Predictors Of Positivity Of [F-18]F-Choline PET-CT In Prostate Cancer Recurrence. Preliminary Results

EP-173 Aim/Introduction: To analyze the validity of [18F]F-Choline PET-CT results in prostate cancer recurrence in our daily practice, based on theoretical cut-off points of prostatespecific antigen (PSA), its kinetic, and PSA doubling time (PSADT), to identify predictors of positivity and modify the indication criteria. Materials and Methods: Prior to the validity analysis, a descriptive, prospective analysis of consecutive patients with prostate cancer treated with curative intent by radical prostatectomy (RP) or radiotherapy (RT), who underwent PET-CT scan with recurrence criteria: PSA =1 or PSA 0.4-1 with PSADT Nadir + 2 after RT, was performed. Results: From April to December 2019, 69 patients were included, 40 were treated with RP (58%) and 29 with RT (42%). In 45 patients (65%) PET-CT was able to identify recurrence of the disease (positive PET) and in 24 it was not (negative PET). Of patients treated with RP, 82, 5% (33/40) had PSA>1, and of those, 61% were positive PET. 17, 5% (7/40) had PSA6months (28/69), in 71% if PSADT6 months, in 61% and 92% if PSADT<6 months and in 77% and 100% if PSADT<3 months. Conclusion: Preliminarily and awaiting validation, it seems that PSA>1 after RP or Nadir +2 after RT is an indicator of PET-CT. There seems to be a tendency that shows that PSA<1 after RP is an indicator of PET-CT if PSADT<3 months. PSADT <3 or <6 months could be the best predictor of positivity of PET-CT with [18F]F-Choline in recurrent prostate cancer

Analysis of results of effective dose estimation obtained from RADAR 2017 dose assessment model for nuclear medicine procedures

EP-296 Aim/Introduction: To analyze the results of effective dose (E) estimation of the most frequent procedures using photon emitters in Nuclear Medicine, obtained from RADAR 2017 dose assessment model. To compare these results with those obtained from ICRP 128 (2015) recommendations, and to assess how using each dose assessment model can change E results. Materials and Methods: E estimation data was collected from photon emitter procedures performed during the last year in our department, obtained from RADAR 2017 dose estimation model for age groups: = 1 year old; >1-5 years old ; >5- 10 years old, >10- 15 years old and adults. Injected activity was the one recommended by international guidelines and EANM Pediatric and Dosimetry Committees. Hybrid exams (SPECT / CT) and procedures for which there is no RADAR 2017 dosimetry estimation were excluded. Results for (E) were compared with those obtained by using ICRP 128 (2015) recommendations. Results: With RADAR 2017 dose evaluation model we obtained a lower mean value of E on most of the procedures that were analyzed, being significantly lower for Renogram, Renal scintigraphy on >10-15 years old, Thyroid scintigraphy, Meckel’s scan and Bone Scan (0.12 to 1.16 mSv, 25% to 67%). Brain perfusion and Renal scintigraphy on ages under 10 obtained a significantly greater difference for E (0.33 to 2.85 mSv, 26% to 29%). Conclusion: These results are an updated collection of estimated E values for photon-emitting radiopharmaceuticals commonly used in Nuclear Medicine, considering RADAR 2017 dose assessment model compared to ICRP 128) recommendations. Methodological changes on estimation lead to lower E for most of diagnostic procedures using photon emitters, this is of special interest for patients undergoing repeated ionizing radiation (dosimetry history)

INPUT DEVICE RESEARCH FOR DIGITAL PATHOLOGY. AN ERGONOMIC OUTLOOK

Introduction/ Background Digital Pathology represents a technological innovation that introduces changes in the traditional work of pathologists. In this regard, an important issue that has not been enough emphasized is the image handling from an ergonomic point of view to avoid work-related musculoskeletal disorders (MSD). Aims The aim of this study was to investigate a proper input device for digital pathology. Methods Research was conducted in two phases: 1. Comparative study to find an optimal external controller. Eight medical students analyzed 11 input devices: keyboard (HP), conventional mouse (HP), vertical mouse (CLS), touchpad (Logitech), 3 trackballs (Logitech, Kensington Expert and Ulove), Rollermouse (Contour), Ergopointer (Märzhäuser Sensotech), gamepad (Logitech) and a touchless device (Leap-Motion), using them with the Image Viewer software (Ventana). The web-based Fitts´ law test (UC Berkeley) was used to objectify the accuracy of each device, randomly. 12 items were included in the questionnaire: comfort, technical aspects (cursor movement and objective achievement), prospects, overall satisfaction, prior experience, and others. 2. Evaluation by two experienced pathologists (MPR and ANO, 55 and 50 year-old, respectively) the best rated input device and comparison with a voice recognition system (Invox Medical Dictation) using a headset microphone (Plantronics), rating perceived workload using NASA Task Load Index with 28 whole slide images. Digital Image Hub (Leica) with a 4 MegaPixel display (Barco) was used. Data were processed with SPSS 21.0. Results Correlation between technical aspects of the evaluated devices and accuracy (Fitts´ law test), and comfort with overall satisfaction existed (p<0.05). The assessment concluded that vertical mouse was the best rated input device. However, it has a slightly higher perceived workload in comparison with the voice recognition system, which was the proper controller for digital pathology in this study. Conclusion: We describe a methodology that can study and compare input devices for future workstations in digital pathology. Pathologists should be involved in this process trying to find ergonomic devices that prevent MSD. Voice recognition can function as a good handsfree device for digital pathology and could be considered in physical disability situations. Further studies using electromyography, accelerometry and 3D reconstruction analysis could provide additional ergonomic information

RNA Interference Is Responsible for Reduction of Transgene Expression after Sleeping Beauty Transposase Mediated Somatic Integration

Integrating non-viral vectors based on transposable elements are widely used for genetically engineering mammalian cells in functional genomics and therapeutic gene transfer. For the Sleeping Beauty (SB) transposase system it was demonstrated that convergent transcription driven by the SB transposase inverted repeats (IRs) in eukaryotic cells occurs after somatic integration. This could lead to formation of double-stranded RNAs potentially presenting targets for the RNA interference (RNAi) machinery and subsequently resulting into silencing of the transgene. Therefore, we aimed at investigating transgene expression upon transposition under RNA interference knockdown conditions. To establish RNAi knockdown cell lines we took advantage of the P19 protein, which is derived from the tomato bushy stunt virus. P19 binds and inhibits 21 nucleotides long, small-interfering RNAs and was shown to sufficiently suppress RNAi. We found that transgene expression upon SB mediated transposition was enhanced, resulting into a 3.2-fold increased amount of colony forming units (CFU) after transposition. In contrast, if the transgene cassette is insulated from the influence of chromosomal position effects by the chicken-derived cHS4 insulating sequences or when applying the Forg Prince transposon system, that displays only negligible transcriptional activity, similar numbers of CFUs were obtained. In summary, we provide evidence for the first time that after somatic integration transposon derived transgene expression is regulated by the endogenous RNAi machinery. In the future this finding will help to further improve the molecular design of the SB transposase vector system

Protein Translation and Cell Death: The Role of Rare tRNAs in Biofilm Formation and in Activating Dormant Phage Killer Genes

We discovered previously that the small Escherichia coli proteins Hha (hemolysin expression modulating protein) and the adjacent, poorly-characterized YbaJ are important for biofilm formation; however, their roles have been nebulous. Biofilms are intricate communities in which cell signaling often converts single cells into primitive tissues. Here we show that Hha decreases biofilm formation dramatically by repressing the transcription of rare codon tRNAs which serves to inhibit fimbriae production and by repressing to some extent transcription of fimbrial genes fimA and ihfA. In vivo binding studies show Hha binds to the rare codon tRNAs argU, ileX, ileY, and proL and to two prophage clusters D1P12 and CP4-57. Real-time PCR corroborated that Hha represses argU and proL, and Hha type I fimbriae repression is abolished by the addition of extra copies of argU, ileY, and proL. The repression of transcription of rare codon tRNAs by Hha also leads to cell lysis and biofilm dispersal due to activation of prophage lytic genes rzpD, yfjZ, appY, and alpA and due to induction of ClpP/ClpX proteases which activate toxins by degrading antitoxins. YbaJ serves to mediate the toxicity of Hha. Hence, we have identified that a single protein (Hha) can control biofilm formation by limiting fimbriae production as well as by controlling cell death. The mechanism used by Hha is the control of translation via the availability of rare codon tRNAs which reduces fimbriae production and activates prophage lytic genes. Therefore, Hha acts as a toxin in conjunction with co-transcribed YbaJ (TomB) that attenuates Hha toxicity

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

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

Galactic Science with the Southern Wide-field Gamma-ray Observatory

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