Nonparametric Research Articles

Risk factors-adjusted performance and persistence during the post-subprime crisis period: evidence from Indian mutual fund industry

PurposeThe main objective of the paper is to find evidence of abnormal returns and performance persistence of actively managed equity funds in the Indian context on an annual basis during the post-subprime crisis period between 2009 and 10 and 2019 and 2020.Design/methodology/approachThe study is exploratory and empirical, used daily net asset value (NAV) of 180 equity funds for 10 years and applied the risk-adjusted, Jensen's (1968) single-factor, Fama and French's (1993) three-factor model and Carhart's (1997) four-factor model to evaluate the performance. The performance persistence has been tested using cross-section regression (Bollen and Busse, 2005), the non-parametric contingency approach, along with the robustness measure, i.e. Malkiel's (1995) Z-score, Brown and Goetzmann's (1995) cross-product ratio (CPR) and Kahn and Rudd's (1995) χ2 value.FindingsThe results show that the Indian equity funds are unable to generate abnormal returns, and the size, value and momentum strategies applied by the fund managers in generating abnormal returns do not work effectively. However, funds provide strong evidence of significant performance persistence on an annual basis in the short-term, mid-term and long-term periods. Both parametric as well as non-parametric tests provide identical evidence of persistence, and the performance persistence is independent of the choice of models, as all the models (i.e. two, three or four-factor models) provide significant evidence of persistence.Research limitations/implicationsThough the study is comprehensive and covered a longer period, there is a scope for future research by examining the influence of fund characteristics, fund rating and macroeconomic factors on performance and persistence. It can be extended over to a longer period covering the post-COVID-19 period, a larger sample size and a comparative study of Indian and foreign mutual funds (MFs).Practical implicationsThe outcomes of this research paper can help wealth-maximizing investors in the identification of persistent equity funds and can apply the previous period’s performance information as a useful investment strategy to generate higher returns in the future. We believe that these outcomes will have significant ramifications for all MF stakeholders and policymakers, especially for the Indian industry in ensuring and establishing the credibility of MF managers, in providing better returns as well as to make MF investment more attractive to Indian retail investors.Originality/valueDespite the exponential growth in the Indian MF industry, limited evidence is available on performance and persistence covering a large sample size during the post-sub-prime crisis period using different return models and parametric and non-parametric approaches. The study is based on the daily data set of a larger sample size representing all the Asset Management Company (AMC) and the longer period following the post-subprime crises, which affected capital flows significantly. Moreover, the application of all the measures enables us to understand performance persistence in a larger context.

Is it Possible for Individuals with Pre-Existing Mental Disorders to Perform Mountain Sports at High Altitude-First Evidence from a Pilot Cross-Sectional Questionnaire Study.

Gstir, Claudia, Timo Schurr, Roxana Ehlers, Johannes Burtscher, Barbara Sperner-Unterweger, and Katharina Hüfner. Is it possible for individuals with pre-existing mental disorders to perform mountain sports at high altitude-First evidence from a pilot cross-sectional questionnaire study. High Alt Med Biol. 00:00-00, 2024. Introduction: Mountain sports at high altitude (HA) are gaining increasing popularity, but little is known about the effect of such activities on mental health, despite a great prevalence of mental disorders. Methods: Data were collected using an online self-report questionnaire assessing mental and somatic disorders in individuals performing mountain sports at HA (>2,500 m above sea level [ASL]) as well as their symptom change. Nonparametric tests were used for analyses. Results: 251 individuals without pre-existing disorders (noD), 34 with somatic disorders (somaD), and 38 with mental disorders (mentalD; mainly depressive, eating, and anxiety disorders) participated in this study. Overall, 44.7% of the mentalD group compared with 14.7% of somaD experienced ameliorated symptoms during mountain sports at HA, while 2.6% and 8.8%, respectively, reported a worsening (χ2[2] =8.13, p = 0.017). People in the mentalD compared with somaD group significantly less frequently inform tour partners (41.9% vs. 90.9%; χ2[2]=16.69, p < 0.001) about their condition or consult their physician (2.6% vs. 26.5%; χ2[1]=8.53, p = 0.003) regarding their plans to perform mountain sports at HA. 14.5% of all participants reported mental symptoms at 2,500-3,500 m ASL, 23.5% between >3,500-5,500 m ASL and 31.8% >5,500 m ASL. Conclusion: Individuals with mental disorders often report improved mental health during mountain sports at HA, possibly due to a combination of physical activity, the alpine natural environment, and/or moderate hypoxia. The fact that tour partners and physicians are rarely informed shows the need to reduce the stigma of mental disorders in the mountain sports community. The study was prospectively registered with the German Clinical Trials Registry (DRKS00024949).

Can systemic antibiotics reduce the need for surgical intervention in treating peri-implantitis?

A retrospective cohort design was used to assess the long-term clinical effectiveness of systemic amoxicillin and metronidazole, used adjunctively with non-surgical peri-implantitis treatment (NST) and whether it prevents the need for further surgical interventions. Of the 57 peri-implantitis patients examined, 45 patients were included in this study. The participants were divided into two subgroups in accordance to who had received NST with or without systemic antibiotics. Selection was based on prior participation in a three-month randomised control trial, ensuring comparability of data regarding peri-implantitis severity and treatment history. Data were extracted pre-treatment, 3-months post-treatment and at a long-term follow-up interval of 36 months. The primary outcome was the need for additional surgical intervention and was analysed via Kaplan-Meier analysis and Cox regression. A multitude of secondary clinical outcomes were evaluated using parametric and non-parametric tests, including peri- implant probing depth, bleeding scores and treatment success. Overall, 62.2% of the 45 NST patients did not need surgical peri-implantitis treatment: 73.9% of the subgroup with antibiotics and 50% of the subgroup without antibiotics respectively. However, the difference between the two groups was not statistically significant (log-rank test, p = 0.110). The Cox regression analysis also displayed no significance over the first three years post-treatment (p = 0.115). Additionally, the study found that deeper peri- implant pockets at baseline significantly predicted the need for future surgical treatment (p = 0.031), highlighting the importance of initial disease severity in treatment outcomes. The study concludes that the adjunctive use of systemic amoxicillin and metronidazole with NST may delay but not statistically reduce or prevent a future surgical need. Although a short-term reduction in clinical inflammatory parameters was evident, the long-term effectiveness in altering the progression of peri-implantitis remains limited.

How Time, Living Situation, and Stress Related to Technology Influence User Acceptance and Usability of a Socialization Service for Older Adults and Their Formal and Informal Caregivers: Six-Month Pilot Study.

Considering the growing population of older adults, addressing the influence of loneliness among this demographic group has become imperative, especially due to the link between social isolation and deterioration of mental and physical well-being. Technology has the potential to be used to create innovative solutions to increase socialization and potentially promote healthy aging. This 6-month study examined the usability and acceptability of a technology-based socialization service and explored how stress and living situation affect older adults' and their ecosystem's perceptions of technology, investigating cross-sectional and longitudinal differences among and across user groups. Participants were recruited in Tuscany and Apulia (Italy) through a network of social cooperatives and a research hospital, respectively. A total of 20 older adults were provided with the same technology installed on a tablet and on a smart television. The technology has three functionalities: video calling, playing games, and sharing news. Additionally, 20 informal caregivers (IC) and 13 formal caregivers (FC) connected to the older adults were included in the study. After both initial training in the use of the system (T0) and 6 months of using the system (T6), questionnaires on usability, acceptability, and technostress were filled in by older adults, IC, and FC. Nonparametric or parametric tests were conducted to investigate group differences at both time points and changes over time. Additional analyses on older adults were done to assess whether differences in usability and acceptability were related to living situation (ie, alone or with someone). Furthermore, correlation analyses were performed between usability, acceptability, and stress toward technology at T0 and T6. At both T0 and T6, older adults had lower usability scores than IC and FC and higher anxiety than IC. Over time, there was a significant decrease in older adults' attitudes toward technology score, depicting a negative attitude over time (T0 median 4.2, IQR 0.5; T6 median 3.7, IQR 0.8; Cohen d=0.7), while there was no change for IC and FC. At T0, those living alone had lower acceptability than those living with someone but this difference disappeared at T6. People or participants living with someone had a decline in anxiety, attitudes toward technology, enjoyment, and perceived usefulness. Stress toward technology affected usability and acceptability in the older adult group entering the study (ρ=-.85) but this was not observed after 6 months. In the IC group, stress affected trust at T0 (ρ=-.23) but not at T6. At the start of the study, older adults judged the system to be less usable and more stressful than did the caregivers. Indeed, at first, technostress was correlated with usability and acceptability; however, with repeated use, technostress did not influence the perception of technology. Overall, getting accustomed to technology decreased anxiety and stress toward technology.

The Relationship Between Nurses' Digital Health Literacy and Their Educational Levels, Professional Roles, and Digital Attitudes: A Cluster Analysis Based on a Cross-Sectional Study.

The current study aimed to identify digital health literacy levels among nurses with respect to their education, role and attitude towards digital technologies. Cross-sectional study. Through convenience sampling, all Registered Nurses, managers/leaders and nurse researchers employed in Hospitals, University Hospitals and Districts were recruited and surveyed using an online questionnaire. The data collection tool assessed: (I) demographics, (II) Digital Health Literacy (DHL) with the Health Literacy Survey19 Digital (HLS19-DIGI) instrument including DHL dealing with digital health information (HL-DIGI), interaction with digital resources for health (HL-DIGI-INT) and use of digital devices for health (HL-DIGI-DD); (III) attitudes on the use of digital technologies in clinical practice. The multiple correspondence analysis was applied to identify three clusters for the education/professional role (A, B, C) and three for digital technologies' use (1, 2, 3). The one-way nonparametric analysis of variance (Kruskal-Wallis test) was applied to compare HL-DIGI, HL-DIGI-INT and the HL-DIGI-DD scores among clusters. Among 551 participants, the median scores of the HL-DIGI, the HL-DIGI-INT and the HL-DIGI-DD questionnaires were 70.2, 72 and 2.00, respectively. The distribution in the clusters 'educational/professional role' was A, (58.8%); B, (16.5%); and C, (24.7%). Nurses in a managerial or coordinator role and with a postgraduate degree used digital resources with greater frequency. The distribution in the clusters 'use of digital technologies' was: 1, (54.6%); 2, (12.2%); and 3, (33.2%). The HL-DIGI-DD and HL-DIGI scores of clusters 1, 2 and 3 differed significantly. DHL among nurses is strongly influenced by the education level, professional role, habits and attitude towards digital technologies. Nurses with coordinator roles used digital technologies with greater frequency and had a higher level of DHL. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used for reporting. No Patient or Public Contribution. Local Ethical Committee of the Polyclinic of Bari (code: DHL7454, date: 21/09/22).

Estetrol Inhibits the Prostate Cancer Tumor Stimulators FSH and IGF-1

Background: The co-treatment of androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) with the fetal estrogen estetrol (E4) may further inhibit endocrine PCa tumor stimulators. We previously reported the suppression of follicle-stimulating hormone (FSH), total and free testosterone, and prostate-specific antigen by ADT+E4. Here, we provide more detailed data on FSH suppression by E4 and present new findings on the effect of ADT+E4 on insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study (the PCombi study) was conducted in advanced PCa patients treated with ADT. The study assessed the effect of E4 co-treatment with LHRH agonist ADT on tumor stimulators, including FSH and IGF-1. Patients starting ADT were randomized 2:1 to receive either 40 mg E4 (n = 41) or placebo (n = 21) for 24 weeks. Non-parametric analyses were performed on the per-protocol population (PP) and individual changes were visualized. Results: The PP included 57 patients (37 ADT+E4; 20 ADT+placebo). ADT+E4 almost completely suppressed FSH in all patients (98% versus 37%; p &lt; 0.0001). IGF-1 levels decreased by 41% with ADT+E4 versus an increase of 10% with ADT+placebo (p &lt; 0.0001). Conclusions: The almost complete suppression of the tumor stimulator FSH using ADT plus E4 observed in all individual patients in this study, along with the augmented suppression of IGF-1 versus an increase by ADT only, may be clinically relevant and suggest the enhanced anti-cancer treatment efficacy of E4 in addition to the previously reported additional suppression of total and free T and PSA.

Artificial Intelligence and Machine Learning with Moment Generating Functions to Enhance Biological Count Data Analysis

This research presents artificial intelligence with supervised machine learning to determine the median count given training data from biological laboratory experimentation. After determining the central moment of the median, machine learning is then used to predict the population median value. When computer programs learn they access available data, then autonomously analyze the information to make informed, data-driven decisions. Moment generating function restrictions identify a parameter of interest by restricting the expected value of the moment generating function. This research proposes a theoretical foundation for achieving such predictions. A summary of the key elements underlying the statistical power of the Mann– Whitney test, a nonparametric hypothesis test for the median of count data, is also presented. A nonparametric approach allows for accurate predictions while relaxing distributional assumptions such as normality.

Spatial and Temporal Dynamics of the Canine Population and Contamination by Canine Feces on an Urban Beach

Objective: The objective of this study was to analyze the spatio-temporal distribution of dogs and feces using the visual census method. The research aimed to quantify the presence of dogs and the number of feces observed in these environments. Method: The visual census was conducted every fifteen days over the course of one year along the Mar Grosso beach shoreline, which was divided into areas and sectors. The data were subsequently tabulated, and statistical analysis was performed using the non-parametric Kruskal-Wallis test. Research Results and Discussions: The highest number of feces and stray dogs were found in the urban sector during the summer. Regarding the areas observed and feces, the area with the highest number of feces was A3 in the urban sector during the summer. As for the number of stray, domiciled, and off-leash dogs, they were more frequently observed in the summer, with stray dogs predominantly in A2 (beach sector), and domiciled and off-leash dogs in A3 and A2, respectively, in the urban sector. Research Implications: The results identify hotspots of feces and dogs along the study area, providing valuable information that can assist in decision-making and the implementation of public policies aimed at controlling animals on beaches and protecting the environment, thereby reducing the risk of disease transmission to the population frequenting these locations. Originality/Value: This study contributes to evidence-based policy implementation to promote environmental health, public health, and animal welfare in coastal areas.

MLA Research Training Institute (RTI) 2018 and 2019: participant research confidence and program effectiveness

Objective: The article reports on an assessment of the effectiveness of the MLA Research Training Institute (RTI) for the years 2018 and 2019. The RTI is a year-long continuing education research methods training and support program for health sciences librarians. The study focuses on assessing RTI participants' research confidence after program completion and compares these results with their perceptions of workshop/program performance and learning outcomes. In addition, the authors discuss how the findings were applied to inform and improve the program. Methods: The study used a 26-item questionnaire, RTI Research Confidence Questionnaire, to gather information on participants’ self-reported research confidence before the workshop, immediately after the workshop, and one year after the workshop to determine statistically significant differences. Differences in research confidence were identified by using three nonparametric statistical tests. Additional workshop and program surveys were used to corroborate the research confidence findings. Results: Post-workshop and one-year-after-workshop research confidence ratings were significantly higher than pre-workshop levels for years 1 and 2. A comparison of median ratings between years 1 and 2 showed significant increases in research confidence for nine items in year 2. Participants’ positive perceptions of workshop/program effectiveness and learning outcomes corroborated these findings. Conclusion: Overall assessment findings indicated that RTI training helped participants understand, use, and apply research skills to conduct research. Findings also revealed that participants’ heightened research confidence persisted at least 12 months postintervention. The RTI Research Confidence Questionnaire proved effective for rigorously assessing and improving the RTI program. This study enhances the currently limited evidence on evidence-based approaches for assessing and improving research instruction for librarians.

The Correlation Between Homesickness and Academic Achievement in Mathematics: Implications for Psychological Well-Being of Secondary School Students

This study examined the correlation between homesickness and academic achievement in mathematics among secondary school students, focusing on its implications for psychological well-being. A correlational research design was employed, involving a sample of 50 secondary school students from Awka South Local Government Area, Anambra State. Data were collected using Scale for Psychological Impact of Homesickness (SPIH) and the Mathematics Achievement Scale (MAS). Validity was ensured through expert consultations and Principal Component Analysis. Reliability was established with Kuder-Richardson formula 21 (K-R21) and Cronbach’s Alpha, yielding α = 0.89 for SPIH and α = 0.86 for MAS. Data were analyzed using SPSS, including non-parametric tests and normality assessments. The Spearman's rho correlation analysis revealed a significant, albeit weak, negative relationship between homesickness and academic achievement, indicating that higher levels of homesickness are associated with lower mathematics performance. Further analysis using the Mann-Whitney U test highlighted significant differences in homesickness levels and academic achievement between boarder and non-boarder students. These findings underscore the importance of addressing emotional challenges in educational settings. The study advocates for the implementation of comprehensive support systems, including counseling and resilience-building programs, to mitigate the impact of homesickness on academic performance. The results emphasize the need for schools to foster supportive environments that enhance students' psychological well-being and academic success. Future research should explore additional factors influencing this relationship to develop targeted interventions..

Trends of fully alcohol-attributable mortality rates before and during COVID-19 in the Baltic and other European countries.

We tested the polarization hypothesis, which postulates that during times of crises, such as the COVID-19 pandemic, alcohol consumption increases among the heaviest drinkers but decreases among most other drinkers, resulting in an overall decrease in consumption among the population. We posited the increase in heavy drinking would lead to increases in 100% alcohol-attributable (AA) mortality. Furthermore, based on the high level of alcohol consumption in the Baltic countries compared to other European countries, we predicted that the increases in AA mortality would be more pronounced in these countries. Data for 100% AA deaths were obtained from the World Health Organization for the period 2010 to 2022, and standardized to the regional age distribution for 2010. Parametric and non-parametric tests were used to test the study hypotheses. The mean age-standardized 100% AA mortality rate increased during the COVID-19 pandemic in the 19 European countries with data by 3.12 deaths per 100,000 population, constituting an 18% increase (tested against no change: t = 2.52; df = 18; p = 0.021). This increase was higher in the Baltic countries (mean difference = 13.41 deaths per 100,000 population; standard deviation (SD) = 7.44; 46% increase) than for other European countries (mean difference = 1.19; SD = 1.55; 8% increase). The increases in 100% AA mortality were associated with decreases in the level of alcohol consumption in the majority of countries. As predicted, 100% AA mortality increased in 19 European countries during the COVID-19 pandemic, with the Baltic countries seeing a higher increase. Renewed alcohol control policy efforts should be considered.

9260 Insulin Receptor Signaling And Racial Disparities In Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P&amp;lt;0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

8212 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P&amp;lt;0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

9260 Insulin Receptor Signaling and Racial Disparities in Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P&amp;lt;0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

8212 Insulin Receptor Signaling And Racial Disparities In Triple Negative Breast Cancer

Abstract Disclosure: A.J. Engel: None. K. Samuel: None. I.R. Bass: None. S. Lin: None. I. Antoniou: None. R. Yagnik: None. D. LeRoith: None. N.A. Bickell: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals. Introduction: Obesity and type 2 diabetes are associated with poor breast cancer (BC) prognosis. These disorders, along with hyperinsulinemia are more common in Black than in White women. Black women also have higher rates of triple negative breast cancer (TNBC), and greater breast cancer mortality than White women. We hypothesized that Black women with TNBC have worse outcomes in part due to tumor promoting effects of hyperinsulinemia via the insulin receptor (IR) signaling pathway. Methods: From our IRB-approved, multi-institutional, cross-sectional, NIH-funded, study of women with newly diagnosed BC, we identified women with TNBC. We performed immunohistochemistry (IHC) analysis of formalin-fixed-paraffin-embedded tumor samples from 45 self-identified Black women and 48 self-identified White women. We quantified the BC expression of IR (n=92), IGF1R (n=92), pERK (n=91), FOXO3a (n=90) for intensity (none=0, weak=1, moderate=2, intense=3). In subsequent analysis, 0 and 1 intensity IHC staining were considered negative, and 2 and 3 were considered positive. Quantification was performed with reviewers blinded to clinical information. Clinical information (age, race, body mass index [BMI], waist circumference, fasting insulin, BC Nottingham Prognostic Index [NPI]) was evaluated after IHC scoring. Statistical proportions were compared using Fishers Exact test, and continuous variables were evaluated using parametric or non-parametric tests, as appropriate. Results: Positive IR staining was seen in 64% of samples (n=59), 74% (n=68) for IGF1R, 68% (n=62) for FOXO3a and 43.3% (n=39) for pERK. Positive IR staining was more prevalent in Black women than White women (P=0.003) but was not significantly associated with age or NPI. IGF1R, FOXO3a, pERK positive staining were not associated with race or NPI. Positive IR staining was also associated with higher BMI, waist circumference, and fasting insulin (P&amp;lt;0.05 for all). Positive IGF1R, FOXO3a, pERK staining were not associated with any of these factors. Conclusions: We found that 64% of TNBCs had positive expression of IR, and IR expression was more prevalent in tumors from Black women and associated with higher insulin levels, suggesting that tumors from Black women may be more sensitive to the tumor promoting effects of systemic hyperinsulinemia. Presentation: 6/2/2024

ASTRAL scale for predicting prognosis following intravenous thrombolysis with anterior versus posterior circulation acute ischemic stroke.

In this study, we compared whether there was any difference between the ASTRAL(Acute Stroke Registry and Analysis of Lausanne, ASTRAL) scale in predicting prognosis after IVT(Intravenous Thrombolysis, IVT) in patients with AIS(Acute Ischemic Stroke, AIS) in the ACI(Anterior Circulation Infarction, ACI) and PCI(Posterior Circulation Infarction, PCI), with the aim of providing more guiding information. Statistical analysis was performed using SPSS 25.0. When comparing the baseline characteristics, the normal distribution test was carried out first, which did not conform to the normal distribution. The continuous variables were expressed in the median and interquartile, and the nonparametric double-independent sample test was carried out. MedCalc software was used to plot ROC(Receiver Operating Characteristic, ROC) curves, calculate AUC(Area Under the Receiver Operating Characteristic Curve, AUC), and compare the prediction performance of the ASTRAL score by Delong text, and the difference of P < 0.05 was statistically significant. The AUCs of ASTRAL in predicting poor prognosis of ACI and PCI patients after IVT were 0.768 and 0.773, respectively. There was no difference in the AUC of ASTRAL score between ACI and PCI(P > 0.05). The ASTRAL scale has consistent prognostic predictive value for AIS in the anterior and posterior circulatory systems and is a reliable tool for predicting poor prognosis of patients with ACI and PCI after IVT.

Hypoxia cycle in shallow lakes during winter (ice-covered to melting period): Stable and decay, hypoxia, and recovery phases

This study investigates hypoxic processes beneath lake ice and explores the interactions between water environmental factors and dissolved oxygen (DO) during winter, aiming to systematically assess the influence of winter climate changes on lake ecosystems through environmental variables (physical, chemical, and biological characteristics of water). A complete hypoxic cycle in a high-altitude shallow lake was recorded using high-frequency monitoring technology, and based on a predetermined hypoxic threshold (DO<2 mg/L), it was divided into three phases: stable and decay phase, hypoxic phase, and recovery phase. Significant trend changes of environmental variables under different levels of DO were analyzed for each phase using the Mann-Kendall non-parametric test. On the basis of evaluating the overall trend of the time series, a GAM multi-factor optimization model integrating interactive effects was constructed to explore the response mechanism of environmental variables to hypoxic processes. The optimized model showed excellent explanatory performance with R2 values of 0.833 for the stable and decay phase and 0.932 for the recovery phase, with AIC values of 1554.72 and 721.03, respectively. The trend test combined with model analysis indicates that: (1) the decay of DO under the ice is primarily affected by the increase in EC, BGA, and EC*Temp, (2) the phytoplankton biomass in shallow lakes during winter has a definite contribution to the occurrence of oxygen deficiency, and (3) the water body experiences rapid reoxygenation after the ice layer breaks, but the DO level is restricted by the increase in temperature. This study highlights the ecosystem characteristics of shallow ice-covered lakes in cold arid regions, advancing our understanding of the response relationship between hypoxic aquatic environments under ice and environmental factors.

12602 The Effect of Three-Month Semaglutide Treatment on Serum TSH and Thyroid Hormones in Individuals with Obesity

Abstract Disclosure: P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. A.J. Kretowski: None. L. Szczerbinski: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a crucial role in managing obesity and diabetes, significantly influencing glycemic control and weight management. Previous studies showed that GLP-1 RAs therapy affects thyroid-stimulating hormone (TSH) levels; however, they were limited by small sample sizes and did not extensively cover newer agents like semaglutide. Thus, the aim of this study was to assess the impact of a three-month semaglutide treatment on thyroid hormones and TSH levels in individuals with obesity, without diabetes, and examine the relationship of these changes with weight loss. Methods: We analyzed data from 290 patients participating in the GAROS study, excluding those on medications affecting thyroid function or with a known history of thyroid disease. All participants underwent a three-month treatment with oral semaglutide, followed by a three-month discontinuation phase. Measurements of TSH, free triiodothyronine (fT3), free thyroxine (fT4), and body weight were taken at baseline, at the end of the treatment period, and three months post-treatment discontinuation. To compare changes in TSH, fT3, and fT4 levels, as well as weight, across the study timelines we used non-parametric tests due to the non-normal distribution of the data. We also employed multiple linear regression models to evaluate the association between thyroid hormone changes and weight loss, both in the aggregate and stratified by sex. Results: Initial fT3, fT4, and TSH levels were 3.13 pg/ml (SD=0.38), 0.94 ng/dl (SD=0.10), and 1.64 mIU/l (SD=0.82), respectively. Post-treatment, fT3 decreased on average by 0.33 pg/ml (p&amp;lt;0.001), TSH by 0.32 mIU/l (p&amp;lt;0.001), and fT4 increased by 0.06 ng/dl (p&amp;lt;0.001). Upon discontinuation, fT3 and fT4 levels did not fully return to baseline values but showed a significant shift in that direction (p&amp;lt;0.001 for fT3 and p=0.006 for fT4, compared to baseline). Conversely, TSH levels adjusted back to their baseline values (p=0.26). Notably, changes in fT4 levels, unlike fT3 and TSH, were significantly negatively associated with weight changes during (p=0.030) and post-treatment (p=0.008), across sex-stratified analyses. Conclusions: Semaglutide treatment significantly alters thyroid hormones and TSH levels in patients with obesity, with some effects reversible post-discontinuation. Except for fT4, these hormonal changes appear to be independent of the weight loss effects of semaglutide. Although the magnitude of these alterations might not be clinically significant, they do imply that GLP-1 RAs may have additional physiological effects. The exact nature of the interaction between semaglutide and thyroid function, however, remains to be fully elucidated, highlighting the need for further research to clarify these mechanisms. Presentation: 6/2/2024

7590 Bone Mineral Content In Women With Functional Hypothalamic Amenorrhea Compared To Eumenorrheic Controls And Recently Menopausal Women

Abstract Disclosure: N. Safwan: None. E.R. Uddenberg: None. M.D. Hurtado: None. M. Saadedine: None. S.S. Faubion: None. O. Obrutu: None. S.L. Berga: None. M.D. Pisarska: None. C. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea due to suppression of GnRH associated hypercortisolemia resulting in chronic hypoestrogenemia. FHA occurs as a result of varying combinations of psychosocial stress, excessive exercise, and/or disordered eating. FHA is associated with decreased bone mineralization; however, it is unknown how bone health compares to older, menopausal women who also experience bone loss. We compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women and evaluated if previous oral contraceptive (OC) use among FHA women has an impact on bone mineral density (BMD). Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. All participants were not on hormone therapy. FHA was defined as amenorrhea &amp;gt;3 consecutive months, estradiol &amp;lt;50 pg/ml, FSH &amp;lt;10 mIU/L, and LH &amp;lt;10 mIU/L, excluding other etiologies including PCOS, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menses confirmed with day 22-24 progesterone &amp;gt;3 ng/ml. Recently menopausal women had natural menopause &amp;lt;3 years of final menstrual period, and FSH &amp;gt;30 mIU/L. DXA bone health parameters were measured using Lunar iDXA (GE) including BMD from the lumbar spine (L1-L4) and hip. Statistical analysis included nonparametric testing with pairwise Wilcoxon rank sum and Kruskal Wallis, reported as median [interquartile ranges]. Results: By design, the mean age of FHA was 28 ± 6 yr, 29 ± 3 yr for controls, and 54 ± 2 yr for recently menopausal women (p&amp;lt;0.0001). There were no differences in weight or BMI among the groups (p=0.27, p=0.30, respectively). BMD L1-L4 differed among the three groups with 1.10 g/cm2 [1.00, 1.24] for FHA, 1.18 [1.15, 1.29] for eumenorrheic controls, and 1.02 [0.96, 1.08] for menopausal women (p=0.002). Pairwise analysis revealed a significant difference in BMD L1-L4 between FHA and controls (p=0.04) and menopausal women and controls (p=0.009, age-adjusted). However, there was no difference in BMD L1-L4 between FHA and menopausal women (p=0.08, age-adjusted). In FHA women with previous OC use, BMD L1-L4 was not different from eumenorrheic controls (p=0.20), while BMD L1-L4 differed from that of recently menopausal women (p=0.004). These differences were not observed at the hip. Conclusion: Compared to eumenorrheic controls, lumbar spine BMD in young women with FHA (mean age 28 yr) was similar to recently menopausal women (mean age 54 yr) emphasizing the profound bone impact of FHA. Previous OC use seems to mitigate FHA bone mineralization changes. Future studies should investigate if bone health differs among women with FHA based on underlying cause and if previous OC use plays a role in maintaining bone health. Presentation: 6/3/2024

A multi-criteria measurement and assessment of human capital development in EU-27 countries: A 10-year perspective

In today's global economy and across various types of organizations, human capital is a fundamental resource that determines their existence and development. This is particularly important in the context of ongoing climate-technological transformation processes based on innovative solutions. The role and importance of personal resources are well understood in the EU-27 countries, which base their future on competent human capital. This paper addresses this critical and timely topic by assessing human capital in the EU-27 countries over the period 2013–2022. The research aims to evaluate these countries' human capital potential, distinguishing between the "new EU-13" and the "old EU-14" countries, and to measure the effectiveness of its development during the study period. A crucial part of the research was to determine the impact of human capital on selected indicators of economic growth, innovation, and sustainable development. To achieve these objectives, an original research methodology was developed, employing the COPRAS method to determine the human capital assessment index and the equal weights and CRITIC methods to establish the weights of indicators characterizing the studied human capital. The impact assessment of this capital, along with innovation and unemployment on economic growth, was conducted using an econometric model. Meanwhile, correlations between the human capital assessment index and the indicators characterizing innovation, economic growth, and sustainability were analyzed using Spearman's non-parametric tests. The results show significant variation in human capital between the EU-27 countries and between the "old EU-14" and "new EU-13" groups. The Netherlands, Denmark, and Sweden achieved the best results in terms of human capital development, while Greece, Romania, and Bulgaria had the weakest outcomes. In contrast, Cyprus, Malta, and Portugal recorded the greatest progress during the review period. These results offer extensive opportunities for multidimensional inference and can be used to assess the current state of the EU-27 economy. They should also inform the development of strategies for individual countries and the EU-27 as a whole.