The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach

Background and objectives: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphomas, characterized by mature, skin-tropic CD4+ T-helper cells. In order to study the immune tumor microenvironment in MF patients, we performed immunohistochemical stains on MF biopsies, digitized whole-slide tissue sections, and performed quantitative analysis of the different immune cell subsets to correlate tissue parameters with the clinical data of patients, such as progression-free survival or overall survival. Patients and methods: Overall, 35 patients who were treated between 2009 and 2019 and for whom one or more paraffin tissue blocks were available have been included in the present study (58 tissue specimens in total). Conventional immunohistochemistry stains for CD3, CD4, CD8, CD20 and CD30 were used for the analysis of the immune phenotype, and quantitative analysis was performed using QuPath as a quantitative digital pathology tool for bioimage analysis of whole slides. Results: Analysis of tissue parameters for prognostic significance revealed that patients with a stronger infiltration by CD8+ lymphocytes within the tumor cell compartment had a higher risk of disease progression (p = 0.031) and showed a shorter progress-free survival (p = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression (p = 0.023) and progression-free survival (p = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression (p = 0.015) and a shorter progression-free survival (p = 0.032) for older patients (>61 years) were observed. Conclusions: Our results demonstrated the prognostic relevance of large-cell transformation in mycosis fungoides and its strong association with the presence of CD30+ lymphocytes. Unlike previous reports, our study suggests an adverse prognostic role for CD8+ T cells in patients with mycosis fungoides. Moreover, our data indicate that the immune phenotype within the tumor microenvironment shows strong temporal heterogeneity and is altered in the course of tumor progression

Should applicants to Nottingham University Medical School study a non-science A-level? A cohort study

<p>Abstract</p> <p>Background</p> <p>It has been suggested that studying non-science subjects at A-level should be compulsory for medical students. Our admissions criteria specify only Biology, Chemistry and one or more additional subjects. This study aimed to determine whether studying a non-science subject for A-level is an independent predictor of achievement on the undergraduate medical course.</p> <p>Methods</p> <p>The subjects of this retrospective cohort study were 164 students from one entry-year group (October 2000), who progressed normally on the 5-year undergraduate medical course at Nottingham. Pre-admission academic and socio-demographic data and undergraduate course marks were obtained. T-test and hierarchical multiple linear regression analyses were undertaken to identify independent predictors of five course outcomes at different stages throughout the course.</p> <p>Results</p> <p>There was no evidence that the choice of science or non-science as the third or fourth A-level subject had any influence on course performance. Demographic variables (age group, sex, and fee status) had some predictive value but ethnicity did not. Pre-clinical course performance was the strongest predictor in the clinical phases (pre-clinical Themes A&B (knowledge) predicted Clinical Knowledge, p < 0.001, and pre-clinical Themes C&D (skills) predicted Clinical Skills, p = < 0.01).</p> <p>Conclusion</p> <p>This study of one year group at Nottingham Medical School provided no evidence that the admissions policy on A-level requirements should specify the choice of third or fourth subject.</p

The Southern Wide-field Gamma-ray Observatory reach for Primordial Black Hole evaporation

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy

Searching for Dark Matter with the Southern Wide-field Gamma-ray Observatory (SWGO)

Despite mounting evidence that dark matter (DM) exists in the Universe, its fundamental nature remains unknown. We present sensitivity estimates to detect DM particles with a future very-high-energy (&amp; TeV) wide field-of-view gamma-ray observatory in the Southern Hemisphere, currently in its research and development phase under the name Southern Wide field-of-view Gamma-ray Observatory (SWGO). This observatory would search for gamma rays from the annihilation or decay of DM particles in many key targets in the Southern sky, such as the Galactic halo, several dwarf galaxies, including the promising Reticulum II, and the Large Magellanic Cloud. With a wide field of view and long exposures, such observatory will have unprecedented sensitivity to DM in the mass range of ∼100 GeV to a few PeV from observations of a large fraction of the Galactic halo around the Galactic Center and from Galactic subhalos targets. These results, combined with those from other present and future gamma-ray observatories, will likely probe the thermal relic annihilation cross section of Weakly Interacting Massive Particles for all masses from ∼80 TeV down to the GeV range in most annihilation channels

Simulating the performance of the Southern Wide-view Gamma-ray Observatory

The Southern Wide-view Gamma-ray Observatory (SWGO) will be a next-generation gamma-ray observatory using a large array of particle detectors at a high elevation site in South America. This project is currently in a three years R&amp;D phase in which the design will be optimised for cost and performance. Therefore it is crucial to efficiently evaluate the impact of different design options on the scientific objectives of the observatory. In this contribution, we will introduce the strategy and the simulation framework in which this evaluation takes place

Study of water Cherenkov detector designs for the SWGO experiment

The Southern Wide-field Gamma-ray Observatory (SWGO) is a next-generation ground-based gamma-ray detector under development to reach a full sky coverage together with the current HAWC and LHAASO experiments in the northern hemisphere. It will complement the observation of transient and variable multi-wavelength and multi-messenger phenomena, offering moreover the possibility to access the Galactic Centre. One of the possible SWGO configurations consists of an array of water Cherenkov tanks, with a high fill-factor inner array and a low-density outer array, covering an overall area of one order of magnitude larger than HAWC. To reach a high detection efficiency and discrimination capability between gamma-ray and hadronic air showers, various tank designs were studied. Double-layer tanks with several sizes, shapes and number of photomultiplier tubes have been considered. Single-particle simulations have been performed to study the tank response, using muons, electrons, and gamma-rays with energies typical of extensive air showers particles, entering the tanks with zenith angles from 0 to 60 degrees. The tank response was evaluated considering the particle detection efficiency, the number of photoelectrons produced by the photomultiplier tubes, and the time resolution of the measurement of the first photon. The study allowed to compare the performance of tanks with circular and square base, to understand which design optimizes the performance of the array. The method used in the study and the results will be discussed in this paper

Benchmarking the Science for the Southern Wide-Field Gamma-ray Observatory (SWGO)

The Southern Wide-field Gamma-ray Observatory (SWGO) is the project to build a new extensive air shower particle detector for the observation of very-high-energy gamma-rays in South America. SWGO is currently planned for installation in the Southern Hemisphere, which grants it a unique science potential among ground-based gamma-ray detectors. It will complement the capabilities of CTA, working as a wide-field instrument for the monitoring of transient and variable phenomena, and will expand the sky coverage of Northern Hemisphere facilities like HAWC and LHAASO, thus granting access to the entire Galactic Plane and the Galactic Center. SWGO aims to achieve excellent sensitivity over a very large target energy range from about 100 GeV to the PeV, and improve on the performance of current sampling array instruments in all observational parameters, including energy and angular resolution, background rejection, and single-muon detection capabilities. The directives for the final observatory design will be given by a number of key science goals which are being defined over the course of the Project’s R&amp;D phase. In this contribution we will present the core science topics and target performance goals that serve as benchmarks to guide SWGO’s design configuration

Lake Deployment of Southern Wide-field Gamma-ray Observatory (SWGO) Detector Units

The Southern Wide-field Gamma-ray Observatory (SWGO) will be a next-generation high altitude gamma-ray survey observatory in the southern hemisphere consisting of an array of water cherenkov detectors. With its energy range, wide field of view, large duty cycle and location it will complement the other existing and planned gamma-ray observatories. In this contribution we describe the lake concept for SWGO, an alternative to a HAWC-like design with individual water tanks and a LHAASO-style design with artificial ponds. In the lake concept, bladders filled with clean water are deployed near the surface of a natural lake, where each bladder is a light-tight stand-alone unit containing one or more photosensors. We will give an overview of the advantages and challenges for this design concept and describe the first results obtained from prototyping

Double-layered Water Cherenkov Detector for SWGO

The Southern Wide-field Gamma-ray Observatory (SWGO) will use the well-established and cost-effective technique of detecting Cherenkov light produced in water-filled detection units for TeV gamma-ray astronomy. Leveraging detector material reflectivity together with an optimised aspect ratio is an option to improve the performance of an array of such detector units. The double-layered Water Cherenkov Detector units comprise chambers with single photosensors in each. A reflective upper compartment enhances sensitivity to impinging secondary particles. A shallow lower compartment enables muon tagging and consequently improves the gamma hadron separation power of the observatory. Here we present detailed studies on the double-layered unit design

Technological options for the Southern Wide-field Gamma-ray Observatory (SWGO) and current design status

The SWGO Collaboration is in the process of designing and prototyping a wide field of view, high duty cycle complement to CTA and the existing ground-based particle detectors of the Northern Hemisphere (HAWC and LHAASO). In this contribution, we will compare the various technological options for designing the detector and present an overarching system design accommodating them. We will introduce a feasible reference configuration that is used for the first large-scale simulations and cost estimates, and show ongoing prototyping work focused on reaching a maintenance-free and cost-effective detector