Electron transport in radiotherapy using local-to-global Monte Carlo

Local-to-Global (L-G) Monte Carlo methods are a way to make three-dimensional electron transport both fast and accurate relative to other Monte Carlo methods. This is achieved by breaking the simulation into two stages: a local calculation done over small geometries having the size and shape of the ``steps`` to be taken through the mesh; and a global calculation which relies on a stepping code that samples the stored results of the local calculation. The increase in speed results from taking fewer steps in the global calculation than required by ordinary Monte Carlo codes and by speeding up the calculation per step. The potential for accuracy comes from the ability to use long runs of detailed codes to compile probability distribution functions (PDFs) in the local calculation. Specific examples of successful Local-to-Global algorithms are given

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Development of Fast and Highly Efficient Gas Ionization Chamber For Patient Imaging and Dosimetry in Radiation Therapy

In radiation therapy of cancer, more accurate delivery techniques spur the need for improved patient imaging during treatment. To this purpose, the megavoltage radiation protocol that is used for treatment is also used for imaging

Electron fluence correction factors for conversion of dose in plastic to dose in water

In radiation dosimetry protocols, plastic is allowed as a phantom material for the determination of absorbed dose to water in electron beams. The electron fluence correction factor is needed in conversion of dose measured in plastic to dose in water. There are large discrepancies among recommended values as well as measured values of electron fluence correction factors when polystyrene is used as a phantom material. Using the Monte Carlo technique, we have calculated electron fluence correction factors for incident clinical beam energies between 5 and 50 MeV as a function of depth for clear polystyrene, white polystyrene and PMMA phantom materials and compared the results with those recommended in protocols as well as experimental rallies from published data. In the Monte Carlo calculations, clinical beams are simulated using the EGS4 user code BEAM for a variety of medical accelerators. The study shows that our calculated fluence correction factor, φ(p)/(w), is a function of depth and incident beam energy Ē0 with little dependence on other aspects of beam quality. However the φ(p)/(w) values at d(max) are indirectly influenced by the beam quality since they vary with depth and d(max) also varies with the beam quality. Calculated φ(p)/(w) values at d(max) are in a range of 1.005-1.045 for a clear polystyrene phantom, 1.005-1.038 for a white polystyrene phantom and 0.996- 1.016 for a PMMA phantom. Our values of φ(p)/(w) are about 1-2% higher than those determined according to the AAPM TG-25 protocol at φ(p)/(w) for clear or white polystyrene. Our calculated values of φ(p)/(w) also explain some of the variations of measured data because of its depth dependence. A simple formula is derived which gives the electron fluence correction factor φ(p)/(w) as a function of R50 at d(max) or at the depth of 0.6R50-0.1 for any clinical electron beam with energy between 5 and 25 MeV for three plastics: clear polystyrene, white polystyrene and PMMA. The study also makes a careful distinction between φ(p)/(w) and the corresponding IAEA Code of Practice quantity, h(m)

The Adjoint Method for The Optimization of Brachytherapy and Radiotherapy Patient Treatment Planning Procedures Using Monte Carlo Calculations

The goal of this project is to investigate the use of the adjoint method, commonly used in the reactor physics community, for the optimization of radiation therapy patient treatment plans. Two different types of radiation therapy are being examined, interstitial brachytherapy and radiotherapy. In brachytherapy radioactive sources are surgically implanted within the diseased organ such as the prostate to treat the cancerous tissue. With radiotherapy, the x-ray source is usually located at a distance of about 1-metere from the patient and focused on the treatment area. For brachytherapy the optimization phase of the treatment plan consists of determining the optimal placement of the radioactive sources, which delivers the prescribed dose to the disease tissue while simultaneously sparing (reducing) the dose to sensitive tissue and organs. For external beam radiation therapy the optimization phase of the treatment plan consists of determining the optimal direction and intensity of beam, which provides complete coverage of the tumor region with the prescribed dose while simultaneously avoiding sensitive tissue areas. For both therapy methods, the optimal treatment plan is one in which the diseased tissue has been treated with the prescribed dose and dose to the sensitive tissue and organs has been kept to a minimum