Mixed Effects Research Articles

Association of per- and polyfluoroalkyl substances with the antioxidant bilirubin across pregnancy

BackgroundIn mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy. MethodsThe study population included 332 participants in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Serum samples were collected up to two times (early pregnancy: 6–18 gestational weeks; late pregnancy: 21–36 gestational weeks) for the measurement of perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and total bilirubin. We analyzed single PFAS with linear mixed effect regression and a mixture of the four PFAS with quantile g-computation. Models were repeated with a multiplicative interaction term to explore effect modification by study visit. ResultsOverall, PFHxS was positively associated with bilirubin (β = 0.08, 95 % CI = 0.01, 0.15). We also found during late pregnancy, there was a positive association of PFHxS and the PFAS mixture with bilirubin (β = 0.12, 95 % CI = 0.02, 0.22; ψ = 0.19, 95 % CI = 0.03, 0.34, respectively). Finally, study visit modified the PFOA-bilirubin association (interaction p-value = 0.09), which was greater during early pregnancy (β = 0.08, 95 % CI = 0.01, 0.15). ConclusionIn a prospective cohort of pregnant African Americans, an increase in PFOA, PFHxS, and the PFAS mixture was associated with an increase in bilirubin. Our results suggest that, depending on pregnancy stage, prenatal PFAS exposure disrupts the maternal liver antioxidant capacity.

Factors influencing patient experience in hospital wards: a systematic review

BackgroundPatient experience plays an essential role in improving clinical effectiveness and patient safety. It’s important to identify factors influencing patient experience and to improve quality of healthcare.ObjectiveTo identify factors that influence patient experience in hospital wards.MethodsWe conducted a systematic review including six databases; they were PubMed, CINAHL, Embase, PsycInfo, ProQuest, and Cochrane. Studies were included if they met the inclusion criteria. The JBI checklist was used to perform quality appraisal. We used 5 domains of the ecological model to organize and synthesize our findings to comprehensively understand the multi-level factors influencing the issue.ResultA total of 138 studies were included, and 164 factors were identified. These factors were integrated into 6 domains. All domains but one (survey-related factors) could be mapped onto the attributes of the ecological framework: intrapersonal, interpersonal, institutional, community, and public policy level factors. All factors had mixed effect on patient experience. The intrapersonal level refers to individual characteristics of patients. The interpersonal level refers to interactions between patients and healthcare providers, such as the caring time spent by a nurse. The institutional level refers to organizational characteristics, rules and regulations for operations, such as hospital size and accreditation. The community level refers to relationships among organizations, institutions, and informational networks within defined boundaries, such as a hospital located in a larger population area. Public policy level refers to local, state, national, and global laws and policies, including health insurance policies. The sixth domain, survey-related factors, was added to the framework and included factors such as survey response rate and survey response time.ConclusionThe factors influencing patient experience are comprehensive, ranging from intrapersonal to public policy. Providers should adopt a holistic and integrated perspective to assess patient experience and develop context-specific interventions to improve the quality of care.PROSPERO registration number CRD42023401066

Lateral Transport Controls the Tidally Averaged Gravitationally Driven Estuarine Circulation: Tidal Mixing Effects

Abstract In classic models of the tidally averaged gravitationally driven estuarine circulation, denser salty oceanic water moves up the estuary near the bottom, while less dense riverine water flows toward the ocean near the surface. Traditionally, it is assumed that the associated pressure gradient forces and salt advection are balanced by vertical mixing. This study, however, demonstrates that lateral (across the estuary width) transport processes are essential for maintaining the estuarine circulation. This is because for realistic estuarine bathymetry, the depth-integrated salt transport up the estuary is enhanced in the deeper estuary channel. A closed salt budget then requires the lateral transport of this excess salt in the deeper channel toward the estuarine flanks. To understand how such lateral transport affects the estuarine salt and momentum balances, we devise an idealized model with explicit lateral transport focusing on tidally averaged lateral mixing effects. Solutions for the along-estuary velocity and salinity are nondimensionalized to depend only on one single nondimensional parameter, referred to as the Fischer number, which describes the relative importance of lateral to vertical tidal mixing. For relatively strong lateral tidal mixing (greater Fischer number), salinity and velocity variations are predominantly vertical. For relatively weak lateral tidal mixing (smaller Fischer number), salinity and velocity variations are predominantly lateral. Overall, lateral transport greatly affects the estuarine circulation and controls the estuarine salinity intrusion length, which is demonstrated to scale inversely with the Fischer number.

Effects of Chloride, Humidity, and Concrete Mix on the Electrochemical Parameters of Steel Reinforcement Corrosion

Effects of Chloride, Humidity, and Concrete Mix on the Electrochemical Parameters of Steel Reinforcement Corrosion

A simple step to improve fat and energy delivery of human milk delivered via bottle-feeding pump: An experimental study.

Enteral feeding pump systems deliver decreased amounts of macronutrients in human milk to neonates. This study determined the macronutrient loss associated with a bottle-feeding pump system and the effect of manually mixing the human milk during extended feeds. Macronutrient content from samples of donor human milk was analyzed after simulated extended feeds with a bottle-feeding pump system, using a human milk analyzer. Simulations were repeated using manual mixing of the bottle every 30 min during feeding. The percentage of the baseline was calculated, and one-sample t tests and analysis of variance compared the effect of manual mixing and the duration of feeding on macronutrient delivery. The delivery of fat and energy was lower over time, but manual mixing considerably improved retention. The length of feeding impacted fat delivery, with less fat delivered over time (P < 0.001). Manually mixing significantly increased fat delivery (P < 0.001). Similar results were found for energy, with a significant reduction in energy delivery over time (P < 0.001) and significantly more energy delivered with mixing (P < 0.001). Mixing and the duration of feeding had minimal effect on protein or carbohydrate delivery. Bottle-feeding pump systems are associated with a significant reduction in the delivery of fat and energy of donor human milk. The manual mixing of donor human milk during prolonged feeds is a simple way to improve fat and energy delivery to the neonate.

Effect of different Ba/Sr ratios on the properties of borosilicate glasses for application in 3D packaging

Borosilicate glass is a promising material for 3D system integration technology due to its high integration and adjustable CTE (coefficient of thermal expansion). However, the structure and composition of borosilicate glasses result in a relatively high melting point and dielectric loss, which hinders the wide application of such glasses. In this study, we analyze the relationship between different Ba/Sr ratios and the structure and properties of the glass. We determine and further analyze the effect of mixed alkaline earth effect on the proportion of the Qn unit, [BO3], and [SiO4] in the glass structure, and consequently, its influence on the dielectric properties. Alkaline earth metals act as network-modifying ions to reconnect the interrupted network of the glass, stabilizing the glass structure and reducing the polarization loss of the glass. Raman analysis showed that the Raman spectrum shifted towards higher frequencies as the ratio of Al2O3/RO increased, with the Raman bands at 1300 cm-1-1500 cm-1 almost disappearing, while the Raman area at 730 cm-1-830 cm-1 increased. This indicated that the [BO3] units formed a ring structure in the glass, thereby enhancing the compactness of the glass network. The thermal expansion coefficient was 4.09 ppm/K when the Ba/Sr ratio was 1:1, and the dielectric constant and dielectric loss were 4.3 and 1.24×10-3, respectively. Overall, the dielectric properties and thermal expansion coefficients of the glass can be effectively reduced by doping with alkaline-earth metals, making the borosilicate glass more suitable for three-dimensional integrated system packaging.

Optical absorption properties in multi-layer InGaN/GaN core-shell quantum dots: The influences of ternary mixed crystal effect and hydrogen-like impurity

Based on the effective mass approximation and the compact density matrix theory, the electronic states and optical absorption properties of intersubband transitions between the conduction-band energy levels in zinc-blende InGaN/GaN/InGaN/GaN core-shell quantum dots (CSQDs) are investigated by using the finite difference method. The effects of hydrogen-like impurity and In component on the wave functions, transition energies, and optical absorption properties are discussed in detail. The results show that hydrogen-like impurity can cause the peak positions of optical absorption coefficients (OACs) and refractive index changes (RICs) to move to high energy area, and the peak values of OACs rise. Increasing In component of InGaN crystal in the core region of a CSQD has the same effect. But an opposite tendency will be found when increasing In component in the shell-well of a CSQD, i.e. optical absorption peaks move to low energy area and their values decrease. Comparing to the shell-well, the core region has more powerful confinement effect on electrons. So the better absorption properties are more likely to be obtained for this type of multi-layer InGaN/GaN CSQDs when In component in the core is larger than that in the shell-well.

Brief Pain Inventory (BPI) Pain Survey Versus Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs). Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1β) were measured before operation and following surgery in patients with MLa. Pain levels were assessed using the Numerical Rating Scale (NRS) and Brief Pain Inventory (BPI) scale, both preoperatively and postoperatively. Casp1 blood levels showed an increasing trend at postoperative day 1 (POP1) and this increase was almost significant in a linear mixed effect model (LME) analysis (p=0.06). Additionally, Casp1 blood levels were higher in patients with cancer than those with benign disease and correlated with IL-18 blood levels (r=0.24, p=0.007). Furthermore, Casp1 blood levels correlated with BPIsev (severity) score values in MLa patients (r=-0.49, p=0.048). A significant correlation was also observed between Casp1 blood levels and NRS scores in patients with MLa. This is the first report to evaluate two pain surveys (NRS and BPI) in MLa patients in relation to blood levels of Casp1 and eight CYTs. This analysis is important in confirming the significant correlation between NRS and BPI pain scales and Casp1 blood levels. Our study is also the first to demonstrate that adequate postoperative analgesia in patients with MLa provides better functional ability and improved patient satisfaction.

The association between governance mechanisms and engagement in commercialisation and entrepreneurship of Romanian public research institutes

This study investigates the connection between the governance structure of a public research institute (PRI) and its inclination towards entrepreneurship and patenting, in the form of spin-offs and granted patents, in Romania, an emerging economy. Employing a combination of negative binomial and Firth logistic regressions, the research examines the links between the composition of the board of directors (BD) and PRI’s knowledge and technology transfer (KTT) and entrepreneurial efforts over a period of eleven years (2012–2022). The results show that gender diversity in the BD does not impact the establishment of new firms and patenting. Moreover, the likelihood of spin-off creation in female-led PRIs is lower than in male-led ones, while the general director’s gender has minimal impact on the patenting process. On the other hand, BD diversity in terms of external directors, namely the industry representatives, strongly influences the entrepreneurial orientation of the PRI. The same connection is shown with the existence of technology transfer offices. Scientific excellence is slightly complementary with patenting. Finally, geographic location has a weak mixed effect on the creation of spin-offs and patenting. Our paper contributes to the industrial organisational literature, which has not paid enough attention to the role of research institutes in science commercialisation, especially in emerging economies.

Relevance of plasma lenvatinib concentrations and endogenous urinary cytochrome P450 3A activity biomarkers in clinical practice.

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6β-hydroxycortisol, deoxycholic acid, and 1β-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM.

Bubble blasts! An adaptation for buoyancy regulation in shallow foraging gray whales.

Foraging efficiency is key to animal fitness. Consequently, animals evolved a variety of kinematic, morphological, physiological, and behavioral adaptations for efficient locomotion to reduce energy expenditure while moving to find, capture, and consume prey. Often suited to specific habitat and prey types, these adaptations correspond to the terrain or substrate the animal moves through. In aquatic systems, adaptations focus on overcoming drag, buoyancy, and hydrostatic forces. Buoyancy both benefits and hinders diving animals; in particular, shallow divers constantly contend with the costs of overcoming buoyancy to dive and maintain position. Pacific Coast Feeding Group (PCFG) gray whales forage in shallow habitats where they work against buoyancy to dive and feed using various foraging tactics. Bubble blasts (underwater exhalations) have been observed during several foraging tactics performed by PCFG whales. As exhalations aid buoyancy regulation in other diving animals, we hypothesize that bubble blasts are performed by longer, more buoyant whales in shallower water and that bubble blasts increase dive duration while accounting for size and tactic. We test our hypotheses using Bayesian linear mixed effects models and a 7-year dataset of drone footage containing concurrent individual morphological and behavioral data. We find that while headstanding - a stationary, head-down tactic - bubble blasts are performed by longer, more buoyant whales and extend the dive duration, whereas whales using forward-swimming tactics are less likely to bubble blast. Our results suggest that PCFG gray whales may use bubble blasts as a behavioral adaption to mitigate the cost of energetically expensive tactics in their shallow habitat foraging niche.

Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia

BackgroundMalaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia.MethodsThirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking.ResultsAmong 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5–14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare.ConclusionsChadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

Randomized Controlled Trial of a Nurse-Led Brief Behavioral Intervention for Dyspnea in Patients With Advanced Lung Cancer.

In patients with lung cancer, dyspnea is one of the most prevalent and disabling symptoms, for which effective treatments are lacking. We examined the efficacy of a nurse-led brief behavioral intervention to improve dyspnea in patients with advanced lung cancer. Patients with advanced lung cancer reporting at least moderate breathlessness (n = 247) were enrolled in a randomized trial of a nurse-led two-session intervention (focused on breathing techniques, postural positions, and fan therapy) versus usual care. At baseline and weeks 8 (primary end point), 16, and 24, participants completed measures of dyspnea (Modified Medical Research Council Dyspnea Scale [mMRCDS]; Cancer Dyspnoea Scale [CDS]), quality of life (Functional Assessment of Cancer Therapy-Lung [FACT-L]), psychological symptoms (Hospital Anxiety and Depression Scale), and activity level (Godin-Shephard Leisure Time Physical Activity Questionnaire). To examine intervention effects, we conducted analysis of covariance and longitudinal mixed effects models. The sample (Agemean = 66.15 years; 55.9% female) primarily included patients with advanced non-small cell lung cancer (85.4%). Compared with usual care, the intervention improved the primary outcome of patient-reported dyspnea on the mMRCDS (difference = -0.33 [95% CI, -0.61 to -0.05]) but not the CDS total score at 8 weeks. Intervention patients also reported less dyspnea on the CDS sense of discomfort subscale (difference = -0.59 [95% CI, -1.16 to -0.01]) and better functional well-being per the FACT-L (difference = 1.39 [95% CI, 0.18 to 2.59]) versus the control group. Study groups did not differ in overall quality of life, psychological symptoms, or activity level at 8 weeks or longitudinally over 24 weeks. For patients with advanced lung cancer, a scalable behavioral intervention alleviated the intractable symptom of dyspnea. Further research is needed on ways to enhance intervention effects over the long-term and across additional outcomes.

Genome-wide association analysis of hypertension and epigenetic aging reveals shared genetic architecture and identifies novel risk loci

Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.

Cross-sectional and longitudinal changes in mind-wandering in older adulthood.

Age-related declines in the frequency of mind-wandering are well established. Theories of mind-wandering have attempted to explain why this decline occurs, but no one theory firmly predicts such changes. One problem with these theoretical views, and the studies that have grown out of them, is their reliance on cross-sectional methods, which do not account for within-person changes over time in mind-wandering, and it is well-documented that cross-sectional and longitudinal changes in some cognitive domains do not align. We present a novel analysis of longitudinal change in subjective and objective indicators of mind-wandering during a sustained attention task. Cognitively normal adults (N = 277, age range 42-94) completed a sustained attention task with thought probes to measure mind-wandering repeatedly over several years. Linear mixed effect models revealed baseline differences in subjective mind-wandering reports among middle-aged and older adults. However, longitudinally, middle-aged participants showed a significant increase in subjective mind-wandering, whereas older participants showed no change. Changes in mind-wandering could not be explained by attentional control ability or contemporaneous estimates of interest and perceived difficulty, but they were explained by baseline levels of conscientiousness. Objective measures of mind-wandering did not show these same patterns and were largely only associated with participants perceived difficulty. Our results build on previous cross-sectional research and suggest that incorporating longitudinal analyses into theories of ageing and mind-wandering and mind-wandering more broadly is important for refining these theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Role of Hospital Characteristics in Clinical and Quality Outcomes for Gastrointestinal Bleeding in a National Cohort.

There is substantial variability in patient outcomes for gastrointestinal bleeding (GIB) across hospitals. This study aimed to identify hospital factors associated with GIB outcomes. This was a retrospective cohort study of Medicare fee-for-service beneficiaries hospitalized for GIB from 2016 to 2018. These data were merged with the American Hospital Association Annual Survey data to incorporate hospital characteristics. We used generalized linear mixed-effect models to estimate the effect of hospital-level characteristics on patient outcomes after adjusting for patient risk factors including anticoagulant and antiplatelet use, recent GIB, and comorbidities. The primary outcome was 30-day mortality, and secondary outcomes included length of stay and a composite outcome of 30-day readmission or mortality. Factors associated with improved GIB 30-day mortality included large hospital size (defined as beds >400, odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90-0.97), greater case volume (OR 0.97, 95% CI 0.96-0.98), increased resident and nurse staffing (OR 0.88, 95% CI 0.83-0.94), and blood donor center designation (OR 0.93, 95% CI 0.88-0.99). Patients treated at a hospital with multiple advanced capabilities, such as availability of advanced endoscopy, advanced intensive care unit (ICU) capabilities (both a medical-surgical ICU and cardiac ICU), blood donor center, and liver transplant center, had a 22% reduction in 30-day mortality risk, compared with those hospitalized in a hospital with none of these services (OR 0.78, 95% CI 0.68-0.91). However, length of stay increased with additional services. Patients hospitalized for GIB at hospitals with multiple advanced specialized capabilities have lower mortality but longer lengths of stay. Further research should examine the processes of care linked to these services that contribute to improved mortality in GIB.

Evaluating carbonation resistance and microstructural behaviors of calcium sulfoaluminate cement concrete incorporating fly ash and limestone powder

This study investigates the effects of accelerated carbonation on calcium sulfoaluminate (CSA) cement concrete, focusing on mixtures enhanced with 20 % fly ash (FA), 20 % remediated fly ash (RF), 15 % limestone powder (LP), and a combination of 20 % FA with 15 % LP (35 %). The study further evaluates the mechanical properties including compressive strength, splitting tensile strength, elastic modulus, along with drying shrinkage and bulk resistivity. To delve into the microstructural characteristics of moist curing versus carbonation exposure on the CSA cement system, X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were employed, particularly analyzing phase assemblage changes. The results show that the addition of FA reduced the carbonation depth in concrete mixtures over time (105 days). However, LP and the combination of FA and LP presented mixed effects. The microstructural analysis highlighted ettringite as the predominant phase in samples moist cured for 3 days. In contrast, carbonation-cured samples were characterized by different calcium carbonate (CaCO3) polymorphs alongside aluminum hydroxide (Al(OH)3) and residual ye'elimite, with the formation of low-pH carbonic acid facilitating the conversion of ettringite into CaCO3. This study highlights the impact of different SCMs on the durability and microstructural characteristics of CSA cement concrete, underscoring the interplay between curing methods, effects of SCM, and carbonation processes.

Nicotine Gum in Thai Smokers with Different CYP2A6 Enzymes: A Population Pharmacokinetic Analysis

Objective: Despite the popularity of nicotine gum in Thailand, population pharmacokinetics of nicotine gum in the Thai population has not been investigated. This study aimed to develop a population pharmacokinetic (POPPK) model of nicotine and to quantify the effects of genetic and non-genetic factors to nicotine pharmacokinetics. Materials and Methods: Secondary data collected from a previous clinical trial assessing cytochrome P450 2A6 (CYP2A6) genotypes in Thai smokers was investigated. Eighteen participants who had received a single dose of 2 mg nicotine gum were included. Blood samples were collected before, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4.5 and 6 hours after nicotine administration. POPPK analysis was performed using nonlinear mixed effect modelling. Results: One-compartment with 1st order elimination and absorption with 6-transit compartments best described the data. CYP2A6 enzyme activity was a significant covariate on the nicotine clearance. Apparent elimination clearance (CL/F) for a person with 100% CYP2A6 activity was 266.0 L/h. CL/F would be 36.0 L/h in a subject with 0% CYP2A6 activity. However, the impact of non-genetic factors (monthly alcohol consumption, Fagerstrom Test for Nicotine Dependence score and the number of cigarettes per day) on pharmacokinetics of nicotine were not found. Conclusion: This first report on population pharmacokinetics of nicotine gum in Thai smokers provided the pharmacokinetic model and quantified CL/F for smokers with different CYP2A6 genotypes. A markedly lower exposure to nicotine in the Thai population compared to others highlights the need for more studies to ensure the efficacy of nicotine gum in the Thai population.

Progression of frailty and cardiovascular outcomes among Medicare beneficiaries.

Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression.

All-cause mortality and cause-specific death in U.S. long-lived siblings: data from the Long Life Family Study.

This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern. In the Long Life Family Study (LLFS), 1,264 proband siblings (Mean age 90.1, SD 6.4) and 172 spouses (83.8, 7.2) from 511 U.S.-based families were recruited and followed over 12 years. Their survival function was compared with a birth cohort-, baseline age-, sex-, and race-matched pseudo sample from U.S. census data. To examine underlying and contributing causes, we examined in detail 338 deaths with complete death adjudication at the University of Pittsburgh Field Center through the year 2018. A familial effect on survival and death pattern was examined using mixed effect models. The LLFS siblings had better survival than the matched U.S. population average. They also had slightly but not significantly better survival than their spouses' (HR=1.18 [95%CI 0.94-1.49]) after adjusting for age and sex. Age at death ranged from 75-104 years, mean 91.4. The leading causes of death were cardiovascular disease (33.1%), dementia (22.2%), and cancer (10.7%). Mixed effect model shows a significant random effect of family in survival, with adjustment of baseline age and sex. There was no significant familial effect in the underlying cause of death or conditions directly contributing to death among siblings recruited by the University of Pittsburgh Field Center. Our findings demonstrate a higher survival in the LLFS siblings than the U.S. census data, with a familial component of survival. We did not find significant correspondence in causes of death between siblings within families.