Rare Event Research Articles

Disentangling the nexus between CSR performance, GRI reporting and institutional environment: international evidence

Purpose This study aims to investigate whether companies partake in Global Reporting Initiative (GRI) adoption primarily for signaling purposes to demonstrate their superior corporate social responsibility (CSR) performance or for greenwashing purposes to obscure their inferior CSR performance. In addition, this research delves into the impact of the institutional context (i.e., environmental development, social progress and institutional governance) on the CSR performance-GRI reporting link. Design/methodology/approach This study examines the relationship between CSR performance and GRI reporting, using a sample derived from the Fortune Global 500 over the period between 2016 and 2023. The empirical models are based on rare events logistic regression (ReLogit) analysis. Findings The results of this study indicate that companies are inclined to publish GRI-based CSR reports as a manifestation of their commitment to CSR, thereby supporting the signaling hypothesis. Furthermore, the findings reveal that the association between CSR performance and GRI reporting is more pronounced in countries characterized by a strong institutional context, implying the significant role of the institutional environment in CSR transparency. Originality/value This research adds to the body of CSR literature investigating the link between CSR performance and GRI adoption, drawing on the arguments of signaling theory and greenwashing tendency. This study enriches prior literature, documenting that the institutional context significantly impacts companies’ motivation to engage in GRI reporting, thereby reducing the propensity for greenwashing behaviors.

Abstract 5144: Prevalence and clinical significance of CBP deficiency and disturbed CBP expression in human cancer

CBP (CREB-binding protein) is a ubiquitously expressed multidomain protein with histone acetyltransferase and transcriptional co-activator activity. As a major histone modifier, it is involved in the regulation of thousands of genes. CBP has a complex role in cancer where both loss-of-function and overexpression can occur. To better comprehend the role of CBP expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. In normal tissues, a strong nuclear CBP staining was ubiquitously seen except few cell types. Among 12,255 evaluable tumors, CBP staining was completely absent (CBP deficiency) in 226 (1.84%) while 232 (1.89%) showed only a faint to moderate staining of a minority of cancer cells (substantial reduction, SR), 384 (3.13%) a 1+, 3,079 (25.12%) a 2+, and 8,334 (68.00%) a 3+ CBP positivity. CBP deficiency or SR was particularly common in pancreatic acinar cell carcinoma (23,5%), endometrioid endometrial carcinoma (22,8%), hepatocellular carcinoma (19.0%), urothelial carcinoma of the renal pelvis (17,4%), medullary carcinoma of the breast (14.3%), serous carcinoma of the endometrium (12.5%), neuroendocrine carcinoma of the pancreas (11.1%), and chromophobe renal cell carcinoma (10.7%). Less than 10% CBP deficient or SR cases were seen in 57 additional tumor categories. Among tumors with detectable CBP expression, low CBP expression levels were linked to advanced pT stage (p<0.0001), high UICC stage (p=0.0005), poor ISUP (p=0.0001), Thoenes (p=0.0001) and Fuhrman (p<0.0001) grades in clear cell renal cell carcinoma (ccRCC). In papillary RCC (pRCC), low CBP was associated with high UICC grade (p=0.0409) and distant metastasis (p=0.0022). Low CBP was furthermore associated with advanced pT stage (p=0.0003) in colorectal carcinoma and reduced overall survival (p=0.0236) in muscle-invasive urothelial carcinoma. High CBP expression was statistically related to nodal metastasis in pancreatic ductal adenocarcinoma (p=0,0201). CBP expression was not unequivocally related to clinico-pathological parameters in breast, ovarian, endometrial and gastric cancer. It is concluded, that CBP deficiency - as a rare event - occurs in many different tumor types and that a reduced or absent CBP expression is linked to aggressive cancer in multiple tumor entities. Citation Format: Viktoria Chirico, Seyma Büyücek, Katharina Möller, Florian Lutz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Elena Bady, Lisa Hornsteiner, Christian Bernreuther, Guido Sauter, Andreas H Marx, Till Krech, Stefan Steurer, Christoph Fraune, Sarah Minner, Natalia Gorbokon, Maximilian Lennartz, Eike Burandt, Anne Menz, Sören Weidemann, Waldemar WIlczak, Morton Freytag, Viktor Reiswich, Ronald Simon, Simon Kind, Ria Schlichter, Nina Schraps. Prevalence and clinical significance of CBP deficiency and disturbed CBP expression in human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5144.

Curse of scale-freeness: Intractability of large-scale optimization with multi-start methods

Abstract This paper investigates the intractability of large-scale optimization with multi-start methods. For the theoretical performance analysis, we focus on random multi-start (RMS), which is one of the representative multi-start methods, including RMS local search and greedy randomized adaptive search procedure (GRASP). Our primary theoretical contribution is to derive, by using extreme value theory, power-law formulas for the two quantities: (i) the expected improvement rate of the best empirical objective value (EOV); (ii) the expected relative gap between the best EOV and the supremum of the EOVs. Notably, the expected relative gap exhibits scale-freeness as a function of the number of iterations. Consequently, the half-life of the expected relative gap is asymptotically proportional to the number of iterations executed by the RMS method. This result can be interpreted as the curse of scale-freeness—a Zeno’s paradox-like phenomenon—expressed by the metaphor “Reaching for the goal makes it slip away.” Through numerical experiments, we observe that several RMS algorithms applied to traveling salesman problems suffer from the curse of scale-freeness. Furthermore, we show that overcoming this curse requires a powerful local search algorithm with effective restart and diversification strategies that exponentially accelerate solution improvement relative to the RMS method.

Abstract 2184: Dynamics between germline immune checkpoint variants and susceptibility for cancer and autoimmunity

Abstract Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are approved for a wide range of malignancies. ICIs block the interactions of checkpoint proteins that limit T cell-mediated immune responses, thereby boosting cytotoxic activity against cancers. The most widely used ICIs act through CTLA-4, PD-1, or PD-L1 pathway blockade, and numerous agents are at various stages of development. Due to increased T cell activity, ICIs are associated with immune-related adverse events, and little is known about their long-term impacts. Individual-level genetic variation mimics the effects that are seen with larger magnitude when the same pathways are perturbed through checkpoint modulation. Leveraging large-scale biobanks with genomics data, proteomics data, and rich health registries can enable us to understand the broad impacts of checkpoint modulation on adverse events and its potential for treatment of common diseases. We utilize FinnGen, a biobank study of 520, 210 Finnish individuals, to investigate germline variants affecting immune checkpoint proteins and their associations with cancer and autoimmunity. The Finnish population, being a genetic isolate, has an unusual enrichment of disease-associated variants compared to many other ancestry groups, enabling variant-disease associations not detectable in many other populations. Using phenome-wide association analysis, we identify several coding variants in checkpoint protein-encoding genes with opposite associations to autoimmune diseases and cancer or other tumors. Such associations are supported by Olink proteomic quantitative trait loci for respective proteins (cis-pQTLs). For example, rs149722682 (LAG3 missense variant; 440x enriched in Finns) is protective of colon adenomas (OR 0.26, p=8.4x10-5) but increases the risk of asthma (OR 1.5, p=1.1x10-4) and hypothyroidism (OR 1.9, p=1.7x10-9). We also identify multiple variants with associations to a range of conditions beyond classical autoimmune diseases, pointing to potentially new or rare adverse events of ICIs. For instance, rs781221749 (LAG3 missense; 2x enrichment) increases the risk of manic episode (OR 23.3, p=1.6x10-4) and COVID-19 infection (OR 4.9, p=1.2x10-4). Finally, we develop checkpoint protein-specific genome-wide polygenic risk scores to quantify the cumulative impacts of cis and trans checkpoint protein-associated variants on different cancer- and autoimmune-related endpoints. Our findings offer insight into the short- and long-term toxicities associated with checkpoint inhibition and provide a framework for detecting common and rare adverse events in current and emerging therapies. Citation Format: Zade Akras, Benjamin M. Neale, Nina Mars. Dynamics between germline immune checkpoint variants and susceptibility for cancer and autoimmunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2184.

Abstract 5988: Microscopic colitis - rare events secondary to immune checkpoint inhibitors therapy

Abstract Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of care for cancer treatment but are associated with immune-related adverse events (irAEs). The combination of Nivolumab and Relatlimab (N+R) was approved in March 2022 for the treatment of unresectable or metastatic melanoma. While colitis is a well-known toxicity of ICIs, microscopic colitis (MC) presenting as watery diarrhea with normal endoscopic mucosal appearance, has not yet been described in Summary of Product Characteristics of N and R. Description: We present the case of a 54-year-old man undergoing treatment with N+R for recurrent BRAFV600Emt cutaneous malignant melanoma with metastases to soft tissues and lymph nodes. Eight weeks after starting therapy, the patient developed grade 3 (per CTCAE v.5) watery diarrhea. Stool tests were negative for infectious agents, including Clostridium difficile. Abdominal imaging with computed tomography did not reveal any signs of colitis. However, due to elevated fecal calprotectin levels (12 times above normal) and N+R treatment, ir-colitis was diagnosed. Intravenous methylprednisolone at 1 mg/kg/day has been administered and led to a temporary reduction of symptoms to grade 1. However, within a week, watery diarrhea worsened again to grade 3 despite ongoing steroid therapy. Due to steroid refractory, another immunomodulator was administered, including two doses of infliximab, without improvement. The patient did not lose weight. Colonoscopy revealed normal-appearing mucosa in the entire colon and terminal ileum. Random biopsies were done throughout the colon and terminal ileum. Histopathological examination revealed inflammatory infiltrates and focal increases in intraepithelial lymphocytosis, confirmed by CD3+ immunohistochemistry across all samples. The treatment with next-generation steroid budesonide (9 mg orally once daily in the morning) was administered, resulting in symptom resolution within two days. Diarrhea did not recur over the following four months. The N+R was finished. The patient received three doses of N+R and achieved a complete response (CR) on imaging, which is ongoing. Conclusion: Various types of colitis were found secondary to ICIs such as pseudomembranous, granulomatous, or collagenous with endoscopically visible changes in the mucosa. MC is suspected to result from increased immune activity in the gut mucosa. It can develop following ICIs therapy and presents with severe symptoms, often requiring hospitalization, steroids, and other immunomodulators. This case highlights that a normal mucosal appearance on colonoscopy does not exclude immune-mediated colitis. Next-generation steroids, such as budesonide, can be effective in managing MC during immunotherapy. Raising awareness of the uncommon irAEs is essential, as some rare events can lead to fatal outcomes. Radiological, endoscopic, and microscopic pictures will be presented on the poster. Citation Format: Barbara Radecka, Michał Piątek, Jacek Pawełczak, Ewa Stobiecka, Krystian Kowalczyk, Patryk Zając. Microscopic colitis - rare events secondary to immune checkpoint inhibitors therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5988.

Abstract 2142: Development and validation of multicolor flow cytometric tetramer assays for use in multi-year clinical cancer immunotherapeutics studies

Abstract Major histocompatibility complex (MHC) tetramers recognize antigen-specific cytotoxic T lymphocytes (CTL). As such, fluorescently labeled tetramers may be used to precisely monitor targeted T cell responses in infectious diseases and autoimmune diseases, like type 1 diabetes. As new biomedical technologies such as T-cell receptor (TCR) therapy gain traction, antigen specific CTL tetramer assays become even more important in current oncology clinical research projects, cancer vaccine development and cancer immunotherapeutics. Tetramer assays are unique and clearly differentiated from more routine applications of flow cytometry. Their specificity and sensitivity allow for the detection of specific cellular CTL, despite their extremely low frequency. We monitor broad anti-tumor immune responses. To do so, along with other phenotypic and functional analyses of T cells using monoclonal antibodies against surface and intracellular biomarkers, we have developed and validated tetramer assays. In practice, flow cytometry-based tetramer assays measure the percentage (%), and median fluorescence intensity (MFI) of target cells. During the development of these assays, to be able to measure rare events and test for binding specificity, we spiked positive CTLs into healthy blood samples and determined the assay’s lower limit of quantification (LLOQ). After a feasibility study, we measured the LLOQ using different dose levels of CTL. Other assay validation parameters assessed included post-collection sample stability and intra- and inter-assay precision, and a comparison of results in analyst-to-analyst and instrument-to-instrument assessments. The general acceptance criteria for these validation parameters are to achieve a 10%-30%CV between replicate results, or a similar percent difference between comparative measurements. The LLOQ of a tetramer assay can be determined during assay development when precision is at a CV of < 35% near the low end. In order to achieve the desired precision in rare event measurements, we established that it is critical to acquire a sufficient number of CD8+ cytotoxic T cells. For example, one single test sample can easily reach more than 2.5 million cell counts to precisely quantify the CTL of interest. Our results indicate that the developed tetramer assays are robust and reproducible, meeting the clearly pre-defined acceptance criteria during validation processes. More importantly, we found that the measurement of CTL as a percentage of CD8+ T lymphocytes in peripheral blood samples are very consistent in complex clinical trial settings over many years. In conclusion, the tetramer assay is suitable for use to accrue highly specific data in the measurement of CTL in multi-year oncology clinical studies. Citation Format: Chengsen Xue, Christina D. Swenson, Simone Di Maulo, Weiguo Zhong, Thomas W. Mc Closkey. Development and validation of multicolor flow cytometric tetramer assays for use in multi-year clinical cancer immunotherapeutics studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2142.

De novo somatic mosaicisms of INF2 and TRPV4 in patients with Charcot-Marie-Tooth disease.

Somatic mosaicism is caused by a postzygotic de novo mutation. It is a very rare genetic event, and mosaic cases have been reported only very limitedly among Korean patients with peripheral neuropathies, including Charcot-Marie-Tooth disease (CMT) so far. This study was performed to identify and characterize somatic mosaicism in Korean families with CMT. Genetic causes were identified by whole exome sequencing (WES) and a subsequent filtering process of the variants. The level of mosaicism for the de novo somatic mutations was determined by counting altered sequences from approximately 100 colonies/mutation and the ratio of altered sequences per total reads at the mutation site using the WES data. We observed two cases of somatic mosaicism in different families with CMT: p.Cys104Tyr in INF2 (male with CMT1) and p.Ser729Arg in TRPV4 (female with CMT2). The approximate levels of mosaicism were determined to be 24% and 30% in the blood, respectively. A man with the INF2 mutation showed very mild symptoms, while a woman with the TRPV4 mutation showed severe clinical phenotypes. The INF2 mutation is specifically considered a case of gonadal mosaicism. In addition, we confirmed that the p.Cys104Tyr in INF2 is associated with the CMT1 phenotype without focal segmental glomerulosclerosis (FSGS). This study may be the first or second report for the INF2 and TRPV4 mosaicism. The degrees of the phenotypic severity for the mosaic mutations probably depend on the mutation sites and the levels of mosaicism in the affected tissues. This study suggests that somatic mosaicism may contribute to inter- or intra-familial phenotypic heterogeneity.

Abstract 1978: Circulating rare events as a biomarker of anti-tumoral effect of ketamine therapy in non-small cell lung cancer

Abstract Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide, with surgical resection (with or without adjuvant chemotherapy) often being the recommended treatment for resectable localized disease. However, even with curative-intent resections, 30% to 55% of localized NSCLC patients experience recurrence and will die from the disease. Tumor-associated cells detected in peripheral blood, referred to here as circulating rare events, are believed to play a key role in metastatic dissemination, underscoring their potential as indicators of treatment response and recurrence risk. Recent retrospective analyses have revealed that the use of intraoperative Ketamine (Ket) during primary tumor resection surgery is associated with a lower recurrence rate, suggesting a potential utility in cancer treatment beyond its approved indication as an adjunct anesthetic. The study presented here investigates the effects of different anesthetic protocols on circulating rare events in NSCLC patients, specifically comparing Ket and dexmedetomidine (Dex) (also commonly employed as an adjunct anesthetic), to assess whether Ket exhibits anti-tumor effects and modulates the systemic tumor environment. Peripheral blood samples (n=60) were collected from 22 early-stage NSCLC patients undergoing primary tumor resection, with samples taken preoperatively (before surgical incision and after surgical closure) and at a three-week follow-up. Circulating rare events were identified through advanced imaging and phenotypic analysis and validated by comparison to blood samples from normal donors, which served as controls. Results indicated no significant differences between the anesthetic agents in pre- and post-surgery samples; however, at the three-week follow-up, Ket was associated with a higher incidence of circulating rare events and an increase in a specific cellular phenotype consistent with endothelial cells. These findings suggest that Ket may influence tumor vasculature and enhance tumor shedding, which could lead to a better prognosis after tumor resection in lung cancer patients. This highlights the potential of Ket as a perioperative agent that modulates tumor biology, as demonstrated by increased rare cell detection, and supports further investigation into a possibly expanded role in surgical oncology for potential to improve long-term outcomes in NSCLC patients. Citation Format: Anya Shah, Stephanie Shishido, Jeremy Mason, George W. Fischer, David Amar, Dawn Desiderio, Joseph R. Scarpa, David R. Jones, Amitabh Gulati, Alessia Pedoto, Alessandro De Camilli, Cosmin Guaran, Jacob C. Jackson, Alexandra Lewis, Michelle Zanone, Lucy Nystrom, Howard Scher, Ethan Barnett, Joshua Mincer, Peter Kuhn. Circulating rare events as a biomarker of anti-tumoral effect of ketamine therapy in non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1978.

Examining Sex-Based Differences in Sexual Violence Perpetration Among Adolescents: A Test of Lifestyle Exposure Theory

ABSTRACT This study explores whether components of lifestyle exposure theory can operate as predictors of adolescent sexual violence perpetration. Multivariate logistic regression models for rare events were used to assess the impact that risky behaviors, victimization, and sexual activity have on adolescent sexual violence perpetration and to explore sex differences in offending. In a sample of 85,004 U.S. adolescents’ responses to the 2022 minnesota Student Survey, multivariate logistic analyses for rare events revealed that older students and males were more likely to engage in sexual violence. Several risky behaviors (i.e. fighting, drug use, running away from home), exposure to domestic violence, parental and sexual abuse, and sexual behaviors increased the risk of adolescent sexual violence perpetration. Interestingly, some factors had slightly similar effects across sex (i.e. age, running away, parental and sexual abuse, early sexual initiation, and transactional sex). The findings are discussed in the context of existing research on adolescents who commit sexual assault, with recommendations for policy and future research areas.

Bridging AI and Financial Markets: A Sentiment Analysis Data-Driven Approaches for Stock Market Prediction

The conventional financial value estimating techniques rely primarily on historical stock data, technical indicators, and fundamental parameters, and frequently ignore the psychological and sentiment-driven characters. The most research efforts in ML-based stock prediction models, focusing on decision fusion techniques, hybrid ensemble learning, deep neural networks, and sentiment-aware financial forecasting models. The recently designed time-series predicting models like RNN, CNN, and LSTM show a certain level of accuracy of the model. However, the market trend is influenced by social media mood, price volatility, investors' mentality, and global cues of fiscal markets. Also, Hybrid approaches that collect information from social media platforms like Twitter, Reddit, financial news, and technical indicators have verified superior projecting accuracy than the conventional models that rely only on historical datasets. The decision fusion paradigm has gained traction in stock forecasting, allowing researchers to combine multiple prediction models to enhance forecasting precision. The effectiveness of ensemble learning models, including XGBoost, GBM, and AdaBoost, in stock price forecasting has been widely studied. DL models such as Transformer-based NLP models have further advanced sentiment analysis applications in finance. The ability of BERT to contextualize textual data and extract nuanced financial sentiment has led to significant improvements in sentiment-aware forecasting models. Additionally, Aspect-Based Sentiment Analysis has been employed to disaggregate financial news sentiment, enabling a more granular understanding of investor perceptions and economic events. The review identifies key limitations in current stock forecasting models, including overfitting issues, interpretability concerns, and data scarcity for rare financial events. Additionally, multimodal financial forecasting frameworks integrating textual, numerical, and visual data sources can provide more comprehensive market insights. The adoption of reinforcement learning-based trading strategies, coupled with real-time streaming sentiment analysis, holds significant potential for improving algorithmic trading performance. This paper bridges the gap between machine intelligence research and real-world stock market applications, contributing to the expanding field of AI-driven financial analytics.

Renal Neoplasia in Birt-Hogg-Dubé Syndrome: Integrated Histopathologic, Bulk, and Single-cell Transcriptomic Analysis.

Renal Neoplasia in Birt-Hogg-Dubé Syndrome: Integrated Histopathologic, Bulk, and Single-cell Transcriptomic Analysis.

Deciphering Complex Electrochemical Reaction Dynamics and Interactions of Single Nanoentities via Evanescent Scattering Microscopy

AbstractElectrochemical reactions at the nanoscale are governed by intricate surface interactions, yet existing imaging techniques often lack the surface sensitivity and throughput needed to resolve these dynamics clearly. Here, we introduce electrochemical evanescent scattering microscopy (EC‐ESM), a high‐throughput, surface‐sensitive imaging technique that enables real‐time tracking of single‐nanoentity electrochemistry with high resolution. Using EC‐ESM, we monitored the motion and dissolution dynamics of silver nanoparticles and identified a clear relationship between nanoparticle velocity and electron transfer rates. The high throughput of EC‐ESM not only ensures statistical reliability but also allows the detection of rare electron transfer events in molecularly modified AgNPs. Additionally, EC‐ESM's high resolution enabled direct imaging of both single and interacting silver nanowires, revealing diverse dissolution behaviors that provide insights into structural and surface properties. We envision EC‐ESM as a powerful platform for advancing nanoscale electrochemical research and interfacial charge transfer studies.

Deciphering Complex Electrochemical Reaction Dynamics and Interactions of Single Nanoentities via Evanescent Scattering Microscopy.

Electrochemical reactions at the nanoscale are governed by intricate surface interactions, yet existing imaging techniques often lack the surface sensitivity and throughput needed to resolve these dynamics clearly. Here, we introduce electrochemical evanescent scattering microscopy (EC-ESM), a high-throughput, surface-sensitive imaging technique that enables real-time tracking of single-nanoentity electrochemistry with high resolution. Using EC-ESM, we monitored the motion and dissolution dynamics of silver nanoparticles and identified a clear relationship between nanoparticle velocity and electron transfer rates. The high throughput of EC-ESM not only ensures statistical reliability but also allows the detection of rare electron transfer events in molecularly modified AgNPs. Additionally, EC-ESM's high resolution enabled direct imaging of both single and interacting silver nanowires, revealing diverse dissolution behaviors that provide insights into structural and surface properties. We envision EC-ESM as a powerful platform for advancing nanoscale electrochemical research and interfacial charge transfer studies.

Hemolytic Disease of the Fetus and Newborn in an Integrated Health Care System.

Hemolytic disease of the fetus and newborn (HDFN) is associated with significant infant morbidity and mortality. Characteristics of pregnancies impacted by HDFN are not well understood. Therefore, this study examines maternal and infant characteristics based on HDFN status in a large, integrated health care system in the United States.This was a population-based, retrospective cohort study of 464,711 pregnancies that received care at Kaiser Permanente Southern California (KPSC) hospitals from January 2008 to June 2022. HDFN cases were ascertained using a validated algorithm of structured and unstructured data elements. HDFN due to ABO alloimmunization alone was excluded. Adjusted odds ratios (aORs) derived from logistic regression were used to describe the association between maternal and infant characteristics and HDFN diagnosis as well as adverse perinatal outcomes. For rare events, Firth's bias-reduced logistic regression was applied.A total of 136 HDFN pregnancies with 138 HDFN births (live births = 137; stillbirth = 1) were observed in the study. Of three twin pregnancies, all but one fetus had an HDFN diagnosis. HDFN diagnosis was associated with a maternal age of ≥35 years (aOR: 1.74; 95% confidence interval [CI]: 1.13-2.67), hypertension (2.07; 0.96-4.50), renal disease (3.43; 1.75-6.70), and multiparity (4.95; 2.73-8.95). Furthermore, HDFN diagnosis was associated with birth at 33 to 34 weeks (aOR: 5.72; 95% CI: 2.78-11.78) and 35 to 36 weeks (3.76; 2.38-5.94), and neonatal jaundice (3.11; 2.20-4.41). Birth weight ≥4,000 g was associated with lower HDFN diagnosis odds than normal weight (2,500-3,999 g; aOR: 0.36; 95% CI: 0.14-0.90). Hispanic race/ethnicity was associated with a lower HDFN diagnosis risk than non-Hispanic White (aOR: 0.63; 95% CI: 0.43-0.93).This study identified clinical and demographic factors linked with HDFN diagnosis, including specific maternal characteristics, medical/obstetrical factors, and neonatal factors, within a large, integrated health care system that can help inform management plans. · Characteristics of HDFN are not well understood.. · This study examined HDFN characteristics in the United States.. · HDFN risk is linked to medical/obstetric factors.. · Increased risk of prematurity associated with HDFN..

Sports Injury is Self-exciting: Modelling AFL Injuries Using Hawkes Processes

Sports injuries can be considered as self-exciting, in that they can be linked to a previous injury or can be a new independently acquired injury. Disentangling which injuries are connected, either directly or indirectly, remains a persistent challenge, but is important for sport and athlete management. In this paper, we consider injuries as a type of Hawkes Process and view estimation as a branching process. We also propose a computationally efficient latent variable formulation in the context of clustering subsequent sporting injuries among professional Australian Football League (AFL) players in a small sample context. The results underscore the broader advantages of utilising such a point process for accurately modelling and estimating the occurrence of rare events. Our approaches are then assessed to demonstrate better estimation performance and compared to determine their suitability for injury forecasting.

Composite probability distribution for fatigue life prediction of API X65 steel via Vickers hardness

Accurate prediction of the fatigue life of API X65 steel is crucial in various applications. However, the traditional bootstrap method has inherent limitations, such as a tendency to deviate from the true distribution with insufficient sample sizes, difficulty in identifying extreme statistics, and an inability to generate distributions closer to the original sample. These deficiencies lead to overly conservative S-N curve designs and pose challenges in data collection, particularly for small samples. To address these issues, we propose an improved bootstrap method using a composite probability distribution. This method enhances the sampling range and improves prediction accuracy for parameter uncertainty ranges by considering both small samples and extended virtual samples’ probability distribution. Comparative analysis through Monte Carlo simulation demonstrates the superior parameter estimation of our method for small samples. Our case analysis further explores the relationships between Vickers hardness, tensile strength, surface roughness factor, and intercept constant. The findings led to a novel method for estimating the S-N curve confidence interval of API X65 steel from Vickers hardness. Analysis of fatigue life test data for API X65 steel yielded favorable results, confirming the effectiveness and feasibility of our improved method.

Case-only analysis in small studies of predictive biomarkers

Characteristics of tumors and patients can be used as predictive biomarkers to guide treatment choice. Although many potential biomarkers are evaluated each year, only few will eventually be used since evidence is usually based on small studies leading to inconclusive results. Such data are often analyzed with Cox proportional hazards regression using a multiplicative interaction term between biomarker and treatment, with insufficient power and possibly biased results. Instead of analyzing patients who do (cases) and do not experience (non-cases) the survival event of interest, case-only analysis with logistic regression has been proposed, however with unknown small sample properties. We evaluated the performance of case-only analysis with bias-eliminating Firth correction and confidence intervals obtained with a profile likelihood method in a simulation study tailored to breast cancer. Our results show that this approach is generally inferior to the full cohort analysis but has acceptable properties when the marker is protective or null among patients treated with the standard treatment, the event rate is low (e.g., a rare event and a protective marker) and treatment assignment is independent of the marker level (e.g., in randomized studies). In such situations, the case-only design offers substantial cost savings. However, the model is sensitive to these assumptions.

The three points approach (3PA) applied to two Chinese and four European cities for knowledge exchange on stormwater challenges and strategies

ABSTRACT Urban stormwater is sometimes a risk, sometimes a resource. To address both aspects, the Three Points Approach (3PA) is advocated. This research applied the 3PA to map stormwater approaches in two Chinese and four European cities. While all cities have targets for the Technical Design Domain, none have targets for all domains; and thereby lack interventions to maximize benefits of frequent small events in the Day-to-Day Domain or minimize flood risks of rare large events in the Extreme Domain. Using open global precipitation data cities’ stormwater targets were expressed as more comparable rain depths, demonstrating that event depths within the Day-to-Day Domain in Chinese cities, cover much of the same range as those within the Technical Design Domain in the European cities. Expressing targets as depths in the context of the 3PA framework may facilitate transdisciplinary and transnational knowledge sharing, paving the way for management strategies covering all three domains.

Radiopurity screening of materials for rare event searches by neutron activation at the TRIGA reactor of Pavia

In the framework of physics experiments searching for rare events, the selection of extremely radiopure materials is a challenging task, as the signal of interest is often hidden by instrumental background. Neutron activation is a powerful technique to measure trace contaminants with high sensitivity but, to be properly applied, it requires a good characterization of neutron irradiation and γ-spectroscopy facilities. This paper presents the state-of-the-art workflow adopted by the Radioactivity Laboratory of the University of Milano-Bicocca for radiopurity screening of materials by neutron activation performed at the TRIGA reactor in Pavia. The ultimate sensitivity of the described workflow, in the absence of interfering activation products and without the application of radiochemical and/or active background rejection techniques, is <10-14 g/g for 40K (<10-10 g/g for elemental K), <10-12 g/g for 238U and of the order of 10-12 g/g for 232Th contaminations. Further details are here provided to address systematic uncertainties related to neutron irradiation that may bias results. To this aim, a dedicated neutron activation campaign was performed and the data were analyzed exploiting a Monte Carlo simulation model of the reactor and applying an unfolding technique to obtain a comprehensive characterization of the neutron flux in typical irradiation configurations. The results of this work provide a valuable benchmark for the application of neutron activation in future radiopurity screening campaigns.

Safety Outcomes in Patients With Ulcerative Colitis Using a Healthcare Administrative Database in the United States.

Several therapies, including sphingosine 1-phosphate receptor modulators, have been approved for ulcerative colitis (UC). Safety findings should be complemented with real-world data (RWD) as rare events may be underestimated in clinical trials due to populations not fully reflecting real-world practice. We used RWD to investigate safety outcomes in 4 cohorts: (1) those receiving any UC treatment (UC overall), (2) those receiving advanced therapies (UC advanced therapy), (3) those meeting the selection criteria of the etrasimod ELEVATE UC clinical program (UC trial-similar), (4) individuals without UC (Non-UC). Data were extracted (1/2016-12/2022) from the Optum® de-identified Electronic Health Record data set. Data from 32 170 (UC overall), 3332 (UC advanced therapy), 1435 (UC trial-similar), and 160 795 (Non-UC) individuals were included. In the UC overall cohort, <11% of patients used advanced therapy. The UC overall cohort had significantly higher incidence rates (IRs) across most safety outcomes compared with the Non-UC cohort (highest: malignancy [excluding non-melanoma skin cancer] at 31.1 compared with 14.1 IRs per 1000 patient-years, respectively), regardless of age or oral corticosteroid use. Incidence rates of safety outcomes for the UC advanced therapy and UC trial-similar (also requiring prior advanced therapy use) cohorts were generally similar or lower than the UC overall cohort. The UC trial-similar and UC advanced therapy cohorts had generally comparable safety outcomes. These findings assist in understanding the background risks of safety events in patients with UC and suggest that the incidence of select safety outcomes is comparable between the ELEVATE UC trials and RWD.