Credible Interval Research Articles

Searches for new physics below twice the electron mass with GERDA

A search for full energy depositions from bosonic keV-scale dark matter candidates of masses between 65 and 1021 keV has been performed with data collected during Phase II of the GERmanium Detector Array (Gerda) experiment. Our analysis includes direct dark matter absorption as well as dark Compton scattering. With a total exposure of 105.5 kg years, no evidence for a signal above the background has been observed. The resulting exclusion limits deduced with either Bayesian or Frequentist statistics are the most stringent direct constraints in the major part of the 140–1021 keV mass range. As an example, at a mass of 150 keV the dimensionless coupling of dark photons and axion-like particles to electrons has been constrained to α′/α<8.7×10-24\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha '/\\alpha <8.7~\ imes 10^{-24}$$\\end{document} and gae<3.3×10-12\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$g_\ extrm{ae}<3.3~\ imes 10^{-12}$$\\end{document} at 90% credible interval (CI), respectively. Additionally, a search for peak-like signals from beyond the Standard Model decays of nucleons and electrons is performed. We find for the inclusive decay of a single neutron in 76\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{76}$$\\end{document}Ge a lower lifetime limit of τn>1.5×1024\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au _\ extrm{n} > 1.5 \ imes 10^{24}$$\\end{document} years and for a proton τp>1.3×1024\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au _\ extrm{p} > 1.3 \ imes 10^{24}$$\\end{document} years at 90% CI. For the electron decay e-→νeγ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$e^\ ext {-} \\rightarrow \ u _\ extrm{e} \\gamma $$\\end{document} a lower limit of τe>5.4×1025\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ au _\ extrm{e} > 5.4\ imes 10^{25}$$\\end{document} years at 90% CI has been determined.

Comparing the efficacy of cipaglucosidase alfa plus miglustat with other enzyme replacement therapies for late-onset Pompe disease: a network meta-analysis utilizing patient-level and aggregate data.

Aim: Late-onset Pompe disease is characterized by progressive loss of muscular and respiratory function. Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Second-generation ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available. Without head-to-head trials comparing aval with cipa+mig, an indirect treatment comparison is informative and timely for understanding potential clinical differentiation. Materials & methods: A systematic literature review was performed to identify relevant studies on cipa+mig and aval. Using patient-level and aggregate published data from randomized controlled trials (RCTs) and phase I/II and open-label extension (OLE) trials, a multi-level network meta-regression was conducted, adjusting for various baseline covariates, including previous ERT duration, to obtain relative effect estimates on 6-minute walk distance (6MWD, meters [m]) and forced vital capacity (FVC, %predicted [pp]). Analyses of two networks were conducted: Network A, including only RCTs, and network B, additionally including single-arm OLE and phase I/II studies. Results: Network B (full evidence analysis) showed that cipa+mig was associated with a relative increase in 6MWD (mean difference 28.93m, 95% credible interval [8.26-50.11m]; Bayesian probability 99.7%) and FVC (2.88pp [1.07-4.71pp]; >99.9%) compared with aval. The comparison between cipa+mig and aval became more favorable for cipa+mig with increasing previous ERT duration for both end points. Analysis of network A showed that cipa+mig was associated with a relative decrease in 6MWD (-10.02m [-23.62 to4.00m]; 91.8%) and FVC (-1.45pp [-3.01 to0.07pp]; 96.8%) compared with aval. Conclusion: Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis.

Sodium-glucose cotransporter 2 inhibitors and renal cancer in the US FDA adverse event reporting system.

Recent evidence suggests an association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and a higher risk of renal cancer. We conducted a pharmacovigilance analysis using the US FDA Adverse Event Reporting System (FAERS) to investigate the disproportionate association between SGLT2 inhibitors and renal cancer. We used AERSMine to mine data from FAERS, covering the period from 2014 Q1 to 2023 Q3. The control group was treated with other glucose-lowering medications (ATC-A10B). Disproportionality analysis results were performed using a proportional reporting ratio (PRR) with a 95% confidence interval (CI) and an information component (IC) with 95% credible interval. Compared to the control group, the SGLT2 inhibitor group had a higher disproportionate renal cancer reporting frequency (0.92 vs 0.27/1000 reports; PRR 3.38; 95% CI 2.68-4.25; p < 0.001) with an IC of 1.36 (0.60-2.06), comprising dapagliflozin (PRR 4.14; 2.95-5.80; p < 0.001), empagliflozin (PRR 2.74; 1.94-3.89; p < 0.001), and canagliflozin (PRR 3.56; 2.48-5.12; p < 0.001). Consistent results were obtained in the diabetes indication with the primary outcomes only for the SGLT2 inhibitors group (not individual molecule). The results of the sensitivity analysis (excluding hypertension indication or antihypertensive drugs, obesity, smoking, alpha-1 blockers, or anti-renal cancer drugs) were highly consistent with the main outcomes, indicating good robustness of the results. The results from 2004 Q1 to 2023 Q3 were similar to those from 2014 Q1 to 2023 Q3, with the exception of empagliflozin. There was a disproportionate association between SGLT2 inhibitors and renal cancer, which supports the current meta-analysis results indicating an increased risk of renal cancer associated with SGLT2 inhibitors.

Association Between Periconceptional Diet Quality and Hypertensive Disorders of Pregnancy: The Japan Environment and Children's Study.

Little is known about the relationship of healthy diets, which are widely recommended to prevent diseases in general populations, with the risk of hypertensive disorders of pregnancy (HDP), particular among non-Western populations with different dietary habits. We aimed to investigate the association between periconceptional diet quality and the risk of HDP among pregnant Japanese women. Dietary intake over 1 year before the first trimester of pregnancy was assessed using a validated, self-administered food frequency questionnaire among 81 113 pregnant Japanese women who participated in a prospective cohort of the Japan Environment and Children's Study. Overall diet quality was assessed by the Balanced Diet Score (BDS) based on adherence to the country-specific dietary guidelines and the Dietary Approaches to Stop Hypertension (DASH) score. Cases of HDP were identified by medical record transcription. The association between diet quality and HDP risk was examined using Bayesian logistic regression models with monotonic effects. We identified 2383 (2.9%) cases of HDP. A higher BDS was associated with a lower risk of HDP. When comparing the highest with the lowest quintile of the BDS, the adjusted odds ratio (aOR) of HDP was 0.83 (95% credible interval [CrI], 0.73-0.94). The DASH score and HDP risk were inversely associated in a monotonic dose-response manner (aOR per 1-quintile increase in the DASH score, 0.92 [95% CrI, 0.89-0.95]). A high-quality diet, which is recommended for disease prevention in general populations, before conception may also reduce the risk of HDP among pregnant Japanese women.

Estimating community-wide indirect effects of influenza vaccination: triangulation using mathematical models and bias analysis.

Understanding whether influenza vaccine promotion strategies produce community-wide indirect effects is important for establishing vaccine coverage targets and optimizing vaccine delivery. Empirical epidemiologic studies and mathematical models have been used to estimate indirect effects of vaccines but rarely for the same estimand in the same dataset. Using these approaches together could be a powerful tool for triangulation in infectious disease epidemiology because each approach is subject to distinct sources of bias. We triangulated evidence about indirect effects from a school-located influenza vaccination program using two approaches: a difference-in-difference (DID) analysis, and an age-structured, deterministic, compartmental model. The estimated indirect effect was substantially lower in the mathematical model than in the DID analysis (2.1% (95% Bayesian credible intervals 0.4 - 4.4%) vs. 22.3% (95% CI 7.6% - 37.1%)). To explore reasons for differing estimates, we used sensitivity analyses and probabilistic bias analyses. When we constrained model parameters such that projections matched the DID analysis, results only aligned with the DID analysis with substantially lower pre-existing immunity among school-age children and older adults. Conversely, DID estimates corrected for potential bias only aligned with mathematical model estimates under differential outcome misclassification. We discuss how triangulation using empirical and mathematical modelling approaches could strengthen future studies.

Is Seeing Believing? A Practitioner's Perspective on High-Dimensional Statistical Inference in Cancer Genomics Studies.

Variable selection methods have been extensively developed for and applied to cancer genomics data to identify important omics features associated with complex disease traits, including cancer outcomes. However, the reliability and reproducibility of the findings are in question if valid inferential procedures are not available to quantify the uncertainty of the findings. In this article, we provide a gentle but systematic review of high-dimensional frequentist and Bayesian inferential tools under sparse models which can yield uncertainty quantification measures, including confidence (or Bayesian credible) intervals, p values and false discovery rates (FDR). Connections in high-dimensional inferences between the two realms have been fully exploited under the "unpenalized loss function + penalty term" formulation for regularization methods and the "likelihood function × shrinkage prior" framework for regularized Bayesian analysis. In particular, we advocate for robust Bayesian variable selection in cancer genomics studies due to its ability to accommodate disease heterogeneity in the form of heavy-tailed errors and structured sparsity while providing valid statistical inference. The numerical results show that robust Bayesian analysis incorporating exact sparsity has yielded not only superior estimation and identification results but also valid Bayesian credible intervals under nominal coverage probabilities compared with alternative methods, especially in the presence of heavy-tailed model errors and outliers.

Reaction Risk to Direct Penicillin Challenges

While direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier. To evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions. Three electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk. Two reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy. Two reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies. The primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions. A total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal. This systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.

Ponsegromab for the Treatment of Cancer Cachexia.

Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels. In this phase 2, randomized, double-blind, 12-week trial, we assigned patients with cancer cachexia and an elevated serum GDF-15 level (≥1500 pg per milliliter) in a 1:1:1:1 ratio to receive ponsegromab at a dose of 100 mg, 200 mg, or 400 mg or to receive placebo, administered subcutaneously every 4 weeks for three doses. The primary end point was the change from baseline in body weight at 12 weeks. Key secondary end points were appetite and cachexia symptoms, digital measures of physical activity, and safety. A total of 187 patients underwent randomization. Of these patients, 40% had non-small-cell lung cancer, 32% had pancreatic cancer, and 29% had colorectal cancer. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg (95% credible interval, 0.37 to 2.25) in the 100-mg group, 1.92 (95% credible interval, 0.92 to 2.97) in the 200-mg group, and 2.81 (95% credible interval, 1.55 to 4.08) in the 400-mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400-mg ponsegromab group relative to placebo. Adverse events of any cause were reported in 70% of the patients in the ponsegromab group and in 80% of those in the placebo group. Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.).

Domestic radon exposure and childhood cancer risk by site and sex in 727 counties in the United States, 2001–2018

BackgroundChildhood cancer has few established risk factors and environmental influences are underexplored. This ecologic study investigated the association between domestic radon exposure and childhood cancer risk in a large sample of United States (U.S.) counties. MethodsMonthly ZIP code-level basement radon estimates from a geographic machine learning model were aggregated annually to counties, analyzed as continuous and dichotomized (cut point: 74 Bq/cubic meter (Bq/m3) or 2.0 picocuries/L (pCi/L)) versions, and lagged by one year. Annual county-level counts of sex- and site-specific (all, leukemia, brain and central nervous system [CNS], and other sites) incident cancer diagnoses among those 0–19 years from 2001 to 2018 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database. Sex- and site-specific counts were modeled as zero-inflated Poisson distributions in a Bayesian spatiotemporal framework and sequentially adjusted for random and fixed confounder effects. ResultsIn 727 counties across 14 states, the average population aged 0–19 years was 41,599 people at baseline. Results from fully adjusted spatiotemporal statistical models indicated 1.05 (95% credible interval, CrI: 1.00, 1.09) times higher relative risks (RRs) of leukemia among both sexes and a RR of 1.06 (95%CrI: 1.00, 1.12) in males from a 50 Bq/m3 (1.35 pCi/L) increase in radon concentration the year prior. For radon exposures ≥74 Bq/m3 (2.00 pCi/L) the year prior, RRs were 1.08 (95%CrI: 1.02, 1.15) for both sexes and 1.12 (95%CrI: 1.04, 1.22) for females. No associations were found with other cancer sites or sexes from prior year radon exposures. ConclusionsCounty-level childhood leukemia risk in both sexes were associated with average radon levels below U.S. Environmental Protection Agency guidelines recommending mitigation (148 Bq/m3 or 4.00 pCi/L). These findings warrant further investigation using population-based and individual-level study designs.

Predictors of spontaneous pregnancy loss in single ventricle physiology

BackgroundPregnant patients with single ventricle (SV) physiology carry a high risk of spontaneous pregnancy loss (SPL), yet the clinical factors contributing to this risk are not well defined.MethodsSingle-centre retrospective study...

Exploring the validity of perceived velocity in lower-limb resistance exercises with a cluster-set configuration

This feasibility study aimed to explore the relationship between mean propulsive velocity (MPV) and a scale of perceived velocity (SPV) in back-squat and deadlift exercises performed with heavy loads during a cluster-sets resistance training (CS-RT). Twelve resistance trained males (24.1[2.94] years; 80.7[9.05] kg; 172[4.7] cm; 19.1[6.17] %BF; 4.71[2.72] years of training experience) participated. Participants visited the laboratory three times, spaced 72 to 96 hours. Load-velocity profiles for each exercise were measured in first visit. During the second and third visits, participants engaged in CS-RT sessions with different intra-set rest period (20 vs 40 seconds, randomly), and consisted of three sets of squat and deadlift exercises at 80%1-RM. Each set concluded upon reaching a 10% velocity loss on two occasions. Bayesian Pearson correlation coefficients (r), 95% credible intervals (95%CrI) and Bayes factors (BF10) were computed to assess the relationship between variables. A low positive correlation was observed between MPV and SPV in deadlift (r=0.368, 95%CrI [0.144, 0.544]), with strong evidence supporting the alternative hypothesis (BF10=20.7). Interestingly, moderate correlation values were observed in the 40-second CS-RT configuration (r=0.47, 95%CrI [0.144, 0.544]) and in the first set of the deadlift (r=0.44, 95%CrI [0.118, 0.654]). Conversely, a negligible Bayesian correlation was identified for squat (r=0.101, 95%CrI [-0.132, 0.319]), with substantial evidence favoring the null hypothesis (BF10=0.208). In conclusion, a positive correlation between MPV and SPV in deadlift during a CS-RT configuration, indicating potential utility for perceived velocity. However, velocity feedback prior SPV use and validity for squatting warrants further investigation. Keywords: Strength training, Perception, Powerlifting, Physical performance, Cluster training.

The impact of demographic change on value set validity and obsolescence.

To investigate the contribution of demographic trends in countries' age and gender composition to value set validity and obsolescence. Time-trade off (TTO) valuation data from 3 EQ-5D-3L value sets of 20 years or older from the United Kingdom, Japan, and the United States were re-analyzed using Bayesian heteroskedastic Tobit models with sex and age group-specific scale parameters. Original value sets were obtained by weighting the original preference structures with the countries' original demographic composition at the time of the data collection. Updated value sets were created using the original preference structure weighted using the countries' most recent demographic composition. The differences between the original and updated value sets were monitored and compared based on 95% credible intervals. The gender and age composition of the investigated countries changed in all 3 countries over time. The modelled health state preferences also depended on the respondents' gender and age. However, the overall impact of this demographic change on the investigated value sets was negligeable in all 3 countries and this finding was robust to accounting for the impact of ethnicity trends in the United States. Value sets may become redundant and obsolete for various reasons, but demographic change was not identified as a contributing factor.

Bayesian spatio-temporal analysis of dengue transmission in Lao PDR

Dengue, a zoonotic viral disease transmitted by Aedes mosquitoes, poses a significant public health concern throughout the Lao People’s Democratic Republic (Lao PDR). This study aimed to describe spatial–temporal patterns and quantify the effects of environmental and climate variables on dengue transmission at the district level. The dengue data from 2015 to 2020 across 148 districts of Lao PDR were obtained from the Lao PDR National Center for Laboratory and Epidemiology (NCLE). The association between monthly dengue occurrences and environmental and climate variations was investigated using a multivariable Zero-inflated Poisson regression model developed in a Bayesian framework. The study analyzed a total of 72,471 dengue cases with an incidence rate of 174 per 100,000 population. Each year, incidence peaked from June to September and a large spike was observed in 2019. The Bayesian spatio-temporal model revealed a 9.1% decrease (95% credible interval [CrI] 8.9%, 9.2%) in dengue incidence for a 0.1 unit increase in monthly normalized difference vegetation index at a 1-month lag and a 5.7% decrease (95% CrI 5.3%, 6.2%) for a 1 cm increase in monthly precipitation at a 6-month lag. Conversely, dengue incidence increased by 43% (95% CrI 41%, 45%) for a 1 °C increase in monthly mean temperature at a 3-month lag. After accounting for covariates, the most significant high-risk spatial clusters were detected in the southern regions of Lao PDR. Probability analysis highlighted elevated trends in 45 districts, emphasizing the importance of targeted control strategies in high-risk areas. This research underscores the impact of climate and environmental factors on dengue transmission, emphasizing the need for proactive public health interventions tailored to specific contexts in Lao PDR.

Real-World Effectiveness of Nirsevimab Against Respiratory Syncytial Virus: A Test-Negative Case-Control Study.

Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings. To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization. This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab-eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative. Nirsevimab immunization, verified through state immunization registries. Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons. The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible. Nirsevimab provided substantial protection against RSV-related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program. Question: What is the effectiveness of nirsevimab against medically attended respiratory syncytial virus (RSV) infections in infants?Findings: 680 RSV test-positive cases and 2,410 RSV test-negative controls were included in this test-negative case-control study. Nirsevimab's effectiveness was 69% against RSV infections, 81% against RSV-associated hospitalization, and 85% against severe RSV disease. Effectiveness against RSV infection declined from 79% at 2 weeks post-immunization to 55% at 14 weeks post-immunization.Meaning: Nirsevimab provides strong protection against a wide range of RSV outcomes, but its effectiveness diminishes over time. These data can be utilized to optimize nirsevimab's implementation and sustain its uptake.

Simultaneous identification of propeller fluctuating forces and unknown parameters based on a Bayesian inversion approach

Accurate quantification of propeller excitation is essential for effective vibro-acoustic analysis and mitigation in marine vessels. This study introduces a Bayesian statistical framework that indirectly reconstruct uncertain forces and system parameters by fusing available prior information, forward modeling and measured vibration responses through Bayesian theorem. The Markov Chain Monte Carlo (MCMC) algorithm, enhanced with Polynomial Chaos Kriging (PC-Kriging) surrogates, is employed to facilitate efficient estimation of likelihood functions and robust uncertainty propagation, providing posterior probabilistic estimates and credible intervals for the identified forces. Additionally, the framework incorporates model class selection based on model evidence to determine the most plausible empirical spectrum model for the propeller broadband thrust spectrum. Specifically, this study proposes and evaluates two candidate empirical spectrum models, the Ornstein–Uhlenbeck (OU)-Gaussian and OU-Weibull models, which effectively capture the frequency–amplitude characteristics of unsteady thrust. Numerical results demonstrate substantial parameter uncertainty reduction, accurate thrust spectrum reconstruction, and effective quantification of statistical properties. Moreover, the OU-Gaussian model is revealed to be more plausible for characterizing the propeller thrust spectrum and response prediction. This framework may offer a practical solution for propeller excitation identification, enabling rapid vibro-acoustic performance assessments of marine vessels.

Bayesian phylogeographic inference of wheat yellow mosaic virus in China and Japan suggests that the virus migration history coincided with historical events

Wheat yellow mosaic virus (WYMV) is one of the most serious viral pathogens causing reductions in wheat yield in East Asia. We investigated the phylodynamics of WYMV by analysing the CP, VPg and P1 genes to understand the origin and dispersal of the virus. A Bayesian phylogenetic analysis revealed that the most recent common WYMV ancestor occurred in approximately 1742 (95% credibility interval, 1439–1916) CE (Common Era), and the evolutionary rates of the VPg, CP and P1 genes were 6.669 × 10−4 (95% credibility interval: 4.575 × 10−4–8.927 × 10−4), 2.468 × 10−4 (95% credibility interval: 1.667 × 10−4–3.338 × 10−4) and 5.765 × 10−5 (95% credibility interval: 3.285 × 10−6–1.252 × 10−4), respectively. Our phylogeographic analysis indicated that the WYMV population may have originated in Henan Province, China, first spreading to Japan in the mid-19th century and stopping after the Japanese surrender in World War II. The second wave spread to Japan from Shandong Province, China, in approximately 1977, a few years after the establishment of diplomatic relations between China and Japan. Before the founding of the People's Republic of China, Henan Province was the emigration centre of WYMV in East Asia, and after the late 20th century, Jiangsu and Shandong Provinces were also the virus emigration centres in East Asia. In addition, there were two migration pathways from Japan to Jiangsu and Shandong Provinces, China, in approximately 1918 and approximately 1999 respectively. Our results suggest that the wide spread of WYMV in East Asia is strongly related to human factors.

A stacked machine learning-based classification model for endometriosis and adenomyosis: a retrospective cohort study utilizing peripheral blood and coagulation markers.

Endometriosis (EMs) and adenomyosis (AD) are common gynecological diseases that impact women's health, and they share symptoms such as dysmenorrhea, chronic pain, and infertility, which adversely affect women's quality of life. Current diagnostic approaches for EMs and AD involve invasive surgical procedures, and thus, methods of noninvasive differentiation between EMs and AD are needed. This retrospective cohort study introduces a novel, noninvasive classification methodology employing a stacked ensemble machine learning (ML) model that utilizes peripheral blood and coagulation markers to distinguish between EMs and AD. The study included a total of 558 patients (329 with EMs and 229 with AD), in whom key hematological and coagulation markers were analyzed to identify distinctive profiles. Feature selection was conducted through ML (logistic regression, support vector machine, and K-nearest neighbors) to determine significant hematological markers. Red cell distribution width, mean corpuscular hemoglobin concentration, activated partial thromboplastin time, international normalized ratio, and antithrombin III were proved to be the key distinguishing indexes for disease differentiation. Among all the ML classification models developed, the stacked ensemble model demonstrated superior performance (area under the curve = 0.803, 95% credibility interval = 0.701-0.904). Our findings demonstrate the effectiveness of the stacked ensemble ML model for classifying EMs and AD. Integrating biomarkers into this multi-algorithm framework offers a novel approach to noninvasive diagnosis. These results advocate for the application of stacked ensemble ML utilizing cost-effective and readily available peripheral blood and coagulation indicators for the early, rapid, and noninvasive differential diagnosis of EMs and AD, offering a potentially transformative approach for clinical decision-making and personalized treatment strategies.

Estimation of the stress–strength reliability for the exponential-Rayleigh distribution

In this current paper, we consider the problem of estimating the stress–strength parameter ψ=P(X<Y). This is done by using Bayesian and non-Bayesian approaches when X and Y are independent random variables from two exponential-Rayleigh distributions with different shape parameters but the same scale parameter. Maximum likelihood and Bayes estimators are used to estimate and construct the asymptotic confidence interval and credible interval of ψ. Finally, an intensive simulation study is performed to compare the proposed methods and analyze a real data set for illustrative purposes.

Analyzing Burr-X competing risk model using adaptive progressive Type-II censored binomial removal data with application to electrodes and electronics

The aim of this paper is to investigate the Burr-X competing risks model in the context of adaptive progressively Type-II censored samples. In this scenario, the removal pattern is assumed to be a random variable that follows the binomial distribution, which is a more realistic assumption compared to assuming a fixed removal pattern. In this study, we explore both classical and Bayesian estimation approaches to estimate the parameters of the Burr-X competing risks model, as well as the reliability parameter and the parameter of the binomial distribution. The interval ranges of different parameters are determined by utilizing the asymptotic normality of the maximum likelihood estimators. Furthermore, the Bayes credible intervals are calculated by sampling from the joint posterior distribution using the Markov Chain Monte Carlo procedure. To assess the efficiency of the acquired estimators, a comprehensive simulation study that considered various types of experimental designs is conducted. Finally, two applications are considered by analyzing data sets of electrodes and electronics.

A two-variant model of SARS-COV-2 transmission: estimating the characteristics of a newly emerging strain

BackgroundThe Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses.MethodsThis paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference.ResultsThe model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15–0.29) and transmission rate of 5.0 (95% CI 2.4–6.6) for the Omicron variant.ConclusionsThe study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses.