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At least 127 records · Page 7

Assessment of Bird Strike Likelihood to Refine Bird Strike Risk Models

In its most basic form, bird strike risk is comprised of a frequency component that reflects the likelihood of a collision and a severity component that reflects the cost (monetary or otherwise) of the incident. The bird strike risk model currently used by United State Department of Agriculture (USDA) Wildlife Services to evaluate the risk posed by individual bird species at airports and establish priorities for management was developed in 2018. The model uses airport-specific data on the number of reported strikes for a species recorded in the Federal Aviation Administration (FAA)’s National Wildlife Strike Database as a measure of frequency and the species’ relative hazard score as a measure of severity. The model was tested against independent data, found to perform well overall, and is being implemented widely across the United States. However, the model has limitations, including that species known to pose risk to aircraft locally, but not present in the strike record database, are not reflected as a major component of risk. Standard bird survey methodology commonly used at airports (e.g. point counts or transects) potentially can be used to complement wildlife strike records to calculate frequency or relative abundance of species. However, these methods generally focus on airport-wide population estimation and often ignore vital information that contributes to the true likelihood of a strike, such as use of runway protection zones and other critical areas, and spatial and temporal overlap with departing or approaching aircraft. As such, a more detailed understanding of space use by birds across landcovers and population fluctuations across the year is needed to accurately estimate the likelihood of bird strikes at airports. In this manuscript, we will review the extant risk model, including a discussion on its limitations. We then discuss approaches for refining our understanding of strike likelihood and briefly touch on needs for estimating probability of strike severity (cost).

bird strike, aircraft collision, damage by wildlif↗

Risk Of Early Onset Osteoporosis Due To Spaceflight

Bone minerals decline in microgravity, and bone mineral density (BMD) losses of approximately -1 to -1.5% per month were calculated for astronauts serving on long-duration missions prior to 2009. It is unclear whether BMD losses will stabilize with time in space, or continue to diminish with time. In addition, it is unknown if fractional gravity, present on the moon and Mars, will mitigate the mineral loss. Clinicians diagnose osteoporosis in premenopausal females and males younger than 50 years on the basis of BMD T-scores < -2.5 (hip and lumbar spine) accompanied by clinical evidence of a fragility fracture. If mission-related changes to the skeleton cannot be corrected by rehabilitation after the mission, crewmembers could be at risk for premature osteoporosis-related fractures in later life. To mitigate this risk it is necessary to understand the dynamics underlying the BMD changes that occur in microgravity, to monitor for the persistence of changes after space flight, and to evaluate if and how current and future osteoporosis treatments might be used to mitigate the risk of long-term skeletal problems in astronauts.

Sibonga, Jean↗

Emergency department visits in California associated with wildfire PM 2.5 : differing risk across individuals and communities

The threats to human health from wildfires and wildfire smoke (WFS) in the United States (US) are increasing due to continued climate change. A growing body of literature has documented important adverse health effects of WFS exposure, but there is insufficient evidence regarding how risk related to WFS exposure varies across individual or community level characteristics. To address this evidence gap, we utilized a large nationwide database of healthcare utilization claims for emergency department (ED) visits in California across multiple wildfire seasons (May through November, 2012–2019) and quantified the health impacts of fine particulate matter <2.5 μm (PM 2.5 ) air pollution attributable to WFS, overall and among subgroups of the population. We aggregated daily counts of ED visits to the level of the Zip Code Tabulation Area (ZCTA) and used a time-stratified case-crossover design and distributed lag non-linear models to estimate the association between WFS and relative risk of ED visits. We further assessed how the association with WFS varied across subgroups defined by age, race, social vulnerability, and residential air conditioning (AC) prevalence. Over a 7 day period, PM 2.5 from WFS was associated with elevated risk of ED visits for all causes (1.04% (0.32%, 1.71%)), non-accidental causes (2.93% (2.16%, 3.70%)), and respiratory disease (15.17% (12.86%, 17.52%)), but not with ED visits for cardiovascular diseases (1.06% (–1.88%, 4.08%)). Analysis across subgroups revealed potential differences in susceptibility by age, race, and AC prevalence, but not across subgroups defined by ZCTA-level Social Vulnerability Index scores. These results suggest that PM 2.5 from WFS is associated with higher rates of all cause, non-accidental, and respiratory ED visits with important heterogeneity across certain subgroups. Notably, lower availability of residential AC was associated with higher health risks related to wildfire activity.

54 ENVIRONMENTAL SCIENCES↗

Gut microbiome dynamics and associations with mortality in critically ill patients

Abstract Background Critical illness and care within the intensive care unit (ICU) leads to profound changes in the composition of the gut microbiome. The impact of such changes on the patients and their subsequent disease course remains uncertain. We hypothesized that specific changes in the gut microbiome would be more harmful than others, leading to increased mortality in critically ill patients. Methods This was a prospective cohort study of critically ill adults in the ICU. We obtained rectal swabs from 52 patients and assessed the composition the gut microbiome using 16 S rRNA gene sequencing. We followed patients throughout their ICU course and evaluated their mortality rate at 28 days following admission to the ICU. We used selbal, a machine learning method, to identify the balance of microbial taxa most closely associated with 28-day mortality. Results We found that a proportional ratio of four taxa could be used to distinguish patients with a higher risk of mortality from patients with a lower risk of mortality (p = .02). We named this binarized ratio our microbiome mortality index (MMI). Patients with a high MMI had a higher 28-day mortality compared to those with a low MMI (hazard ratio, 2.2, 95% confidence interval 1.1–4.3), and remained significant after adjustment for other ICU mortality predictors, including the presence of the acute respiratory distress syndrome (ARDS) and the Acute Physiology and Chronic Health Evaluation (APACHE II) score (hazard ratio, 2.5, 95% confidence interval 1.4–4.7). High mortality was driven by taxa from theAnaerococcus(genus) andEnterobacteriaceae(family), while lower mortality was driven byParasutterellaandCampylobacter(genera). Conclusions Dysbiosis in the gut of critically ill patients is an independent risk factor for increased mortality at 28 days after adjustment for clinically significant confounders. Gut dysbiosis may represent a potential therapeutic target for future ICU interventions.

Gastroenterology & Hepatology↗

Digitalization mapping and assessment process supporting ION strategic transformation activities

The existing fleet of commercial nuclear power plants (NPPs) are an important asset in the nation’s portfolio of electrical generating resources. Their continued safe and reliable operation are critical to providing a large source of carbon-free electricity to power the nation’s economy. The United States Department of Energy’s (DOE) Light Water Reactor Sustainability (LWRS) Program develops the scientific bases, methods, and tools, for the continued safe and economical operation of the nation's commercial NPPs. The Plant Modernization Pathway within LWRS Program focuses on providing guidance to industry on the full-scale implementation of modernization solutions for NPPs that significantly reduce the technical and financial risks associated with modernization. This research is focused on helping the nuclear industry understand how to digitize and digitalize their NPPs so that they can design their modernization solutions to be scalable, sustainable, and integrated both laterally and horizontally within their organization. That is, this research creates a digital transformation in NPPs by reshaping cultural mindsets and by identifying business efficiencies. In partnership with industry, and using four previously established guiding principles for digitalization, this research supported NPP modernization through assessing readiness for digitalization as a means to achieve integrated operations for nuclear. Specifically, this research created an assessment to review an entire organization’s work processes to gather information about the digitalization health of the plant. The assessment tools were administered to plant employees, and the results were used to develop a digitalization plan. The survey assessment identified the optimal candidate processes that would most benefit from a digitalization initiative which were revealed through analytical frameworks. One analysis calculated mean digitalization health indicator scores for all endorsed activities which allowed the researchers to rank and color code the results for easy identification. Individual health indicator scores are also provided, should our industry partner wish to understand these findings according to their own organizational priorities, business considerations and desired end-state. The results were also analyzed from the perspective that organizations are comprised of different types of innovators (e.g., generators, optimizers, conceptualizers, and implementers), which differentially affects the organization’s ability to comprehend and adapt to change (i.e., opportunities to innovate). Understanding the relative composition of innovator types at an NPP allows them to gather insights into the strengths and weaknesses they have in innovating how work is performed. For the utility that partnered with this research team, the results showed that implementers make up the largest portion of respondents and conceptualizers the smallest portion. Knowing the proportion of innovator types gave this organization insights on how they can effectively implement their innovation solutions. Additionally, the results were analyzed from a technical, economic, and risk perspective to identify and quantify work reduction opportunities (WROs). Recognizing that not all cost-saving opportunities are the same, a Technical, Economic and Risk Assessment (TERA) was performed to evaluate WROs to identify areas of greatest potential and lowest risk. The key results from TERA included a digitalization opportunity score for each activity, and a calculation of potential cost savings. These two outputs formed the bases for calculating a priority index and rank for the activities/processes assessed. From the prioritization calculations, TERA can then help the utility 1) decide what digitalization priorities to invest money in implementing and then 2) calculates how much should be invested in the digitalization initiatives selected to achieve cost savings and/or an acceptable return on investment. Last, onsite interviews revealed several inefficiencies in the standard work processes that occur cross-departmentally that are due to the absence of digitized and digitalized processes. Examples of these include time spent scanning paper documents and then uploading the documents electronically, obtaining signatures, and searching for desired information. This represents a digital but not digitalized process. Over 15 opportunities to improve work processes were identified through this multi-method digitalization assessment. The various analytical assessments used (e.g., TERA, digitalization health indicator scores), as well as discussions with the utility partner, corroborated that all the opportunities identified had a strong potential to make work processes more efficient and to improve overall performance of the NPP.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Application of Multi-Criteria Decision Analysis Techniques for Informing Select Agent Designation and Decision Making

The Centers for Disease Control and Prevention (CDC) Select Agent Program establishes a list of biological agents and toxins that potentially threaten public health and safety, the procedures governing the possession, utilization, and transfer of those agents, and training requirements for entities working with them. Every 2 years the Program reviews the select agent list, utilizing subject matter expert (SME) assessments to rank the agents. In this study, we explore the applicability of multi-criteria decision analysis (MCDA) techniques and logic tree analysis to support the CDC Select Agent Program biennial review process, applying the approach broadly to include non-select agents to evaluate its generality. We conducted a literature search for over 70 pathogens against 15 criteria for assessing public health and bioterrorism risk and documented the findings for archiving. The most prominent data gaps were found for aerosol stability and human infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. Analysis of results obtained from a two-dimensional plot of weighted scores for difficulty of attack (i.e., exposure and production criteria) vs. consequences of an attack (i.e., consequence and mitigation criteria) provided greater fidelity for understanding agent placement compared to a 1-to-n ranking and was used to define a region in the upper right-hand quadrant for identifying pathogens for consideration as select agents. A sensitivity analysis varied the numerical weights attributed to various properties of the pathogens to identify potential quantitative (x and y) thresholds for classifying select agents. The results indicate while there is some clustering of agent scores to suggest thresholds, there are still pathogens that score close to any threshold, suggesting that thresholding “by eye” may not be sufficient. The sensitivity analysis indicates quantitative thresholds are plausible, and there is good agreement of the analytical results with select agent designations. A second analytical approach that applied the data using a logic tree format to rule out pathogens for consideration as select agents arrived at similar conclusions.

60 APPLIED LIFE SCIENCES↗

Plan evaluation for heat resilience: complementary methods to comprehensively assess heat planning in Tempe and Tucson, Arizona

Abstract Escalating impacts from climate change and urban heat are increasing the urgency for communities to equitably plan for heat resilience. Cities in the desert Southwest are among the hottest and fastest warming in the U.S., placing them on the front lines of heat planning. Urban heat resilience requires an integrated planning approach that coordinates strategies across the network of plans that shape the built environment and risk patterns. To date, few studies have assessed cities’ progress on heat planning. This research is the first to combine two emerging plan evaluation approaches to examine how networks of plans shape urban heat resilience through case studies of Tempe and Tucson, Arizona. The first methodology, Plan Quality Evaluation for Heat Resilience, adapts existing plan quality assessment approaches to heat. We assess whether plans meet 56 criteria across seven principles of high-quality planning and the types of heat strategies included in the plans. The second methodology, the Plan Integration for Resilience Scorecard™ (PIRS™) for Heat, focuses on plan policies that could influence urban heat hazards. We categorize policies by policy tool and heat mitigation strategy and score them based on their heat impact. Scored policies are then mapped to evaluate their spatial distribution and the net effect of the plan network. The resulting PIRS™ for Heat scorecard is compared with heat vulnerability indicators to assess policy alignment with risks. We find that both cities are proactively planning for heat resilience using similar plan and strategy types, however, there are clear and consistent opportunities for improvement. Combining these complementary plan evaluation methods provides a more comprehensive understanding of how plans address heat and a generalizable approach that communities everywhere could use to identify opportunities for improved heat resilience planning.

Environmental Sciences & Ecology↗

Flood Susceptibility Mapping Using Machine Learning and Geospatial-Sentinel-1 SAR Integration for Enhanced Early Warning Systems

This study presents a comprehensive framework for flood susceptibility mapping by integrating geospatial factors with both statistical and machine learning models. Thirteen Flood-related factors, including DEM, slope, TWI, NDVI, etc., are extracted as features of models, and historical flood data derived from Sentinel-1 SAR from 2018 to 2023 are used as the target variables of the models. These datasets are analyzed using a frequency-based statistical model and three machine learning models, including Random Forest, XGBoost, and CNN, to generate flood susceptibility maps. The performance of each model is evaluated through AUC; and SHAP scores are separately generated for Machine learning (ML) models to explain each feature contribution in the ML model. The generated susceptibility maps are validated by high-flood-risk locations monitored by flood sensors, BLE inundation models, and flood-prone areas suggested by the Local Community Task Force. The results indicate that the XGBoost model outperforms all other models, with an AUC of 0.92 and demonstrates the highest alignment with recommended high-flood-risk locations, while the frequency-based statistical model showed the weakest performance with an AUC of 0.65. SHAP value graphs highlight the elevation, slope, and TWI as the most influential features across all models. The susceptibility maps generated by the machine learning model show strong agreement with the BLE map and high-flood-risk areas identified by the local Community Task Force.

Google Engine↗

Philadelphia Health & Air Quality: Assessing Land Surface Temperature, Vegetation Cover, and Compounding Vulnerability Factors to Identify High Priority Areas for Cooling Initiatives in Philadelphia, Pennsylvania

Heat is the leading cause of weather-related deaths in the US, with heat-related hospitalizations increasing by 2-5% between 2001-2010. In Philadelphia alone, 137 heat-related deaths were recorded between 2010-2018, while a total of 18 daily temperature records have been set since 2010. Temperature is relatively higher in cities compared to rural areas, a phenomenon known as the urban heat island effect. This effect exaggerates daytime maximum temperatures and nighttime heat retention in urban areas, which increases heat exposure in urban environments and especially impacts vulnerable populations. Vulnerability to heat-related illnesses is determined by a combination of risk factors, such as demographics, socioeconomic status, and preexisting health conditions. This project supported the Philadelphia Department of Public Health and Office of Sustainability by identifying priority areas for cooling interventions, such as heat danger educational outreach and urban tree planting. The team developed heat vulnerability scores for each census tract within Philadelphia. Remotely sensed land surface temperature, normalized difference vegetation index, normalized difference built-up index, normalized difference water index, and albedo data were calculated from Aqua Moderate Resolution Imaging Spectroradiometer and Landsat 8 Operational Land Imager/Thermal Infrared Sensor instruments. These variables were weighted against socioeconomic variables and preexisting health conditions using a principal component analysis. A total of 74 census tracts clustered were identified as high-risk areas for heat-related illnesses. 15 of these census tracts also had very low tree density (lower 20th percentile) and should be targeted for tree planting initiatives. The findings of this project will help target interventions to mitigate heat-related health issues and improve the overall wellness of Philadelphia residents.

Health & Air Quality↗

Philadelphia Health & Air Quality: Assessing Land Surface Temperature, Vegetation Cover, and Compounding Vulnerability Factors to Identify High Priority Areas for Cooling Initiatives in Philadelphia, Pennsylvania

Heat is the leading cause of weather-related deaths in the US, with heat-related hospitalizations increasing by 2-5% between 2001-2010. In Philadelphia alone, 137 heat-related deaths were recorded between 2010-2018, while a total of 18 daily temperature records have been set since 2010. Temperature is relatively higher in cities compared to rural areas, a phenomenon known as the urban heat island effect.This effect exaggerates daytime maximum temperatures and nighttime heat retention in urban areas, which increases heat exposure inurban environments and especially impacts vulnerable populations. Vulnerability to heat-related illnesses is determined by a combination of risk factors, such as demographics, socioeconomic status, and preexisting health conditions. This project supported the Philadelphia Department of Public Health and Office of Sustainability by identifying priority areas for cooling interventions, such as heat danger educational outreach and urban tree planting. The team developed heat vulnerability scores for each census tract within Philadelphia. Remotely sensed land surface temperature, normalized difference vegetation index, normalized difference built-up index, normalized difference water index, and albedo data were calculated from Aqua Moderate Resolution Imaging Spectroradiometer and Landsat 8 Operational Land Imager/Thermal Infrared Sensor instruments. These variables were weighted against socioeconomic variables and preexisting health conditions using a principal component analysis. A total of 74 census tracts clustered were identified as high-risk areas for heat-related illnesses. 15 of these census tracts also had very low tree density (lower 20th percentile) and should be targeted for tree planting initiatives. The findings of this project will help target interventions to mitigate heat-related health issues and improve the overall wellness of Philadelphia residents.

Health & Air Quality↗

An Integrated Framework for Effective Management of Delivery Risk in Electricity Markets: From Batteries to Insurance and Beyond

Net load imbalances due to imperfect day-ahead forecasts can cause variability in real-time electricity prices and higher system operations costs. We propose a novel market product called Flexibility Options that allow participants to hedge uncertainty by buying flexibility from flexible resources. Simulations show that flexibility options can reduce total system operating costs by up to 15% and can reduce variability in market participant revenues. To better quantify the flexibility that DER aggregators can provide, we develop DER flexibility scores that account for asset flexibility and uncertainty from occupant behavior and weather. Preliminary results show that realistic sets of DERs have significant variability in flexibility and uncertainty metrics.

delivery risk↗

A Workflow for Characterizing Legacy Wells as Potential Leakage Pathways for Integration to NRAP-Open-IAM

Carbon capture and storage is a crucial component of climate change mitigation strategies, involving the capture of carbon dioxide (CO2) from point sources and its injection into permeable subsurface formation. Many suitable CO2 storage sites coincide with legacy wells since the conditions that kept hydrocarbons in-situ for thousands of years are also ideal for storage of carbon dioxide. To protect underground sources of drinking water (USDW) during greenhouse gas injection, the Environmental Protection Agency (EPA) mandates area of review evaluations. These evaluations ensure that drinking water sources would not be contaminated by injected fluids. They include identification of legacy wellbores, integrity assessments, and implementing any necessary corrective action. Previous assessment approaches of legacy wells include high-level scoring of regional data and well construction and abandonment evaluation. This work describes a novel methodology that evaluates well construction and abandonment, ranks them based on complexity, and performs a risk assessment with NRAP-Open-IAM. A workflow of the methodology is presented, highlighting its capabilities and limitations.

Wise, Jarrett↗

Enter Gaussian Mixture Modeling Extensions for Improved False Discovery Rate Estimation in GC-MS Metabolomics

Identifying small molecules (e.g., metabolites) is key towards driving scientific advancement in metabolomics, and gas chromatography–mass spectrometry (GC-MS) is an analytic method that may be applied to facilitate this process. The typical GC-MS identification workflow involves quantifying the similarity of an observed sample spectrum and other features (e.g. retention index) to that of several references, noting the compound of the best-matching reference spectrum as the identified metabolite. While a deluge of similarity metrics exists, none characterize the error rate of generated identifications, thereby presenting an unknown risk of false identification or discovery. To quantify this unknown risk, we propose a model-based framework for estimating the false discovery rate (FDR) among a set of identifications. Extending the traditional mixture modeling framework, our method incorporates both similarity score and experimental information in estimating the FDR. We apply these models to identification lists derived from across 548 samples of varying complexity and sample type (e.g., fungal species, standard mixtures, etc.), comparing their performance to that of the traditional Gaussian mixture model (GMM). Through simulation, we additionally assess the impact of reference library size on the accuracy of FDR estimates. In comparing the best performing model extensions to the GMM, our results indicate relative decreases in median absolute estimation error (MAE) ranging from 12% to 70%, based on comparisons of the median MAEs across all hit-lists. Results indicate that these relative performance improvements generally hold despite library size, however FDR estimation error typically worsens as the set of reference compounds diminishes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Determining the Most Influencing Medical Conditions in MEDPRAT’s SIN Directed Graph

INTRODUCTION: The Susceptibility Inference Network (SIN) is a network of medical conditions, part of the Medical Extensible Probabilistic Risk Assessment Tool (MEDPRAT) developed by NASA to assess human health and medical risk to space exploration missions. The SIN is subject matter expert informed and acts as a prototype that provides relationships and dependencies between events modeled by MEDPRAT. Each vertex in the SIN has a weight which evaluates the severity of having the condition regardless of the progression from or to that condition. In this presentation, we consider two statistics to measure that stand alone risk: Quality Time Lost (QTL) and Loss of Crew Life (LOCL). Our goal is to identify the medical conditions that contribute the most to crew members QTL and LOCL risks due to progression of conditions in the network. We investigate how different computation parameters result in different condition rankings and address the choice of parameters that allows appropriate interventions to ensure space mission success. METHODS: The Katz score, one of many centrality measures created for ranking purposes in network analysis, takes into account all possible walks through the network, penalizing each additional step in a walk by a factor α called the Katz parameter. The literature does not provide specific values for the choice of α. We derive an analytical relationship between α and the maximum path length which has influence on the Katz score and ranking. Based on the probability of progression of each condition in the SIN, we identify that maximum path length of interest and calculate α that is then used in the Katz formula to rank the conditions in the SIN. RESULTS AND CONCLUSION: The effective probabilities of the SIN matrix generally fall below 10−6, which is below the level of the least influencing condition in the set. This corresponds to the probability of at most six consecutive progressions of a condition. Consequently, we calculate the Katz Parameter α and get 0.32. We rank the medical conditions and find that Acute Radiation Symptom is the condition the most prone to contribute to quality time loss due to progression.

risk analysis↗

A computer-based Safety Assessment for Flight Evacuation - SAFE

The Safety Assessment for Flight Evacuation (SAFE) system has been developed for the computerized evaluation of safety in civil Emergency Medical Service (EMS) operations. The speed of the microprocessor used to analyze data allows many individual factors to be considered, as well as the interactions among those factors. SAFE's data base is structured as if-then conditional statements. SAFE also allows the most important of the factors to be given greater weight in the final score. The questionnaire filled by EMS crews encompassed mission-, crew-, organization-, environment-, and aircraft-related factors; each of these was subdivided into as many as eight variables affecting the EMS-mission risk of that factor.

Shively, Robert J.↗

Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.

Mir Project↗

Lunar Surface Habitat Configuration Assessment: Methodology and Observations

The Lunar Habitat Configuration Assessment evaluated the major habitat approaches that were conceptually developed during the Lunar Architecture Team II Study. The objective of the configuration assessment was to identify desired features, operational considerations, and risks to derive habitat requirements. This assessment only considered operations pertaining to the lunar surface and did not consider all habitat conceptual designs developed. To examine multiple architectures, the Habitation Focus Element Team defined several adequate concepts which warranted the need for a method to assess the various configurations. The fundamental requirement designed into each concept included the functional and operational capability to support a crew of four on a six-month lunar surface mission; however, other conceptual aspects were diverse in comparison. The methodology utilized for this assessment consisted of defining figure of merits, providing relevant information, and establishing a scoring system. In summary, the assessment considered the geometric configuration of each concept to determine the complexity of unloading, handling, mobility, leveling, aligning, mating to other elements, and the accessibility to the lunar surface. In theory, the assessment was designed to derive habitat requirements, potential technology development needs and identify risks associated with living and working on the lunar surface. Although the results were more subjective opposed to objective, the assessment provided insightful observations for further assessments and trade studies of lunar surface habitats. This overall methodology and resulting observations will be describe in detail and illustrative examples will be discussed.

Carpenter, Amanda↗

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

Abstract Background Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. Methods We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. Results We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations inTP53,PLXNB3, Zinc finger genes, and fewer mutations inSDC2,CDH1,PIK3CA,SVIL, andPTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, includingKIAA1522,DCK,FOXO3,MYO9B,ARID1A,EPRS,ZC3HAV1, andRBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. Conclusions This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

Oncology↗