A Brief Account of New Petrographic and Isotopic Insights into the Hertfordshire and Buckinghamshire Puddingstones of SE England

Determining the process of silicification in silcretes is essential to understanding their environmental significance. For the late Paleocene silcretes of the Anglo-Paris basin this is of particular interest due to their association with the PETM (Paleocene-Eocene Thermal Maximum). Here puddingstone samples from Hertfordshire and Buckinghamshire have been examined by optical, BSEM and CL petrography, X-ray diffraction and oxygen isotope analysis. The range of quartz sand luminescence colours indicates a diverse provenance. Flint pebbles show little variability, consistent with a single source. The oxygen isotope compositional range of the flint pebbles is consistent with chemical sedimentation at normal temperatures from Cretaceous seawater, and with the pebbles being derived from the Chalk Group (Upper Cretaceous). The majority of pebbles are well rounded and have an outer zone that is either iron-stained or weathered. Fracturing of pebbles typically post-dates the weathering/oxidation and pre-dates deposition of the pebble bed. A small proportion of the pebbles have been fractured in situ; this fracturing post-dates deposition and pre-dates silicification. Matrix fabrics are diverse, ranging from very fine sand with a cryptocrystalline quartz cement to medium sand with macro-quartz cement with luminescence zoning. Minor formation of authigenic Ti oxides has occurred and locally authigenic Fe oxides are abundant. Ti oxides formed during, or immediately before, silcrete formation, while the Fe oxides are possibly associated with more recent weathering. The oxygen isotope data for the silica cement are consistent with silcrete formation from highlands-derived, low-18O meteoric groundwater at warm near-surface temperatures

Interprofessional Team Reasoning Framework as a Tool for Case Study Analysis with Health Professions Students: A Randomized Study

Background: This pilot study evaluated the efficacy of the Interprofessional Team Reasoning Framework (IPTRF) to facilitate teaching and learning case studies with health professions students.Methods and Findings: Eighteen interprofessional students were randomized to teams of six and were videotaped while completing a case. Team 1 (control) received only the case; team 2 received the case plus framework; and team 3 received the case, framework, and was shown videotaped examples of interprofessional interactions. The primary endpoint was students’ perceptions of interprofessional skills as measured pre and post intervention using a modified Team Skills Scale. The secondary endpoint was student performance as assessed by blinded individuals using a standardized rubric. The results revealed that students’ perceptions of team skills were significantly improved in team 2 and team 3 but not team 1. Students’ performance of their case as assessed by blinded faculty was significantly better in team 3 compared with teams 1 and 2.Conclusions: In this study of six disciplines, the IPTRF, in combination with modeled examples of interprofessional communication, was an effective tool to teach skills necessary to workup a patient case, which included collaboration, communication, and values/ethics. As the landscape of interprofessional education evolves, tools like the IPTRF will facilitate incorporation of these skills into health professions education

Low temperature, authigenic illite and carbonates in a mixed dolomite-clastic lagoonal and pedogenic setting, Spanish Central System, Spain

The aim of this study was to further our understanding of the pedogenic and lacustrine modification of clay minerals. Some of these modifications are of special interest because they constitute reverse weathering reactions, rare in surface environments, and because there is not yet an accurate assessment of their global relevance in mineralogical and geochemical cycles. For this study, two sections from the Central System in Spain were selected. Both are sections through the Uppper Cenomanian-Turonian mixed clastic and carbonate succession, containing both calcite and dolomite, in the Sierra de Guadarrama. Mid-Turonian sea level fall resulted in the formation of a coastal plain environment in which extensive pedogenesis occurred around saline lagoons. The mineralogical changes that have occurred as a result of sedimentation in saline lagoons and as a consequence of pedogenesis are described. Textural relationships indicate that the dolomite cement pre-dates the calcite. Silicate minerals are represented by quartz, kaolinite, illite-smectite, illite, minor plagioclase and alkali feldspar, and trace chlorite and palygorskite. There is a positive correlation between the intensity of pedogenesis and the proportion of illite in the clay assemblage in one of the sections, indicating pedogenic illitisation. In this section, the intensity of the illitisation process increases up, reaching a maximum where pedogenesis is most intense in the middle part, and then decreases as marine influence increases towards the top of the Alcorlo Formation and the overlying marine Tranquera Formation. The clay assemblages are consistent with a slow transformation process from 42 kaolinite to illite by way of illite-smectite, taking place under surface conditions. The illitisation process has resulted in a less Fe-rich, more Mg-, and Al-rich illite than the majority of previously documented cases in the near surface. Formation of Al-rich illite is not therefore restricted to the deep subsurface. The mechanism for low temperature illitisation involves enhanced layer charge resulting from Mg2+ substitution for Al3+ (or Fe3+) and Fe3+ to Fe2+ reduction. Mg2+ enrichment may have occurred principally in saline lagoons or lakes, while Fe3+ to Fe2+ reduction occurred as a result of wetting and drying in a pedogenic environment. So far as it has been possible to establish, this dual mechanism has not previously been documented. This study indicates clearly that the dolomite and calcite are authigenic cements that precipitated in a clastic sediment, probably soon after deposition. Dolomitisation and Mg enrichment of the clay may have occurred at the same time. Seawater is the most probable source of Mg

Mineralogical and geochemical characterisation of warm water, shallow marine glaucony from the Tertiary of the London Basin

Glaucony is present in the Palaeocene sediments of the London Basin, from the Thanet Sand Formation to the gravel beds at the base of the Lower Mottled Beds of the Reading Formation. The Upnor Formation glaucony is a rare example of formation in warm, shallow brackish water and this, combined with the ready availability of fresh material from boreholes, make this study important in developing our understanding of this mineral. Glaucony comprises up to 50% of the Upnor Formation, a grey to green sandstone, of variable thickness and composition, that was deposited in a warm, shallow marine to estuarine environment, ~55.6-56.2 Ma. Using morphological criteria, X-ray diffraction data and K+ abundance, the Upnor glaucony may be defined as evolved. The underlying shallow marine Thanet Sand contains <5% of nascent to slightly evolved glaucony. The REE data for the Upnor Formation suggest more than one source for the sediment from which the Upnor glaucony formed, while the Thanet REE data are consistent with a high detrital clay component. In the Upnor Formation, the high proportion of glaucony that occurs as granule fragments rather than whole granules, and the high energy estuarine to shallow marine environment of deposition, are indicative of reworking. The Upnor glaucony is inferred to be intraformationally reworked, rather than derived from the Thanet Sand Formation. The glaucony may have formed in sediments deposited away from the main estuarine channel, and been subsequently reworked into higher energy sediments. Warm seas with freshwater mixing are more typically characteristic of verdine formation than of glaucony. The shallow, brackish environment of deposition suggests that there is not a clear distinction between the environmental requirements of verdine (or odinite) and glaucony (or glauconite), as is often proposed. The highly fractured, delicate nature of some granules indicates that they have experienced some maturation in situ, after reworking. The oxygen and hydrogen isotopic compositions of Upnor Formation shark teeth and glaucony point to formation in low salinity water at ~23±3°C, also consistent with formation in the Upnor Formation, rather than in a fully marine sediment and subsequent reworking. A higher than normal temperature of formation may have increased the rate of evolution of glaucony. Our multidisciplinary study considers many of the factors relating to depositional environment that must be considered when glaucony rich facies are encountered in comparable palaeoenvironmental settings elsewhere in the geological record

Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB

With the emergence of multidrug-resistant strains of <i>Mycobacterium tuberculosis</i> there is a pressing need for new oral drugs with novel mechanisms of action. Herein, we describe the identification of a novel morpholino–thiophenes (MOT) series following phenotypic screening of the Eli Lilly corporate library against <i>M. tuberculosis</i> strain H37Rv. The design, synthesis, and structure–activity relationships of a range of analogues around the confirmed actives are described. Optimized leads with potent whole cell activity against H37Rv, no cytotoxicity flags, and in vivo efficacy in an acute murine model of infection are described. Mode-of-action studies suggest that the novel scaffold targets QcrB, a subunit of the menaquinol cytochrome <i>c</i> oxidoreductase, part of the bc1-aa3-type cytochrome <i>c</i> oxidase complex that is responsible for driving oxygen-dependent respiration

Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for use in the treatment of African animal trypanosomiasis

African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites Trypanosoma congolense and Trypanosoma vivax, is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12

Evolution of the Toarcian (Early Jurassic) carbon-cycle and global climatic controls on local sedimentary processes (Cardigan Bay Basin, UK)

The late Early Jurassic Toarcian Stage represents the warmest interval of the Jurassic Period, with an abrupt rise in global temperatures of up to ∼7 °C in mid-latitudes at the onset of the early Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma). The T-OAE, which has been extensively studied in marine and continental successions from both hemispheres, was marked by the widespread expansion of anoxic and euxinic waters, geographically extensive deposition of organic-rich black shales, and climatic and environmental perturbations. Climatic and environmental processes following the T-OAE are, however, poorly known, largely due to a lack of study of stratigraphically well-constrained and complete sedimentary archives. Here, we present integrated geochemical and physical proxy data (high-resolution carbon-isotope data (δ13C), bulk and molecular organic geochemistry, inorganic petrology, mineral characterisation, and major- and trace-element concentrations) from the biostratigraphically complete and expanded entire Toarcian succession in the Llanbedr (Mochras Farm) Borehole, Cardigan Bay Basin, Wales, UK. With these data, we (1) construct the first high-resolution biostratigraphically calibrated chemostratigraphic reference record for nearly the complete Toarcian Stage, (2) establish palaeoceanographic and depositional conditions in the Cardigan Bay Basin, (3) show that the T-OAE in the hemipelagic Cardigan Bay Basin was marked by the occurrence of gravity-flow deposits that were likely linked to globally enhanced sediment fluxes to continental margins and deeper marine (shelf) basins, and (4) explore how early Toarcian (tenuicostatum and serpentinum zones) siderite formation in the Cardigan Bay Basin may have been linked to low global oceanic sulphate concentrations and elevated supply of iron (Fe) from the hinterland, in response to climatically induced changes in hydrological cycling, global weathering rates and large-scale sulphide and evaporite deposition

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy