New Insight into the depositional and tectonic constraints over the Paleogene and Neogene evolution within the Arabian Peninsula

Geological studies over the Arabian Peninsula were initiated in the 1930s, and 30 years later an area equivalent to 3.5 million km2 was covered, laying the groundwork for the stratigraphic nomenclature of the Arabian Peninsula. Since then, not much has changed in terms of formation ages and formation naming, where subsequent authors largely took the results of the earlier work for granted. This thesis will evaluate the sedimentological and depositional facies of exposed rock units in the countries of Kuwait and Bahrain with the objective of developing a depositional facies model that can explain the complex facies architecture. During this study, it was revealed that the exposed rock units in Kuwait at the Jal Az-Zor escarpment all belong to the Lower Fars Formation (also known as Kuwait Formation), whereas previous interpretations assigned these rocks to Ghar, Lower Fars, and Dibdibba formations. This study further revealed that the depositional environment of the Lower Fars Formation is dominated by marginal marine deposits manifested by a riverine to tidally influenced estuary setting, which is contrasting to the fluvio-deltaic setting within previous interpretations. The origin of the NE-SW trending Jal Az-Zor escarpment has been disputed in Kuwait, where it has been proposed either a surface erosion expression, or an underlying unspecified basement fault. Detailed 2D seismic processing and interpretation revealed unprecedented structural features such as detachment, tight concentric and recumbent folds, thrust faults, and fault propagation folds. Tectonic deformation of the Kuwait Formation within the subsurface at the Jal Az-Zor escarpment reflects the initial stage of fault propagation folding resulting from the Kuwait Arch plunge towards the south of the Jal Az-Zor area. Kinematic analysis suggests that the Jal Az-Zor escarpment is a surface expression of a principal displacement zone that is dominated by dextral strike-slip motion and is found to play a major role in the rotation of the Arabian Plate since the early Pleistocene (Calabrian). Throughout this study, it has been observed that detachment could have occurred along the Dammam and Rus formations. Subsequent analysis of the composition of these two formations indicates that the Rus Formation exhibits a greater potential for generating detachment surfaces. The Rus Formation was earlier thought to be dominated by evaporites which favours detachment and was considered a regional seal covering the majority of the Arabian Peninsula. However, detailed sedimentological field work at the Horse-Racing Club outcrop in Bahrain and subsequent published borehole data suggest that the Rus Formation in Bahrain is predominantly composed of dolomites. These changes in understanding facies types and spatial distribution open the door for an in-depth evaluation of the whole Arabian Peninsula facies distribution. The complexity of the Arabian Peninsula's sedimentology and structural development was highlighted in this thesis, demonstrating the need for a re-evaluation of the region's facies nomenclature and tectonic history in light of current geological knowledge and newly available data.----- Arabian niemimaan geologiset tutkimukset alkoivat 1930-luvulla. 30 vuotta myöhemmin tutkimukset kattoivat koko 3.5 miljoonan neliökilometrin suuruisen alueen sekä olivat luoneet pohjan Arabian niemimaan stratigrafiselle terminologialle. Sen jälkeen monetkaan asiat muodostumien iän ja nimeämisen suhteen eivät ole muuttuneet, koska uudempien tutkimustulosten julkaisijat ovat pitäneet aiempien töiden tuloksia pitkälti itsestäänselvyytenä. Tässä opinnäytetyössä esitetään ja läpikäydään Kuwaitin ja Bahrainin alueella paljastuneiden kivilajiyksiköiden sedimentologisia ominaispiirteitä, ja työn tavoitteena on laatia näiden yksiköiden perusteella kerrostumismalli, niin kutsuttu fasiesmalli, joka selittää niiden monimutkaisen ilmenemisen nykypäivänä. Tutkimuksessa havaittiin, että Kuwaitin Jal Az-Zorin kivilajiyksiköt kuuluvat kaikki Alempaan Farsin Muodostumaan (tunnetaan myös nimellä Kuwaitin Muodostuma; Fm), kun taas aikaisempien tulkintojen mukaan yksiköt kuuluvat muodostumiin Ghar Fm, Alempi Fars Fm ja Dibdibba Fm. Tutkimuksessa havaittiin lisäksi, että Alemman Farsin Muodostuman kerrostumisympäristöä hallitsee matalan meren kerrostumisympäristö, jota luonnehtii mm. joki- ja vuorovesivaikutteisen suistoalueen sedimentaatio. Tämän tyyppinen kerrostumisympäristö on ristiriidassa aiempien tulkintojen mukaisen joki-delta ympäristön kanssa. Kuwaitissa sijanitsevan, Koillis-lounas -suuntaisen Jal Az-Zorin jyrkänteen alkuperä on kiistelty, ja sen synty on liitetty joko maankamaran eroosioon tai jyrkänteen alapuolella olevan, muuten tuntemattoman siirroksen olemassaoloon. Seismisten aineistojen yksityiskohtaisen 2D-prosessoinnin ja tulkinnan perusteella kohteesta tunnistettiin mm. aiemmin tuntemattomia ylityöntösiirroksia sekä näihin liittyviä poimuja. Niiden perusteella Kuwaitin Muodostuman tektoninen deformaatio Jal Az-Zorin jyrkänteen alapuolisessa kallioperässä heijastaa siirroksen etenemiseen liittyvän poimutuksen varhaisia vaiheita, jotka voidaan edelleen yhdistää Kuwaitin kaaren kohti etelää suuntautuneeseen kohoamiseen. Nyt tuotettu kinemaattinen analyysi viittaa siihen, että Jal Az-Zorin jyrkänne on ilmentymä syvemmällä olevasta siirrosvyöhykkeestä, jota luonnehtii oikeakätinen vaakasuuntainen siirtymä, ja jolla oli merkittävä myötävaikutus Arabian laatan kiertymisessä myötäpäivään varhaisen Pleistoseeniepookin (Calabrian) aikana. Kauttaaltaan tässä tutkimuksessa on havaittu, että Dammam ja Rus Muodostumissa voi esiintyä rakenteellisia irtautumisvyöhykkeitä. Näiden kahden muodostuman koostumuksen tarkempi analyysi osoitti, että irtautumisvyöhykkeet esiintyvät todennäköisemmin Rus Muodostumassa. Aiemmissa töissä Rus Muodostuman arveltiin koostuvan vallitsevasti evaporiiteista, joka suosii teoriaa irtautumisvyöhykkeiden syntymisestä. Samalla muodostumaa pidettiin hydraulisesti johtamattomana sulkupintana (seal), joka peittää suurimman osan Arabian niemimaasta. Yksityiskohtaiset sedimentologiset kenttätyöt Horse-Racing Clubin paljastumalla Bahrainissa, ja myöhemmin julkaistut kairaustiedot viittaavat kuitenkin siihen, että Bahrainin puolella oleva Rus Muodostuma koostuu pääasiassa dolomiiteista. Nämä muutokset alueen fasiestyyppeihin ja niiden alueellisen jakautumiseen auttavat ymmärtämään koko Arabian niemimaan kallioperän litofasieksia aivan uudella tavalla ja avaavat uusia näkökulmia niiden syvälliseen tarkasteluun. Tässä opinnäytetyössä korostettiin Arabian niemimaan sedimentologian ja rakenteellisen kehityksen monimutkaisuutta. Tutkimus osoittaa, että alueen fasieksiin liittyvää terminologiaa ja tektonista historiaa on arvioitava uudelleen nykyisen geologisen tiedon ja uusien aineistojen valossa

Insights into the development of peri-biliary fibrosis following hepatic ischaemia-reperfusion injury and the ameliorating effect of PXR activation

PhD ThesisDespite progress in liver transplantation, biliary complications such as nonanastomotic biliary strictures (NABS) remain its “Achilles heel” and our understanding of the pathogenesis of these lesions remains limited. An inflammatory process following reperfusion injury of the liver is a possible cause for this pathology. The pregnane X receptor (PXR) has gained interest in recent years as a potential therapeutic target for inflammatory bowel and liver conditions. Its role in ischaemia reperfusion injury (IRI) following liver transplantation remains unexplored. The aim of this project was to investigate the development of biliary pathology following ischaemia reperfusion injury and the potential beneficial effect of PXR activation on these lesions. In vitro studies on the pro-fibrotic effect of varying oxygen conditions on human biliary epithelial cells were carried out initially, followed by an in vivo rat model of hepatic ischaemia reperfusion injury to sequentially examine the progression of fibrosis following hepatic IRI and the potential ameliorating effect of PXR activation on this. The project culminates in a retrospective clinical study to confirm the benefit of PXR activation in a cohort of liver transplant recipients The in vitro studies highlighted an active pro-inflammatory role for biliary epithelial cells when subjected to oxygen after a period of hypoxia. Moreover, hepatic IRI was found to cause persistent inflammatory and fibrotic changes beyond the initial ischaemic insult in the in vivo rat model. Activation of the PXR led to a reduction in post-IRI cellular damage, inflammation and fibrosis in the animal model and these promising findings were supported in the clinical study which highlighted a beneficial role for PXR activation in reducing anastomotic biliary strictures and ultimately improving patient survival following liver transplantation This project provides further insight into the pathogenesis of biliary lesions following reperfusion injury and shed further light on the potential role for PXR activation in improving graft outcomes following liver transplantation. It also opens the door for novel therapies such as the use of PXR activators in perfusion fluid, potentially optimising the organ donation pool.Libyan Ministry of Higher Education and Scientific Researc

007 Khaled Amrouni et.al,2015-Poster of Petrographic Methods: Integrated Quantitative and Qualitative Petrographic and Diagenetic Methods to define Carbonate Outcrop and Reservoir...

The petrographic and diagenetic lab work of the Cyrenaican Miocene carbonate rocks northeast Libya involves an intensive study of 503 hand samples and their thin sections. 148 samples of the measured field section A1 of 74m thick were selected at 0.5 m intervals and then prepared to be studied. Proper thin sections preparation required insertion of some dyes and chemical treatments. Blue dye was inserted into the epoxy of all thin sections to enhance porosity identification. Alizarin Red-S stain was used to distinguish between calcite and dolomite minerals, and potassium ferricyanide stain was used to differentiate ferroan from non-ferroan carbonate minerals. For the petrographic work, a three part thin section description scheme was established and followed. It includes: 1) quantitative analysis, 2) qualitative analysis, and 3) diagenetic process and their paragenetic sequence. The quantitative part involved determining the type and percentage of grains/fossils, matrix, cement, and pores. The qualitative studies rock textures (fabrics and grain size), sedimentary structures (primary and secondary), and trace fossils. Diagenetic processes includes micritization, dissolution/leaching (pore creations), cementation (pore destruction), compaction (mechanical and chemical), and neomorphism (recrystallization, inversion, and replacement). Through the cross cutting relationship the paragenetic sequence were defined by putting each diagenetic event in its proper relative time order of occurrence. The most important final products of these integrated petrographic and diagenetic methods are curves that define vital reservoir rocks characterizations such as high/low porosity zones and their types, high/low cement zones and their types, grain dominated versus mud dominated zones, high/low diagenetically affected zones and type of diagenesis, bio-zones, dolomite versus calcite zones, carbonate texture curves, dolomite types and zones, and a chart of the paragenetic sequence of the diagenetic events and their processes. In addition, the depositional and diagenetic reservoir properties are interpreted in the sedimentological and sequence stratigraphic context of the studied Cyrenaican Miocene sequence to determine the extent at which the relative sea level changes and tectonics could control the carbonate reservoir properties

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Expression of Mesenchymal and alpha-Cell PhenotypicMarkers in Islet beta-Cells in Recently Diagnosed Diabetes

OBJECTIVE: Relative contributions of reversible β-cell dysfunction and true decrease in β-cell mass in type 2 diabetes remain unclear. Definitive rodent lineage-tracing studies have identified β-cell dedifferentiation and subsequent reprogramming to α-cell fate as a novel mechanism underlying β-cell failure. The aim was to determine whether phenotypes of β-cell dedifferentiation and plasticity are present in human diabetes. RESEARCH DESIGN AND METHODS: Immunofluorescence colocalization studies using classical endocrine and mesenchymal phenotypic markers were undertaken using pancreatic sections and isolated islets from three individuals with diabetes and five nondiabetic control subjects. RESULTS: Intraislet cytoplasmic coexpression of insulin and vimentin, insulin and glucagon, and vimentin and glucagon were demonstrated in all cases. These phenotypes were not present in nondiabetic control subjects. CONCLUSIONS: Coexpression of mesenchymal and α-cell phenotypic markers in human diabetic islet β-cells has been confirmed, providing circumstantial evidence for β-cell dedifferentiation and possible reprogramming to α-cells in clinical diabetes

Treatment of Visceral Transplant Pseudoaneurysms Using Physician-Modified Fenestrated Stent Grafts: Initial Experience

Pseudoaneurysms after visceral transplantation represent a significant risk to patients. We report the successful treatment of three transplant (pancreas, liver and kidney) artery anastomotic pseudoaneurysms using physician-modified fenestrated endovascular stent grafts. In all cases, surgical repair was considered high risk and would have compromised the arterial supply to the graft. The endovascular approach in all cases obviated the need for surgical intervention and maintained graft arterial supply

Progenitor-derived hepatocyte-like (B-13/H) cells metabolise 1'-hydroxyestragole to a genotoxic species via a SULT2B1-dependent mechanism

Rat B-13 progenitor cells are readily converted into functional hepatocyte-like B-13/H cells capable of phase I cytochrome P450-dependent activation of pro-carcinogens and induction of DNA damage. The aim of the present study was to investigate whether the cells are also capable of Phase II sulphotransferase (SULT)-dependent activation of a pro-carcinogen to an ultimate carcinogen. To this end we therefore examined the bioactivation of the model hepatic (hepato- and cholangio-) carcinogen estragole and its proximate SULT1A1-activated genotoxic metabolite 1'-hydroxyestragole. Exposing B-13 or B-13/H cells to estragole (at concentrations up to 1mM) resulted in the production of low levels of 1'-hydroxyestragole, but did not result in detectable DNA damage. Exposing B-13/H cells - but not B-13 cells - to 1'-hydroxyestragole resulted in a dose-dependent increase in DNA damage in comet assays, confirmed by detection of N2-(trans-isoestragol-3'-yl)-2'-deoxyguanosine adducts. Genotoxicity was inhibited by general SULT inhibitors, supporting a role for SULTS in the activation of 1-hydroxyestragole in B-13/H cells. However, B-13 and B-13/H cells did not express biologically significant levels of SULT1A1 as determined by qRT-PCR, Western blotting and its associated 7-hydroxycoumarin sulphation activity. B-13 and B-13/H cells expressed - relative to intact rat liver - high levels of SULT2B1 (primarily the b isoform) and SULT4A1 mRNAs and proteins. B-13 and B-13/H cells also expressed the 3'-phosphoadenosine 5'-phosphosulphate synthase 1 required for the generation of activated sulphate cofactor 3'-phosphoadenosine 5'-phosphosulphate. However, only B-13/H cells expressed functional SULT activities towards SULT2B1 substrates DHEA, pregnenolone and 4 methylumbelliferone. Since liver progenitor cells are bi-potential and also form cholangiocytes, we therefore hypothesised that B-13 cells express a cholangiocyte-like SULT profile. To test this hypothesis, the expression of SULTs was examined in liver by RT-PCR and immunohistochemistry. SULT2B1 - but not SULT1A1 - was determined to be expressed in both rat and human cholangiocytes. Since 1'-hydroxyestragole exposure readily produced DNA injury in B-13/H cells, these data suggest that cholangiocarcinomas generated in rats fed estragole may be dependent, in part, on SULT2B1 activation of the 1'-hydroxyestragole metabolite

Cardiorespiratory Optimisation By Arteriovenous fistula Ligation after renal Transplantation (COBALT): study protocol for a multicentre randomised interventional feasibility trial

IntroductionCardiovascular events are a major cause of mortality following successful kidney transplantation.Arteriovenous fistulas (AVFs) are considered the best option for haemodialysis, but may contribute to this excess mortality because they promote adverse cardiac remodelling and ventricular hypertrophy. This raises the question whether recipients with a well-functioning kidney transplant should undergo elective AVF ligation.Methods and analysisThe COBALT feasibility study is a multicentre interventional randomised controlled trial (RCT) that will randomise renal transplant patients with stable graft function and a working AVF on a 1:1 basis to standard care (continued conservative management) or to AVF ligation. All patients will perform cardiopulmonary exercise testing (CPET) on recruitment and 6 months later. Daily functioning and quality of life will be additionally assessed by questionnaire completion and objective measure of physical activity. The primary outcome—the proportion of approached patients who complete the study (incorporating rates of consent, receipt of allocated intervention and completion of both CPETs without withdrawal)—will determine progression to a full-scale RCT. Design of the proposed RCT will be informed by an embedded qualitative assessment of participant and healthcare professional involvement.Ethics and disseminationThis study has been approved by the East Midlands—Derby Research Ethics Committee (22/EM/0002) and the Health Research Authority. The results of this work will be disseminated academically through presentation at national and international renal meetings and via open access, peer-reviewed outputs. Existing networks of renal patient groups will also be used to disseminate the study findings to other key stakeholders.Trial registration numberISRCTN49033491.</jats:sec

Sustained Isoprostane E2 Elevation, Inflammation and Fibrosis after Acute Ischaemia-Reperfusion Injury Are Reduced by Pregnane X Receptor Activation

<div><p>Liver grafts donated after cardiac death are increasingly used to expand the donor pool but are prone to ischaemic-type biliary lesions. The anti-inflammatory effects of the activated pregnane X receptor have previously been shown to be beneficial in a number of inflammatory liver conditions. However, its role in reducing peri-portal inflammation and fibrosis following ischaemia-reperfusion injury has not been investigated. Hepatic injury and its response to pregnane X receptor activation was examined after partial hepatic ischaemia-reperfusion injury induced by surgically clamping the left and middle lobar blood vessels in rats. Molecular and pathological changes in the liver were examined over the following 28 days. Ischaemia-reperfusion injury resulted in transient cholestasis associated with microvillar changes in biliary epithelial cell membranes and hepatocellular injury which resolved within days after reperfusion. However, in contrast to chemically-induced acute liver injuries, this was followed by sustained elevation in isoprostane E2, peri-portal inflammation and fibrosis that remained unresolved in the ischaemic reperfused lobe for at least 28 days after clamping. Administration of pregnenolone-16α-carbonitrile—a rodent-specific pregnane X receptor activator—resulted in significant reductions in cholestasis, hepatic injury, ischaemic lobe isoprostane E2 levels, peri-portal inflammation and fibrosis. Hepatic ischaemia-reperfusion injury therefore results in inflammatory and fibrotic changes that persist well beyond the initial ischaemic insult. Drug-mediated activation of the pregnane X receptor reduced these adverse changes in rats, suggesting that the pregnane X receptor is a viable drug target to reduce ischaemic-type biliary lesions in recipients of liver transplants donated after cardiac death.</p></div