Cumulative Distribution Function Research Articles

Real-World Effectiveness of Risankizumab in Patients with Moderate-to-Severe Psoriasis: Interim Analysis from the VALUE Global Prospective Post-marketing Observational Study at 25Months.

Risankizumab is approved for treating moderate-to-severe psoriasis. This interim analysis at 25 months evaluated the effectiveness of risankizumab compared with other approved biologics (OtherBios) among patients with moderate-to-severe psoriasis in the 37-month VALUE post-marketing observational study. Patients diagnosed with psoriasis were enrolled in a 2:1 ratio to risankizumab or OtherBios, as prescribed by their physicians. A ≥ 90% improvement in Psoriasis Area Severity Index (PASI) 90 at months 4, 13, and 25 and the time to first treatment change at 25 months were evaluated. Additionally, PASI 100 and 75, static Physician Global Assessment (sPGA 0/1), Dermatology Life Quality Index (DLQI), and Treatment Satisfaction Questionnaire for Medication (TSQM) scores were evaluated. All patients treated with ≥ 1 dose of biological therapy with ≥ 1 post-baseline measurement were included in the analysis. Modified non-responder imputation was used to handle missing data, and propensity score matching accounted for imbalances between comparison groups. Overall, 1765 patients received risankizumab and 874 received OtherBios. At baseline, the mean (SD) age of the overall population was 48.5 (14.7) years and mean (standard deviation [SD]) PASI scores were 15.0 (9.0) and 13.9 (8.8) in the risankizumab and OtherBios groups, respectively. At 25 months, 70.9% of those treated with risankizumab vs. 51.5% of those treated with OtherBios achieved PASI 90. The cumulative treatment change probability was 0.16 (95%, confidence interval [CI] 0.14, 0.18) in the risankizumab group and 0.29 (95% CI 0.26, 0.32) in the OtherBios group. At 25 months, a higher proportion of patients achieved PASI 100 (56.6% vs. 40.2%), PASI 75 (84.3% vs. 67.7%), sPGA 0/1 (82.6% vs. 66.2%), and DLQI 0/1 (70.0% vs. 52.9%) in the risankizumab vs. OtherBios group, respectively, and the change in mean TSQM global score was higher in the risankizumab group (86.0 vs. 79.4). All comparisons were nominally significant (P < 0.0001). No new safety signals were identified. In this prospective study, risankizumab demonstrated higher effectiveness, longer drug survival, and better improvement of patient-reported outcomes at 25 months compared with OtherBios. ClinicalTrials.gov identifier: NCT03982394.

Evaluation of intrarenal vein flow patterns during routine echocardiography.

Intrarenal vein flow (IRVF) abnormalities can predict cardiovascular events including heart failure. This study aimed to evaluate the utility of short IRVF scans during routine comprehensive transthoracic echocardiography (TTE) examinations in a standard TTE laboratory. We screened consecutive patients who underwent elective TTE at our Ultrasound Imaging Laboratory between March 2018 and July 2019 and prospectively enrolled those who completed a 5min IRVF scan during the 30min TTE procedure. Among the 2101 screened patients, 1326 were included in the study cohort (age: 73 ± 13years, 756 men). IRVF abnormalities were detected in 13 (1.0%) patients. Twenty-one cardiac events were observed (1.6%, 21/1326): one myocardial infarction and 20 heart failures. Cumulative survival probability plots were generated using the Kaplan-Meier method within 6months after the TTE index day and assessed using the log-rank test. The plots revealed significantly worse prognoses in patients with elevated right arterial pressure (RAP) and abnormal IRVF, when compared to normal RAP or normal IEVF (p < 0.0001 and p < 0.0001, respectively). In a receiver operating curve analysis to predict the occurrence of cardiovascular events, E/e' had moderate predictive potential (area under the curve: 0.795, p < 0.0001), and the combination of E/e' and IRVF abnormality had better predictive potential than did E/e' alone (p = 0.043). Although rarely observed on TTE, IRVF abnormalities improve the ability of E/e' to detect cardiac events, especially heart failure. Further large-scale prospective studies are required to confirm our findings.

Moderating carbohydrate digestion rate in mice promotes fat oxidation and metabolic flexibility revealed through a new approach to assess metabolic substrate utilization.

Superior metabolic flexibility, or the ability to efficiently switch between oxidation of carbohydrate and fat, is inversely associated with obesity and type 2 diabetes. The influence of dietary factors on metabolic flexibility is incompletely understood. This study examined the impact of dietary carbohydrate digestion rate on metabolic flexibility and metabolic substrate utilization. We employed percent relative cumulative frequency (PRCF) analyses coupled with a new application of modeling using the Mixed Weibull Cumulative Distribution function to examine respiratory exchange ratio (RER) data from adult wild-type mice and mice lacking the mucosal maltase-glucoamylase enzyme (Mgam) under different dietary carbohydrate conditions, with diets matched for total carbohydrate contents and containing different ratios of slowly digestible starch (SDS) and resistant starch (RS), or that were high in sucrose or fat. Fungal amyloglucosidase (AMG) was administered in drinking water to increase carbohydrate digestion rate. We devised a Metabolic Flexibility Factor (MFF) to quantitate metabolic flexibility for each dietary condition and mouse genotype, with higher MFF indicating higher metabolic flexibility. Diets high in SDS exhibited lower average RER and higher metabolic flexibility (MFF) than diets high in resistant starch, sucrose, or fat. Diets containing high and intermediate amounts of SDS led to a more complete shift to fat oxidation. While mouse genotype had minimal effects on substrate oxidation and MFF, AMG supplementation shifted substrate utilization to carbohydrate oxidation and generally decreased MFF. Consumption of slowly digestible carbohydrates improved measures of metabolic substrate utilization at the whole-body level in adult mice.

Effects of maternal healthcare service utilization on modern postpartum family planning access in Bangladesh: insights from a National representative survey.

Access to modern family planning is critical for improving maternal and child health outcomes, yet it remains severely lacking in low- and middle-income countries, including Bangladesh. Maternal healthcare utilization during and after pregnancy is vital for promoting postpartum family planning. This study examined the effects of maternal healthcare service utilization on postpartum family planning uptake in Bangladesh. Reproductive calendar data from 4,081 women with recent live births were extracted from the cross-sectional 2017/18 Bangladesh Demographic and Health Survey and analyzed. The outcome variable was uptake of modern postpartum family planning methods and the exposure variables were different types of maternal healthcare services. Kaplan-Meier methods were used to calculate cumulative probabilities of modern postpartum family planning method uptake within 12 months post-delivery, and modified Poisson regression models were used to estimate the effects of utilizing maternal healthcare services on modern postpartum family planning method uptake. Modern family planning methods in the 12 month postpartum period were used by 72% of women, with over 60% starting after day 40. Less than 4% used long-acting family planning methods, while almost 40% relied on the oral contraceptive pill. Utilizing maternal healthcare services was associated with up to a 7% higher uptake of modern postpartum family planning methods compared to non-users. Three-quarters of Bangladeshi women use modern family planning within the 12 months postpartum, but often rely on less effective methods. Additionally, 25% of these women resort to traditional or no use of contraceptive methods, increasing the risks of unintended pregnancy, short birth intervals, and adverse maternal and infant health outcomes. Maternal healthcare services, including private facilities, should prioritize modern postpartum family planning provision, along with education and counseling on the benefits of long-acting contraception.

The Mollified (Discrete) Uniform Distribution and Its Applications

ABSTRACTThe mollified uniform distribution is rediscovered, which constitutes a “soft” version of the continuous uniform distribution. Important stochastic properties are presented and used to demonstrate potential fields of applications. For example, it constitutes a model covering platykurtic, mesokurtic, and leptokurtic shapes. Its cumulative distribution function may also serve as the soft‐clipping response function for defining generalized linear models with approximately linear dependence. Furthermore, it might be considered for teaching, as an appealing example for the convolution of random variables. Finally, a discrete type of mollified uniform distribution is briefly discussed as well.

Applications of Ujlayan and Dixit Fractional Uniform Probability Distribution

In this work, we consider the Ujlayan-Dixit (UD) fractional derivative and integral to present the fractional probability density function for the Continuous Uniform Distribution (CUD). Some applications for this distribution using the UD approach are developed by introduce new fractional notions on the probability theory, which involve cumulative distribution, survival and hazard functions. For continuous random variables, various additional concepts and applications are established, including the fractional expectation, the fractional variance and the fractional moments. Finally, the UD fractional standard deviation and the UD fractional Shannon entropy are provided.

Assessment of the Rainfed Wheat Productivity in a Changing Climate in Irbid, Jordan Using Statistical Downscaling and Random Forest Regression Prediction Under RCP4.5 & 8.5 Pathways.

Jordan faces risks associated with climate change and endeavors to sustain resources through the SDGs. This study examines the impacts of climate change on rainfed wheat productivity in Irbid Governorate during the historical period (1994-2021) and simulated for the future (2024-2100) using climate models (SDGs 1, 2, 11, 12, 13, & 15). Monthly precipitation, mean temperature, and annual wheat yield data were collected for the period (1994-2021) and analyzed using the Mann-Kendall test with Sen’s slope to investigate the historical trends and elaborate Phi-k correlation coefficient to determine their association. Monthly precipitation and mean temperature projections were collected from CSIRO-MK3.6.0 & GFDL-ESM2M CMIP5 ensemble models under two concentration pathways: RCP4.5 and RCP8.5. The projections were biased and corrected by the dynamic bilinear interpolation method and Delta, EQM, and QM statistical downscaling to enhance the projections' reliability and performance in capturing the region's climate. Taylor diagram was utilized to choose the best model to represent observed data. Cumulative Distribution Function and Probability Density Function Curves were plotted to describe the changes over decades based on climate models. Future wheat yields were predicted using the Random Forest Regression model. The results revealed a non-significant increase in total annual precipitation of 1.8% and 13.8% and a rise in annual mean temperature of 5.4% and 2.7% for Irbid and Baqura stations, respectively during the baseline timeframe on which wheat yield increased by 21.3%. The CSIRO model outperformed the GFDL model with greater fidelity in simulating historical monthly precipitation and mean temperatures. The CSIRO-MK3.6.0 model indicates precipitation and temperature shifts for near and far future periods. Temperature increases are expected to have more severe impacts in the far future (2073-2100) while projected decreases in precipitation of 0.06 mm/day and 0.10 mm/day under RCP4.5 and RCP8.5 affect yield reductions by 11.42 kg/ha and 12.21 kg/ha. Temperature increases of 2.7°C and 4.1°C under RCP 4.5 & 8.5 correspond to yield decreases of 24.825 kg/ha and 33.395 kg/ha, respectively. The study highlights the need for enhanced adaptation strategies; cultivating resilient wheat varieties, promoting crop rotation, improving meteorological monitoring and risk response approaches, and providing timely weather forecasts to mitigate the adverse effects of climate change on wheat productivity and ensure sustainable agriculture in Jordan.

Long-Term Reassurance with Negative High-Risk Human Papillomavirus (HR-HPV) and Clear Margins After Large Loop Excision of the Transformation Zone (LLETZ)

Background/Objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan–Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55–15.26), involved margins (HR = 3.94, 95% CI = 1.68–9.25), uncertain margins (HR = 4.42, 95% CI = 1.55–12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19–7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial.

Abstract TP334: Racial Disparities in Functional Outcomes and Stroke Recurrence in Young Patients with Ischemic Stroke

Introduction: Studies have reported racial disparities in acute stroke treatment and follow-up care in young patients which lead to less desirable outcomes for minorities. This study aimed to identify potentially modifiable factors for better stroke treatment and prevention in minority populations. Methods: Young patients aged 18-50 years who were admitted with ischemic stroke during 09/2016-12/2022 were retrospectively identified and stratified as non-Hispanic White (WH), non-Hispanic Black (BL), and Hispanic (HS). Racial differences in risk factors, stroke etiology, acute intervention, and follow-ups were examined using Chi-square and Kruskal-Wallis tests as appropriate. Cumulative probabilities of stroke recurrence were estimated using the Kaplan-Meier (KM) method and tested with the Log-rank (Mantel-Cox) test. A logistic regression was used to evaluate the odds ratio of favorable functional outcomes (mRS ≤2) by 90 days. A backward stepwise Cox regression was conducted to identify predictors of stroke recurrence reported as hazard ratio (HR) and a 95% confidence interval (CI). Results: A total of 318 patients were identified with a median age of 43 and 57.5% male, covering 57.2% WH, 22.3% BL, and 20.4% HS. Compared to WH, more BL and HS were comorbid with diabetes, hypertension, and prior stroke (p&lt;0.05). The rates of other risk factors did not vary by race. The distribution of stroke etiologies and rate of acute interventions (IV tPA, thrombectomy) were similar among the three. After discharge, 77.3% of young patients had ≥1 follow-ups at stroke clinic. The total number of stroke clinic follow-ups were similar among racial groups. At 90 days, 89.6% of patients achieved mRS≤2; the odds of having this favorable functional outcome were similar among racial groups ( p =0.207). The KM curve indicates that the first-year risks of stroke recurrence were similar among racial groups and that a trend showed BL had the highest risk of recurrent strokes, followed by HS, and WH had the lowest risk in 1-3 year follow up. Yet, these differences were not statistically significant ( p =0.056. BL was found to have 2.7 times higher risk to have a recurrent stroke than whites (HR: 3.7; 95% CI: 1.4-10.1; p=0.01). Conclusions: Findings highlighted high prevalence of hypertension and diabetes in young BL and HS and a higher risk of recurrent stroke in young BL, suggesting tailored interventions for comorbidities are urged for better stroke prevention in minorities.

Outcomes of Age-Friendly Health Systems: Return to Clinic After 4Ms Care Delivery.

The Age-Friendly Health System (AFHS) movement continues to grow in the United States as more health systems implement the 4Ms framework. Despite this growth, there are relatively few studies that evaluate outcomes related to AFHS implementation. This study assessed patient satisfaction with AFHS by analyzing the rate at which patients returned to the clinic for future health care, serving as a measure of quality. A retrospective cohort design using electronic health record (EHR) data obtained from patients 65 years of age and older who received care at a large national network of convenient care clinics in the U.S. (N = 987,197) between January 2021 and March 2024. We assessed the level of AFHS 4Ms care received by these individuals in relation to their subsequent visit back to the clinic through descriptive statistics, a time-to-event analysis using the Kaplan-Meier cumulative incidence approach, and a Cox proportional Hazards model, adjusted for age, race, sex, prior appointments, and number of ICD-10 code diagnoses. Throughout the study period, patients who received complete AFHS 4Ms care exhibited greater rates of returning to the convenient care clinic compared to those who received partial or no 4Ms 4Ms care. Kaplan-Meier curves demonstrated that the cumulative probability of returning to the clinic was higher in patients that received 4Ms over time, compared to patients that did not receive 4Ms. Results from the Cox Proportional Hazards model demonstrated a risk ratio of 3.91 (p < .001) of returning to the clinic, after adjustment. The results indicate that patients are more likely to seek additional care in the future at the same health system when they receive complete 4Ms care, possibly due to increased satisfaction with care. As patient satisfaction is an indicator of quality care, this finding can further inform and spread the AFHS movement.

Long-term efficacy and safety of perampanel monotherapy in patients with newly diagnosed or currently untreated recurrent focal-onset seizures: Results from the open-label extension phase of FREEDOM (Study 342).

FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12-74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS). In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period. Patients could enter Extension to continue treatment upon the completion of the Core Study. Seizure-freedom rates, time to seizure recurrence or withdrawal since the initiation of maintenance treatment, and safety outcomes were assessed. In FREEDOM, 89 patients who received ≥ 1 perampanel dose were included for safety assessments (Safety Analysis Set), and 73 of them entered the 4-‍‍‍mg/day Maintenance Period (the modified Intent-to-Treat Analysis set) with 21 patients having perampanel up-titrated to 8 mg/day; 46 patients entered Extension with 38 patients completing. Overall, 42/89 (47.2 %) patients had cumulative exposure to perampanel for > 52 weeks. Among patients who entered Extension, 52.2 % (n = 24/46; 95 % confidence interval [CI] 36.9, 67.1) remained seizure free for 52 weeks at perampanel 4 mg/day and 67.4 % (n = 31/46; 95 % CI 52.0, 80.5) at 4-8 mg/day. The cumulative probabilities of seizure recurrence and withdrawal at 4-8 mg/day over 52 weeks were 28.9 % (95 % CI 19.0, 42.4) and 43.8 % (95 % CI 33.4, 55.9), respectively. Treatment-emergent adverse events (TEAEs) occurred in 74/89 (83.1 %) patients, with 9/89 (10.1 %) discontinuing because of TEAEs. Dizziness occurred in 34/89 (38.2 %) patients and was the most common event. Patients with untreated FOS (with or without FBTCS) are able to maintain seizure freedom for up to 52 weeks with perampanel monotherapy at a dose of 4-8 mg/day. The tolerability profile was manageable, and the safety profile was consistent with previous findings.

Effects of early supplemental parenteral nutrition on new-onset infection in adults with acute severe stroke: a single-center retrospective case–control study

BackgroundEarly adequate feeding reduces mortality in patients with acute severe stroke. Supplemental parenteral nutrition (SPN) may address enteral nutrition (EN) deficiency and mitigate the risk of nosocomial infection. The benefit of the EN plus early SPN strategy over the full EN strategy is unknown in acute severe stroke patients.MethodsWe retrospectively enrolled 20 patients with acute severe stroke in the SPN group who received EN plus early SPN (more than 50% of the energy target within 72 h after admission). Forty control patients in the EN group who received full EN were matched by age, sex and lesion site. The time to new-onset pneumonia or nosocomial infections was analyzed by Student’s t test and the Breslow generalized Wilcoxon test.ResultsThe baseline characteristics did not differ significantly between the SPN group and the EN group, except for higher serum leukocyte counts, neutrophil counts, and neutrophil-to-lymphocyte ratios in the SPN group (P < 0.05). Compared with that in the EN group, the time to new-onset pneumonia was significantly delayed in the SPN group (7.6 days vs. 5.2 days; mean difference, 2.5 days; 95% CI, 0.65 to 4.31; P = 0.009), as was the time to new-onset nosocomial infections (7.1 days vs. 4.8 days; mean difference, 2.3 days; 95% CI, 0.46 to 4.07; P = 0.015). Kaplan–Meier analysis revealed similar cumulative probabilities of new-onset pneumonia and new-onset nosocomial infections in the two groups (P > 0.05). The rates of digestive intolerance events were similar between the two groups (40% in the SPN group vs. 52.5% in the EN group, P = 0.361).ConclusionsIn patients with acute severe stroke, the application of EN plus early SPN could delay the onset of pneumonia and nosocomial infections especially in the early phase.

EM Algorithm in the Slash 2S-Lindley Distribution with Applications

In this work, we present a new distribution, which is a slash extension of the distribution of the sum of two independent Lindley random variables. This new distribution is developed using the slash methodology, resulting in a distribution with more flexible kurtosis, i.e., the ability to model atypical data. We study the density function of the new model and some of its properties, such as the cumulative distribution function, moments, and its asymmetry and kurtosis coefficients. The parameters are estimated by the maximum likelihood method with the EM algorithm. Finally, we apply the proposed model to two real datasets with high kurtosis, showing that it provides a better fit than two distributions known in the literature.

Improved Outcomes and Resource Use With Normothermic Machine Perfusion in Liver Transplantation

Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. DBD and DCD livers preserved on NMP or SCS. The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) (P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Reduced SARS-CoV-2 Infection Rates in Lab Workers Conducting Nucleic Acid Testing: Controlling for the Healthy Worker Effect

BackgroundDuring the COVID-19 outbreak in December 2022 in China, some laboratory workers in SARS-CoV-2 nucleic acid testing (NAT) laboratories remained uninfected.ObjectivesTo evaluate if the incidence of SARS-CoV-2 infection was reduced in laboratory workers who performed SARS-CoV-2 NAT, and whether this reduction resulted from the healthy worker effect.MethodsThis retrospective cohort study included 423 laboratory workers from 14 SARS-CoV-2 NAT laboratories in Xiamen, China. The incidence of SARS-CoV-2 infection among laboratory workers was analysed based on whether and how long they were engaged in NAT. The healthy worker effect among the laboratory workers engaged in NAT was examined.ResultsThe incidence of SARS-CoV-2 infection was lower in workers engaged in SARS-CoV-2 NAT, with a gradual reduction observed as the cumulative time of SARS-CoV-2 NAT increased. A healthy worker effect was observed and eliminated after matching and stratification based on gender, age, education level, and vaccination. Workers who had ever participated in SARS-CoV-2 NAT had a lower cumulative probability of SARS-CoV-2 infection and a longer duration from vaccination to SARS-CoV-2 infection, and this trend was found to be more prominent with a longer cumulative time to SARS-CoV-2 NAT.ConclusionsA reduction in SARS-CoV-2 infections was observed among laboratory workers conducting SARS-CoV-2 NAT after controlling for the healthy worker effect. This finding has broader implications for understanding the role of natural immunity and its interaction with vaccine immunity in defending against SARS-CoV-2 infection.

Significance of Morphology in Characterizing Human Health Risk from di(2-ethylhexyl) Phthalate in Polyvinyl Chloride Microplastics in Groundwater

In this study, a human health risk assessment was performed on the ingestion route of groundwater containing polyvinyl chloride (PVC) microplastics (MPs), and the carcinogenic and non-carcinogenic risks of di(2-ethylhexyl) phthalate (DEHP), a representative additive, were determined. In particular, the impact of volume diversity according to the shape (morphology) of PVC MP (fragment, fiber, film) on the risk characterization was intensively explored. Firstly, a continuous particle size distribution following a power function was derived using the abundance ratio of PVC MPs by size in the investigated groundwater, and human health risk assessment for DEHP in the PVC MPs was performed through the volume distribution according to the shape of MPs. DEHP human health risk assessment showed an excess cancer risk (ECR) of below 10−6 for a 95% cumulative probability for all MP shapes, but the values varied depending on the shape. Sensitivity analysis showed that the parameter that most affected human health risk was MP volume, second to concentration, which is dependent on MP shape. Therefore, it is necessary to consider the variety of MP shapes during human health risk assessment, and it can be achieved through probabilistic risk assessment utilizing the probability distribution for size and shape of MPs.

High-energy Neutrino Source Cross-correlations with Nearest-neighbor Distributions

The astrophysical origins of the majority of the IceCube neutrinos remain unknown. Effectively characterizing the spatial distribution of the neutrino samples and associating the events with astrophysical source catalogs can be challenging given the large atmospheric neutrino background and underlying non-Gaussian spatial features in the neutrino and source samples. In this paper, we investigate a framework for identifying and statistically evaluating the cross-correlations between IceCube data and an astrophysical source catalog based on the k-nearest-neighbor cumulative distribution functions (kNN-CDFs). We propose a maximum likelihood estimation procedure for inferring the true proportions of astrophysical neutrinos in the point-source data. We conduct a statistical power analysis of an associated likelihood ratio test with estimations of its sensitivity and discovery potential with synthetic neutrino data samples and a WISE–2MASS galaxy sample. We apply the method to IceCube’s public ten-year point-source data and find no statistically significant evidence for spatial cross-correlations with the selected galaxy sample. We discuss possible extensions to the current method and explore the method’s potential to identify the cross-correlation signals in data sets with different sample sizes.

Review of the Simulators Used in Pharmacology Education and Statistical Models When Creating the Simulators

Animal experiments have long been used as an educational tool in pharmacological education; however, from the perspective of animal welfare, it is necessary to decrease the number of animals used. ingAlthough using of simulators is effective, the development of these simulators is necessary when there is no existing simulator for animal experiments. In this review, we describe free, downloadable, and commercial simulators that are currently used in pharmacological education. Furthermore, we introduce two strategies to create simulators of animal experiments: (1) bioassay, and (2) experiments that measure the reaction time. We also describe five sigmoid curves (logistic curve, cumulative distribution function [CDF] of normal distribution, Gompertz curve, von Bertalanffy curve, and CDF of Weibull curve) to fit the results and their inverse functions. Using this strategy, it is possible to create a simulator that calculates the reaction time following drug administration. Moreover, we introduce a statistical model for local anesthetic agents using hierarchical Bayesian modeling. Considering the correlation among estimated parameters, we suggest it is possible to create simulators that give results more similar to those of animal experiments. The pharmacological education will be possible by these simulators at educational institutions where animal experiments are difficult due to various restrictions. It is expected that the number of simulator-based education programs will increase in the future.

Uptake of Recommended Vaccines During Pregnancy Among Publicly and Privately Insured People in the United States, December 2020-September 2022.

Objectives. To estimate maternal COVID-19, influenza, and pertussis vaccine uptake during pregnancy by insurance type and identify factors characterizing those vaccinated and unvaccinated. Methods. We conducted a US cohort study of pregnant individuals (for pregnancies ending December 11, 2020-September 30, 2022) using insurance claims data. We calculated vaccination probability using Kaplan-Meier methods and identified factors associated with vaccination through binomial regression with inverse probability weights. Results. Among 695 887 pregnant individuals (median age = 32 years for privately and 27 years for publicly insured), the cumulative probability of COVID-19 vaccination was 43.0% (privately insured) and 11.8% (publicly insured). We observed marked disparities between influenza (33.2% vs 14.2%) and pertussis (70.3% vs 42.8%) vaccination. Only 6.8% (privately insured) and 1.1% (publicly insured) received all 3 vaccines. COVID-19 and influenza vaccination odds were lower among drug and tobacco users. People with high-risk medical conditions, particularly the publicly insured, commonly were vaccinated. Conclusions. Marked vaccine uptake disparities exist between privately and publicly insured pregnant people. Understanding structural barriers, particularly for Medicaid enrollees, is critical to improving maternal vaccine access. (Am J Public Health. Published online ahead of print January 23, 2025:e1-e10. https://doi.org/10.2105/AJPH.2024.307899).

Baseline Fasting Glucose Level, Age, Sex, and Body Mass Index and the Development of Diabetes in US Adults

Understanding the interplay between diabetes risk factors and diabetes development is important to develop individual, practice, and population-level prevention strategies. To evaluate the progression from normal and impaired fasting glucose levels to diabetes among adults. This retrospective community-based cohort study used data from the Rochester Epidemiology Project, in Olmsted County, Minnesota, on 44 992 individuals with at least 2 fasting plasma glucose (FPG) measurements from January 1, 2005, to December 31, 2017. People who met criteria for diabetes on or before their first FPG measurement were excluded. Data were electronically retrieved in December 2019 with analyses finalized in November 2024. The exposure was baseline FPG level, with covariates including the following measures that are consistently recorded in the electronic health record: body mass index (BMI), age, and sex. The cumulative probability of freedom from diabetes was estimated and presented graphically using a Kaplan-Meier curve. Multivariable Cox proportional hazards regression modeling was used to estimate the partial hazard ratios (HRs) for variables of interest. Diabetes was defined as an FPG level greater than 125 mg/dL. A total of 44 992 individuals (mean [SD] age at baseline, 43.7 [11.8] years; 26 025 women [57.8%]) were included. The baseline mean (SD) BMI was 28.9 (6.6). Over a median follow-up of 6.8 years (IQR, 3.6-9.7 years), 3879 individuals (8.6%) developed diabetes. The Kaplan-Meier 10-year cumulative risk of incident diabetes was 12.8% (95% CI, 12.4%-13.2%). All initial FPG levels outside a range of 80 to 94 mg/dL were associated with increased risk for diabetes (ie, FPG <70 mg/dL: HR, 3.49 [95% CI, 2.19-5.57]; FPG 120-125 mg/dL: HR, 12.47 [10.84-14.34]). Other independent risk factors were male sex (HR, 1.31 [95% CI, 1.22-1.40]), older age (≥60 years: HR, 1.97 [95% CI, 1.71-2.28]), and any abnormal category of BMI, including underweight (BMI <18.5: HR, 2.42 [95% CI, 1.77-3.29]; BMI ≥40: HR, 4.03 [95% CI, 3.56-4.56]). There was a significant additive association of variables, particularly FPG level and BMI. For instance, a woman aged 55 to 59 years with a BMI of 18.5 to 24.9 and an FPG level of 95 to 99 mg/dL had an estimated 10-year diabetes risk of 7.0%. However, an almost doubling of risk to 13.0% was observed if the BMI was 30.0 to 34.9, and risk more than doubled again to 28.0% if FPG level also increased to 105 to 109 mg/dL. A nomogram was generated to facilitate individual classification into one of four 10-year risk categories. This retrospective cohort study of 44 992 individuals suggests that FPG level, age, BMI, and male sex were all associated with development of diabetes, with significant interaction between these variables. These data contribute to understanding the clinical course of diabetes and highlight the substantial individual variation in diabetes risk according to commonly measured clinical variables. The findings facilitate lifestyle and pharmacologic interventions to treat those at highest risk of diabetes to reduce future morbidity and mortality. Further work is needed to validate this risk categorization tool for different populations.