Multiple Hazards Research Articles

The Peptide DHα-(4-pentenyl)-ANPQIR-NH2 Exhibits Antifibrotic Activity in Multiple Pulmonary Fibrosis Models Induced by Particulate and Soluble Chemical Fibrogenic Agents.

Interstitial lung diseases (ILDs) are a group of restrictive lung diseases characterized by interstitial inflammation and pulmonary fibrosis. The incidence of ILDs associated with exposure to multiple hazards such as inhaled particles, fibers, and ingested soluble chemicals is increasing yearly, and there are no ideal drugs currently available. Our previous research showed that the novel and low-toxicity peptide DHα-(4-pentenyl)-ANPQIR-NH2 (DR3penA) had a strong antifibrotic effect on a bleomycin-induced murine model. Based on the druggability of DR3penA, we sought to investigate its effects on respirable particulate silicon dioxide (SiO2)- and soluble chemical paraquat (PQ)-induced pulmonary fibrosis in this study by using western blot, quantitative reverse-transcription polymerase chain reaction (RT-qPCR), immunofluorescence, H&E and Masson staining, immunohistochemistry, and serum biochemical assays. The results showed that DR3penA alleviated the extent of fibrosis by inhibiting the expression of fibronectin and collagen I and suppressed oxidative stress and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Further study revealed that DR3penA may mitigate pulmonary fibrosis by negatively regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway and mitogen-activated protein kinase (MAPK) pathway. Unexpectedly, through the conversion of drug bioavailability under different routes of administration, DR3penA exerted antifibrotic effects equivalent to those of the positive control drug pirfenidone (PFD) at lower doses. In summary, DR3penA may be a promising lead compound for various fibrotic ILDs. SIGNIFICANCE STATEMENT: Our study verified that DHα-(4-pentenyl)-ANPQIR-NH2 (DR3penA) exhibited positive antifibrotic activity in pulmonary fibrosis induced by silicon dioxide (SiO2) particles and soluble chemical paraquat (PQ) and demonstrated a low-dose advantage compared to the small-molecule drug pirfenidone (PFD). The peptide DR3penA can be further developed for the treatment of multiple fibrotic lung diseases.

A Multi-Hazard Climate, Displacement and Socio-Vulnerability Score for New York City

Understanding and quantifying the compounding effects of climate change, displacement and socio-vulnerability is crucial for the development and implementation of timely mitigation and adaptation policies. Here, we present a new Climate Displacement and Socio-Vulnerability (CDSV) score over NYC that accounts for several climate hazards (coastal and riverine flooding, heatwaves, hurricanes and winter weather), displacement and social vulnerability metrics with the ultimate goal of identifying those areas where risk of the combination of the three factors is the highest (e.g., hotspots due to compounding effects). To our knowledge, this is the first time that multiple climate hazards have been studied in conjunction with displacement and socio-vulnerability for NYC. We discuss those areas that are exposed to high CDSV values for the different hazards, where multiple hazards show overlapping high values of CDSV and analyze how socio-demographic characteristics have changed over the past two decades. We find that Black and Latin/Hispanic people are exposed to the compounding effects of multiple hazards, especially in areas located in the south Bronx, south Brooklyn and Queens, with maximum CDSV scores reaching values close to ~80 over a scale of 100, and with the increased exposure of Black, Latinx/Hispanix and Asians since the beginning of the century. We find that, except for the case of coastal flooding, the percentage of White people living in areas characterized by CDSV values decreases as CDSV scores increase where the percentage of Black people and Latin/Hispanic people increases, with the latter showing the strongest correlation. We also find a statistically significant relationship between the number of people with asthma and diabetes and the CDSV score in the case of heatwaves.

Assessing Water Quality Spatial Heterogeneity from Multiple Pollution Sources in the Boung Cheung Ek Wetland, Phnom Penh, Cambodia

Phnom Penh, the capital of Cambodia, as with many other world megacities, is exposed to multiple major ecological and environmental hazards. Without a proper wastewater treatment facility, it is difficult for local residents to obtain a health-compliant water supply. In this study, a hybrid aggregation method using principal component analysis (PCA) and weighted means was used to calculate a water quality index (WQI) to map the water quality of the entire Boeung Cheung Ek (BCE) wetland region. We used Universal Kriging to map eight water quality parameters: DO, pH, TDS, F, Cl, NO3−, PO43−, and NH4+. The restricted maximum likelihood method was used for model fitting. Data were collected from groundwater and surface water for different rainfall seasons between March 2017 and February 2018. The principal component analysis (PCA) used to compute a water quality index (WQI) is based on the resulting dimensions of the highest variation among all water quality parameters. The results show that the northern part of the study area has a worse water quality than the southern region, which is caused by the discharge of municipal wastewater directly into the BCE wetland area. The results for different rainfall seasons also show that groundwater has a relatively better quality than surface water. The results of this analysis can serve as a supplementary study to support sustainable development goals because they might confirm the need for a wastewater treatment facility being under construction at the time of writing this article with funding from the Japan International Cooperation Agency (JICA).

A framework to integrate virtual reality into international standard safety trainings

PurposeThe objective of this research is to propose an immersive framework that integrates virtual reality (VR) technology with directives international safety training certification bodies to enhance construction safety training, which eventually leads to safer construction sites.Design/methodology/approachThe adopted methodology combines expert insights and experimentation to maximize the effectiveness of construction safety training. The first step was identifying key considerations for VR models such as motion sickness prevention and adult learning theories. The second step was developing a game-like VR model for safety training, with multiple hazards and scenarios based on the considerations of the previous step. After that, safety experts evaluated the model and provided valuable feedback on its alignment with international safety training practices. Finally, the developed model is tested by senior students, where the testing format followed the Institution of Occupational Safety and Health (IOSH) working safely exam structure.FindingsAn advanced immersive VR safety training model was developed based on extensive lessons learned from the literature, previous work and psychology-informed adult learning theories. Model testing – through focus groups and hands-on experimentation – demonstrated significant benefit of VR in upgrading and complementing traditional training methods.Originality/valueThe findings presented in this paper make a significant contribution to the field of safety training within the construction industry and the broader context of immersive learning experiences. It also fosters further exploration into immersive learning experiences across educational and professional contexts.

A general method for multi–hazard intensity assessment for cultural resources: Implementation in the region of Eastern Macedonia and Thrace, Greece

The protection of cultural resources from natural and human–induced hazards has been an area of intense scientific interest over time. The literature highlights that, despite the intensive research efforts to date, there is a lack of a commonly accepted hazard assessment framework that supports decision–making to limit their negative effects and contribute to the protection of cultural heritage. In this paper a general method for assessing the intensity of multiple hazards on cultural resources is developed and applied. The proposed method utilizes a) the capabilities of Geographic Information Systems (GIS), b) open geospatial hazard data and c) an original 7–step integrated method developed in this research. Key features of the proposed method are its ability to consider and synthesize intensities of both quantitative hazards such as earthquake, flood and hazards expressed on a qualitative scale, such as wildfire and landslide. The proposed method is applied to assess the exposure of 918 cultural resources of the Region of Eastern Macedonia and Thrace, Greece, to earthquake, flood, landslide, sea level rise, wildfire, soil erosion and industrial–technological accident and develop an aggregate multi–hazard intensity index (mhii) for each of the cultural resources in this region. The proposed method can be applied to hazard intensity assessment for resources other than cultural, such as the human capital of a region, infrastructure, environment, and economic facilities. This provides researchers, scientists, and managers of cultural sites with a tool to set priorities for the design of appropriate mitigation strategies to reduce the negative impacts of hazards.

Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma.

Clear cell renal carcinoma (ccRCC) stands as the prevailing subtype among kidney cancers, making it one of the most prevalent malignancies characterized by significant mortality rates. Notably,mitochondrial permeability transition drives necrosis (MPT-Driven Necrosis) emerges as a form of cell death triggered by alterations in the intracellular microenvironment. MPT-Driven Necrosis, recognized as a distinctive type of programmed cell death. Despite the association of MPT-Driven Necrosis programmed-cell-death-related lncRNAs (MPTDNLs) with ccRCC, their precise functions within the tumor microenvironment and prognostic implications remain poorly understood. Therefore, this study aimed to develop a novel prognostic model that enhances prognostic predictions for ccRCC. Employing both univariate Cox proportional hazards and Lasso regression methodologies, this investigation distinguished genes with differential expression that are intimately linked to prognosis.Furthermore, a comprehensive prognostic risk assessment model was established using multiple Cox proportional hazards regression. Additionally, a thorough evaluation was conducted to explore the associations between the characteristics of MPTDNLs and clinicopathological features, tumor microenvironment, and chemotherapy sensitivity, thereby providing insights into their interconnectedness.The model constructed based on the signatures of MPTDNLs was verified to exhibit excellent prediction performance by Cell Culture and Transient Transfection, Transwell and other experiments. By analyzing relevant studies, we identified risk scores derived from MPTDNLs as an independent prognostic determinant for ccRCC, and subsequently we developed a Nomogram prediction model that combines clinical features and associated risk assessment. Finally, the application of experimental techniques such as qRT-PCR helped to compare the expression of MPTDNLs in healthy tissues and tumor samples, as well as their role in the proliferation and migration of renal clear cell carcinoma cells. It was found that there was a significant correlation between CDK6-AS1 and ccRCC results, and CDK6-AS1 plays a key role in the proliferation and migration of ccRCC cells. Impressive predictive results were generated using marker constructs based on these MPTDNLs. In this research, we formulated a new prognostic framework for ccRCC, integrating mitochondrial permeability transition-induced necrosis. This model holds significant potential for enhancing prognostic predictions in ccRCC patients and establishing a foundation for optimizing therapeutic strategies.

Multi-Hazard Extreme Scenario Quantification Using Intensity, Duration, and Return Period Characteristics

Many modern frameworks for community resilience and emergency management in the face of extreme hydrometeorological and climate events rely on scenario building. These scenarios typically cover multiple hazards and assess the likelihood of their occurrence. They are quantified by their main characteristics, including likelihood of occurrence, intensity, duration, and spatial extent. However, most studies in the literature focus only on the first two characteristics, neglecting to incorporate the internal hazard dynamics and their persistence over time. In this study, we propose a multidimensional approach to construct extreme event scenarios for multiple hazards, such as heat waves, cold spells, extreme precipitation and snowfall, and wind speed. We consider the intensity, duration, and return period (IDRP) triptych for a specific location. We demonstrate the effectiveness of this approach by developing pertinent scenarios for eight locations in Greece with diverse geographical characteristics and dominant extreme hazards. We also address how climate change impacts the scenario characteristics.

Association between hair trace element and all-cause death in elderly people in Hainan

Objective: To explore the association between hair trace element and all-cause death in the elderly in Hainan Province. Methods: The subjects of the study were elderly people from China Hainan Centenarian Cohort Study, a total of 163 elderly were included. The association between hair trace element level and all-cause death was analyzed by using Cox proportional risk regression model. Results: After fully adjusting the covariates, the multiple Cox proportional hazards regression analyses showed that selenium (Se), manganese (Mn), strontium (Sr) concentrations in hair were significantly associated with all-cause mortality, the hazard ratio (HR) were 0.72 (95%CI: 0.54-0.98, P=0.035), 1.50 (95%CI: 1.07-2.11, P=0.020) and 0.54 (95%CI: 0.37-0.79, P=0.001), respectively. Subgroup and cross analysis showed that hair copper (Cu) were significant association with death in the people with anemia, the HR were 1.81 (95%CI: 1.13-2.88, P=0.013). And, hair Mn interacted with anemia, the HR was 0.46 (95%CI: 0.22-0.94, P=0.033). Conclusions: Se, Mn and Sr concentrations in hair were associated with the elevated risk for all-cause death in the elderly in Hainan. Se, Mn and Sr concentrations in hair can be used as a reference index for the prediction of the death risk of long-lived elderly in community, suggesting that the daily diet of elderly people are rich and diverse, in order to maintain normal and balanced trace element content in the body.

Reclassifying historical disasters: From single to multi-hazards

Multi-hazard events, characterized by the simultaneous, cascading, or cumulative occurrence of multiple natural hazards, pose a significant threat to human lives and assets. This is primarily due to the cumulative and cascading effects arising from the interplay of various natural hazards across space and time. However, their identification is challenging, which is attributable to the complex nature of natural hazard interactions and the limited availability of multi-hazard observations. This study presents an approach for identifying multi-hazard events during the past 123 years (1900–2023) using the EM-DAT global disaster database. Leveraging the ‘associated hazard’ information in EM-DAT, multi-hazard events are detected and assessed in relation to their frequency, impact on human lives and assets, and reporting trends. The interactions between various combinations of natural hazard pairs are explored, reclassifying them into four categories: preconditioned/triggering, multivariate, temporally compounding, and spatially compounding multi-hazard events. The results show, globally, approximately 19 % of the 16,535 disasters recorded in EM-DAT can be classified as multi-hazard events. However, the multi-hazard events recorded in EM-DAT are disproportionately responsible for nearly 59 % of the estimated global economic losses. Conversely, single hazard events resulted in higher fatalities compared to multi-hazard events. The largest proportion of multi-hazard events are associated with floods, storms, and earthquakes. Landslides emerge as the predominant secondary hazards within multi-hazard pairs, primarily triggered by floods, storms, and earthquakes, with the majority of multi-hazard events exhibiting preconditioned/triggering and multivariate characteristics. There is a higher prevalence of multi-hazard events in Asia and North America, whilst temporal overlaps of multiple hazards predominate in Europe. These results can be used to increase the integration of multi-hazard thinking in risk assessments, emergency management response plans and mitigation policies at both national and international levels.

The Methodologies and Main Challenges of Assessment the Multi-Hazard Interaction and Risk Management Associated with Roads Infrastructures and Dam Safety: A Review

The idea of multi-hazard interactions and risk assessment, particularly in relation to both natural hazards and hazards triggered by anthropogenic processes, has been widely used, especially in recent decades. Numerous areas worldwide, as well as various sectors, face exposure to multiple hazards. These hazards encompass natural phenomena like floods, earthquakes, hurricanes, and more. In comparison, the human-induced or anthropogenic processes associated with infrastructure development, along with other potential human activities such as, land and cover use change, contribute to the overall hazard landscape. Both natural hazards and anthropogenic-induced directly led to infrastructure collapse and loss of functionality with other consequences for human lives, economy, beside the environment impacts. Limited studies have been conducted on the implementation of the comprehensive multi-hazard interaction approach, which is globally or regionally required, along with detailed studies on the interaction between different multi-hazard sources and their interrelationships in short-term or long-term scenarios. The current research aims to review previous literature and studies on the multi-hazard interaction approach, methodologies of visualization and classification, as well as explores the potential of multi-hazard associated with road networks, infrastructures, and dams. The research utilizes simulation various models and tools such as, Geographic Information System (GIS) beside Remote Sensing (Rs) techniques. The current study concludes that using multi-hazard maps, hazard matrix, and fragility curves represents highly valuable and very useful and flexible tools for implementing and visualization hot spot areas exposure by multi-hazard consequences and vulnerability analysis for short and long-term scenarios. In addition, the current review highlighted for development a holistic conceptual framework for multi-hazard and risk assessment associated with hydraulic structures such as dams, road networks and infrastructures with hazard exposure analysis to be used as tools for a decision support system (DSS) in order to develop urban resilience, risk management and hazard mitigations.

Changing climates, compounding challenges: a participatory study on how disasters affect the sexual and reproductive health and rights of young people in Fiji

Pacific youth are at the forefront of the climate crisis, which has important implications for their health and rights. Youth in Fiji currently bear a disproportionate burden of poor experiences...

Identifying decision support needs for emergency response to multiple natural hazards: an activity theory approach

Planning and decision making in emergency response systems face new challenges due to climate changes and the increased risk of multiple or compound natural hazards. This is especially the case in areas with inexperience of such events. The aim of this paper is to identify important activities concerning planning and decision-making during responses to natural hazards, and their potential need for decision support. The knowledge base of the study consists of interviews with 12 representatives from the Swedish emergency response system, supplemented by documents covering policies, operations, and responsibility. Thematic coding was applied to the interview data for identification of important planning and decision activities. Needs of decision support were identified by applying activity theory to the identified activities. We found needs of decision support connected to eight identified key activities concerning consequence analysis, national reinforcements, and resource management. The results illuminate a lack of technology to support response activities during both single and multiple natural hazards. The findings can inform policy makers of emergency response of where to concentrate the development of tools for collaborative preparedness and response work to cope with future challenges from natural hazards.

Hurricane risk assessment in a multi-hazard context for Dominica in the Caribbean

Hurricanes can trigger widespread landslides and flooding creating compound hazards and multiple risks for vulnerable populations. An example is the island of Dominica in the Caribbean, where the population lives predominantly along the coast close to sea level and is subject to storm surge, with steep topography rising behind, with a propensity for landslides and flash river flooding. The simultaneous occurrence of the multiple hazards amplifies their impacts and couples with physical and social vulnerabilities to threaten lives, livelihoods, and the environment. Neglecting compound hazards underestimates overall risk. Using a whole island macroscale, (level-I) analysis, susceptibility scenarios for hurricanes, triggered landslides, and floods were developed by incorporating physical process parameters. The susceptibilities were combined with vulnerability indicators to map spatial patterns of hurricane multi-risks in Dominica. The analysis adopted a coupled approach involving the frequency ratio (FR), analytic hierarchy process (AHP), and geographic information system (GIS). Detailed hazard modelling was done at selected sites (level-II), incorporating storm surge estimates, landslide runout simulations, and steady flow analysis for floods. High-resolution terrain data and simulation models, the Rapid Mass Movement Simulation (RAMMS) and the hydrologic engineering center’s river analysis system (HEC-RAS), were employed. Ground validation confirmed reasonable agreement between projected and observed scenarios across different spatial scales. Following the United Nations Office for disaster risk reduction (UNDRR) call for the inclusion of local, traditional, and indigenous knowledge, feedback, and expert opinion to improve understanding of disaster risk, 17 interviews with local experts and 4 participatory workshops with residents were conducted, and findings were incorporated into the analysis, so as to gain insights into risk perceptions. The study’s outcomes encompass projections and quantification of hurricane compound hazards, vulnerabilities, accumulated risks, and an understanding of local priorities. These findings will inform decision-making processes for risk mitigation choices and community actions by providing a new framework for multi-hazard risk assessment that is easy to implement in combining different data forms.

Effects of Different Frying Oils Composed of Various Fatty Acids on the Formation of Multiple Hazards in Fried Pork Balls.

Oil oxidation products can react with food substrates to produce harmful substances, and oil saturation is closely related to oil oxidation in the process of frying. Therefore, the influence of the composition of fatty acids in oil on the formation of harmful substances in fried pork balls was explored. The five frying oils with the lowest unsaturated fatty acid (UFA) content, ranked in ascending order, were palm oil, peanut oil, soybean oil, corn oil, and colza oil (64.94%, 79.94%, 82.65%, 83.07%, and 92.26%, respectively). The overall levels of four harmful substances (acrylamide, polycyclic aromatic hydrocarbons, heterocyclic amines, and trans fatty acids) found in the oil used to fry pork balls followed a descending order: canola oil, corn oil, peanut oil, soybean oil, and palm oil (33.66 μg/kg, 27.17 μg/kg, 23.45 μg/kg, 18.67 μg/kg, and 13.19 μg/kg, respectively). This order was generally consistent with the trend in the content of UFAs. Therefore, the formation of harmful substances is closely related to the saturation of oil. Compared with other frying oils, soybean oil as a household oil produces relatively low amounts of harmful substances and has less negative impact on the quality (oil content, moisture content, and higher protein digestibility) of fried products.

Fatal Occupational Asthma in Cannabis Production - Massachusetts, 2022.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

Abstract 15263: Prognostic Impact of the Hyper-Polypharmacy on the Long-Term Outcomes in Patients With Chronic Heart Failure Following Cardiac Resynchronization Therapy

Introduction: Optimal drug therapy improves long-term prognosis in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction, but it exposes patients to the risk of polypharmacy. Hypothesis: This study aimed to determine the association between hyper-polypharmacy and adverse events in patients with CHF after cardiac resynchronization therapy (CRT). Methods: This retrospective study evaluated 134 patients (90 male, mean age 70.6 ± 9.7 years; 31 (23%) old myocardial infarction, 57 (43%) dilated cardiomyopathy, 46 (34%) others) who underwent CRT implantation between 2004 and 2020 and were followed for at least one year after the operation (mean, 1071 ± 649 days). The hyper-polypharmacy group (n = 74) was defined as patients taking total of 10 or more medications at discharge. The primary endpoint was major adverse cardiovascular events (MACE) including cardiovascular death, hospitalization for heart failure (HHF), cerebral infarction, acute myocardial infarction, and cardiac arrest. The secondary endpoints include HHF and all-cause mortality. Results: MACE occurred in 62 (46%), HHF occurred in 55 (41%) and all-cause mortality occurred in 24 (18%) patients. Kaplan-Meier survival analysis demonstrated that hyper-polypharmacy group had a higher incidence of MACE (log-rank 8.29; P = 0.004), HHF (log-rank 8.55; P = 0.0035) and all-cause mortality (log-rank 7.83; P = 0.0051). Cox proportional hazards regression analysis also revealed that the hyper-polypharmacy group had a higher incidence of MACE (HR 2.15; 95% CI:1.28 - 3.75, P = 0.0036), HHF (HR 2.39; 95% CI:1.32 - 4.19, P = 0.0031) and all-cause mortality (HR 3.72; 95% CI:1.49 - 11.2, P = 0.0038). Multiple Cox proportional hazards analysis revealed that hyper-polypharmacy was an independent predictor of MACE (hazard ratio 2.00; 95% CI:1.18 - 3.50, P = 0.01). Conclusions: Hyper-polypharmacy may predict the occurrence of MACE in patients with CHF undergoing CRT implantation.

Multi-hazard susceptibility model based on high spatial resolution data-a case study of Sali settlement (Dugi otok, Croatia).

The world has been facing an increase in various natural hazards. The coastal regions are recognized as one of the most vulnerable due to high population pressure and climate change intensity. Mediterranean countries have one of the most burnable ecosystems in the world, one of the most exposed to pluvial floods, and have the highest erosion rates within the EU. Therefore, the aim of this study was to develop the first multihazard susceptibility model in Croatia for the Sali settlement (island of Dugi otok). The creation of a multi-hazard susceptibility model (MHSM) combined the application of geospatial technology (GST) with a local perception survey. The methodology consisted of two main steps: (1) creating individual hazard susceptibility models (soil erosion, wildfires, pluvial floods), and (2) overall hazard susceptibility modeling. Multicriterial GIS analyses and the Analytical Hierarchy Process were used to create individual hazard models. Criteria used (32) to create models are derived from very-high-resolution (VHR) models. Two versions of MHSM are created: 1) all criteria with equal weighting coefficients and 2) weight coefficients determined based on public perception. According to MHSM 1, most of the research (58%) area is moderately susceptible to multiple hazards. Highly and very highly susceptible areas are 27% of the drainage basin and are mostly located near roads and houses. MHSM 2 reveals similar results to MHSM 1. The public perceives that the research area is the most susceptible to wildfires. The wildfire ignition risk is ranked as moderate (3.00) with a standard deviation of 1.16. Pluvial flood risk is ranked low (2.78), with a standard deviation of 1.15. The risk of soil is most inferior (2.24) with a standard deviation of 0.91. The the most significant difference between public perception and the GIS-MCDA model of hazard susceptibility is related to soil erosion. However, the accuracy of the soil erosion model was confirmed by ROC curves based on recent traces of soil erosion in the research area. The proposed methodological framework of multi-hazard susceptibility modeling can be applied, with minor modifications, to other Mediterranean countries.

Multi-objective optimization of mitigation strategies for buildings subject to multiple hazards

Natural hazards can have a devastating impact on communities, leading to social and economic losses. These effects are particularly severe in multi-hazard contexts, where multiple disruptive events occur simultaneously or consecutively (such as earthquakes and tsunamis). To reduce the impact of such events, it is critical to enhance community resilience and make it more capable of withstanding and recovering from diverse types of damage. In this study, we propose a multi-objective optimization model to determine optimal retrofitting strategies to enhance community resilience under multiple hazards. We used the proposed model to analyze the impact of earthquake and tsunami hazards on the community of Seaside, Oregon. It assesses the effectiveness of different retrofitting strategies at the individual building level, considering the conflicting objectives of reducing overall economic loss, population dislocation, and building repair times. Our results demonstrate that retrofitting buildings to achieve higher seismic codes can significantly reduce the impact of natural hazards on structural damage, population dislocation, and building repair times. Additionally, our findings reveal the importance of considering geographical location and mitigation measures when optimizing retrofitting strategies. By considering budget constraints and community resilience metrics, our model identifies the most effective retrofitting strategies for individual buildings of Seaside, which ultimately helps the community make informed decisions about investments to reduce the impact of natural hazards. Overall, this study provides valuable insights into the importance of enhancing community resilience in multi-hazard contexts and showcases the use of a multi-objective optimization model to identify optimal retrofitting strategies.

Acute Myeloid Leukemia with Inv(3) or t(3;3): A Clinical and Cytogenetic Characterization of 40 Patients

Background: Acute myeloid leukemia (AML) with inv(3) or t(3;3) is an extremely aggressive and rare subtype of AML. Leukemogenesis in inv(3) AML is in part due to juxtaposition of the GATA2 enhancer in close proximity to the MECOM/EVI1 promoter; as the result, the fusion drives EVI1 overexpression and uncontrolled proliferation of myeloid progenitors. Given its rarity, published clinical outcome data are limited. To improve our understanding of the clinical outcomes of inv(3) AML, we conducted a retrospective study to describe the clinical features of a cohort of newly diagnosed inv(3)/t(3;3) AML patients treated at Stanford Cancer Center between 2002 and 2023. Methods: Data were retrospectively collected from databases associated with the Stanford Health Care electronic health record (EHR), and diagnosis dates came from the Stanford Cancer Registry. Inv(3)/t(3;3) AML diagnosis was defined according to WHO criteria as the presence of ≥20% blasts in the bone marrow (BM) or peripheral blood (PB) and the presence of inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) on cytogenetic analysis at initial diagnosis. Response to first induction, salvage, and consolidation therapy as well as allogeneic hematopoietic stem cell transplant (alloHSCT) were captured. CR was defined as the presence of <5% of blasts in the BM evaluation by morphological evaluation after each line of treatment. Overall survival (OS) was defined as time from diagnosis to death from any cause. A descriptive study of the main demographic, clinical, hematologic, and cytogenetic variables of patients who received intensive and non-intensive therapy was performed. The analysis was performed using R 4.3.1. A p value of < 0.05 was defined to be statistically significant. Results: A total of 40 patients met inclusion criteria including 68% (n=27) with de novo AML, 25% (n=10) with secondary AML from an antecedent hematological disorder and 7.5% (n=3) therapy-related AML. Clinical characteristics of the patients are summarized in Figure 1A. The median age at time of diagnosis was 56 (range, 19-78). There was a slight female predominance, with 58% (n=23) female and 42% (n=17) males. Ninety-three percent of patients had an ECOG score ≤1 (n=37). Median leukocyte, hemoglobin, and platelet counts were 4.5 K/uL, [1.3-761], 9.4 g/dL, [3.4-13.6], and 98 K/uL [9-592], respectively. The median blast percentage in BM and PB was 49% [13-98] and 30% [0-95], respectively. Inv(3)/t(3;3) was the only cytogenetic aberration in 10 patients (25%) and chromosome (chr) 7 abnormalities were the most common additional aberration, present in 22 patients (55%). CR after the first induction therapy was achieved in 9 patients (22%); 6 patients (15%) died during or shortly after induction therapy, and the remaining 25 (63%) were resistant. Salvage therapies for patients included re-induction with 7+3, FLAG-Ida, mitoxantrone-containing regimens, clofarabine-based protocols, or combination of hypomethylating agents with venetoclax. Seventeen (43%) patients underwent alloHSCT (10 in CR and 7 with active disease). When comparing intensive vs non-intensive induction regimen, no statistical significance was identified for complete remission (CR) rate (p= 1.00), overall survival (OS) rate (p=0.65) or relapse-free survival (RFS) rate (p=0.86). Similarly, no statistically significant prognostic factors (age, WBC, BM blast %, platelet count, hemoglobin, ANC, or time to transplant) for OS were identified. Interestingly, chr 7 abnormalities in inv(3) patients conferred a worse prognosis in this cohort (OS 41% vs. 59%, p= 0.0064, Figure 1B). This association was confirmed using a multiple Cox proportional hazards regression adjusting for age and blast percentage. Moreover, while chr 7 abnormality was also associated with a lower response rate (CR 14% vs. 40%), it did not reach statistical significance (p=0.12). Conclusions: In summary, de novo AML inv(3)/t(3;3) is a rare and aggressive subtype of AML conferring extremely poor prognosis. There appears to be an increase of incidence in females affecting a slightly younger demographic. Consistent with previous studies, the presence of chr 7 abnormalities was associated with even worse outcomes, which interestingly also drive EVI1 overexpression. The exact link between 3q26 loci rearrangements and chr 7 abnormalities warrants further investigation.

Can Dual Mobility Cups Reduce Revision and Dislocation Risks? An Analysis of 107,528 Primary Total Hip Arthroplasties in the United States

BackgroundDual mobility acetabular cups (DMC) were designed to increase the effective femoral head size and improve stability with the goal of reducing revision risk at the potential cost of polyethylene thickness. We sought to evaluate revision risk following primary elective total hip arthroplasty with DMC compared to highly cross-linked polyethylene (XLPE). MethodsA cohort study was conducted using data from a Kaiser Permanente’s total joint arthroplasty registry. Patients ≥18 years who underwent primary elective total hip arthroplasty using DMC, unipolar Metal-on-XLPE (MoXLPE), or unipolar Ceramic-on-XLPE (CoXLPE) were identified (2010 to 2021). The final sample comprised 2,219 DMC, 48,251 MoXLPE, and 57,058 CoXLPE. Multiple Cox proportional hazard regressions were used to evaluate aseptic revision and any dislocation regardless of revision within 6 years follow-up. ResultsIn adjusted analyses, no differences in aseptic revision risk were observed for MoXLPE (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.72 to 1.51) or CoXLPE (HR = 0.98, 95% CI = 0.69 to 1.40) compared to DMC. No differences in dislocation risk were observed for MoXLPE (HR = 1.42, 95% CI = 0.93 to 2.15) or CoXLPE (HR = 1.25, 95% CI = 0.84 to 1.87) compared to DMC. ConclusionsIn a US-based cohort, 6-year aseptic revision risk of DMC was similar to metal or ceramic femoral head unipolar constructs. Furthermore, no difference in dislocation risk was observed. Continued longer-term follow-up may reveal if there is a reduced risk of dislocation that comes at the cost of increased late revision. Level of EvidenceLevel III.