Survival Function Research Articles

Heterogeneous Mediation Analysis for Cox Proportional Hazards Model With Multiple Mediators.

This study proposes a heterogeneous mediation analysis for survival data that accommodates multiple mediators and sparsity of the predictors. We introduce a joint modeling approach that links the mediation regression and proportional hazards models through Bayesian additive regression trees with shared typologies. The shared tree component is motivated by the fact that confounders and effect modifiers on the causal pathways linked by different mediators often overlap. A sparsity-inducing prior is incorporated to capture the most relevant confounders and effect modifiers on different causal pathways. The individual-specific interventional direct and indirect effects are derived on the scale of the logarithm of hazards and survival function. A Bayesian approach with an efficient Markov chain Monte Carlo algorithm is developed to estimate the conditional interventional effects through the Monte Carlo implementation of the mediation formula. Simulation studies are conducted to verify the empirical performance of the proposed method. An application to the ACTG175 study further demonstrates the method's utility in causal discovery and heterogeneity quantification.

Prosthesis-patient mismatch is associated with long-term mortality following surgical aortic valve replacement

Abstract Background Prosthesis-patient mismatch (PPM) refers to a situation where the indexed effective orifice area (iEOA) of an implanted prosthetic valve is too small relative to the patient's body size, resulting in hemodynamic compromise. Studies examining the long-term consequences of PPM after surgical aortic valve replacement (SAVR) have yielded conflicting results. Purpose To evaluate the impact of PPM on long-term outcomes in patients undergoing primary isolated SAVR. Methods All patients who underwent isolated first-time SAVR from 1990-2014 were included in this observational, single-center study. PPM was defined as a predicted iEOA <0.85 cm2/m2 and severe PPM was defined as an iEOA <0.65 cm2/m2. Patient demographics, surgical details, and in-hospital outcomes were prospectively collected in our institutional database. Cases were linked to provincial administrative databases at an independent, non-profit research institute whose legal status allows it to collect and analyze health care and demographic data. The primary outcome of interest was all-cause mortality. Secondary outcomes were aortic valve reoperation (surgical or transcatheter) and post-operative hospitalization for heart failure. Multivariable Cox regression analysis identified risk factors for long-term mortality. Kaplan-Meier curves were generated for long-term survival and cumulative incidence functions for aortic valve reoperation and heart failure hospitalization. Results A total of 1,798 patients were included (no PPM: 770 [43%]; moderate PPM: 943 [52%]; and severe PPM: 85 [5%]). Mean age was 64±13 years, and 750 (42%) were female. 451 (25%) patients received a mechanical valve, and 1347 (75%) received a stented bioprosthetic valve. Concomitant aortic root enlargement was performed in 492 (27%) patients. At 20 years, survival was 47.8% (95% CI: 43.2%–52.2%) in the "no PPM group" compared with 29.5% (95% CI: 25.6%–33.5%) and 24.7% (95% CI: 12.7%–38.8%) in the moderate and severe PPM groups, respectively (p<0.001) (Figure 1). On multivariable analysis, iEOA was independently associated with long-term mortality (HR 0.95 per 0.10 increase in iEOA, 95% CI [0.91–0.98]; p=0.007). In a pre-specified subgroup analysis, iEOA was found to be associated with late mortality in patients younger than 65 years (p<0.001) but not in patients 65 years and older (p=0.23). Readmission for heart failure was more frequent among patients who had PPM than those who did not (Figure 2). There was no difference in aortic valve reintervention in patients with or without PPM (p=0.654). Conclusions Prosthesis-patient mismatch is common after SAVR and is associated with late mortality and hospitalization for heart failure. The deleterious impact of PPM on survival appears more pronounced in young patients. These findings may have important implications for the lifetime management of patients with aortic valve disease.Survival post SAVRHeart failure hospitalization post SAVR

Cardiovascular disease history as a predictor for adverse outcomes in frail older adults admitted to acute geriatric settings: 12-month outcomes from an Australian frailty registry

Abstract Introduction Frailty is common in older adults with cardiovascular disease (CVD), with prevalence between 25-62% (1). The incidence of CVD increases with age, yet the outcomes of frail older adults with a history of CVD who present to acute geriatric settings, is not well understood. Purpose To report the association of CVD and rehospitalisation and/or mortality at 12 months in a cohort of frail older adults enrolled in an Australian frailty registry. Methods A convenience sample of participants enrolled in the frailty registry, with 12-month follow-up completed. The frailty registry is a prospective cohort study of adults admitted to the rehabilitation and aged care departments at two Australian hospitals. Frailty was assessed using the Clinical Frailty Scale (CFS), a score of 1-4 is ‘non-frail’, 5-6 is ‘mild-moderately frail’ and 7-9 is ‘severely frail’ (2). For this study, ‘CVD’ was defined as having a history of either heart failure, stroke, or atrial fibrillation. The cumulative incidence of first rehospitalisation and/or death during the first 12 months post discharge was estimated using one minus the Kaplan-Meier estimate of the survival function. Association between CVD (history of CVD, and type of CVD condition) and the composite endpoint were analysed. Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox models incorporating variables of interest and potential confounders. Results A total of 592 participants were included, median age was 82 years, 59% (n= 349) were female. The majority were frail with 50% (n= 295) classified as mild-moderately frail and 21% (n= 123) classified as severely frail. Almost half (45%, n= 265) had a history of CVD. The incidence of frailty (CFS score ≥5, mild-severely frail) was higher in those with CVD compared to those without CVD (76% vs 66%). A history of CVD was significantly associated with higher rate of first readmission or death within 12 months, compared to no history of CVD (p=0.017) (Figure 1). Of the three CVD conditions, heart failure was the only independent predictor of the composite endpoint (HR 1.60 [CI 1.14 -2.24], p=0.007). A CFS score of mild-moderately frail (HR 1.51 [CI 1.18 - 1.93, p=0.001) and severely frail were also independent predictors of the composite endpoint (HR 1.83 [CI 1.35- 2.48], p=<0.001) (Table 1). Conclusions A history of CVD has a significant impact on adverse outcomes in frail older adults admitted to acute geriatric settings. Frailty according to the CFS was independently predictive of rehospitalisation and mortality in this cohort. Heart failure was the only independent predictor of the composite endpoint. These findings underscore the importance of identifying and addressing CVD and in the context of frailty, emphasising the need for targeted interventions to improve outcomes in this vulnerable population.Figure 1.Table 1.

Blood pressure and cardiovascular risk in relation to birth weight and urinary sodium: an individual-participant meta-analysis of European family-based population studies

Abstract Background While the relation of salt intake with blood pressure (BP) is linear, it is U-shaped for mortality and cardiovascular disease (CVD). Purpose This individual-participant meta-analysis explored whether the relation of hypertension, death or CVD with 24 h urinary sodium excretion (UVNA) or sodium-to-potassium (UNAK) ratio was modified by birth weight. Methods Families were randomly enrolled in the Flemish Study on Genes, Environment and Health Outcomes (1985-2004) and the European Project on Genes in Hypertension (1999-2001). Categories of birth weight, UVNA and UNAK (≤2500, >2500-4000, >4000 g; <2.3, 2.3-4.6 and >4.6 g; and <1, 1-2 , >2, respectively) were coded using deviation-from-mean coding and analyzed by Kaplan-Meier survival functions and linear and Cox regression. Results The study population was subdivided into the Outcome (n=1945), Hypertension (n=1460) and BP cohorts (n=1039) to analyze the incidence of mortality and cardiovascular endpoints, hypertension and BP changes as function of UVNA changes. The prevalence of low/medium/high birth weight in the Outcome Cohort was 5.8/84.5/9.7%. Over 16.7 years (median), rates were 4.9%, 8.0% and 27.1% for mortality, CVD and hypertension, respectively, but were not associated with birth weight. Multivariable-adjusted hazard ratios were not significant for any endpoint in any of the BW, UVNA and UNAK strata. Adult body weight tracked with birth weight (P<0.0001). The partial r in the low birth weight group associating changes from baseline to follow-up in UVNA and systolic BP was 0.68 (P=0.023), but not significant in other birth weight groups. Conclusion This study did not substantiate its prior hypothesis, but showed tracking of adult with birth weight and suggest that low birth weight increases salt sensitivity.Figure 1Figure 2

A New Marshall-Olkin Generalized-k Family of Distributions with Applications

Abstract In this article, we describe a new Marshall-Olkin family of distributions based on the Marshall-Olkin family of distributions by employing a different generator. We have derived several statistical properties of the new Marshall-Olkin family, including survival function, hazard rate function, quantile function, moments, and linear representation. We have taken the Weibull distribution as a baseline distribution and found that the new Marshall-Olkin Weibull distribution exhibits a variety of shapes for its hazard rates and densities. We have tested the performance of various estimation methods for the new Marshall-Olkin family of distributions, including eight different estimation methods. Additionally, we conducted extensive simulations to assess the robustness of the estimation methods across various scenarios and determine which methods are most effective for varying sample sizes. To further validate the new Marshall-Olkin Weibull distribution, we have used two different data sets to compare the fitted new Marshall-Olkin Weibull distribution with the well-known comparative models. By testing the performance of different estimation methods and using multiple data sets, we can demonstrate the versatility and usefulness of the new Marshall-Olkin family of distributions for modeling a wide range of phenomena.

Likelihood-Based Inference of Log-Logistic Accelerated Hazards Regression Models for Cross Hazards Data

ABSTRACT The proportional hazards model and accelerated failure time model are two important classes for analyzing survival data. However, the two models cannot capture time-scaled effects such as crossing hazard or the gradual effect of treatment over time. For the purpose of this detection, accelerated hazards model has been studied. In this paper, we propose the use of log-logistic distribution for the baseline hazard function of the accelerated hazards model which allows for time-dependent group effect. In particular, the log-logistic distribution gives various forms (e.g. non-monotone) of hazard function and also an easy implementation for likelihood-based model fitting due to an explicit form of hazard and survival functions. The likelihood-based estimation procedures of the accelerated hazards models are derived. Our method is demonstrated with two practical data sets, via the procedures of systematic model checking.

Two-stage pseudo maximum likelihood estimation of semiparametric copula-based regression models for semi-competing risks data.

We propose a two-stage estimation procedure for a copula-based model with semi-competing risks data, where the non-terminal event is subject to dependent censoring by the terminal event, and both events are subject to independent censoring. With a copula-based model, the marginal survival functions of individual event times are specified by semiparametric transformation models, and the dependence between the bivariate event times is specified by a parametric copula function. For the estimation procedure, in the first stage, the parameters associated with the marginal of the terminal event are estimated using only the corresponding observed outcomes, and in the second stage, the marginal parameters for the non-terminal event time and the copula parameter are estimated together via maximizing a pseudo-likelihood function based on the joint distribution of the bivariate event times. We derived the asymptotic properties of the proposed estimator and provided an analytic variance estimator for inference. Through simulation studies, we showed that our approach leads to consistent estimates with less computational cost and more robustness than the one-stage procedure developed in Chen YH (Lifetime Data Anal 18:36-57, 2012), where all parameters were estimated simultaneously. In addition, our approach demonstrates more desirable finite-sample performances over another existing two-stage estimation method proposed in Zhu H et al., (Commu Statistics-Theory Methods 51(22):7830-7845, 2021) . An R package PMLE4SCR is developed to implement our proposed method.

Time to recovery from necrotizing enterocolitis and its predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar, Ethiopia: A retrospective follow up study, 2022.

Necrotizing enterocolitis is one of the most common, life-threatening, gastrointestinal disorders in neonates. The recovery time for neonates with NEC varies depending on disease severity, prompt diagnosis, and effective treatment. Therefore, this study was intended to assess the time to recover from necrotizing enterocolitis and its' predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar City, Ethiopia. An institution-based retrospective follow-up study design was employed. A sample of 361 medical records of neonates with necrotizing enterocolitis was selected using systematic random sampling. Diagnosis of NEC in this study required clinical, laboratory and radiographic findings. The survival function was described using Kaplan Meier survival curve and log-rank test. Bivariate and multivariate Cox-proportional hazard (Cox-PH) regression models were used for analysis. The median recovery time from necrotizing enterocolitis for neonates in the neonatal intensive care unit was 12 days. The multivariable Cox-PH model showed that neonates classified as Stage III NEC (AHR: 0.42, 95% CI = 0.23-0.77) and those exposed to perinatal asphyxia (AHR: 0.51, 95% CI: 0.35-0.74) had a negative impact on NEC recovery time. However, neonates with a birth weight of 1500-2499gm (AHR: 1.65, 95% CI: 1.05-2.58) and a platelet count greater than 150,000 (AHR: 1.75, 95% CI: 1.24-2.48) had a positive effect on NEC recovery time. The recovery time for neonates in the neonatal intensive care unit with necrotizing enterocolitis was longer. Comorbidities and advanced stage of NEC were associated with prolonged recovery time from NEC. However, neonates with better platelet count and birth weight greater than 1500mg had shorter recovery time from NEC.

Iodine Assessment of Carbon Dioxide Angiography in Iliac Branched Repair.

The objective of this study was to investigate whether the use of carbon dioxide (CO2) angiography decreases the intraoperative use of iodine contrast medium (ICM), thereby decreasing the risk of developing postoperative renal damage in patients undergoing iliac branch device (IBD) implantation. Patients undergoing IBD implantation at a single tertiary center between May 2013 and August 2019 were screened for inclusion in the study. A cohort of patients in whom an intraoperative imaging protocol using predominantly CO2 was compared with a control group in whom ICM was used (CO2 and ICM groups). Fusion imaging was used in both groups. Retrospective review of the medical charts and all imaging was performed. Variables were expressed as median with interquartile range (IQR) or absolute number and percentage. Wilcoxon-Mann-Whitney and χ2 tests were used to compare continuous and categorical variables, respectively. P values of <0 .05 were considered statistically significant. Twenty-three patients were included in the CO2 group and 21 in the ICM group without significant differences in patient characteristics between the groups. Intraoperative iodine exposure was lower in the CO2 group than in the ICM group (8.2 g [IQR, 7.1-10.9 g) vs 15.8 g (IQR 7.6-21 g); P = 0.015, respectively). There were no differences in technical success, clinical success, fluoroscopy time, and dose-area product in the 2 groups. There were no adverse events that could be related to the intraoperative use of CO2. There was no difference in postoperative survival nor renal function assessment between the groups despite the higher number of accessory renal arteries embolized in the CO2 group (P = 0.221). Reduction of intraoperative ICM exposure during IBD implantation is feasible through the predominant use of CO2 automated angiography. This can be done safely without affecting the technical success or radiation exposure. The immediate postoperative renal damage was low when a modern intraoperative imaging protocol with ICM was used and was not significantly reduced by the use of CO2. Further and larger studies are needed to investigate the long-term effects. This study aimed to investigate how to minimize intraoperative risk during iliac branched repair exploring the intraoperative use of automated carbon dioxide angiography in order to decrease the use of contrast media protecting renal function and thereby potentially impacting long-term survival.

Hidden in plain text: Uncovering hidden heterogeneity and social stratification in Ireland AD 1150-1800.

Between the Irish late medieval (AD 1150-c.1550) (LMP) and post-medieval (AD c.1550-1800) (PMP) periods, colonial practices changed land ownership. Contextualizing these periods within a biocultural political economy framework supports increasing social inequality in the PMP, which we expect to be reflected in different skeletal markers of longevity and stress. Therefore, we hypothesized that widespread exposure to stressors and resource deprivation contributed to lower longevity in the PMP compared to the LMP, and that there would be greater variation between sites in the frequency of linear enamel hypoplasias (LEH) in the PMP. We estimated age and counted matched pairs of LEH on 526 adult skeletons from the Irish counties of Dublin, Kildare, Louth, and Meath. Age-at-death was compared through Kaplan-Meier survival functions and non-parametric tests. Linear enamel hypoplasias prevalences were analyzed with Mann-Whitney U tests and Generalized Linear Models. Age-at-death distribution changed between the LMP and PMP for males, with males experiencing an increase in median-age-at-death. The same was untrue for females, who show no changes in median age-at-death. Analysis of LEH frequency per individual showed that variation between sites was significant in the post-medieval period but not in the late medieval period. These results suggest that social organization contributed to embodied health experiences that varied across time periods. Specifically, populations from the PMP appear to have embodied greater social inequality in their more varied susceptibility to stress. Our work demonstrates the strength of pairing historical texts with the analysis of skeletal remains to evaluate the impact of social structures on biological frailty.

A Study in Pituitary Neuroendocrine Tumors (PitNETs): Real-Life Data Amid Baseline and Serial CT Scans.

We aimed to evaluate CT-related PIs diameters following 3 aspects: a cross-sectional analysis based on the age' groups at first PI diagnosis and on the gender distribution and a longitudinal analysis in PIs with <0.5 cm versus ≥0.5 cm as the largest diameter at baseline. A retrospective, real-life, multi-centric study in adults with NF micro-PIs was performed. 208 subjects (92.79% females) were included (average age 43.18 ± 12.58 y). The mean largest diameter (between transversal and longitudinal diameters) was 0.55 ± 0.16cm, and 44.71% of the PIs were located on the right part of the pituitary gland. The patients were divided into 10 age-groups (21 to 70 y), and no difference was observed between the mean largest diameters of these groups (p = 0.693). Females and males had a similar age at PIs diagnosis (p = 0.353), transverse diameter (p = 0.910), longitudinal diameter (p = 0.229), and PI location (p = 0.368). Serial CT scans (2 to 4 per patient) included a median (Q1-Q3) of 20 (12-36) months for the second CT scan, 58 (36-84) for the third CT scan, 78 (53-118) for the fourth CT scan, and a total follow-up between baseline and last CT scan of 40 (13-72) months. The initial largest diameter correlated with the diameter change between the baseline and the last CT (r = -0.575, p = 0.000). The largest PI diameter was similar between each serial CT scan (p = 0.840). According to the cut-off value of 0.5 cm diameter (for initial largest tumor diameter), group A (N = 78, 37.50%, <0.5 cm) and group B (N = 130, 62. 50%; ≥0.5 cm) had similar age at baseline (43.83 ± 12.72 versus 42.79 ± 12.54 y, p = 0.565) and PIs locations (right, left, median). The largest PI diameter remained smaller in group A versus B amid the second CT scan (p = 0.000) and the last CT scan (p = 0.009). The largest diameter change from the first to the last CT scan showed an increase in group A (median of +0.10 cm, p = 0.000) and a decrease in group B (median of -0.01 cm, p = 0.002); this diameter change was different in group A versus B (p = 0.000). The cumulative probability of tumor-growth-free survival showed different survival functions (log rank p = 0.000): group A exhibited a more gradual decrease versus B; at 60 months, the cumulative probability was 0.32 ± 0.08 for group A versus 0.75 ± 0.07 for B. During follow-up, all PIs remained NF, and no hypopituitarism was noted (as limits, we mention that dynamic hypopituitarism testing was selectively performed). NF micro-PIs in adults showed a similar age and sex distribution. During follow-up, PIs with a largest diameter < 0.5 cm increased after a median of 40 months but remained <1 cm, while in PIs with ≥0.5 cm, the largest diameter decreased. This highlights a lower predictability in tumor behavior than expected, particularly in larger micro-PIs that, overall, remained without relevant clinical implications after surveillance.

Effectiveness of Adjunctive Drug Therapy to Endoscopic Stenting in Liver Cirrhosis Complicated by Refractory Variceal Bleeding

AIM OF THE STUDY. Comparative clinical analysis of the efficacy of terlipressin and octreotide as additional drug therapy to mechanical hemostasis with nitinol stent in patients with liver cirrhosis complicated by bleeding from esophageal varices refractory to endoscopic treatment.MATERIAL AND METHODS. Thirty-one patients with liver cirrhosis complicated by esophageal variceal bleeding refractory to endoscopic treatment , in whose complex treatment program, as a first-line life­saving measure, hemostasis with a self-expanding hemostasis was performed nitinol stent were randomly assigned to two groups. In group A, 20 patients were treated with terlipressin as an adjuvant to mechanical hemostasis, and in group B, 11 patients were treated with octreotide. Unpaired Student’s t-test was used for statistical analysis of the results. Graphs for assessing the survival function of patients for 8 weeks after the end of treatment were constructed using the Kaplan-Meier method.RESULTS. In the acute observation period terlipressin and octreotide were equally effective in treating refractory variceal bleeding. In the subacute observation period, the administration of octreotide was generally accompanied by a greater number of side effects (54.5%) than terlipressin (30.0%) (p=0.453). In the remote observation period, 8-week survival in the group of patients receiving terlipressin was higher than in the group of patients receiving octreotide.CONCLUSION. Terlipressin is as effective as octreotide as an adjunct to endoscopic stenting in drug therapy for liver cirrhosis complicated by esophageal variceal bleeding refractory to endoscopic treatment. At the same time, terlipressin has a greater effect than octreotide on reducing 8-week mortality, which approaches statistical significance. In this regard, terlipressin may be the vasoactive drug of choice in acute refractory variceal bleeding.

A New Lifetime Distribution and its Application to Cancer Data

Introduction: Recently, researchers have introduced new generated families of univariate lifetime distributions. These new generators are obtained by adding one or more extra shape parameters to the underlying distribution or compounding two distributions to get more flexibility in fitting data in different areas such as medical sciences, environmental sciences, and engineering. The addition of parameter(s) has been proven useful in exploring tail properties and for improving the goodness-of-fit of the family of the proposed distributions. Methods:A new Three-Parameter Weibull-Generalized Gamma distribution which provides more flexibility in modeling lifetime data is developed using a two-component mixture of Weibull distribution (with parameters θ and λ) and Generalised Gamma distribution (with parameters α=4,θ and λ). Some of its mathematical properties such as the density function, cumulative distribution function, survival function, hazard rate function, moment generating function, Renyi entropy and order statistics are obtained. The maximum likelihood estimation method was used in estimating the parameters of the proposed distribution and a simulation study is performed to examine the performance of the maximum likelihood estimators of the parameters. Results: Real life applications of the proposed distribution to two cancer datasets are presented and its fit was compared with the fit attained by some existing lifetime distributions to show how the Three-Parameter Weibull-Generalized Gamma distribution works in practice Conclusion: The results suggest that the proposed model performed better than its competitors and it’s a useful alternative to the existing models.

On The Modeling of Biomedical Data Sets with a New Generalized Exponentiated Exponential Distribution

Introduction: Many experts in the field of distribution theory have focused on extending probability distributions utilizing extended families of continuous distributions to improve the modeling adaptability of the conventional probability distributions. Methods: This research employed a continuous family of probability distributions as introduced in the literature using the T-X methodology. Through this, some of statistical and mathematical properties of the model were derived and studied Results: This study had introduced a brand-new, five-parameter generalized exponentiated exponential distribution, which is a continuous probability distribution. With the aid of the quantile function, moments, moment generating function, survival function, hazard function, mean, and median, among other mathematical and statistical aspects, the new distribution's shape was deduced and researched. It was also possible to derive the probability density function for the minimum and maximum order statistics for this distribution. The method of maximum likelihood estimate was used to produce a conventional estimation of the unknown parameters. A simulation study was carried out to assess the efficiency and consistency of the estimation method used. To evaluate the fit and adaptability of the new model, it was applied to four real-world datasets in the field of medicine. Conclusion: The analysis's findings demonstrated that the new model performs better than its counterparts and offers a better fit than the Topp-Leone exponentiated exponential, Topp-Leone Kumaraswamy exponential, exponentiated exponential, and exponential distributions.

Using non-inferiority test of proportions in design of randomized non-inferiority trials with time-to-event endpoint with a focus on low-event-rate setting.

For cancers with low incidence, low event rates, and a time-to-event endpoint, a randomized non-inferiority trial designed based on the logrank test can require a large sample size with significantly prolonged enrollment duration, making such a non-inferiority trial not feasible. This article evaluates a design based on a non-inferiority test of proportions, compares its required sample size to the non-inferiority logrank test, assesses whether there are scenarios for which a non-inferiority test of proportions can be more efficient, and provides guidelines in usage of a non-inferiority test of proportions. This article describes the sample size calculation for a randomized non-inferiority trial based on a non-inferiority logrank test or a non-inferiority test of proportions. The sample size required by the two design methods are compared for a wide range of scenarios, varying the underlying Weibull survival functions, the non-inferiority margin, and loss to follow-up rate. Our results showed that there are scenarios for which the non-inferiority test of proportions can have significantly reduced sample size. Specifically, the non-inferiority test of proportions can be considered for cancers with more than 80% long-term survival rate. We provide guidance in choice of this design approach based on parameters of the Weibull survival functions, the non-inferiority margin, and loss to follow-up rate. For cancers with low incidence and low event rates, a non-inferiority trial based on the logrank test is not feasible due to its large required sample size and prolonged enrollment duration. The use of a non-inferiority test of proportions can make a randomized non-inferiority Phase III trial feasible.

MODELING THE BENEFITS OF A MARRIAGE REVERSE ANNUITY CONTRACT WITH DEPENDENCY ASSUMPTIONS USING ARCHIMEDEAN COPULA

Social security benefits may not be enough for retirement. Equity release products like marriage reverse annuities can boost retirement income for older couples. Marriage reverse annuity’s contract convert all or part of the real estate value of elderly spouses while they are living (joint life status) or after one partner dies (last survivor status). Since husband and wife face the same death risk, the chance of death between spouses is believed to be dependent for realism. Thus, copula models the future dependency model of a husband and wife. Sklar's theorem states that copulas link bivariate distribution and marginal cumulative functions. One of the most common copulas is Archimedean copula. Clayton, Gumbel, and Frank are Archimedean copula that will be used in this investigation. The Indonesian Mortality Table IV data is used to obtain the marginal distribution of the male and female which will then be used to construct copulas (Clayton, Gumbel, and Frank) that combine two marginal distributions into a joint distribution. The marginal distribution of Indonesian Mortality Table IV is uncertain, hence Canonical Maximum Likelihood parameter estimation is utilized to estimate the parameter of copulas. Multiple-state models depict the marriage reverse annuity model for joint life and last survivor status. The probability structure is based on Sklar's theorem and copula survival function. The contract benefits calculation utilizing copulas (Clayton, Gumbel, and Frank) shows that joint life status benefits are higher than last survivor status. Joint life status uses the dependence assumption with Frank's copula to calculate the smallest annual benefit value of a marriage reverse annuity contract, while last survivor status uses the independence assumption (without copula).

The Two Component Generalized Finite Erlang Mixture and its Properties and Special Cases

This research proposes the construction of a two-component generalized finite Erlang mixture with four parameters. Three distinct cases of this mixture are presented, differing in their mixing weights and corresponding component probability (Erlang) distributions. Special cases of these mixtures, including the one-, two-, and three-parameter finite Erlang mixtures, have also been derived. The statistical properties examined for these mixtures include the distribution function, survival function, hazard function, moment generating function, raw and central moments, mean, variance, coeffcient of skewness, coeffcient of kurtosis, and order statistics. Parameter estimation for the finite Erlang mixtures was conducted using both the method of moments and maximum likelihood estimation. Furthermore, the 4-parameter mixed Erlang distributions were applied to a real dataset on the relief times of patients receiving an analgesic, to evaluate their goodness of fit. The results demonstrate the potential of these mixtures to provide robust modeling for empirical data, suggesting their applicability in various statistical and practical contexts.

Oogenesis and Spermatogenesis of the Triploid Black Tiger Shrimp, Penaeus monodon

Triploidy (3n) induction of Penaeus monodon was performed separately by Australian and Thai groups of researchers 14 years ago, incidentally at the same period. The Australian group employed the chemical induction method, while the Thai group the cold shock one, and both groups obtained 3n P. monodon in their attempts. The success has led to several studies on the physiology of the 3n P. monodon, including growth, survival and reproductive functions. Both groups reported sterility of the 3n shrimp. The Australian group reported defected oogenesis and spermatogenesis of the 3n shrimp examined at subadult stage. Since the evaluation of the reproductive functions should be performed at the adult stage of the animals, we, therefore, performed in-depth studies on oogenesis and spermatogenesis of adult 3n P. monodon induced by cold shock. The studies include gross observation of the ovary, light (LM) and transmission electron (TEM) microscopy and image analysis of sex cells. The ovary of the 3n P. monodon females could not develop to full-maturation and their gonadosomatic index (GSI) was significantly lower than that of the 2n shrimp. Oogenesis of the 3n females proceeded from oogonia to cortical rod oocytes, but with significantly lower percentage than that of the 2n shrimp. The GSI of the 3n males was significantly lower than that of the 2n shrimp. Their spermatogenesis, however, proceeded normally from spermatogonia to spermatozoa, but with low density of spermatozoa in the seminiferous tubule and vas deferens, and none in the terminal ampoule. The average nuclear area of the 3n spermatozoa was significantly lower than that of the 2n shrimp as well. Altogether, these results suggest that 3n P. monodon induced by cold shock had defect in both oogenesis and spermatogenesis, probably more in quantity than in quality. HIGHLIGHTS Oogenesis and spermatogenesis of the triploid black tiger shrimp, monodon, induced by cold shock were studied. The study found abnormalities in the spermatogenesis, but not oogenesis, of the triploid P. monodon induced by cold shock. It may be concluded that triploidy condition of P. monodon induced by cold shock affects meiotic, but not mitotic activity of the sex cells. GRAPHICAL ABSTRACT

Ablation of Type 2 IP3R, a Calcium Channel Located on the Organelle Contact Site, Improves the Repairment of Cell Survival and Endoplasmic Reticulum-Mitochondria Function in Tubular Cells

Ablation of Type 2 IP3R, a Calcium Channel Located on the Organelle Contact Site, Improves the Repairment of Cell Survival and Endoplasmic Reticulum-Mitochondria Function in Tubular Cells

Survival Analysis on Lung Cancer Patients in Damaturu-Nigeria

Cancer is one of the leading causes of death by lung cancer in particular, is the leading cause of cancer death in both men and women, accounting for 23% of all cancer deaths in 2019 according to the Centers for Disease Control and Prevention. One particular problem with lung cancer is that it usually has a poor prognosis. With such a deadly disease, it is crucial to predict the survival likelihood of cancer patients. However, this is not an easy task due to the many factors affecting the disease progression. Survival time has become an essential outcome of clinical trial, which began to emerge among the latter half of the 20th century. A present study was carried out on the survival analysis for patients with lung cancer. The data was obtained from Yobe State Specialist Hospital, Damaturu where each sample was collected from the recipients of the treatment of radical prostatectomy. The Kaplan Meier method was used to obtain and estimate the survival function and median. The log-rank test was used to test the differences in the survival curves. The cox proportional hazard (PH) model provided an effective covariate on the hazard function. As a result of cox PH model, the influence of standard clinical prognostic factors is based on the hazard rate of lung cancer patients. We performed rigorous cross-examination on each feature's relationship and the model for each feature type using data analysis information and survival analysis models. For each feature type, we used one representative survival analysis model from semi-parametric methods (Cox proportional hazards model), one from non-parametric methods (Kaplan-Meier estimator), and one from machine learning approaches (random survival forests). Using the results obtained from these different methods, we identified the best feature types and model combinations to get the top performance for various follow-up periods. The best model is Cox proportional hazards model based on the AIC and log-likelihood functions respectively.