , Deficiencia de alfa 1-Antitripsina/cirugíaRESUMEN
Social context often has profound effects on behavior, yet the neural and molecular mechanisms which mediate flexible behavioral responses to different social environments are not well understood. We used the African cichlid fish, Astatotilapia burtoni, to examine aggressive defense behavior across three social contexts representing different motivational states: a reproductive opportunity, a familiar male and a neutral context. To elucidate how differences in behavior across contexts may be mediated by neural gene expression, we examined gene expression in the preoptic area, a brain region known to control male aggressive and sexual behavior. We show that social context has broad effects on preoptic gene expression. Specifically, we found that the expression of genes encoding nonapeptides and sex steroid receptors are upregulated in the familiar male context. Furthermore, circulating levels of testosterone and cortisol varied markedly depending on social context. We also manipulated the D2 receptor (D2R) in each social context, given that it has been implicated in mediating context-dependent behavior. We found that a D2R agonist reduced intruder-directed aggression in the reproductive opportunity and familiar male contexts, while a D2R antagonist inhibited intruder-directed aggression in the reproductive opportunity context and increased aggression in the neutral context. Our results demonstrate a critical role for preoptic gene expression, as well as circulating steroid hormone levels, in encoding information from the social environment and in shaping adaptive behavior. In addition, they provide further evidence for a role of D2R in context-dependent behavior.
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Agresión , Proteínas de Peces/genética , Área Preóptica/metabolismo , Receptores de Dopamina D2/genética , Animales , Cíclidos/genética , Cíclidos/fisiología , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Proteínas de Peces/metabolismo , Hidrocortisona/metabolismo , Masculino , Área Preóptica/efectos de los fármacos , Receptores de Dopamina D2/metabolismo , Conducta Espacial , Testosterona/metabolismoRESUMEN
The metabolic activity of tumor cells is known to be higher as compared to that of normal cells, which has been previously exploited to deliver nanomedicines to highly metabolic tumor cells. Unfortunately, current strategies, which are mostly based on complex energy sources, such as sugars, showed insufficient accumulation at the target sites. We here report the coating of IONPs with two essential units of cellular metabolism: adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). ATP and NADPH were directly bound to the IONPs' surface using a simple aqueous method. Both molecules were used as coatings, i.e. as stabilizing agents, but also simultaneously as targeting molecules to deliver IONPs to highly metabolic tumor cells. Indeed, we found that the uptake of ATP-IONPs and NADPH-IONPs is correlated with the metabolic activity of tumor cells, especially regarding their cellular ATP levels and NADPH consumption. We also measured one of the highest MRI r2 relaxivities for both ATP-IONPs and NADPH-IONPs. With the direct coating of IONPs with ATP and NADPH, we therefore provide an optimal platform to stabilize IONPs and at the same time promising properties for the targeting and detection of highly metabolic tumor cells.
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Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics.