118 research outputs found
Seismic travel time forward modelling and inversion of fluid flow conduits in marine sediments using ocean bottom seismometers
The increasing concentration of greenhouse gases in the atmosphere and hydrosphere is causing changes to global climate. Geological carbon sequestration is a proven technology for reducing anthropogenic emissions in the atmosphere. However, leakage of CO2 along natural fluid pathways, which are imaged as seismic pipes and chimneys, may affect storage formation integrity. These fluid flow conduits are observed in marine basins globally, passing vertically through kilometres of sedimentary overburden. However, the nature and physical properties of fluid flow conduits are currently poorly understood. In this thesis, I characterise active fluid conduits in the Central North Sea and at the Svalbard Margin, as well as analogous onshore in Varna, Bulgaria. I present three-dimensional seismic P-wave travel time tomographies using ocean bottom seismometers to constrain the geometry, the geophysical properties and the material inside of fluid flow conduits. A key aim is to compare fluid flow conduits in marine basins based on the studies of a pipe structure beneath the Scanner Pockmark, Central North Sea, and a chimney below the Lunde Pockmark, Svalbard Margin. My results imply a diverse range of the internal structures of fluid flow conduits. The analysis of the 3D P-wave velocity demonstrates that fluid flow conduits are fundamentally different in their geophysical and hydraulic characteristics depending on depth and the geological setting. The results of my thesis highlight the complexity in evaluating fluid flow conduits, the necessity of their detailed assessment for any offshore carbon storage site selection, and the necessity to investigate their potential to function as pathways for CO2 and to ensure the integrity of the reservoir for CO2 sequestration
Mechanisms underlying reductions in mother-to-child transmission of human immunodeficiency virus type-1 by short-course antiretrovirals
Student Number : 8044255 -
PhD thesis -
School of Pathology; Discipline Virology -
Faculty of Health SciencesKnowledge of the timing of mother-to-child transmission (MTCT) of HIV-1 is an important issue in reducing the risk of infant infection. Prior to giving birth therefore an HIV-1 positive mother should be provided with anti-HIV-1 drugs (antiretrovirals) during the shortest time possible to ensure both efficacy and minimal toxicity of the antiretrovirals to the newborn. However, in the absence of timeous administration of nevirapine (NVP) or zidovudine (AZT) to the mother at the onset of labour, infants are given post-exposure prophylaxis (PEP). Despite antiviral prophylaxis some infants still become infected. In an attempt to mimic the in vivo scenario we investigated, in Chapter Three, the replication ability of a primary isolate (M502L) in peripheral blood mononuclear cells (PBMC) isolated from healthy donors exposed to different concentrations of NVP or AZT either prior to or post-infection, but that reflected mean neonatal plasma concentrations measured following maternal dosing. In phytohaemagglutinin (PHA) stimulated cultures M502L exhibited some growth. Maintaining NVP and AZT in the culture medium resulted in decreased viral growth over time. In contrast to that expected certain donors demonstrated elevated p24 antigen levels in the presence of HIV-1 and NVP or AZT. This suggested that cells were more conducive to HIV-1 replication either because of cellular activation or due to cellular production of cytokines/chemokines. The in vitro study highlighted (i) the differential permissiveness of cells from different donors for HIV-1 infection, (ii) different abilities of antiretrovirals (ART) to circumvent infection in different individuals and (iii) immunomodulatory effects of ART in vitro.
Commencing in Chapter Four we elected to investigate, in vivo, the immunomodulatory consequences of HIV-1 exposure and infection in two groups of HIV-1-exposed newborns whose mothers either received NVP at the onset of labour or who only received NVP as PEP within 72 hours of birth. Short-course antiretroviral drug regimens are known to reduce the risk of MTCT of HIV-1 but mechanisms affording protection of such interventions remain poorly defined. Since T-cell activation is an important factor in productive HIV-1 infection, we tested the hypothesis that single-dose NVP reduces immune activation, which in turn reduces the likelihood of transmission. We compared concentrations of cord and maternal blood plasma immune activation markers, neopterin, ÎČ2-microglobulin (ÎČ2-m) and soluble L-selectin (sL-selectin) in the two groups of HIV-1-exposed newborns and among HIV-unexposed controls. In utero exposure of the infant to HIV-1, regardless of NVP exposure, led to demonstrable increases in levels of immune activation markers, this being most notable in the presence of pre-existing infection. Contrary to what was hypothesized, immune activation was increased by pre-birth exposure to single-dose NVP, with this effect being enhanced in infants already infected at birth. Our data suggest that reductions in immune activation do not explain transmission prevention effects of single-dose NVP. Our data also suggest a biological explanation for why HIV-1 infected infants exposed perinatally to antiretroviral drugs might experience hastened disease progression, namely that the immunological mileau in some HIV-1 infected individuals treated with NVP favours increased HIV-1 replication.
Cytokines and chemokines function to stimulate, or suppress cellular proliferation and differentiation and have unique immunomodulatory properties. Furthermore, they have the potential to protect against HIV-1 infection or to regulate HIV-1 replication. In Chapter Five we therefore questioned whether exposure to HIV-1 or NVP influences cytokine/chemokine levels of infants born to HIV-1 infected mothers. We compared levels of interleukin (IL)-7, IL-10, stromal cell-derived factor: SDF-1α (CXCL12), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage inflammatory protein-1α: MIP-1α (CCL3), macrophage inflammatory protein-1ÎČ: MIP-1ÎČ (CCL4) and regulated upon activation, normal T-cell expressed and secreted: RANTES (CCL5) of the two groups of HIV-1-exposed newborns and among the HIV-unexposed controls. HIV-1 exposure in the absence of single-dose NVP was not found to impact significantly on the levels of IL-7, IL-10, GM-CSF, CXCL12, CCL3, CCL4 or CCL5 and single-dose NVP had no appreciable effect on these cytokine/chemokine levels. Cord blood plasma levels of IL-7, CXCL12 and GM-CSF were found to be independent of mothersâ levels. Single-dose NVP reduced the ability of cord blood mononuclear cell (CBMC) to produce GM-CSF spontaneously. Maternal and infant (HIV-1 exposed NVP unexposed) IL-10 levels were significantly correlated. Significantly elevated levels of IL-10 were associated with pre-existing infection in NVP unexposed newborns. CCL3, CCL4 and CCL5 levels in NVP unexposed uninfected infants were not different from those of control infants but correlated significantly with IL-7 levels.
HIV-1 specific cellular immune responses are elicited in a proportion of infants born to HIV-1 seropositive mothers and have been associated with protection from maternal HIV-1 transmission. In Chapter Six, levels of the immune activation markers neopterin, ÎČ2-m, sL-selectin, the immunomodulatory and haematopoietic factors IL-7, CXCL12, GM-CSF and the immunoregulatory cytokine IL-10 were examined amongst the group of newborns, that received NVP as PEP within 72 hours of birth, of which a proportion had specific cellular responses to HIV-1 envelope (Env) peptides. It was our aim to determine in infants that elicit HIV-1 specific cellular immune responses (Env+) and those that lack the specific responses (Env-), whether these factors could predict transmission and whether the former group of infants exhibit unique immune features that might distinguish them from Env- non-responders. Our data suggested that none of the factors tested were predictive of HIV-1 transmission but confirmed that infants with cellular responses to HIV-1 envelope peptides were associated with lack of subsequent infection. In particular, our data demonstrated an association between HIV-1 specific cellular immune responses, lower maternal viral load and lack of infection suggesting that sustained exposure to antigen (reduced maternal viral load) may be responsible for the strong priming effect. Furthermore, an association between reduced GM-CSF levels and the presence of HIV-1 specific responses was demonstrated, which suggested therefore that newborn infants that elicited HIV-1 specific cellular immune responses exhibited different immune capabilities from those without responses.
Finally, in Chapter Seven we looked at how immune activation and priming impact on thymic output of T-cells in newborn infants. Unfortunately, sample volumes of the two groups of HIV-1-exposed newborns used in the previous three Chapters became limited with the result that we chose to address these questions using anonymously collected cord blood samples from infants, some of which were used to supplement the placebo group of the the UNAIDS-sponsored clinical trial of short-course zidovudine-lamivudine (AZT-3TC). At the time the AZT-3TC trial was conducted short-course antiviral prophlyaxis was not the standard of care for the prevention of MTCT of HIV-1. The thymus is known to be essential for establishing diversity of the T-cell pool, and morphological thymic changes and effects on naĂŻve T-cells and T-cell receptor excision circle (TREC) concentrations have been reported in studies of HIV-1 infected children and adults. As it is not known to what extent in utero exposure to HIV-1 and infection affects T-cell division in newborn infants, we elected to determine TREC levels of infants born to HIV-1 seropositive mothers that were not exposed to antiretrovirals. The impact of increased immune activation on TREC levels and the consequence of HIV-1 exposure or infection on circulating levels of IL-7 (raised levels indicative of T-cell depletion) was also investigated. HIV-1 exposure or infection did not result in significant losses of TREC. TREC levels were not affected by immune activation associated with HIV-1 exposure and infection and IL-7 levels were not raised. Infants that elicited HIV-1 specific cellular immune responses exhibit TREC levels that were similar to those of infants without HIV-1 specific responses. These data suggested that newborn infants of HIV-1 seropositive mothers demonstrated no altered thymopoietic ability compared to control infants. Furthermore, HIV-1 specific immune responses, (indicative of post-thymic memory T-cell expansion) did not influence thymic output measured in newborn infants.
In conclusion, the in vitro study demonstrated that there is a high degree of variability between PBMC isolated from different donors with respect to viral replication and drug effectivity which suggests that these phenomena are likely to exist within patient (infant as well as adult) populations. While immune activation is considered central to productive infection we demonstrated that immune activation is increased by HIV-1 exposure and by single-dose NVP. Exposure to HIV-1 alone or with NVP did not influence birth levels of IL-7, IL-10, CXCL12, GM-CSF, CCL3, CCL4 and CCL5. Furthermore, levels of these factors did not predict infection outcome in the infant. Immune activation and haematopoietic growth factors are modulated independently of the mother but maternal factors such as IL-10 and exposure to single-dose NVP, which reduces responsiveness of CBMC, could impact on the infant. HIV-1 specific cellular immune responses at birth, which are elicited in a proportion of infants born to HIV-1 positive mothers, are of immunological significance and can predict lack of subsequent infection. Disturbances in thymic output are not readily detectable at birth when using TREC to assess de novo T-cell synthesis, alternatively there is a homeostatic balance between thymic output and peripheral T-cell proliferation in newborns of HIV-1 infected mothers. Overall our data suggests that (i) there are immune consequences of being born to an HIV-1 positive mother, (ii) short-course antiretroviral prophylaxis does impact on the developing immune system of the infant and (iii) while the direct effects of single-dose NVP are not disputed, there are indirect consequences of NVP exposure on immune cells. Despite the consequences of HIV-1 exposure or the result of being born to a HIV-1 seropositive mother or exposure to single-dose NVP, our data proposes that the immune system of newborn infants is capable of responding as demonstrated by the enhanced immune activation. It remains important to determine the correlates of immune protection for the development of novel immuno-therapeutic and vaccine strategies and maternal-infant transmission of HIV-1 provides a model which can address questions of protective immune processes. Understanding the influence of antiretrovirals on immune processes remains an important component of the drug mechanisms, (aside from their direct antiretroviral activity), that may underlie reductions in maternal-infant transmission of HIV-1. Furthermore, how antiretrovirals influence immune processes and immune development (together with exposure to HIV-1/consequences of being born to an HIV-1 seropositive mother), may impact on subsequent immune responsiveness to infectious organisms or childhood vaccines
QualitĂ€tskriterien transdisziplinĂ€rer Forschung : ein Leitfaden fĂŒr die formative Evaluation von Forschungsprojekten
TransdisziplinĂ€re Forschung befasst sich mit lebensweltlichen Problemstellungen. Bei der Forschungsarbeit mĂŒssen Experten/innen aus verschiedenen FĂ€chern bzw. Disziplinen und aus der Praxis zusammenwirken, um die komplexe Problematik umfassend behandeln zu können. Diese Vielfalt, die besondere Formen der Kooperation, der Differenzierung und Integration, Methoden und Theorien impliziert, bringt es mit sich, dass gĂ€ngige, bei der fachbezogenen Bewertung hinreichende Verfahren der Evaluation und der QualitĂ€tssicherung nicht unmittelbar auf solche Forschungsvorhaben ĂŒbertragen werden können. Diesem Mangel an Kriterien und Methoden der Evaluation begegnet Evalunet, das Evaluationsnetzwerk fĂŒr transdisziplinĂ€re Forschung, mit dem vorgelegten Leitfaden fĂŒr die Forschungspraxis, der vor allem ausfĂŒhrlich beschriebene QualitĂ€tskriterien enthĂ€lt und ebenso Aussagen zu methodischen und Verfahrensfragen macht. Er ist aus der empirischen Auswertung konkreter transdisziplinĂ€rer Forschungsprojekte und unter Mithilfe zahlreicher Experten und Expertinnen aus verschiedenen Fachrichtungen entstanden. Der Leitfaden dient dem Zweck der Evaluation von transdisziplinĂ€ren Forschungsprojekten, wobei dieses Instrument auf den Aspekt des Lernens aus dem Evaluationsvorgang (formative Evaluation) zugeschnitten ist und bei der Aus- und Bewertung auf einen Diskurs setzt (diskursive Evaluation). Neben einer Evaluierung mittels der ausfĂŒhrlich beschriebenen Detailkriterien ist auch eine weniger aufwĂ€ndige Evaluation mit Hilfe einer Kriterienauswahl (Basiskriterien) möglich. Die QualitĂ€tskriterien können auch fĂŒr die Konzipierung neuer transdisziplinĂ€rer Forschungsvorhaben genutzt werden.Transdisciplinary research projects investigate problems from everyday life. Experts from various disciplines and practitioners from the practical field in question have to co-operate to cope with the problem appropriately. Multiple forms of co-operation, differentiation and integration, methods and theories are significant for such projects. So conventional methods of disciplinary evaluation cannot be transferred and applied directly. In this situation, Evalunet, the Network for Transdisciplinary Evaluation, offers this guide, which provides researchers with very detailed evaluation criteria and descriptions of evaluation methods and practices. The criteria and procedures were identified in an empirical process by evaluating a number of transdisciplinary research projects. In this process, the Evalunet team was supported by numerous experts from various research areas. The main purpose of the guide is to provide guidance for the evaluation of transdisciplinary research projects. The criteria mainly support discursive evaluation processes that initiate learning processes for researchers and evaluators (formative evaluation). A set with a reduced number of criteria (Basiskriterien) offers a basic procedure for the evaluation, while the larger set with more detailed criteria (Detailkriterien) provides explanations and assistance in making a judgement. Criteria can also be used for conceiving and constructing new research projects
Stress Constraints From Shear-Wave Analysis in Shallow Sediments at an Actively Seeping Pockmark on the W-Svalbard Margin
Mechanisms related to sub-seabed fluid flow processes are complex and inadequately understood. Petrophysical properties, availability of gases, topography, stress directions, and various geological parameters determine the location and intensity of leakage which change over time. From tens of seafloor pockmarks mapped along Vestnesa Ridge on the west-Svalbard margin, only six show persistent present-day seepage activity in sonar data. To investigate the causes of such restricted gas seepage, we conducted a study of anisotropy within the conduit feeding one of these active pockmarks (i.e., Lunde Pockmark). Lunde is âŒ400â500 m in diameter, and atop a âŒ300â400 m wide seismic chimney structure. We study seismic anisotropy using converted S-wave data from 22 ocean-bottom seismometers (OBSs) located in and around the pockmark. We investigate differences in symmetry plane directions in anisotropic media using null energy symmetries in transverse components. Subsurface stress distribution affects fault/fracture orientations and seismic anisotropy, and we use S-wave and high-resolution 3D seismic data to infer stress regimes in and around the active seep site and study the effect of stresses on seepage. We observe the occurrence of changes in dominant fault/fracture and horizontal stress orientations in and around Lunde Pockmark and conclude minimum (NE-SW) and maximum (SE-NW) horizontal stress directions. Our analysis indicates a potential correlation between hydrofractures and horizontal stresses, with up to a âŒ32% higher probability of alignment of hydrofractures and faults perpendicular to the inferred minimum horizontal stress direction beneath the Lunde Pockmark area
Correction of scan time dependence of standard uptake values in oncological PET
BACKGROUND: Standard uptake values (SUV) as well as tumor-to-blood standard uptake ratios (SUR) measured with [ (18)F-]fluorodeoxyglucose (FDG) PET are time dependent. This poses a serious problem for reliable quantification since variability of scan start time relative to the time of injection is a persistent issue in clinical oncological Positron emission tomography (PET). In this work, we present a method for scan time correction of, both, SUR and SUV. METHODS: Assuming irreversible FDG kinetics, SUR is linearly correlated to K(m) (the metabolic rate of FDG), where the slope only depends on the shape of the arterial input function (AIF) and on scan time. Considering the approximately invariant shape of the AIF, this slope (the âPatlak timeâ) is an investigation independent function of scan time. This fact can be used to map SUR and SUV values from different investigations to a common time point for quantitative comparison. Additionally, it turns out that modelling the invariant AIF shape by an inverse power law is possible which further simplifies the correction procedure. The procedure was evaluated in 15 fully dynamic investigations of liver metastases from colorectal cancer and 10 dual time point (DTP) measurements. From each dynamic study, three âstatic scansâ at T=20,35,and 55 min post injection (p.i.) were created, where the last scan defined the reference time point to which the uptake values measured in the other two were corrected. The corrected uptake values were then compared to those actually measured at the reference time. For the DTP studies, the first scan (acquired at (78.1 ± 15.9) min p.i.) served as the reference, and the uptake values from the second scan (acquired (39.2 ± 9.9) min later) were corrected accordingly and compared to the reference. RESULTS: For the dynamic data, the observed difference between uncorrected values and values at reference time was (-52±4.5)% at T=20 min and (-31±3.7)% at T=35 min for SUR and (-30±6.6)% at T=20 min and (-16±4)% at T=35 min for SUV. After correction, the difference was reduced to (-2.9±6.6)% at T=20 min and (-2.7±5)% at T=35 min for SUR and (1.9% ± 6.2)% at T=20 min and (1.7 ± 3.3)% at T=35 min for SUV. For the DTP studies, the observed differences of SUR and SUV between late and early scans were (48 ± 11)% and (24 ± 8.4)%, respectively. After correction, these differences were reduced to (2.6 ± 6.9)% and (-2.4±7.3)%, respectively. CONCLUSION: If FDG kinetics is irreversible in the targeted tissue, correction of SUV and SUR for scan time variability is possible with good accuracy. The correction distinctly improves comparability of lesion uptake values measured at different times post injection
Investigations of the Oligocene-Miocene opening of the Ligurian Basin using refraction seismic data
The Ligurian Basin is located north-west of Corsica at the transition from the western Alpine orogen to the Apennine system. The Back-arc basin was generated by the southeast trench retreat of the Apennines-Calabrian subduction zone. The opening took place from late Oligocene to Miocene. While the extension led to extreme continental thinning and un-roofing of mantle material little is known about the style of back-arc rifting.
To shed light on the present day crustal and lithospheric architecture of the Ligurian Basin, active seismic data have been recorded on short period ocean bottom seismometers in the framework of SPP2017 4D-MB, the German component of AlpArray. An amphibious refraction seismic profile was shot across the Ligurian Basin in an E-W direction from the Gulf of Lion to Corsica. The profile extends onshore Corsica to image the necking zone of continental thinning.
The majority of the refraction seismic data show mantle phases at offsets up to 70 km. The arrivals of seismic phases were picked and inverted in a travel time tomography. The results show a crust-mantle boundary in the central basin at ~12 km depth below sea surface. The mantle shows rather high velocities >7.8 km/s. The crust-mantle boundary deepens from ~12 km to ~18 km within 25 - 30 km towards Corsica. The results do not map an axial valley as expected for oceanic spreading. However, an extremely thinned continental crust indicates a long lasting rifting process that possibly does not initiated oceanic spreading before the opening of the Ligurian Basin stopped
Pockmarks in the Witch Ground Basin, central north sea
Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. Quantitative estimates for methane release from marine sediments are scarce, and a poorly constrained temporal variability leads to large uncertainties in methane emission scenarios. Here, we use 2âD and 3âD seismic reflection, multibeam bathymetric, geochemical, and sedimentological data to (I) map and describe pockmarks in the Witch Ground Basin (central North Sea), (II) characterize associated sedimentological and fluid migration structures, and (III) analyze the related methane release. More than 1,500 pockmarks of two distinct morphological classes spread over an area of 225 km2. The two classes form independently from another and are corresponding to at least two different sources of fluids. Class 1 pockmarks are large in size (>6 m deep, >250 m long, and >75 m wide), show active venting, and are located above vertical fluid conduits that hydraulically connect the seafloor with deep methane sources. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller (0.9â3.1 m deep, 26â140 m long, and 14â57 m wide) and are limited to the soft, fineâgrained sediments of the Witch Ground Formation and possibly sourced by compactionârelated dewatering. Buried pockmarks within the Witch Ground Formation document distinct phases of pockmark formation, likely triggered by external forces related to environmental changes after deglaciation. Thus, greenhouse gas emissions from pockmark fields cannot be based on pockmark numbers and presentâday fluxes but require an analysis of the pockmark forming processes through geological time
Sector collapse kinematics and tsunami implications - SEKT, Cruise No. M154/1, April 3 - April 25, 2019, Mindelo (Cape Verde) - Point-ĂĄ-Pitre (Guadeloupe)
Summary
Deep-seated collapses of volcanic islands have generated the largest volume mass flows worldwide. These mass flows might trigger mega-tsunamis. The way in which these collapse events are emplaced is poorly understood, even though this emplacement process determines the scale of associated tsunamis. Key questions such as whether they are emplaced in single or multiple events, how they may incorporate seafloor sediment to increase their volume, and how they are related to volcanic eruption cycles and migration of volcanic centers, remain to be answered. This project forms a part of the comprehensive study of large volcanic island landslide deposits and is directly linked to IODP drilling campaign in the Lesser Antilles (IODP Leg 340). Unfortunately, Leg 340 only recovered material from a single site within the volcanic landslide deposits off Montserrat, and even at this site, recovery was not continuous. This single IODP site is insufficient to document lateral variation in landslide character, which is critical for understanding how it was emplaced. The main scientific goals of this project are to determine where the landslides are sourced from; to understand how these landslides are emplaced; and to understand the relationship between landslides, eruption cycles and initiation of new volcanic centres. Combining 3D seismology (Leg 1) and MeBo cores (Leg 2) provides a unique dataset of the internal structure, composition and source of material throughout a volcanic island landslide. The results will significantly contribute to understanding the emplacement of volcanic island landslides and they will allow us to assess the associated tsunami risk
Volcanic Flank Collapse, Secondary Sediment Failure and FlowâTransition:MultiâStage Landslide Emplacement Offshore Montserrat, Lesser Antilles
Volcanic flank collapses, especially those in island settings, have generated some of the most voluminous mass transport deposits on Earth and can trigger devastating tsunamis. Reliable tsunami hazard assessments for flank collapseâdriven tsunamis require an understanding of the complex emplacement processes involved. The seafloor sequence southeast of Montserrat (Lesser Antilles) is a key site for the study of volcanic flank collapse emplacement processes that span subaerial to submarine environments. Here, we present new 2D and 3D seismic data as well as MeBo drill core data from one of the most extensive mass transport deposits offshore Montserrat, which exemplifies multiâphase landslide deposition from volcanic islands. The deposits reveal emplacement in multiple stages including two blocky volcanic debris avalanches, secondary seafloor failure and a lateâstage erosive density current that carved channelâlike incisions into the hummocky surface of the deposit about 15 km from the source region. The highly erosive density current potentially originated from downslopeâacceleration of fineâgrained material that was suspended in the water column earlier during the slide. Lateâstage erosive turbidity currents may be a more common process following volcanic sector collapse than has been previously recognized, exerting a potentially important control on the observed deposit morphology as well as on the runout and the overall shape of the deposit
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