High Probability Research Articles

Can the infection risk in elevators be negligible? A comparative study of airborne infection probability in elevators and conference rooms

People in crowded and poorly ventilated elevators are at risk of respiratory infection. However, due to the short duration of the elevator ride, the transmission of respiratory diseases in elevators does not get enough attention. To evaluate the infection risk, this study investigated the airborne transmission of respiratory diseases in the hospital elevator by comparison to the conference room. A validated computational fluid dynamics (CFD) model was adopted to simulate airflow, temperature and tracer gas dispersion in the elevator and conference room. We used Wells-Riley model to evaluate the infection probability of the susceptible persons. In addition, the influences of source patient posture and ventilation strategy on the transmission of tracer gas were analyzed. The results showed that the infection probability in the elevator with 5 min (average 2.70%) was higher than that in the conference room with 50 min (average 1.77%). The effects of source patient posture and ventilation strategy on the infection probability in the elevator were more significant than those in the conference room. Local air circulation could gather the tracer gas inside a confined space in the elevator and led to a high infection probability. The infection risk of respiratory diseases in the elevator was non-negligible.

Late gadolinium enhancement and outcome of cardiac resynchronization therapy in non-ischemic cardiomyopathy

BackgroundIt is uncertain whether CRT with defibrillator (CRTD) is superior to CRT with pacemaker (CRTP) in NICM. Patients with low arrhythmic risk and high probability of response to CRT might be ideal candidates for CRTP.We aimed to evaluate predictors of ventricular arrhythmias and of echocardiographic response to cardiac resynchronization therapy (CRT) in non-ischemic cardiomyopathy (NICM). MethodsMulticenter, retrospective observational study of NICM patients with left ventricular ejection fraction (LVEF) ≤35 %, cardiac magnetic resonance with analysis of late gadolinium enhancement (LGE) available and de-novo CRT implant. Echocardiographic response to CRT was defined as an improvement in LVEF ≥10 %. The combined arrhythmic endpoint included sustained ventricular tachycardia, appropriate ICD therapy, resuscitated cardiac arrest and sudden death. ResultsWe included 167 patients, with a median follow-up of 63 months. LGE was present in 77 (46 %). Response to CRT occurred in 68 % of patients, more frequently in LGE- than in LGE+ (81 % vs 53 %, p < 0.001). Absence of LGE (OR 3.4, p = 0.002), was an independent predictor of response to CRT. The arrhythmic endpoint occurred in 19 patients (11 %). Among LGE- patients there were zero arrhythmic events as compared to a 25 % cumulative incidence in LGE+ (p < 0.001). Presence of LGE (HR 22.5, p < 0.001), was an independent predictor of the arrhythmic endpoint. ConclusionAbsence of LGE identifies patients at minimal arrhythmic risk and with high probability of response to CRT. Thus, they might be ideal candidates to CRT-P.

Coevolution promotes the coexistence of Tasmanian devils and a fatal, transmissible cancer.

Emerging infectious diseases threaten natural populations, and data-driven modeling is critical for predicting population dynamics. Despite the importance of integrating ecology and evolution in models of host-pathogen dynamics, there are few wild populations for which long-term ecological datasets have been coupled with genome-scale data. Tasmanian devil (Sarcophilus harrisii ) populations have declined range-wide due to devil facial tumor disease (DFTD), a fatal transmissible cancer. Although early ecological models predicted imminent devil extinction, diseased devil populations persist at low densities, and recent ecological models predict long-term devil persistence. Substantial evidence supports evolution of both devils and DFTD, suggesting coevolution may also influence continued devil persistence. Thus, we developed an individual-based, eco-evolutionary model of devil-DFTD coevolution parameterized with nearly two decades of devil demography, DFTD epidemiology, and genome-wide association studies. We characterized potential devil-DFTD coevolutionary outcomes and predicted the effects of coevolution on devil persistence and devil-DFTD coexistence. We found a high probability of devil persistence over 50 devil generations (100 years) and a higher likelihood of devil-DFTD coexistence, with greater devil recovery, than predicted by previous ecological models. These novel results add to growing evidence for long-term devil persistence and highlight the importance of eco-evolutionary modeling for emerging infectious diseases.

Breast and Prostate Cancer Screening by Life Expectancy in Patients with Kidney Failure on Dialysis.

The Choosing Wisely campaign suggests an individualized approach to cancer screening among patients receiving dialysis. We aimed to evaluate breast and prostate cancer screening among patients receiving maintenance hemodialysis (HD) by kidney transplant waitlist status and five-year survival probability. We conducted a retrospective cohort study using a nationally representative population of HD patients. Patients receiving HD each calendar year from 2003-2018, ≥1 year of Medicare as the Primary Payer, and age 50-69 years were included. The cohort was split into prognosis and cancer screening sets. Models of five-year survival were built in the prognosis set using logistic regression. Five-year survival probabilities were generated in the cancer screening set, excluding patients with prior breast or prostate cancer, and screening over the next year was assessed. 160,537 patients contributed 356,165 person-years to the cancer screening set (59% of the person-years were contributed by males, median age was 60 years). Compared to a benchmark rate of 50% (e.g., mammography every other year), 42% of waitlisted female-years were screened by mammography. Overall, 17% of non-waitlisted female-years were screened (20% among those with >50% probability of five-year survival and 8% among those with <10% probability of five-year survival). Compared to a benchmark rate of 20% [e.g., serum prostate-specific antigen (PSA) screening up to five years apart], 24% of waitlisted male-years were screened with serum PSA. Overall 15% of non-waitlisted male-years were screened (13% among those with >50% probability of five-year survival and 1% among those with <10% probability of five-year survival). Patterns were similar after age-standardization. Patients with higher predicted survival have higher rates of cancer screening, suggesting providers consider life expectancy. However, non-waitlisted patients with high probability of five-year survival were less likely to be screened compared to waitlisted patients. Interventions may be needed to close this screening gap.

Sporadic Creutzfeldt Jakob disease: Case series in Peru.

A series of 6 cases with a probable diagnosis of sporadic CJD, treated in a Peruvian national reference hospital, are presented. The relevant clinical signs were rapidly progressive dementia and myoclonus, followed by akinetic mutism and pyramidal signs. Of the cases presented, 80% were men, with an average age of presentation of 65 years and duration from diagnosis to death of 6.5 months. Laboratory tests, images (Brain Resonance) and protein dosage 14.3.3 were performed to support the clinical suspicion. There is no effective treatment at the moment for said pathology. Creutzfeldt-Jakob disease (CJD) is a progressive, fatal, neurodegenerative disease of low prevalence and incidence. Great clinical suspicion and the exclusion of other etiologies are required. Currently there is no treatment for this entity and there is a high probability of death before one year.

Sensitivity analysis of human error in the steel industry: exploring the effects of psychosocial and mental health risk factors and burnout using Bayesian networks.

Human error and the high rates of fatalities and other occupational accidents in the steel industry are of significant global relevance. The aim of this study was to investigate the effect of psychosocial, mental health, and burnout risk factors on human error probabilities in an industrial environment using Bayesian networks. This cross-sectional study was conducted in 2023. The participants were 252 employees of a steel company. Error probabilities related to the tasks of participants were estimated using the Human Error Assessment and Reduction Technique (HEART). Other data was collected using a survey that consisted of demographic information, the Maslach Burnout Inventory, Depression Anxiety Stress Scales, and a short version of the Copenhagen Psychosocial Questionnaire. A theoretical model was drawn in GeNIe academic software (version 2.3). The results showed that all the studied variables were able to significantly affect the distribution of human error probabilities. Considering a distribution of 100% for the high state of these variables, the results showed that the greatest increases in error probability were related to two burnout dimensions: emotional exhaustion (29%) and depersonalization (28%). All the variables, with a probability of 100%, increased the probability of high human error probabilities by 46%. The most important variables in terms of their effect on human error probabilities were burnout dimensions, and these variables also had a mediation effect on the psychosocial and mental health variables. Therefore, preventive measures to control human error should first focus on managing the risks of burnout in workers. This, in turn, can also reduce the effect of psychosocial risk factors and mental health problems on human error in the workplace.

Finding and Mitigating a Vulnerability of the Color Wheel PIN Protocol

There is an increasing usage in the banking sector of Smartphones enabled with Near Field Communication (NFC), to improve the services offered for the customers. This usage requires a security enhancement of the systems that employ this technology like the Automated Teller Machines (ATMs). One example is the Color Wheel Personal Identification Number (CWPIN) security protocol designed to authenticate users on ATMs using NFC enabled smartphones without typing the PIN code directly. CWPIN has been compared in the literature to several other protocols and was considered easier to use, more cost-effective and more resistant to various attacks on ATMs such as card reader skimming, keylogger injection, shoulder surfing, etc. Nevertheless, we demonstrate in this paper that CWPIN is vulnerable to the multiple video recordings intersection attack. We do so through concrete examples and a thorough analysis that reveals a high theoretical probability of attack success. A malicious party can use one or two hidden cameras to record the ATM and smartphone screens during several authentication sessions, then disclose the user's PIN code by intersecting the information extracted from the video recordings. In a more complex scenario, these video recordings could be obtained by malware injected into the ATM and the user's smartphone to record their screens during CWPIN authentication sessions. Our intersection attack requires a few recordings, usually three or four, to reveal the PIN code and can lead to unauthorized transactions if the user's smartphone is stolen. We also propose a mitigation of the identified attack through several modifications to the CWPIN protocol and discuss its strengths and limitations.

Development and Multinational Validation of an Ensemble Deep Learning Algorithm for Detecting and Predicting Structural Heart Disease Using Noisy Single-lead Electrocardiograms.

AI-enhanced 12-lead ECG can detect a range of structural heart diseases (SHDs) but has a limited role in community-based screening. We developed and externally validated a noise-resilient single-lead AI-ECG algorithm that can detect SHD and predict the risk of their development using wearable/portable devices. Using 266,740 ECGs from 99,205 patients with paired echocardiographic data at Yale New Haven Hospital, we developed ADAPT-HEART, a noise-resilient, deep-learning algorithm, to detect SHD using lead I ECG. SHD was defined as a composite of LVEF<40%, moderate or severe left-sided valvular disease, and severe LVH. ADAPT-HEART was validated in four community hospitals in the US, and the population-based cohort of ELSA-Brasil. We assessed the model's performance as a predictive biomarker among those without baseline SHD across hospital-based sites and the UK Biobank. The development population had a median age of 66 [IQR, 54-77] years and included 49,947 (50.3%) women, with 18,896 (19.0%) having any SHD. ADAPT-HEART had an AUROC of 0.879 (95% CI, 0.870-0.888) with good calibration for detecting SHD in the test set, and consistent performance in hospital-based external sites (AUROC: 0.852-0.891) and ELSA-Brasil (AUROC: 0.859). Among those without baseline SHD, high vs. low ADAPT-HEART probability conferred a 2.8- to 5.7-fold increase in the risk of future SHD across data sources (all P<0.05). We propose a novel model that detects and predicts a range of SHDs from noisy single-lead ECGs obtainable on portable/wearable devices, providing a scalable strategy for community-based screening and risk stratification for SHD.

Re-arquitecturar los territorios, un desafío ineluctable para la sostenibilidad compartida

The dynamic - historical reading of the planning, andthe balances of what we consider as a structural “bad urbanrural development” of the territories (at least since the 60s), is essential. This position, although open to debate, has become evident taking into account the also dynamic reading of the great challenges of sustainable transitions and "resilience”, that have marked planning and management intentions in Central American planning history. This statement necessarily leads torethinking global architectures inherited (built form, forms of management and planning, governance) to define the intensities of the changes. Moving towards this, implies to define the method and the transition system to be implemented, and to define the instruments that allow rehabilitating, reconstructing,remodeling, “re-architecturing” territories and institutions inherited. However, the re-architecture proposed will depend on the collective clarity, first of the pasts carried over, and second the desired futures. Accounting for the "arts" or the "politicalsocialinstitutional techniques" that created (and continue to do) the "metropolitan areas", is today an essential stage to be able to move towards new development models. Indeed, many local and metropolitan challenges, such as the “right to sustainable housing for all” (which has a high component of physicalconstructive design), contain high probabilities of never being effective in the current and trending context. Given that the current political, institutional, economic and social capacities, to make considerable changes in the management of the territories, seem to be compromised. Forging new capabilities and new abilities (financial, environmental, social, and including technical-constructive) is a collective challenge. And collectively conceiving a new urban planning and territorial planning (corrective – preventive and collaborative) is an urgency. ILIA: Investigaciones Latinoamericanas en Ingeniería y Arquitectura, No. 01, 2024: 167-173.

Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study.

The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes. Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants. The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

Monte Carlo safeguarding of key links through multiple random walks in large network

Safeguarding important links is a useful way to promote network vulnerability, especially in sparse networks where random link failures can disconnect the network. Sustaining network connectivity is the main goal of safeguarding and can be handled by selectively safeguarding links belonging to certain cuts of a network. However, due to the inherent high complexity of cut enumeration, existing algorithms can only handle small‐scale networks with limited nodes. It is important to find practical algorithms that are feasible for large‐scale graphs, as a significant portion of real‐world graphs under investigation are not as small as dozens of nodes. To address the problem, we propose to use a high‐precision approximate approach to accelerate the first step of the two‐step safeguard process and thus accelerate the whole process. A Monte Carlo algorithm is proposed to exploit efficient random paths for small cuts enumeration, which can help locate important edges with high probability in large‐scale sparse networks. These edges will then be utilized to find the approximated minimum cost edge set whose safeguarding can sustain the expected network connectivity. The algorithm is validated using various sizes of graphs of random/Barbasi–Albert scale‐free/Clustered scale‐free/unit disk/Watts–Strogatz small‐world and real‐world graphs. The experimental results show that the algorithm can perfectly sustain the network connectivity, and the acceleration ratio of more than 105 can be achieved with a little additional overhead. Specifically, in large graphs of one million nodes, approximated safeguard solutions survive at least 99.9% random link failures, and the solution time can be further reduced to dozens of seconds when the algorithm steps are easily implemented in full parallel.

European eel (Anguilla anguilla) survival modeling based on a 22-year capture-mark-recapture survey of a Mediterranean subpopulation.

Since the 1980s, the European eel (Anguilla anguilla) has declined by over 90% in recruitment across its European and North African distribution area. This diadromous fish spawns at sea and migrates into continental waters, where it grows for three to more than 30 years, depending on habitat conditions and location. During their growth, different habitat use tactics can locally influence the life-history traits of eels, including their survival rates. Thus, the spatio-temporal dimension of this species is crucial for management. Based on a rare Mediterranean long-term survey of more than 20 years (2001-2022) in an artificial drainage canal connected to a vast brackish lagoon (the Vaccarès lagoon), we aimed to study the dynamics of one subpopulation's life-history traits. We used Bayesian multistate capture-mark-recapture (CMR) models to assess the temporal variability in survival and abundance at both seasonal and inter-annual scales, considering life-stage structure. High survival rates and low detection probabilities were found for the undifferentiated and female yellow stages. In contrast, female silver eels exhibited lower survival rates and higher capture probabilities. Estimating detection probabilities and survival rates enabled accurate assessment of relative abundance across different life stages and time periods. Our findings indicated a substantial decrease in the abundance of undifferentiated and female yellow eels in the early 2000s, whereas the abundance of female silver eels remained consistently low yet stable throughout the study period. Considering the life stage seemed essential to study the dynamics of the eel during its continental growing period. The present results will provide key elements to propose and implement suitable sustainable environmental management strategies for eel conservation.

Deprescribing of proton pump inhibitors in older patients: A cost-effectiveness analysis.

Over-prescribing of proton-pump inhibitors (PPIs) is widely observed in older patients. Clinical findings have showed that deprescribing service significantly decreased inappropriate PPIs utilization. We aimed to examine the cost-effectiveness of PPI deprescribing service from the perspective of Hong Kong public healthcare provider. A decision-analytic model was constructed to examine the clinical and economic outcomes of PPI deprescribing service (deprescribing group) and usual care (UC group) in a hypothetical cohort of older PPI-users aged ≥65 years in the ambulatory care setting. The model inputs were retrieved from literature and public data. The model time-frame was one-year. Base-case analysis and sensitivity analysis were performed. Primary model outcomes were direct medical cost and quality-adjusted life-years (QALYs) loss. In base-case analysis, the deprescribing service (versus UC) reduced total direct medical cost by USD235 and saved 0.0249 QALY per PPI user evaluated. The base-case results were robust to variation of all model inputs in one-way sensitivity analysis. In probabilistic sensitivity analysis, the deprescribing group was accepted as cost-effective (versus the UC group) in 100% of the 10,000 Monte Carlo simulations. In conclusion, the PPI deprescribing service saved QALYs and reduced total direct medical cost in older PPIs users, and showed a high probability to be accepted as the cost-effective option from the perspective of public healthcare provider in Hong Kong.

УПРАВЛІННЯ РИЗИКАМИ ДОРОЖНЬОГО БУДІВНИЦТВА

The development of the road network plays a key role in the social, economic and environmental development of a country, region cities. A key aspect for achieving the set goals and ensuring the sustainability and efficiency of road construction projects is the management of risks that arise during project planning and execution. The purpose of the work is the research and classification of risks that arise during the implementation of road construction projects, the formation of a risk management system and the search for ways to minimize their negative consequences. The paper proposes a road construction risk management mechanism, the main purpose of which is to ensure the successful implementation of the road construction project, taking into account all possible risks that may affect the process of its implementation and results. The classification of road construction risks by origin, nature, stages of the project, impact on participants, scale, which will ensure the identification of potential risks, the probability of their occurrence and the establishment of the scale of consequences from their impact, is considered. The successful implementation of road construction projects is ensured by measures to minimize the negative consequences of the impact of risks. The authors identified the main areas of risk minimization during road construction, including detailed planning, risk analysis, use of technologies and innovations, reserve time planning, quality control, stakeholder participation, insurance, environmental management, creation of reserve funds, contingency scenario or plans. A contingency scenario of risk minimization in road construction is proposed, which makes it possible to define measures and strategies for the active management of risks that may arise during a road construction project. A contingency scenario allows you to prepare for unforeseen circumstances and negative events that may occur during the implementation of a road construction project. The application of this scenario is absolutely necessary in cases where there is a high probability of the occurrence of specific risks or when these risks can have a serious impact on the project

Testing a spaceborne passive‐microwave severe hail retrieval over Argentina using ground‐based dual‐polarization radar data

AbstractPassive‐microwave hail detection methods rely on the scattering signal produced by large ice hydrometeors. Recently, passive‐microwave hail retrieval methods have been trained by pairing Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and Global Precipitation Measurement (GPM) Microwave Imager (GMI) data with United States surface hail reports to present a global hail climatology. In particular, Southeastern South America (SESA) stands out as a hotspot for hail occurrence, more specifically northeastern Argentina. However, the analysis performed with the available ground hail reports in Argentina shows some differences from the available ground hail reports in Argentina, as it locates the most frequent hail storms in the southwestern (Mendoza and Córdoba) and northeastern (Misiones) regions of SESA. To assess the retrieval from a regional perspective, we take a case study approach and focus on polarization‐corrected temperature features (PCTFs) with a detected . We mainly rely on polarimetric weather radars and a hydrometeor identification algorithm (HID) as a proxy for ground truth. Results indicate that the hail retrieval responds mainly to low 37‐GHz polarized corrected (brightness) temperatures (PCTs) and large PCTF area, while HID outputs show that high probabilities of hail also correspond to abundantly suspended graupel. The observed passive‐microwave hail detection hotspot could be influenced by mesoscale convective systems with deep columns of graupel‐sized frozen hydrometeors, common in northeastern Argentina.

SSIM-Based Autoencoder Modeling to Defeat Adversarial Patch Attacks

Object detection systems are used in various fields such as autonomous vehicles and facial recognition. In particular, object detection using deep learning networks enables real-time processing in low-performance edge devices and can maintain high detection rates. However, edge devices that operate far from administrators are vulnerable to various physical attacks by malicious adversaries. In this paper, we implement a function for detecting traffic signs by using You Only Look Once (YOLO) as well as Faster-RCNN, which can be adopted by edge devices of autonomous vehicles. Then, assuming the role of a malicious attacker, we executed adversarial patch attacks with Adv-Patch and Dpatch. Trying to cause misdetection of traffic stop signs by using Adv-Patch and Dpatch, we confirmed the attacks can succeed with a high probability. To defeat these attacks, we propose an image reconstruction method using an autoencoder and the Structural Similarity Index Measure (SSIM). We confirm that the proposed method can sufficiently defend against an attack, attaining a mean Average Precision (mAP) of 91.46% even when two adversarial attacks are launched.

Roma undergraduates’ partner selection and social embeddedness

ABSTRACT This study investigates Roma undergraduates’ partner selection patterns, examines the main factors in students’ partner selection attitudes, and analyzes the structural role in students’ network. We rely on data from semi-structured life-narratives and contact diaries of 67 Roma undergraduates. Three main partner selection patterns were distinguished among Roma students: (1) Roma and non-Roma partners with low educational attainment, (2) non-Roma partners with secondary or higher education, and (3) Roma partners with secondary or higher education. Partners’ sociodemographic backgrounds show correspondence with the size of students’ egocentric networks and indicates ties from the same social group with higher probability. Our results imply that in the choice between a typically low-status Roma environment and a high-status university environment, or in the delicate balancing act between the two, the chosen partner plays a key role.

7798 A Prospective Within-Patient Comparison of Molecular Imaging Ligands for Detection Of Surgically Curable Primary Aldosteronism (PA), and an Assessment of Accuracy in Cortisol Co-Secretors

Abstract Disclosure: E. Goodchild: None. X. Wu: None. R. Senanayake: None. J. MacFarlane: None. G. Argentesi: None. K. Laycock: None. C. Cabrera: None. S.M. O'Toole: None. J. Salsbury: None. D. Benu: None. Y. Lee: None. A. Chua: None. M. Mattson: None. P. Laila: None. N. Hilliard: None. M. Alison: None. D. Berney: None. K. Drew: None. C. Mein: None. E. Wozniak: None. J. Kearney: None. A. Sahdev: None. N. Bird: None. G. Smith: None. M. Hird: None. V. Warnes: None. D. Gillett: None. F. Aigbirhio: None. A. McIntosh: None. A. McConnachie: None. K. Cruickshank: None. H. Cheow: None. M. Gurnell: None. W. Drake: None. M.J. Brown: None. Introduction: Molecular imaging could reduce the need for invasive, scarcely-available adrenal sampling (AVS) to identify aldosterone-producing adenomas (APAs). Easily-distributable ligands for widespread use will be needed. Imidazole ligands lacking selectivity ex vivo for CYP11B1 and CYP11B2 are rendered selective in vivo by pre-treatment with dexamethasone. Aims To determine whether post-dexamethasone para-chloro-2-[[1]8F]fluoroethyletomidate PET-CT (CETO) (T ½ 110min), is interchangeable with previously validated [[1][1]C]-metomidate PET-CT (MTO) (T ½ 20min) for the diagnosis of APA. To identify whether a non-fully-suppressed cortisol after prolonged (72h) low-dose dexamethasone forewarns of an increased risk of a false-positive MTO result, in the MATCH study cohort.1Experimental design Prospective within-patient comparison of diagnostic interventions (n=31), with independent scoring of each as high, medium, low probability of unilateral PA, blind to scoring of the other scan or AVS. Prospective measurements of cortisol after prolonged low-dose dexamethasone suppression (PLDDF) and urinary hybrid steroids, with 6-month post-operative PASO biochemical outcomes and APA somatic genotyping when high probability (MTO or AVS) mandated surgery. Major results MTO and CETO agreed in 29/31, kappa=0.85 [95%CI 0.68,1.00]. Scatter was evenly distributed on either side of zero on Bland-Altman analysis (bias -0.04, [95% CI -0.12,0.04]. Of all 174 MATCH-study patients (n=174) PLDDF was available in 156, 32 had PLDDF &amp;gt;25nmol/L. Of these, MTO scored 16 as high probability of unilateral PA, in whom there was complete PASO biochemical success in 14 (88%), and absent in 2 (12%), indicating possible false-positives (AVS had failed in both). In patients with PLDDF &amp;lt;/=25nmol/L, MTO identified unilateral disease in 22, 19 (86.3%) of whom had complete biochemical success at 6 months, 3 (13.6%) with partial or absent success. 22 patients had both an elevated PLDDF and urinary hybrid steroid profiles measured, of whom 4 had an elevated 18OH/F ratio. PLDDF in unilateral and not-unilateral MTO outcome were comparable (unpaired T test p= 0.92). A known somatic genotype mutation was found in 21 patients with PLDDF &amp;gt;25nmol/l. PLDDF was highest in KCNJ5 mutants (12/21, mean 55.3nmol/L), compared to ATP1A1 (3/21, mean 44nmol/L), CACNA1D (4/21, mean 31nmol/L), ATP2B3 (1/21, 36nmol/L) and GNAQ (1/21, 28nmol/L). All had complete biochemical success at 6 months post-op. Conclusion: CETO is interchangeable with MTO, which is non-inferior to AVS, in lateralising aldosterone excess in PA patients. False-positives rarely occurred by MTO, and autonomous cortisol secretion did not increase the chance of a false-positive MTO result, compared to patients without, in this cohort. Reference: (1) Wu X et al. Nature Medicine. 2023;29:190-202. Presentation: 6/3/2024

Cryo-EM investigation of ryanodine receptor type 3.

Ryanodine Receptor isoform 3 (RyR3) is a large ion channel found in the endoplasmic reticulum membrane of many different cell types. Within the hippocampal region of the brain, it is found in dendritic spines and regulates synaptic plasticity. It controls myogenic tone in arteries and is upregulated in skeletal muscle in early development. RyR3 has a unique functional profile with a very high sensitivity to activating ligands, enabling high gain in Ca2+-induced Ca2+ release. Here we solve high-resolution cryo-EM structures of RyR3 in non-activating and activating conditions, revealing structural transitions that occur during channel opening. Addition of activating ligands yields only open channels, indicating an intrinsically high open probability under these conditions. RyR3 has reduced binding affinity to the auxiliary protein FKBP12.6 due to several sequence variations in the binding interface. We map disease-associated sequence variants and binding sites for known pharmacological agents. The N-terminal region contains ligand binding sites for a putative chloride anion and ATP, both of which are targeted by sequence variants linked to epileptic encephalopathy.

8042 A Rare Case of Papillary Thyroid Carcinoma in a Patient with Li-Fraumeni Syndrome

Abstract Disclosure: K.M. Bakhtawar: None. G. Jaiswal: None. Li-Fraumeni syndrome (LFS) is an autosomal dominant syndrome with a high lifetime probability of cancer at an early age. The spectrum of cancers primarily includes osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, leukemia, and Adenoid cystic carcinoma. Prior studies have estimated the cumulative cancer risk to be about 50% by age 40 and as high as 90% by age 60. As screening for TP53 mutations has improved and more patients are identified, the LFS cancer spectrum has expanded to include thyroid cancer. However, the occurrence of thyroid cancer in LFS has not been extensively assessed in the literature. A recent study examined cancer patients carrying the Brazilian p.R337H TP53 mutation which demonstrated that out of 101 patients, 11 had thyroid cancer (10.9%). In our case, a 45-year-old female with a past medical history of Li-Fraumeni syndrome, Von Willebrand disease, Pulmonary embolism, HER-2 positive invasive ductal carcinoma of the left breast status post chemotherapy, and bilateral mastectomy presented for evaluation of papillary thyroid carcinoma (PTC). An enlarged thyroid was initially identified on physical exam by the PCP with a follow-up thyroid ultrasound showing bilateral nodules. The right upper pole 1.9 x 1.3 x 1.6 cm nodule was biopsied revealing PCT. Following neck ultrasound demonstrated mildly enlarged lymph nodes on the right side, level 2A 1.5 cm and level 3 1.6 cm. The patient subsequently underwent total thyroidectomy and lymph node dissection. The pathology report revealed a 1.4 cm PTC in the upper right pole, a 0.9 cm PCT in the isthmus, and a 0.8 cm PTC in the left midpole. 4/62 lymph nodes were positive with the largest deposit of 1 cm. All margins were negative for carcinoma with no angioinvasion or lymphatic invasion. She was staged as T1bN1bM0. We are awaiting post-operative Thyroglobulin level to assess the need for Radioactive iodine. BRAFV600E and P53 mutation was identified. The patient carries known heterozygous mutation p.R1755H in the TP53 gene with an estimated lifetime cancer risk of 93%. This particular mutation has not been associated with thyroid cancer in prior studies. Although thyroid cancer is an uncommon manifestation of LFS, this case begs the importance of further studies to explore this association which may then lead to early screening and treatment of thyroid cancer in individuals with founder TP53 mutations. Presentation: 6/1/2024