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At least 361 records · Page 20

Monoclonal antibodies directed against surface molecules of multicell spheroids

The objective of this project is to generate a library of monoclonial antibodies (MAbs) directed against surface molecules of tumor and transformed cells grown as multicell spheroids (MCS). These MCS are highly organized, 3-dimensional multicellular structures which exhibit many characteristics of in vivo organized tissues which are not found in conventional monolayer or suspension culture. In brief, MCS combine the relevance or organized tissues with in vitro methodology making the MCS a good model system to study the interactions of mammalian cells, and thereby provide a functional assay for surface adhesion molecules. This project also involves investigations of cell-cell interactions in a gravity-based environment. It will provide an important base of scientific information for future comparative studies on the effects of hypergravity and simulated microgravity environments on cell-cell interactions. This project also has the potential to yield important materials (e.g. cellular products) which may be useful for the diagnosis and/or treatment of certain human diseases. Moreover, this project supports the training of one undergraduate and one graduate student; thus, it will also assist in developing a pool of future scientists with research experience in gravitational biology research.

Martinez, Andrew O.↗

Tropical Pacific moisture variability

The research objectives were to describe synoptic scale variability of moisture over the tropical Pacific Ocean and the systems leading to this variability, to implement satellite analysis procedures to accomplish that objective, to incorporate additional satellite information into operational analysis/forecast systems at the National Meteorological Center (NMC), and to synthesize knowledge gained from satellite observations through diagnosis and numerical models. In the past year, three significant satellite data analysis tasks were accomplished: comparisons for upwelling radiance fields for 1983 and 1984 were completed for the purpose of testing the sensitivity of water vapor/greenhouse feedback to local sea surface temperature variations; the interaction between tropical plumes, wave features over Central America, traveling waves in the upper tropospheric tropics, and the tropical interseasonal oscillation was examined; and planning and early efforts on the construction of a model and the infrared based climatology of daily precipitable water was completed. Research on tropical plume mechanisms included is briefly discussed.

Mcguirk, James P.↗

Adaptive control with an expert system based supervisory level

Adaptive control is presently one of the methods available which may be used to control plants with poorly modelled dynamics or time varying dynamics. Although many variations of adaptive controllers exist, a common characteristic of all adaptive control schemes, is that input/output measurements from the plant are used to adjust a control law in an on-line fashion. Ideally the adjustment mechanism of the adaptive controller is able to learn enough about the dynamics of the plant from input/output measurements to effectively control the plant. In practice, problems such as measurement noise, controller saturation, and incorrect model order, to name a few, may prevent proper adjustment of the controller and poor performance or instability result. In this work we set out to avoid the inadequacies of procedurally implemented safety nets, by introducing a two level control scheme in which an expert system based 'supervisor' at the upper level provides all the safety net functions for an adaptive controller at the lower level. The expert system is based on a shell called IPEX, (Interactive Process EXpert), that we developed specifically for the diagnosis and treatment of dynamic systems. Some of the more important functions that the IPEX system provides are: (1) temporal reasoning; (2) planning of diagnostic activities; and (3) interactive diagnosis. Also, because knowledge and control logic are separate, the incorporation of new diagnostic and treatment knowledge is relatively simple. We note that the flexibility available in the system to express diagnostic and treatment knowledge, allows much greater functionality than could ever be reasonably expected from procedural implementations of safety nets. The remainder of this chapter is divided into three sections. In section 1.1 we give a detailed review of the literature in the area of supervisory systems for adaptive controllers. In particular, we describe the evolution of safety nets from simple ad hoc techniques, up to the use of expert systems for more advanced supervision capabilities.

Sullivan, Gerald A.↗

Mission simulation as an approach to develop requirements for automation in Advanced Life Support Systems

This paper examines mission simulation as an approach to develop requirements for automation and robotics for Advanced Life Support Systems (ALSS). The focus is on requirements and applications for command and control, control and monitoring, situation assessment and response, diagnosis and recovery, adaptive planning and scheduling, and other automation applications in addition to mechanized equipment and robotics applications to reduce the excessive human labor requirements to operate and maintain an ALSS. Based on principles of systems engineering, an approach is proposed to assess requirements for automation and robotics using mission simulation tools. First, the story of a simulated mission is defined in terms of processes with attendant types of resources needed, including options for use of automation and robotic systems. Next, systems dynamics models are used in simulation to reveal the implications for selected resource allocation schemes in terms of resources required to complete operational tasks. The simulations not only help establish ALSS design criteria, but also may offer guidance to ALSS research efforts by identifying gaps in knowledge about procedures and/or biophysical processes. Simulations of a planned one-year mission with 4 crewmembers in a Human Rated Test Facility are presented as an approach to evaluation of mission feasibility and definition of automation and robotics requirements.

NASA Discipline Number 61-10↗

Cutaneous and local radiation injuries

The threat of a large-scale radiological or nuclear (R/N) incident looms in the present-day climate, as noted most recently in an editorial in Scientific American (March 2021). These large-scale incidents are infrequent but affect large numbers of people. Smaller-scale R/N incidents occur more often, affecting smaller numbers of people. There is more awareness of acute radiation syndrome (ARS) in the medical community; however, ionising radiation-induced injuries to the skin are much less understood. Here, this article will provide an overview of radiation-induced injuries to the skin, deeper tissues, and organs. The history and nomenclature; types and causes of injuries; pathophysiology; evaluation and diagnosis; current medical management; and current research of the evaluation and management are presented. Cutaneous radiation injuries (CRI) or local radiation injuries (LRI) may lead to cutaneous radiation syndrome, a sub-syndrome of ARS. These injuries may occur from exposure to radioactive particles suspended in the environment (air, soil, water) after a nuclear detonation or an improvised nuclear detonation (IND), a nuclear power plant incident, or an encounter with a radioactive dispersal or exposure device. These incidents may also result in a radiation-combined injury; a chemical, thermal, or traumatic injury, with radiation exposure. Skin injuries from medical diagnostic and therapeutic imaging, medical misadministration of nuclear medicine or radiotherapy, occupational exposures (including research) to radioactive sources are more common but are not the focus of this manuscript. Diagnosis and evaluation of injuries are based on the scenario, clinical picture, and dosimetry, and may be assisted through advanced imaging techniques. Research-based multidisciplinary therapies, both in the laboratory and clinical trial environments, hold promise for future medical management. Great progress is being made in recognising the extent of injuries, understanding their pathophysiology, as well as diagnosis and management; however, research gaps still exist.

61 RADIATION PROTECTION AND DOSIMETRY↗

Fault detection and diagnosis using neural network approaches

Neural networks can be used to detect and identify abnormalities in real-time process data. Two basic approaches can be used, the first based on training networks using data representing both normal and abnormal modes of process behavior, and the second based on statistical characterization of the normal mode only. Given data representative of process faults, radial basis function networks can effectively identify failures. This approach is often limited by the lack of fault data, but can be facilitated by process simulation. The second approach employs elliptical and radial basis function neural networks and other models to learn the statistical distributions of process observables under normal conditions. Analytical models of failure modes can then be applied in combination with the neural network models to identify faults. Special methods can be applied to compensate for sensor failures, to produce real-time estimation of missing or failed sensors based on the correlations codified in the neural network.

Kramer, Mark A.↗

The Diagnostic Challenge Competition: Probabilistic Techniques for Fault Diagnosis in Electrical Power Systems

Reliable systems health management is an important research area of NASA. A health management system that can accurately and quickly diagnose faults in various on-board systems of a vehicle will play a key role in the success of current and future NASA missions. We introduce in this paper the ProDiagnose algorithm, a diagnostic algorithm that uses a probabilistic approach, accomplished with Bayesian Network models compiled to Arithmetic Circuits, to diagnose these systems. We describe the ProDiagnose algorithm, how it works, and the probabilistic models involved. We show by experimentation on two Electrical Power Systems based on the ADAPT testbed, used in the Diagnostic Challenge Competition (DX 09), that ProDiagnose can produce results with over 96% accuracy and less than 1 second mean diagnostic time.

Ricks, Brian W.↗

Basic Diagnosis and Prediction of Persistent Contrail Occurrence using High-resolution Numerical Weather Analyses/Forecasts and Logistic Regression. Part I: Effects of Random Error

Straightforward application of the Schmidt-Appleman contrail formation criteria to diagnose persistent contrail occurrence from numerical weather prediction data is hindered by significant bias errors in the upper tropospheric humidity. Logistic models of contrail occurrence have been proposed to overcome this problem, but basic questions remain about how random measurement error may affect their accuracy. A set of 5000 synthetic contrail observations is created to study the effects of random error in these probabilistic models. The simulated observations are based on distributions of temperature, humidity, and vertical velocity derived from Advanced Regional Prediction System (ARPS) weather analyses. The logistic models created from the simulated observations were evaluated using two common statistical measures of model accuracy, the percent correct (PC) and the Hanssen-Kuipers discriminant (HKD). To convert the probabilistic results of the logistic models into a dichotomous yes/no choice suitable for the statistical measures, two critical probability thresholds are considered. The HKD scores are higher when the climatological frequency of contrail occurrence is used as the critical threshold, while the PC scores are higher when the critical probability threshold is 0.5. For both thresholds, typical random errors in temperature, relative humidity, and vertical velocity are found to be small enough to allow for accurate logistic models of contrail occurrence. The accuracy of the models developed from synthetic data is over 85 percent for both the prediction of contrail occurrence and non-occurrence, although in practice, larger errors would be anticipated.

Duda, David P.↗

Foreign Object Damage Identification in Turbine Engines

This report summarizes the collective work of a five-person team from different organizations examining the problem of detecting foreign object damage (FOD) events in turbofan engines from gas path thermodynamic and bearing accelerometer sensors, and determining the severity of damage to each component (diagnosis). Several detection and diagnostic approaches were investigated and a software tool (FODID) was developed to assist researchers detect/diagnose FOD events. These approaches include (1) fan efficiency deviation computed from upstream and downstream temperature/ pressure measurements, (2) gas path weighted least squares estimation of component health parameter deficiencies, (3) Kalman filter estimation of component health parameters, and (4) use of structural vibration signal processing to detect both large and small FOD events. The last three of these approaches require a significant amount of computation in conjunction with a physics-based analytic model of the underlying phenomenon the NPSS thermodynamic cycle code for approaches 1 to 3 and the DyRoBeS reduced-order rotor dynamics code for approach 4. A potential application of the FODID software tool, in addition to its detection/diagnosis role, is using its sensitivity results to help identify the best types of sensors and their optimum locations within the gas path, and similarly for bearing accelerometers.

Strack, William↗

Super-resolution and segmentation deep learning for breast cancer histopathology image analysis

Traditionally, a high-performance microscope with a large numerical aperture is required to acquire high-resolution images. However, the images’ size is typically tremendous. Therefore, they are not conveniently managed and transferred across a computer network or stored in a limited computer storage system. As a result, image compression is commonly used to reduce image size resulting in poor image resolution. Here, we demonstrate custom convolution neural networks (CNNs) for both super-resolution image enhancement from low-resolution images and characterization of both cells and nuclei from hematoxylin and eosin (H&E) stained breast cancer histopathological images by using a combination of generator and discriminator networks so-called super-resolution generative adversarial network-based on aggregated residual transformation (SRGAN-ResNeXt) to facilitate cancer diagnosis in low resource settings. The results provide high enhancement in image quality where the peak signal-to-noise ratio and structural similarity of our network results are over 30 dB and 0.93, respectively. The derived performance is superior to the results obtained from both the bicubic interpolation and the well-known SRGAN deep-learning methods. In addition, another custom CNN is used to perform image segmentation from the generated high-resolution breast cancer images derived with our model with an average Intersection over Union of 0.869 and an average dice similarity coefficient of 0.893 for the H&E image segmentation results. Finally, we propose the jointly trained SRGAN-ResNeXt and Inception U-net Models, which applied the weights from the individually trained SRGAN-ResNeXt and inception U-net models as the pre-trained weights for transfer learning. The jointly trained model’s results are progressively improved and promising. We anticipate these custom CNNs can help resolve the inaccessibility of advanced microscopes or whole slide imaging (WSI) systems to acquire high-resolution images from low-performance microscopes located in remote-constraint settings.

60 APPLIED LIFE SCIENCES↗

Comparison of Full-Field and Integrated CFD Convergence Based on Richardson Extrapolation

This work investigated the usefulness of Richardson extrapolation--based discretization error estimates across all points in a solution field to produce a spatial convergence field for a computational fluid dynamics (CFD) simulation. The presented work used previously developed methods for Richardson extrapolation to compute the convergence orders of a CFD simulation at all points of the base (coarsest) mesh solution. Three test cases of increasing complexity were considered: Poiseuille flow, incompressible flow around a sharp corner, and transonic flow over an RAE 2822 airfoil. These test cases highlighted the potential of the proposed method to identify error sources and their relation to the model system-response-quantity convergence orders. However, these test cases also revealed the immaturity of the proposed method stemming from the unreliability of computing observed convergence orders at single points. Nonetheless, the test cases highlighted that the observed convergence orders allow for a more accurate diagnosis of constructive and destructive error transport than mesh pair error estimates. In the long run, the proposed method can be a tool for developing efficient and advanced error management strategies like adaptive mesh refinement.

Weinmeister, Justin↗

Lung cancer mortality among construction workers: implications for early detection

Objectives This study examined predictors of lung cancer mortality, beyond age and smoking, among construction workers employed at US Department of Energy (DOE) sites to better define eligibility for low-dose CT (LDCT) lung cancer screening. Methods Predictive models were based on 17 069 workers and 352 lung cancer deaths. Risk factors included age, gender, race/ethnicity, cigarette smoking, years of trade or DOE work, body mass index (BMI), chest X-ray results, spirometry results, respiratory symptoms, beryllium sensitisation and personal history of cancer. Competing risk Cox models were used to obtain HRs and to predict 5-year risks. Results Factors beyond age and smoking included in the final predictive model were chest X-ray changes, abnormal lung function, chronic obstructive pulmonary disease (COPD), respiratory symptoms, BMI, personal history of cancer and having worked 5 or more years at a DOE site or in construction. Risk-based LDCT eligibility demonstrated improved sensitivity, specificity and positive predictive value compared with current US Preventive Services Task Force guidelines. The risk of lung cancer death from 5 years of work in the construction industry or at a DOE site was comparable with the risk from a personal cancer history, a family history of cancer or a diagnosis of COPD. LDCT eligibility criteria used for DOE construction workers, which includes factors beyond age and smoking, identified 86% of participants who eventually would die from lung cancer compared with 51% based on age and smoking alone. Conclusions Results support inclusion of risk from occupational exposures and non-malignant respiratory clinical findings in LDCT clinical guidelines.

Public, Environmental & Occupational Health↗

Assessing Self-Definition and Relatedness in Level of Personality Functioning

The two polarities model (TPM) of personality organizes psychological assessment and psychotherapy and connects to personality disorder diagnosis using the DSM-5 Alternative Model for Personality Disorders (AMPD). The authors developed scales assessing the TPM from an existing self-report measure for level of personality functioning (LPF), a core component of the AMPD. Iterative content analyses of the LPF measure yielded scales for Autonomy and Communion corresponding to dimensions of the TPM. The scales were refined via internal consistency analyses using a measure of psychological attachment and studied in development and validation samples. Associations with relevant external criteria were explored in a series of multiple regressions. Furthermore, the new content-based LPF scales were illustrated with a case vignette. Although the new Autonomy/Communion scales await further validation prior to clinical use, initial evidence suggests that they may bridge the nomological nets of the TPM and AMPD and potentially offer clinical utility in assessment and treatment planning.

60 APPLIED LIFE SCIENCES↗

Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging

Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 ( 18 F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, setting, and participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [ 18 F]Flortaucipir PET in the discovery cohort (n = 1135) or [ 18 F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main outcomes and measures: Baseline [ 18 F]flortaucipir/[ 18 F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [ 18 F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R 2 , 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aβ-positive CU group (R 2 , 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [ 18 F]RO948 PET cohort. MRI mediated the association between [ 18 F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [ 18 F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

59 BASIC BIOLOGICAL SCIENCES↗

A proven knowledge-based approach to prioritizing process information

Many space-related processes are highly complex systems subject to sudden, major transients. In any complex process control system, a critical aspect is rapid analysis of the changing process information. During a disturbance, this task can overwhelm humans as well as computers. Humans deal with this by applying heuristics in determining significant information. A simple, knowledge-based approach to prioritizing information is described. The approach models those heuristics that humans would use in similar circumstances. The approach described has received two patents and was implemented in the Alarm Filtering System (AFS) at the Idaho National Engineering Laboratory (INEL). AFS was first developed for application in a nuclear reactor control room. It has since been used in chemical processing applications, where it has had a significant impact on control room environments. The approach uses knowledge-based heuristics to analyze data from process instrumentation and respond to that data according to knowledge encapsulated in objects and rules. While AFS cannot perform the complete diagnosis and control task, it has proven to be extremely effective at filtering and prioritizing information. AFS was used for over two years as a first level of analysis for human diagnosticians. Given the approach's proven track record in a wide variety of practical applications, it should be useful in both ground- and space-based systems.

Corsberg, Daniel R.↗

Enhancing the Operational Resilience of Advanced Reactors with Digital Twins by Recurrent Neural Networks

Because of a lack of operation data during abnormal and accident scenarios, along with the existence of uncertainty in the evaluation model for transient and accident analysis, the established abnormal and emergency operating procedures can be biased in characterizing the reactor states and ensuring operational resilience. To improve state awareness and ensure operational flexibility for minimizing effects on the system due to anomaly, digital twin (DT) technology is suggested to support operator's decision-making by effectively extracting and using knowledge of the current and future plant states from the knowledge base. To demonstrate DT's capability for recovering the complete states of reactors and for predicting the future reactor behaviors, this paper develops and assesses both the diagnosis and prognosis DTs in a nearly autonomous management and control system for an Experimental Breeder Reactor-II simulator during different loss-of-flow scenarios.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database

Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. The study population included 3,812,588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62–8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80–6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25–5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68–4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93–5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82–13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44–3.29]) compared with controls. Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. In conclusion, this study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

60 APPLIED LIFE SCIENCES↗

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

60 APPLIED LIFE SCIENCES↗