РОЛЬ EZH2 И ARID1A В ДИАГНОСТИКЕ ПЛОСКИХ УРОТЕЛИАЛЬНЫХ ОПУХОЛЕЙ С АТИПИЕЙ

Background. Diagnosis of urothelial carcinoma in situ is of great importance because it has prognostic and therapeutic value.We aim to determine the utility of EZH2 and ARID1A as a new tool in the diagnosis of carcinoma in situ.Material and Methods. This retrospective cross-sectional study included Twenty-four specimens of flat urothelial lesions, twenty specimens of CIS, and 10 of normal adjacent urothelium that was taken by cystoscopic resection biopsy procedure. immunohistochemical expression of EZH2 and ARID1A. were evaluated in all studied cases.Results. All normal urothelium specimens showed high nuclear staining for ARID1A and negative nuclear staining for EZH2. High EZH2 expression was observed in 80 % of CIS specimens compared to 20 % of flat urothelial lesions with atypia (p=0.001 ), while high ARID1A expression was observed in 70.8 % of flat urothelial lesions with atypia compared to 25 % of CIS specimens (p=0.001). EZH2 was more accurate and specific in the diagnosis of carcinoma in situ.Conclusion. EZH2 and ARID1A are promising diagnostic markers for urothelial CIS. EZH2 is more accurate and specific than ARID1A in the diagnosis of carcinoma in situ versus other flat urothelial lesions. Актуальность. Диагностика уротелиальной карциномы in situ имеет большое значение, поскольку обладает прогностической и терапевтической ценностью.Целью исследования было определить роль EZH2 и ARID1A в диагностике карциномы in situ.Материал и методы. Ретроспективное перекрестное исследование включало 24 образца плоских уротелиальных опухолей, 20 образцов CIS и 10 образцов нормального прилегающего уротелия, взятых при цистоскопической биопсии. Во всех случаях была оценена иммуногистохимическая экспрессия EZH2 и ARID1A.Результаты. Все образцы нормального уротелия показали высокое ядерное окрашивание на ARID1A и отрицательное ядерное окрашивание на EZH2. Высокая экспрессия EZH2 наблюдалась в 80 % образцов CIS по сравнению с 20 % плоских уротелиальных опухолей с атипией (p=0,001), в то время как высокая экспрессия ARID1A наблюдалась в 70,8 % плоских уротелиальных опухолей с атипией по сравнению с 25 % образцов CIS (р=0,001). EZH2 был более точным и специфичным при диагностике карциномы in situ.Заключение. EZH2 и ARID1A являются перспективными диагностическими маркерами уротелиальной карциномы in situ. EZH2 более точен и специфичен, чем ARID1A, в диагностике карциномы in situ по сравнению с другими плоскими уротелиальными опухолями.

Signatures of Thermal Dilepton Radiation at RHIC

The properties of thermal dilepton production from heavy-ion collisions in the RHIC energy regime are evaluated for invariant masses ranging from 0.5 to 3 GeV. Using an expanding thermal fireball to model the evolution through both quark-gluon and hadronic phases various features of the spectra are addressed. In the low-mass region, due to an expected large background, the focus is on possible medium modifications of the narrow resonance structures from $\omega$ and $\phi$ mesons, whereas in the intermediate-mass region the old idea of identifying QGP radiation is reiterated including effects of chemical under-saturation in the early stages of central Au+Au collisions.Comment: 17 pages ReVTeX including 16 figure

Cyber security fear appeals:unexpectedly complicated

Cyber security researchers are starting to experiment with fear appeals, with a wide variety of designs and reported efficaciousness. This makes it hard to derive recommendations for designing and deploying these interventions. We thus reviewed the wider fear appeal literature to arrive at a set of guidelines to assist cyber security researchers. Our review revealed a degree of dissent about whether or not fear appeals are indeed helpful and advisable. Our review also revealed a wide range of fear appeal experimental designs, in both cyber and other domains, which confirms the need for some standardized guidelines to inform practice in this respect. We propose a protocol for carrying out fear appeal experiments, and we review a sample of cyber security fear appeal studies, via this lens, to provide a snapshot of the current state of play. We hope the proposed experimental protocol will prove helpful to those who wish to engage in future cyber security fear appeal research

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development.

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described

Drone-Assisted Confined Space Inspection and Stockpile Volume Estimation

From MDPI via Jisc Publications RouterHistory: accepted 2021-08-18, pub-electronic 2021-08-24Publication status: PublishedThe accuracy of stockpile estimations is of immense criticality to process optimisation and overall financial decision making within manufacturing operations. Despite well-established correlations between inventory management and profitability, safe deployment of stockpile measurement and inspection activities remain challenging and labour-intensive. This is perhaps owing to a combination of size, shape irregularity as well as the health hazards of cement manufacturing raw materials and products. Through a combination of simulations and real-life assessment within a fully integrated cement plant, this study explores the potential of drones to safely enhance the accuracy of stockpile volume estimations. Different types of LiDAR sensors in combination with different flight trajectory options were fully assessed through simulation whilst mapping representative stockpiles placed in both open and fully confined areas. During the real-life assessment, a drone was equipped with GPS for localisation, in addition to a 1D LiDAR and a barometer for stockpile height estimation. The usefulness of the proposed approach was established based on mapping of a pile with unknown volume in an open area, as well as a pile with known volume within a semi-confined area. Visual inspection of the generated stockpile surface showed strong correlations with the actual pile within the open area, and the volume of the pile in the semi-confined area was accurately measured. Finally, a comparative analysis of cost and complexity of the proposed solution to several existing initiatives revealed its proficiency as a low-cost robotic system within confined spaces whereby visibility, air quality, humidity, and high temperature are unfavourable

Cross-scale analysis of social-ecological systems:Policy options appraisal for delivering NetZero and other environmental objectives in Scotland

Public policy confronts complex, contested, wicked problems such as climate and biodiversity crises with challenges of how issues are framed, analysed, codified, and interpreted. Social-ecological systems provide an analytical framework that couples the biosphere and technosphere, recognising biophysical limits and emphasising the importance of critical reflection within policy decision-making. Conducting policy-options appraisals is increasingly seen as a transdisciplinary research-policy endeavour with researchers engaging policy actors in an extended peer community (post-normal science). This paper presents a case study of analysis undertaken with researchers, policy analysts, policy makers and other stakeholders to support decisions on how to implement future agriculture support in Scotland, so that the policy programme better delivers across social, economic and environmental objectives. The key change being considered in the future agricultural support programme is Enhanced Conditionality (EC) where the level of financial support provided to farm-businesses will depend on their undertaking agri-environmental measures that deliver against the key priorities of reducing greenhouse gas emissions and reversing biodiversity losses. The paper outlines the policy context within which the EC options appraisal takes place – highlighting how EC is a crucial component in making the wider suite of policy measures work. The transdisciplinary approach, Quantitative Story Telling (QST) is presented, emerging from decision support, participatory research, and post-normal science for policy domains. The stages of QST highlight the importance of analysis that underpins any quantification (decision on how issues are framed and what it included in the analysis) and the expectation that research outputs with be deliberated on with, and interpreted from, stakeholder perspectives. The project specific analyses are outlined, combining top-down options appraisal of how macro-policy decisions could constrain EC and bottom-up analysis of potential uptake and effectiveness of EC measures, undertaken in inter-disciplinary workshops with domain experts from biodiversity, soils and waters. The paper highlights challenges for implementation and evaluation at meso-scale with interactions between farm-businesses and catchment, landscape and regional objectives. The conclusions of the analysis, in policy terms, are that EC presents an opportunity to significantly realign how agricultural land management is conducted in Scotland, so that it is more effective in delivering climate change and biodiversity objectives, but there are formidable challenges in resolving the policy “sudoku”. Meso-scale issues are likely to mean the need to integrate alternative modelling paradigms such as spatial, empirical agent-based modelling (ABM) into policy option appraisals. By taking multi-scale, social-ecological systems perspectives on EC it has been possible to identify key policy decisions at a range of scales on which the success of EC will depend, to have a realistic understanding of how effective the EC measures might be in heterogenous Scottish environments and what are the likely barriers to uptake. The analysis also highlighted where outcomes of the policy change are likely to be challenging to monitor-evaluate; and where there are dependencies between farm-businesses that mean EC measures need to be supplemented with mechanisms that (1) promote cooperation between land managers and (2) identify and respond to agreed local priorities. The value of the participatory QST process was in making sure the analyses being undertaken were salient and the outputs seen as credible – but the challenges of interpreting necessarily complex outputs remain. The greatest value of QST may be that it provides a structured way to navigate complexity with policy makers rather than seeking to control or eliminate it.</p

Cross-scale analysis of social-ecological systems:Policy options appraisal for delivering NetZero and other environmental objectives in Scotland

Public policy confronts complex, contested, wicked problems such as climate and biodiversity crises with challenges of how issues are framed, analysed, codified, and interpreted. Social-ecological systems provide an analytical framework that couples the biosphere and technosphere, recognising biophysical limits and emphasising the importance of critical reflection within policy decision-making. Conducting policy-options appraisals is increasingly seen as a transdisciplinary research-policy endeavour with researchers engaging policy actors in an extended peer community (post-normal science). This paper presents a case study of analysis undertaken with researchers, policy analysts, policy makers and other stakeholders to support decisions on how to implement future agriculture support in Scotland, so that the policy programme better delivers across social, economic and environmental objectives. The key change being considered in the future agricultural support programme is Enhanced Conditionality (EC) where the level of financial support provided to farm-businesses will depend on their undertaking agri-environmental measures that deliver against the key priorities of reducing greenhouse gas emissions and reversing biodiversity losses. The paper outlines the policy context within which the EC options appraisal takes place – highlighting how EC is a crucial component in making the wider suite of policy measures work. The transdisciplinary approach, Quantitative Story Telling (QST) is presented, emerging from decision support, participatory research, and post-normal science for policy domains. The stages of QST highlight the importance of analysis that underpins any quantification (decision on how issues are framed and what it included in the analysis) and the expectation that research outputs with be deliberated on with, and interpreted from, stakeholder perspectives. The project specific analyses are outlined, combining top-down options appraisal of how macro-policy decisions could constrain EC and bottom-up analysis of potential uptake and effectiveness of EC measures, undertaken in inter-disciplinary workshops with domain experts from biodiversity, soils and waters. The paper highlights challenges for implementation and evaluation at meso-scale with interactions between farm-businesses and catchment, landscape and regional objectives. The conclusions of the analysis, in policy terms, are that EC presents an opportunity to significantly realign how agricultural land management is conducted in Scotland, so that it is more effective in delivering climate change and biodiversity objectives, but there are formidable challenges in resolving the policy “sudoku”. Meso-scale issues are likely to mean the need to integrate alternative modelling paradigms such as spatial, empirical agent-based modelling (ABM) into policy option appraisals. By taking multi-scale, social-ecological systems perspectives on EC it has been possible to identify key policy decisions at a range of scales on which the success of EC will depend, to have a realistic understanding of how effective the EC measures might be in heterogenous Scottish environments and what are the likely barriers to uptake. The analysis also highlighted where outcomes of the policy change are likely to be challenging to monitor-evaluate; and where there are dependencies between farm-businesses that mean EC measures need to be supplemented with mechanisms that (1) promote cooperation between land managers and (2) identify and respond to agreed local priorities. The value of the participatory QST process was in making sure the analyses being undertaken were salient and the outputs seen as credible – but the challenges of interpreting necessarily complex outputs remain. The greatest value of QST may be that it provides a structured way to navigate complexity with policy makers rather than seeking to control or eliminate it.</p

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

A pilot study on the kinetics of metabolites and microvascular cutaneous effects of nitric oxide inhalation in healthy volunteers

RATIONALE: Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked. OBJECTIVES: We investigated the kinetics of nitrite and S-nitrosothiol-hemoglobin (SNO-Hb) in plasma derived from inhaled NO subjects and how this modifies the cutaneous microvascular response. FINDINGS: We enrolled 15 healthy volunteers. Plasma nitrite levels at baseline and during NO inhalation (15 minutes at 40 ppm) were 102 (86-118) and 114 (87-129) nM, respectively. The nitrite peak occurred at 5 minutes of discontinuing NO (131 (104-170) nM). Plasma nitrate levels were not significantly different during the study. SNO-Hb molar ratio levels at baseline and during NO inhalation were 4.7E-3 (2.5E-3-5.8E-3) and 7.8E-3 (4.1E-3-13.0E-3), respectively. Levels of SNO-Hb continued to climb up to the last study time point (30 min: 10.6E-3 (5.3E-3-15.5E-3)). The response to acetylcholine iontophoresis both before and during NO inhalation was inversely associated with the SNO-Hb level (r: -0.57, p = 0.03, and r: -0.54, p = 0.04, respectively). CONCLUSIONS: Both nitrite and SNO-Hb increase during NO inhalation. Nitrite increases first, followed by a more sustained increase in Hb-SNO. Nitrite and Hb-SNO could be a mobile reservoir of NO with potential implications on the systemic microvasculature