Cenozoic epeirogeny of the Indian peninsula

Peninsular India is a cratonic region with asymmetric relief manifest by eastward tilting from the 1.5 km high Western Ghats escarpment toward the flood-plains of eastward-draining rivers. Oceanic residual depth measurements on either side of India show that this west-east asymmetry is broader scale, occurring over distances of >2,000 km. Admittance analysis of free-air gravity and topography shows that the elastic thickness is 10 ± 3 km, suggesting that regional uplift is not solely caused by flexural loading. To investigate how Indian physiography is generated, we have jointly inverted 530 river profiles to determine rock uplift rate as a function of space and time. Key erosional parameters are calibrated using independent geologic constraints (e.g. emergent marine deposits, elevated paleosurfaces, uplifted lignite deposits). Our results suggest that regional tilt grew at rates of up to 0.1 mm a‾¹ between 25 Ma and the present day. Neogene uplift initiated in the south and propagated northward along the western margin. This calculated history is corroborated by low-temperature ther- mochronologic observations, by sedimentary flux of clastic deposits into the Krishna- Godavari delta, and by sequence stratigraphic architecture along adjacent rifted margins. Onset of regional uplift predates intensification of the Indian monsoon at 8 Ma, suggesting that rock uplift rather than climatic change is responsible for modern-day relief. A positive correlation between residual depth measure- ments and shear wave velocities beneath the lithosphere suggests that regional uplift is generated and maintained by temperature anomalies of ±100 ⁰C within a 200 ± 25 km thick asthenospheric channel

Reassessing the Thermal Structure of Oceanic Lithosphere With Revised Global Inventories of Basement Depths and Heat Flow Measurements

Half-space cooling and plate models of varying complexity have been proposed to account for changes in basement depth and heat flow as a function of lithospheric age in the oceanic realm. Here, we revisit this well-known problem by exploiting a revised and augmented database of 2028 measurements of depth to oceanic basement, corrected for sedimentary loading and variable crustal thickness, and 3597 corrected heat flow measurements. Joint inverse modeling of both databases shows that the half-space cooling model yields a mid-oceanic axial temperature that is >100°C hotter than permitted by petrologic constraints. It also fails to produce the observed flattening at old ages. Then, we investigate a suite of increasingly complex plate models and conclude that the optimal model requires incorporation of experimentally determined temperature- and pressure-dependent conductivity, expansivity and specific heat capacity, as well as a low conductivity crustal layer. This revised model has a mantle potential temperature of 1300 ± 50°C, which honors independent geochemical constraints and has an initial ridge depth of 2.6 ± 0.3 km with a plate thickness of 135 ± 30 km. It predicts that the maximum depth of intraplate earthquakes is bounded by the 700°C isothermal contour, consistent with laboratory creep experiments on olivine aggregates. Estimates of the lithosphere-asthenosphere boundary derived from studies of azimuthal anisotropy coincide with the 1175 ± 50°C isotherm. The model can be used to isolate residual depth and gravity anomalies generated by flexural and sub-plate convective processes.Natural Environment Research Council PhD Studentshi

The precession constant and its long-term variation

The dynamical flattening of the Earth, H, related to the precession constant, is a fundamental astro-geodetic parameter that appears in studies of the Earth's rotation and orbital evolution. We present numerical predictions and observations of the variation in H over time scales ranging from tens of millions of years to decades. The geophysical processes controlling this variation include solid-state convection in the rocky mantle of the Earth that drives plate tectonics, isostatic adjustments due to ice age loading, and ice-ocean mass transfer linked to modern global climate change. The time dependence of H is complex and non-linear, and thus, in contrast to previous suggestions, cannot be captured by a constant rate parameter

The effect of lateral variations in Earth structure on Last Interglacial sea level

It is generally agreed that the Last Interglacial (LIG; ∼130–115 ka) was a time when global average temperatures and global mean sea level were higher than they are today. However, the exact timing, magnitude and spatial pattern of ice melt is much debated. One difficulty in extracting past global mean sea level from local observations is that their elevations need to be corrected for glacial isostatic adjustment (GIA), which requires knowledge of Earth’s internal viscoelastic structure. While this structure is generally assumed to be radially symmetric, evidence from seismology, geodynamics and mineral physics indicates that large lateral variations in viscosity exist within the mantle. In this study, we construct a new model of Earth’s internal structure by converting shear wave speed into viscosity using parametrizations from mineral physics experiments and geodynamic constraints on Earth’s thermal structure. We use this 3-D Earth structure, which includes both variations in lithospheric thickness and lateral variations in viscosity, to calculate the first 3-D GIA prediction for LIG sea level. We find that the difference between predictions with and without lateral Earth structure can be metres to 10s of metres in the near field of former ice sheets, and up to a few metres in their far field. We demonstrate how forebulge dynamics and continental levering are affected by laterally varying Earth structure, with a particular focus on those sites with prominent LIG sea level records. Results from four 3-D GIA calculations show that accounting for lateral structure can act to increase local sea level by up to ∼1.5 m at the Seychelles and minimally decrease it in Western Australia. We acknowledge that this result is only based on a few simulations, but if robust, this shift brings estimates of global mean sea level from these two sites into closer agreement with each other. We further demonstrate that simulations with a suitable radial viscosity profile can be used to locally approximate the 3-D GIA result, but that these radial profiles cannot be found by simply averaging viscosity below the sea level indicator site

Sales of over-the-counter products containing codeine in 31 countries, 2013-2019: a retrospective observational study

ABSTRACTIntroductionOpioid prescribing trends have been investigated in many countries. However, the patterns of over-the-counter purchases of opioids without a prescription, such as codeine combinations, are mostly unknown.ObjectiveWe aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over six years.MethodsWe conducted a retrospective observational study using electronic point-of-sale data from the human data science company, IQVIA, for countries that had such data, including Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, Latvia, Lithuania, Mexico, The Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, the UK, and the USA. We calculated annual mean sales (dosage units per 1000 of the population) and public expenditure (GBP, £ per 1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by IQVIA. We quantified changes over time and the types of products sold.Results31.5 billion dosage units (adjusted: 42.8 billion dosage units) of codeine, costing £2.55 billion (adjusted: £3.68 billion), were sold over-the-counter in 31 countries between April 2013 and March 2019. Total adjusted sales increased by 11% (3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (£263/1000 in 2013 to £451/1000 in 2019). Sales were not equally distributed; South Africa sold the most (36 mean dosage units/person), followed by Ireland (30 mean dosage units/person), France (20 mean dosage units/person), the UK (17.2 mean dosage units/person), and Latvia (16.8 mean dosage units/person). Types of products (n=569) and formulations (n=12) sold varied.ConclusionIn many parts of the world, substantial numbers of people may be purchasing and consuming codeine from over-the-counter products. Clinicians should ask patients about their use of over-the-counter products, and public health measures are required to improve the collection of sales data and the safety of such products.Study protocol pre-registrationhttps://osf.io/ay4mcThe pre-print version of this work is available on medRxiv:https://doi.org/10.1101/2021.04.21.21255888Key pointsCodeine is one of the most accessible pain medicines available worldwide, yet data on its use as an over-the-counter drug has been limited.We found that total sales and expenditure of over-the-counter products containing codeine increased from April 2013 to March 2019, but there was substantial variation in mean sales between countries and the coverage of data reported by IQVIA, with South Africa, France, Japan, the UK, and Poland accounting for 90% of all sales data.In countries with access to over-the-counter codeine products, sales data should be collected, made available, and reviewed to inform regulatory decisions and public health measures to ensure safety.</jats:sec

Cost-Effectiveness of Collaborative Care for Depression in UK Primary Care: Economic Evaluation of a Randomised Controlled Trial (CADET)

Background: Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking. Aims: To assess the cost-effectiveness of collaborative care in a UK primary care setting. Methods: An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane. Results: The collaborative care intervention had a mean cost of £272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: –0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of £270.72 (95% CI: –202.98, 886.04), and resulted in an estimated mean cost per QALY of £14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual. Conclusion: Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting

diArk 2.0 provides detailed analyses of the ever increasing eukaryotic genome sequencing data

<p>Abstract</p> <p>Background</p> <p>Nowadays, the sequencing of even the largest mammalian genomes has become a question of days with current next-generation sequencing methods. It comes as no surprise that dozens of genome assemblies are released per months now. Since the number of next-generation sequencing machines increases worldwide and new major sequencing plans are announced, a further increase in the speed of releasing genome assemblies is expected. Thus it becomes increasingly important to get an overview as well as detailed information about available sequenced genomes. The different sequencing and assembly methods have specific characteristics that need to be known to evaluate the various genome assemblies before performing subsequent analyses.</p> <p>Results</p> <p>diArk has been developed to provide fast and easy access to all sequenced eukaryotic genomes worldwide. Currently, diArk 2.0 contains information about more than 880 species and more than 2350 genome assembly files. Many meta-data like sequencing and read-assembly methods, sequencing coverage, GC-content, extended lists of alternatively used scientific names and common species names, and various kinds of statistics are provided. To intuitively approach the data the web interface makes extensive usage of modern web techniques. A number of search modules and result views facilitate finding and judging the data of interest. Subscribing to the RSS feed is the easiest way to stay up-to-date with the latest genome data.</p> <p>Conclusions</p> <p>diArk 2.0 is the most up-to-date database of sequenced eukaryotic genomes compared to databases like GOLD, NCBI Genome, NHGRI, and ISC. It is different in that only those projects are stored for which genome assembly data or considerable amounts of cDNA data are available. Projects in planning stage or in the process of being sequenced are not included. The user can easily search through the provided data and directly access the genome assembly files of the sequenced genome of interest. diArk 2.0 is available at <url>http://www.diark.org</url>.</p

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

Cost-utility analysis of molnupiravir plus usual care versus usual care alone as early treatment for community-based adults with COVID-19 and increased risk of adverse outcomes in the UK PANORAMIC trial

BACKGROUND: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. AIM: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over six months. DESIGN AND SETTING: Economic evaluation of the PANORAMIC trial in the UK. METHOD: A cost-utility analysis that adopted a UK National Health Service and personal social services perspective and a six-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. RESULTS: In the base case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] 445 to 453) and higher mean QALYs of 0.0055 (95% CI 0.004 to 0.007) than usual care (mean incremental cost per QALY of £81190). Sensitivity and subgroup analyses showed similar results, except those aged ≥75 years with a 55% probability of being cost-effective at a £30000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15000 per QALY threshold. CONCLUSION: Molnupiravir at the current cost of £513 per course is unlikely to be cost-effective relative to usual care over a six-month time horizon among mainly vaccinated COVID-19 patients at increased risk of adverse outcomes, except those aged ≥75 years

Comparative Genome Analysis Reveals an Absence of Leucine-Rich Repeat Pattern-Recognition Receptor Proteins in the Kingdom Fungi

Background: In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack. Methodology/Principal Findings: A survey of genome sequences from 101 species, representing a broad cross-section of the eukaryotic phylogenetic tree, reveals an absence of leucine rich repeat-domain containing receptors in the fungal kingdom. Uniquely, however, fungi possess adenylate cyclases that contain distinct leucine rich repeat-domains, which have been demonstrated to act as an alternative means of perceiving the presence of bacteria by at least one fungal species. Interestingly, the morphologically similar osmotrophic oomycetes, which are taxonomically distant members of the stramenopiles, possess pattern recognition receptors with similar domain structures to those found in plants. Conclusions: The absence of pattern recognition receptors suggests that fungi may possess novel classes of patternrecognition receptor, such as the modified adenylate cyclase, or instead rely on secretion of anti-microbial secondary metabolites for protection from microbial attack. The absence of pattern recognition receptors in fungi, coupled with their abundance in oomycetes, suggests this may be a unique characteristic of the fungal kingdom rather than a consequence o