Upper Ordovician hardgrounds – from localized surfaces to global biogeochemical events

Upper Ordovician hardgrounds display a spectrum of complexity reflecting a range of local to global-scale processes. Hardgrounds are cemented seafloor surfaces typically marked by the presence of encrusting taxa and borings. Many hardgrounds show evidence for successive episodes of colonization by hard substrate specialists and are associated with localized evidence of seafloor erosion such as overhangs and reworked concretions. They commonly show trace amounts of pyrite and dolomite cements indicating an association with sulfate reduction. The most widespread hardgrounds are highly complex and unravelling their history provides insights into global biogeochemical events. The Curdsville and Kirkfield hardgrounds in the Appalachian Basin (Kentucky and Ontario) represent relatively simple end members of the hardground spectrum. They covered 10s to 100s km2 and formed relatively quickly during the early Katian. They display both planar to subplanar and hummocky to topographically complex surfaces (cm-scale) and contain highly diverse encrusting echinoderm faunas. Study of these surfaces yields important insights into the evolutionary history of encrusting communities. By contrast, the slightly younger hardground at the top of the Galena Group (Ka1) is a surface that is present throughout most of the Midcontinent Basin (>7.5 à 105km2). It is an example of a highly complex surface that was repeatedly modified by erosion and mineralization. Near the eastern margin of the basin in Indiana, the capping Galena hardground is pinnacled with cavity-filling sharpstone clasts, phosphate grains and bored crusts, iron ooids, and pyritic impregnated surfaces. It is onlapped by graptolitic shales of the Kope Formation (Fm) (Ka1) indicating an unconformity of approximately 1 m.y. To the west, in Illinois, the Kope Fm is erosionally truncated and the hardground is directly overlain by graptolitic shales of the Waynesville Fm (Ka3), where the unconformity expands to nearly 4 m.y. Toward Iowa, the hardground is onlapped by meters of phosphorite. Taken together, these observations reveal that the capping Galena Group hardground reflects a complicated history of repeated subaerial exposure, karsting, and marine flooding by a dysoxic to anoxic water mass with fluctuating redox conditions, similar to the age equivalent hardground at the base of the Fjäcka Shale in the Baltic Basin. Thus, hardground studies provide important insights for resolving the temporal continuity of the Upper Ordovician rock record and unravelling processes that controlled carbonate precipitation and dissolution and the evolution of sea floor communities. Some simple hardgrounds may have formed through random exhumation of cemented sediments on the sea floor through the effects of storm scour. However, their clustering into certain portions of the Upper Ordovician suggests that processes that affected sea water chemistry may also be involved. The most complex surfaces reflect major environmental perturbations with large amplitude sea level oscillations and redox changes that in some cases generated rare-earth enriched phosphorites

Penetrometry of granular and moist planetary surface materials: Application to the Huygens landing site on Titan

The Huygens probe landed on the then unknown surface of Titan in January 2005. A small, protruding penetrometer, part of the Surface Science Package (SSP), was pushed into the surface material measuring the mechanical resistance of the ground as the probe impacted the landing site. We present laboratory penetrometry into room temperature surface analogue materials using a replica penetrometer to investigate further the nature of Titan's surface and examine the sensor's capabilities. The results are then compared to the flight instrument's signature and suggest the Titan surface substrate material consists of sand-sized particles with a mean grain size ~2 mm. A possible thin 7 mm coating with mechanical properties similar to terrestrial snow may overlie this substrate, although due to the limited data we are unable to detect any further layering or grading within the near-surface material. The unusual weakening with depth of the signature returned from Titan has, to date, only been reproduced using a damp sand target that becomes progressively wetter with depth, and supports the suggestion that the surface may consist of a damp and cohesive material with interstitial liquid contained between its grains. Comparison with terrestrial analogues highlights the unusual nature of the landing site material

The late Katian Elkhorn event: precursor to the Late Ordovician mass extinction

The late Katian Elkhorn event is a biogeochemical perturbation preceding the Late Ordovician mass extinction (LOME) with an exceptional record in the United States (U.S.). Results of our recent studies in this interval allow revised temporal ordering to strata across multiple basins providing insights into the magnitude of environmental disturbance and associated processes and feedbacks. The record of the Elkhorn event spans portions of the Appalachian and Midcontinent basins in the eastern U.S. and the Williston Basin and Cordilleran margin in the west. Our work focuses heavily on the Midcontinent Basin in particular, as it shares many characteristics of size, tectonic setting, and lithofacies with the Baltic Basin, providing the potential for resolving global signatures of the event. In its type-area, the Cincinnatian Series ends with the Elkhorn event. The succession is marked by shallowing from subtidal to marginal marine facies, capped by a karstic sequence boundary. Our new conodont data demonstrate that an overlying white to pink crinoidal grainstone package, previously assigned to the basal Silurian âwhiteâ Brassfield Formation near the Ohio-Indiana state line, is in fact Upper Ordovician. Further, δ13Ccarb values in this unit are elevated, in line with later phases of the Elkhorn event (2â° more positive than reported Rhuddanian values). These findings support a correlation of the grainstone interval with the Fernvale Formation of central Tennessee. To the east, much of the northern Appalachian Basin was overfilled with widespread marginal marine to terrestrial red beds by the onset of the Elkhorn event, while the Midcontinent Basin to the west remained relatively sediment starved. In the southern Midcontinent, the mid-Elkhorn event sequence boundary was onlapped by ironstone deposition (lower Fernvale Formation). The ironstones are overlain by sparry and hematitic grainstones with localized bioherms. In Arkansas, where the Fernvale is thickest (>30 m), the sparry phase gives way upward to manganese carbonates and bioherms. Across the region, the Fernvale is, in turn, cut by a sequence boundary, suggesting a yet higher Katian sequence, and is perforated by paleokarst pockets that are filled and overlain by upper Katian (Ka4) sediments. This sequence boundary is onlapped by black shales and the thickest (>10 m) phosphorite of the Ordovician at the end of the Elkhorn event. Previous studies have suggested age equivalence of the Elkhorn and Paroveja δ13Ccarb excursions in Laurentia and Baltica. Despite the attraction of aligning the latest Richmondian and Pirgu regional stages, our data sets demonstrate that this is a miscorrelation. Critical to this revision are new integrated biostratigraphic and chemostratigraphic data sets in a transect from the margin of the Appalachian Basin into the Midcontinent Basin. The new data reveal that the Elkhorn Shale and Fernvale Formation are overlain by the Brainard and laterally equivalent Sylvan, and Mannie shales. These shale successions contain graptolites of the complanatusand pacificus zones. Thus, the Elkhorn event occurred in the latest manitoulinensis Zone, suggesting correlation with the Baltic Moe δ13Ccarb excursion. Our extensive new data sets provide regional chronostratigraphic correlation of strata deposited during the Elkhorn event. When temporally ordered, these records provide evidence for high amplitude sea level oscillations, major redox fluctuations, and reef pulses that demonstrate the waxing and waning of continental ice sheets on Gondwana and the spread of oceanic anoxia only a few million years before the LOME. These findings further call into question traditional models of rapid glaciation during a long-lived greenhouse state as the sole driver of the LOME and emphasize the need for new integrated Upper Ordovician research initiatives to better characterize Katian events

New regulations regarding Postgraduate Medical Training in Spain: perception of the tutor's role in the Murcia Region

<p>Abstract</p> <p>Background</p> <p>Recently introduced regulatory changes have expanded the Tutor role to include their primary responsibility for Postgraduate Medical Training (PMT). However, accreditation and recognition of that role has been devolved to the autonomic regions. The opinions of the RT may be relevant to future decisions;</p> <p>Methods</p> <p>A comprehensive questionnaire, including demographic characteristics, academic and research achievement and personal views about their role, was sent to 201 RTs in the Murcia Region of Spain. The responses are described using median and interquartile ranges (IQR);</p> <p>Results</p> <p>There were 147 replies (response rate 73%), 69% male, mean age 45 ± 7 yrs. RTs perception of the residents' initial knowledge and commitment throughout the program was 5 (IQR 4-6) and 7 (IQR 5-8), respectively. As regards their impact on the PMT program, RTs considered that their own contribution was similar to that of senior residents. RTs perception of how their role was recognised was 5 (IQR 3-6). Only 16% did not encounter difficulties in accessing specific RT training programs. Regarding the RTs view of their various duties, supervision of patient care was accorded the greatest importance (64%) while the satisfactory completion of the PMT program and supervision of day-to-day activities were also considered important (61% and 59% respectively). The main RT requirements were: a greater professional recognition (97%), protected time (95%), specific RT training programs (95%) and financial recognition (86%);</p> <p>Conclusions</p> <p>This comprehensive study, reflecting the feelings of our RTs, provides a useful insight into the reality of their work and the findings ought to be taken into consideration in the imminent definitive regulatory document on PMT.</p

Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

Rapid spatiotemporal variations in rift structure during development of the Corinth Rift, central Greece

The Corinth Rift, central Greece, enables analysis of early rift development as it is young (<5Ma) and highly active and its full history is recorded at high resolution by sedimentary systems. A complete compilation of marine geophysical data, complemented by onshore data, is used to develop a high-resolution chronostratigraphy and detailed fault history for the offshore Corinth Rift, integrating interpretations and reconciling previous discrepancies. Rift migration and localization of deformation have been significant within the rift since inception. Over the last circa 2Myr the rift transitioned from a spatially complex rift to a uniform asymmetric rift, but this transition did not occur synchronously along strike. Isochore maps at circa 100kyr intervals illustrate a change in fault polarity within the short interval circa 620-340ka, characterized by progressive transfer of activity from major south dipping faults to north dipping faults and southward migration of discrete depocenters at ~30m/kyr. Since circa 340ka there has been localization and linkage of the dominant north dipping border fault system along the southern rift margin, demonstrated by lateral growth of discrete depocenters at ~40m/kyr. A single central depocenter formed by circa 130ka, indicating full fault linkage. These results indicate that rift localization is progressive (not instantaneous) and can be synchronous once a rift border fault system is established. This study illustrates that development processes within young rifts occur at 100kyr timescales, including rapid changes in rift symmetry and growth and linkage of major rift faults

Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids

To progress from the laboratory to commercial applications, it will be necessary to develop industrially scalable methods to produce large quantities of defect-free graphene. Here we show that high-shear mixing of graphite in suitable stabilizing liquids results in large-scale exfoliation to give dispersions of graphene nanosheets. X-ray photoelectron spectroscopy and Raman spectroscopy show the exfoliated flakes to be unoxidized and free of basal-plane defects. We have developed a simple model that shows exfoliation to occur once the local shear rate exceeds 10(4) s(-1). By fully characterizing the scaling behaviour of the graphene production rate, we show that exfoliation can be achieved in liquid volumes from hundreds of millilitres up to hundreds of litres and beyond. The graphene produced by this method performs well in applications from composites to conductive coatings. This method can be applied to exfoliate BN, MoS2 and a range of other layered crystals

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation