Natural hydraulic fractures in the Wessex Basin, SW England: widespread distribution, composition and history

International audienceBedding-parallel veins of fibrous calcite ('beef') are historical in the Wessex Basin. The veins are common in Mesozoic mudstones and shales, especially of Liassic to Mid-Cretaceous ages. Cone-in-cone structures, which consist of multiple nested cones, are also well developed within the 'beef'. To investigate the distribution and the context of formation of 'beef' in the basin, we have made several field studies and analysed numerous samples. The veins are widespread vertically and horizontally in the sedimentary sequence, but they are especially common near or within potential source rocks for petroleum or near major tectonic faults. The internal structures of some 'beef' veins have revealed that they formed during Late Cretaceous to Tertiary compressional inversion of the basin. The typical composition for 'beef' is of calcite, with some pyrite and fragments of shale. However, inclusions or patches of hydrocarbons (liquid or solid) occur within calcite crystals or between fibres, respectively. According to some previous studies, as well as ours, 'beef' veins of the Wessex Basin represent natural hydraulic fractures, which formed as a result of fluid overpressure. This may have resulted in part from chemical compaction of petroleum source rocks, during Late Cretaceous to Tertiary times. Indeed, source rocks at outcrop in the Wessex Basin could be more mature than previously thought and the 'beef' veins may be good markers of maturation

Cenozoic reactivation of the Great Glen Fault, Scotland: additional evidence and possible causes

International audienceThe Great Glen Fault trends NNE-SSW across northern Scotland. According to previous studies, the Great Glen Fault developed as a left-lateral strike-slip fault during the Caledonian Orogeny (Ordovician to Early Devonian). However, it then reactivated right-laterally in the Tertiary. We discuss additional evidence for this later phase. At Eathie and Shandwick, minor folds and faults in fossiliferous Jurassic marine strata indicate post-depositional right-lateral slip. In Jurassic shale, we have found bedding-parallel calcite veins ('beef' and 'cone-in-cone') that may provide evidence for overpressure development and maturation of organic matter at significant depth. Thus, the Jurassic strata at Eathie and Shandwick accumulated deeper offshore in the Moray Firth and were subject to Cenozoic exhumation during right-lateral displacement along the Great Glen Fault, as suggested by previous researchers. Differential sea-floor spreading along the NE Atlantic ridge system generated left-lateral transpressional displacements along the Faroe Fracture Zone from the Early Eocene to the Late Oligocene (c. 47-26 Ma), a period of uplift and exhumation in Scotland. We suggest that such differential spreading was responsible for reactivation of the Great Glen Fault. Indeed, leftlateral slip along the Faroe Fracture Zone is compatible with right-lateral reactivation of the Great Glen Fault

Surpression de fluides et fracturation de roches mères en différents contextes tectoniques (modélisation analogique et exemples de terrain)

L'étude des surpressions de fluide et de fracturation hydraulique des roches mères peut nous renseigner sur les mécanismes de génération qui en sont à l'origine. Ces dernières années, l'intérêt pour ces phénomènes s'est largement accru, notamment sous l'influence des sociétés pétrolières qui exploitent les ressources non-conventionnelles au cœur des problèmes énergétiques actuels. Dans ce travail de thèse, nous avons choisi deux approches différentes pour l'étude de ces mécanismes : (1) des exemples de cas géologiques naturels, et (2) le développement de la modélisation analogique. Ainsi, nous montrons que ces phénomènes sont très répandus au sein des bassins sédimentaires et que leurs manifestations s'expriment notamment par la génération de veines fibreuses parallèles à la stratification de la roche (beef), mais également par la formation de veines d'hydrocarbures solides (bitume). Nous démontrons également que les surpressions de fluides peuvent profondément changer le style de déformation d'un bassin sédimentaire par la génération de niveaux de décollement localisés au sein même des roches mères. Enfin, à l'aide de la modélisation analogique, nous avons pu identifier les mécanismes à l'origine des surpressions de fluide et de la fracturation hydraulique. En effet, lors de la génération d'hydrocarbures la transformation de solide à liquide de la matière organique conduit à la compaction chimique des sédiments. Par un mécanisme de transfert de charge lors de ce processus, ainsi que par l'accroissement de volume associé, des surpressions de fluides se développent et atteignent des pressions lithostatiques, capables de fracturer hydrauliquement les roches.The study of fluid overpressures and hydraulic fracturing in source rocks can help us to understand the mechanisms, which are responsable for these phenomena. During the last few years, the interest in such processes has highly grown, especially through the influence of petroleum companies, which extract hydrocarbons from unconventional reservoirs. In this work, we have chosen to develop two different approaches for the study of these mechanisms: (1) field studies and (2) physical modelling. Thereby, we show that fluid overpressures and hydraulic fracturing are common in sedimentary basins worldwide. Bedding-parallel fibrous veins (beef) and solid hydrocarbon veins (bitumen) are the resulting structures. We also show that fluid overpressures can highly affect the deformation style in sedimentary basins, especially by causing thrust-detachments within source rocks. By the using of a new physcial modelling technique, we have identified the mechanisms, which are responsible for fluid overpressures and hydraulic fracturing. Indeed, during hydrocarbon generation, the solid organic matter becomes liquid, which leads to chemical compaction of the sediment. By a mechanism of load transfer, fluid overpressures rise to lithostatic values. However, volume changes also contribute, and are able to induce hydraulic fractures in the rocks.RENNES1-Bibl. électronique (352382106) / SudocSudocFranceF

Geological evidence for fluid overpressure, hydraulic fracturing and strong heating during maturation and migration of hydrocarbons in Mesozoic rocks of the northern Neuquén Basin, Mendoza Province, Argentina

International audienceIn the northern Neuquén Basin of Argentina (especially in Mendoza Province), there is strong geological evidence for fluid overpressure in the past. The evidence takes the form of bitumen veins and bedding-parallel veins of fibrous calcite ('beef'). Such veins are widespread in the fold-and-thrust belt of the Malargűe area, where bitumen mining has been active for a century or so. So as to collect information on the development of fluid overpressure in this part of the Neuquén Basin, several old mines were visited and studied in the Malargűe area. Here the bitumen veins have intruded mainly the Late Jurassic to Early Cretaceous Mendoza Group, but also the Late Cretaceous Neuquén Group. The veins have the forms of bedding-parallel sills or dykes and they are especially thick within anticlines, forming saddle-reefs in several places. Beef veins are also numerous in the Malargűe area. They contain bitumen and therefore seem to have formed at the same time as the bitumen veins. Near many outcrops of bitumen and beef, we have found fine-grained volcanic intrusive bodies. The best examples are from the La Valenciana syncline. According to 39 Ar-40 Ar dating, these bodies are mainly of Mid-Miocene age. More generally, volcanism, deformation and maturation of source rocks seem to have reached a climax in Miocene times, when the subducting Pacific slab became relatively flat

Physical modelling of chemical compaction, overpressure development, hydraulic fracturing and thrust detachments in organic-rich source rock

International audienceGeological evidence for overpressure is common worldwide, especially in petroleum-rich sedimentary basins. As a result of an increasing emphasis on unconventional resources, new data are becoming available for source rocks. Abnormally high values of pore fluid pressure are especially common within mature source rock, probably as a result of chemical compaction and increases in volume during hydrocarbon generation. To investigate processes of chemical compaction, overpressure development and hydraulic fracturing, we have developed new techniques of physical modelling in a closed system. During the early stages of our work, we built and deformed models in a small rectangular box (40 40 10 cm), which rested on an electric flatbed heater; but more recently, in order to accommodate large amounts of horizontal shortening, we used a wider box (77 75 10 cm). Models consisted of horizontal layers of two materials: (1) a mixture of equal initial volumes of silica powder and beeswax micro-spheres, representing source rock, and (2) pure silica powder, representing overburden. By submerging these materials in water, we avoided the high surface tensions, which otherwise develop within pores containing both air and liquids. Also we were able to measure pore fluid pressure in a model well. During heating, the basal temperature of the model surpassed the melting point of beeswax (w62 C), reaching a maximum of 90 C. To investigate tectonic contexts of compression or extension, we used a piston to apply horizontal displacements. In experiments where the piston was static, rapid melting led to vertical compaction of the source layer, under the weight of overburden, and to high fluid overpressure (lithostatic or greater). Crosssections of the models, after cooling, revealed that molten wax had migrated through pore space and into open hydraulic fractures (sills). Most of these sills were horizontal and their roofs bulged upwards, as far as the free surface, presumably in response to internal overpressure and loss of strength of the mixture.We also found that sills were less numerous towards the sides of the box, presumably as a result of boundary effects. In other experiments, in which the piston moved inward, causing compression of the model, sills also formed. However, these were thicker than in static models and some of them were subject to folding or faulting. For experiments, in which we imposed some horizontal shortening, before the wax had started to melt, fore-thrusts and back-thrusts developed across all of the layers near the piston, producing a high-angle prism. In contrast, as soon as the wax melted, overpressure developed within the source layer and a basal detachment appeared beneath it. As a result, thin-skinned thrusts propagated further into the model, producing a low-angle prism. In some experiments, bodies of wax formed imbricate zones within the source layer. Thus, in these experiments, it was the transformation, from solid wax to liquid wax, which led to chemical compaction, overpressure development and hydraulic fracturing, all within a closed system. According to the measurements of overpressure, load transfer was the main mechanism, but volume changes also contributed, producing supra-lithostatic overpressure and therefore tensile failure of the mixture

Effects of margin-parallel shortening and density contrasts on back-arc extension during subduction: Experimental insights and possible application to Anatolia

International audienceSo as to investigate the parameters influencing subduction and back-arc extension, we have done three series of laboratory experiments (32 in all) on physical models. Each model consisted of adjacent oceanic and continental plates, floating on an asthenosphere. In experiments of Series A, a wide rigid piston, moving horizontally, controlled the rate of convergence of the oceanic and continental plates, whereas, in Series B or C, a wide or narrow piston produced lateral compression, parallel to the continent-ocean boundary (COB) and perpendicular to the subduction direction. The parameters that we tested were (1) the velocity of plate convergence (Series A), (2) the width of the compressing piston (Series B and C), and (3) the density ratio between oceanic and continental plates (Series B and C). This density ratio was a key factor. For a ratio of 1.4, the amount of extension in the continental plate increased regularly throughout time; for a ratio of 1.3, the extension remained small, until the piston stopped moving laterally; and for a ratio of 1.1, there was little or no extension. The width of the compressing piston had a smaller effect, although a narrow piston provided more space, into which the continental plate could extend. One possible application of our models is to Anatolia. Despite similar geological settings, the areas north of the Hellenic and Cyprus subduction zones differ, in that extension is large in the former and much smaller in the latter. We suggest that one of the main driving forces for Aegean extension may have been a high density ratio between subducting oceanic lithosphere and a Hellenic-Balkanic upper plate

Calcium transients in single adrenal chromaffin cells detected with aequorin

AbstractThe effect of 55 mM K+ and nicotine on intracellular free calcium was monitored in bovine adrenal chromaffin cells microinjected with aequorin. In contrast to results with quin 2, which suggested that stimulation of chromaffin cells resulted in sustained rises in free calcium, aequorin measurements showed that 55 mM K+ and nicotine resulted in a transient (60–90 s) elevation of free calcium. The peak free calcium and duration of the transient elicited by nicotine were dose-dependent. The concentration of nicotine (10 μM) giving a maximal secretory response gave a peak rise in free calcium of up to 1 μM. 55 mM K+ which only releases 30% of the catecholamine released by 10 μM nicotine generated a calcium transient indistinguishable from that due to 10 μM nicotine. These results support the idea that nicotinic agonists generate an alternative second messenger in addition to the rise in free calcium

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival