Catalytic performance and mechanism study of the isomerization of 2,5-dichlorotoluene to 2,4-dichlorotoluene.

This work investigates the influence of catalyst HZSM-5 on the isomerization of 2,5-dichlorotoluene (2,5-DCT) to produce 2,4-dichlorotoluene (2,4-DCT). We observe that hydrothermal treatment leads to a decrease in total acidity and Brønsted/Lewis ratio of HZSM-5 while generating new secondary pores. These characteristics result in excellent selectivity for post-hydrothermal modified HZSM-5 in the isomerization reaction from 2,5-DCT to 2,4-DCT. Under atmospheric pressure at 350 °C, unmodified HZSM-5 achieves a selectivity of 66.4% for producing 2,4-DCT, however after hydrothermal modification the selectivity increases to 78.7%. Density Functional Theory (DFT) calculations explore the thermodynamic aspects of adsorption between the HZSM-5 surface and 2,4-DCT. The kinetic perspective investigates the mechanism involving proton attack on the methyl group of 2,5-DCT followed by rearrangement leading to formation of 2,4-DCT during isomerization. The consistency between simulation and experimental results provides evidence for the feasibility of isomerizing 2,5-DCT to 2,4-DCT. This work fills the gap in the low value-added product 2,5-DCT isomer conversion, indicating its significant practical application potential and provides a valuable reference and guidelines for industrial research in this field.

Electrochemical decarboxylative alkylation of ß-ketoacids with phenol derivatives.

An electrochemical method for the decarboxylative alkylation of ß-ketoacids with phenol derivatives has been developed. The protocol was carried out in readily available unseparated cells at room temperature in the absence of catalysts and oxidants. The corresponding aryl ketones were obtained in satisfactory yields without additional electrolytes, and were easy to produce in gram-scale synthesis. Based on control experiments and cyclic voltammetry, a plausible reaction mechanism was proposed.

Impact of Limited English Proficiency on Medication-Related Problems and Emergency Room Visits Among Community-Dwelling Older People.

Background Older people have higher risk of experiencing medication-related problems (MRPs), leading to increased morbidity, health care use, and mortality. Few studies have examined the pathway between limited English proficiency (LEP) among older people and health service use through MRPs. Objective This study aimed to explore the association of LEP among Latino older people with MRPs and their relationship to emergency room (ER) visits. Methods Researchers used secondary enrollment data from a community medication program for older people (N = 180). Researchers conducted linear regression to examine the relationship between ethnicity/English proficiency and MRPs, and logistic regression to explore the association between MRPs and ER visits. Generalized structural equation modeling (GSEM) with bootstrapping was used to test the indirect effect between LEP Latino through MRPs to ER visits. Results The sample included 70% non-Latino participants, 12% English-speaking Latinos, and 18% LEP Latinos. Analysis LEP Latinos were associated with having 3.4 more MRPs than non-Latino participants, after controlling for covariates. Additionally, each additional MRP was associated with a 10% increased probability of having an ER visit. The GSEM results illustrated there was a significant indirect effect between LEP through MRPs to ER visits (ß = 0.27, 95% CI 0.07-0.61). Conclusion Though LEP was not directly related to increased ER visits, it may have inhibited the ability of Latinos to read and understand medication instructions, contributing to their elevated risk of experiencing MRPs, thus indirectly increasing potential risks of having ER visits.

The establishment of a recombinase polymerase amplification technique for the detection of mouse poxvirus.

BACKGROUND: Ectromelia virus (ECTV) is the causative agent of mousepox in mice. In the past century, ECTV was a serious threat to laboratory mouse colonies worldwide. Recombinase polymerase amplification (RPA), which is widely used in virus detection, is an isothermal amplification method. RESULTS: In this study, a probe-based RPA detection method was established for rapid and sensitive detection of ECTV.Primers were designed for the highly conserved region of the crmD gene, the main core protein of recessive poxvirus, and standard plasmids were constructed. The lowest detection limit of the ECTV RT- RPA assay was 100 copies of DNA mol-ecules per reaction. In addition, the method showed high specificity and did not cross-react with other common mouse viruses.Therefore, the practicability of the RPA method in the field was confirmed by the detection of 135 clinical samples. The real-time RPA assay was very similar to the ECTV real-time PCR assay, with 100% agreement. CONCLUSIONS: In conclusion, this RPA assay offers a novel alternative for the simple, sensitive, and specific identification of ECTV, especially in low-resource settings.

Rapid detection of goose astrovirus genotypes 2 using real-time reverse transcription recombinase polymerase amplification.

BACKGROUND: Goose astrovirus (GoAstV) is an important pathogen that causes joint and visceral gout in goslings. It has been circulating in many provinces of China since 2017. Goose astrovirus genotypes 2 (GoAstV-2) is the main epidemic strain, and its high morbidity and mortality have caused huge economic losses to the goose industry. An accurate point-of-care detection for GoAstV-2 is of great significance. In this study, we developed a real-time reverse transcription recombinase polymerase amplification (RT-RPA) method for the on-site detection of GoAstV-2 infection. RESULTS: The real-time RT-RPA reaction was carried out at a constant temperature of 39 °C, and the entire detection time from nucleic acid preparation to the end of amplification was only 25 min using the portable device. The results of a specificity analysis showed that no cross-reaction was observed with other related pathogens. The detection limit of the assay was 100 RNA copies/µL. The low coefficient of variation value indicated excellent repeatability. We used 270 clinical samples to evaluate the performance of our established method, the positive concordance rates with RT-qPCR were 99.6%, and the linear regression analysis revealed a strong correlation. CONCLUSIONS: The established real-time RT-RPA assay showed high rapidity, specificity and sensitivity, which can be widely applied in the laboratory, field and especially in the resource-limited settings for GoAstV-2 point-of-care diagnosis.

Ligand-Mediated Regulation of the Chemical/Thermal Stability and Catalytic Performance of Isostructural Cobalt(II) Coordination Polymers.

Regulating the chemical/thermal stability and catalytic activity of coordination polymers (CPs) to achieve high catalytic performance is topical and challenging. The CPs are competent in promoting oxidative cross-coupling, yet they have not received substantial attention. Here, the ligand effect of the secondary ligand of CPs for oxidative cross-coupling reactions was investigated. Specifically, four new isostructural CPs [Co(Fbtx)1.5(4-R-1,2-BDC)]n (denoted as Co-CP-R, Fbtx = 1,4-bis(1,2,4-triazole-1-ylmethyl)-2,3,5,6-tetrafluorobenzene, 4-R-1,2-BDC = 4-R-1,2-benzenedicarboxylate, R = F, Cl, Br, CF3) were prepared. It was found that in the reactions of oxidative amination of benzoxazoles with secondary amines and the oxidative coupling of styrenes with benzaldehydes, both the chemical and thermal stabilities of the four Co-CPs with the R group followed the trend of -CF3 > -Br > -Cl > -F. Density functional theory (DFT) calculations suggested that the difference in reactivity may be ascribed to the effect of substituent groups on the electron transition energy of the cobalt(II) center of these Co-CPs. These findings highlight the secondary ligand effect in regulating the stability and catalytic performance of coordination networks.

Preparation of a new monoclonal antibody against nucleocapsid protein of swine acute diarrhea syndrome coronavirus and identification of its linear antigenic epitope.

Swine acute diarrhea syndrome coronavirus (SADS-CoV), which causes severe diarrhea in newborn piglets, was first identified in Southern China in 2017. Since the Nucleocapsid (N) protein in SADS-CoV is highly conserved and plays a key role in virus replication, it is often used as a target protein in scientific research. In this study, the N protein of SADS-CoV was successfully expressed, and a new monoclonal antibody (mAb), 5G12, against the protein was generated successfully. The mAb 5G12 can be used to detect SADS-CoV strains by indirect immunofluorescence assay (IFA) and western blotting. The mAb 5G12 epitope was located to amino acids 11 EQAESRGRK 19 by evaluating the antibody for reactivity with a series of truncated N protein segments. The biological information analysis showed that the antigenic epitope had a high antigenic index and conservation. This study will help further understand the protein structure and function of SADS-CoV and in the establishment of specific SADS-CoV detection methods.

Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS-CoV-2.

S-217622 (Ensitrelvir) is a reversible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro) inhibitor which obtained emergency regulatory approval in Japan for the treatment of SARS-CoV-2 infection on Nov 22, 2022. Herein, analogs of S-271622 with deuterium-for-hydrogen replacement were synthesized for comparison of the antiviral activities and pharmacokinetic (PK) profiles. Compared to the parent compound, C11-d2-S-217622 compound YY-278 retained in vitro activity against 3CLpro and SARS-CoV-2. X-ray crystal structural studies showed similar interactions of SARS-CoV-2 3CLpro with YY-278 and S-271622. The PK profiling revealed the relatively favorable bioavailability and plasma exposure of YY-278. In addition, YY-278, as well as S-217622, displayed broadly anti-coronaviral activities against 6 other coronaviruses that infect humans and animals. These results laid the foundation for further research on the therapeutic potential of YY-278 against COVID-19 and other coronaviral diseases.

Engineering of oxygen vacancy defect in CeO2 through Mn doping for toluene catalytic oxidation at low temperature.

Catalytic oxidation is considered a highly effective method for the elimination of volatile organic compounds. Oxygen vacancy defect engineering in a catalyst is considered an effective approach for high-performance catalysts. Herein, a series of doped MnxCe1-xO2 catalysts (x = 0.05-0.2) with oxygen vacancy defects were synthesized by doping low-valent Mn in a CeO2 lattice. Different characterization techniques were utilized to inspect the effect of doping on oxygen vacancy defect generation. The characterization results revealed that the Mn0.15Ce0.85O2 catalyst has the maximum oxygen vacancy concentration, leading to increased active oxygen species and enhanced oxygen mobility. Thus, Mn0.15Ce0.85O2 catalyst showed an excellent toluene oxidation activity with 90% toluene conversion temperature (T90) of 197 °C at a weight hourly space velocity of 40,000 mL g-1 h-1 as compared to undoped CeO2 (T90 = 225 °C) and Ce based oxides in previous reports. In addition, the Mn0.15Ce0.85O2 catalyst displayed strong recyclability, water resistant ability and long-time stability. The in situ DRIFT results showed that the Mn0.15Ce0.85O2 catalyst has a robust oxidation capability as toluene is quickly adsorbed and actuated as compared to CeO2. Thus, the present work lays the foundation for designing a highly active catalyst for toluene elimination from the environment.

Electron-transfer pathways insights into contaminants oxidized by Cu-OOSO3- intermediate: Effects of oxidation states of Cu and solution pH values.

The copper-peroxy complex (Cu-OOSO3-) metastable intermediate has been confirmed to oxidize contaminants via a single-electron-transfer pathway or an oxygen-atom-transfer pathway. And the effects of Cu oxidation states and reaction pH conditions on the intermediate properties have not been explored in depth. Here, copper oxide (CuOx) catalysts with different Cu oxidation states were synthesized by a simple precipitation method by controlling the reaction temperature from 0 to 45 °C. CuOx displayed a strong catalytic dependence on the Cu oxidation state, and CuOx-30 with Cu average valence on the catalyst surface of 1.61 was more reactive for catalytic degradation of bisphenol A with peroxymonosulfate (PMS). Notably, CuOx-30, with the best electron-accepting ability, was easier to bonding with PMS to form the Cu-OOSO3- reactive complex, and the generated intermediate exhibited the strongest capacity to obtain electrons from contaminants. Moreover, the electron-transfer pathways were closely related to the average valence of Cu, and the contribution of the oxygen-atom-transfer pathway changed volcanic with increasing Cu valence. Meanwhile, the reaction predominantly involved the oxygen-atom-transfer pathway under acidic conditions (pH=3), while the contribution of the single-electron-transfer pathway raised with increasing pH values. Hence, this work was devoted to providing new insights into the CuOx-inducing PMS activation and vital supplementary to the properties of the Cu-OOSO3- intermediate.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and nucleotide analog GS-441524 conjugates with potent in vivo efficacy against coronaviruses.

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5'-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041, exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta-genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies.

Influences of different surface oxygen species on oxidation of toluene and/or benzene and their reaction pathways over Cu-Mn metal oxides.

Catalytic oxidation is considered as the most effective and economical method to remove low concentration volatile organic compounds (VOCs). Activation of oxygen to form active oxygen species on metal oxides catalyst plays a key role in the process. Three copper-manganese oxide catalysts with cubic Cu1.5Mn1.5O4 phases were prepared by microwave heating (CM-MW), sol-gel (CM-SG) and co-precipitation (CM-CP) methods, and applied for the elimination of toluene and benzene as representative aromatic VOCs. These catalysts exhibit different catalytic oxidation performance due to their different physicochemical properties. Various characterizations were used to clarify the role of different oxygen species in the oxidation of VOCs, and the reaction pathway. In situ DRIFTS were carried out to explore the function of surface adsorbed oxygen, oxygen vacancy, and surface lattice oxygen in the catalytic oxidation of VOCs over three catalysts. Various types of intermediate species and detailed reaction pathways are also explored by combining in situ DRIFTS and mass spectrometry. Among these catalysts, CM-MW with nanosheet morphology shows the best catalytic oxidation performance of toluene and/or benzene with/without H2O due to the most abundant active oxygen species, and the highest oxygen vacancy concentration which is beneficial to activate oxygen. Meanwhile, toluene and benzene do not interfere with each other during the mixture oxidation. This study can provide new inspiration for rational design of metal oxide catalysts to remove VOCs.

Simultaneous Detection of Three Subgroups of Avian Leukosis Virus Using the Nanoparticle-Assisted PCR Assay.

Nanoparticle-assisted polymerase chain reaction (nanoPCR) is a novel method for the rapid detection of pathogens. A sensitive and specific multiple nanoPCR assay was developed for simultaneous detection of avian leucosis virus (ALV) subgroups A, B and J. In this study, three pairs of primers were designed, based on the conserved region of the gp85 gene. An exploration of the optimal primer concentration and annealing temperature were carried out, for better performance of the nanoPCR assay. According to the results, the multiple nanoPCR assay amplified 336 pb, 625 bp and 167 bp fragments of ALV-A, -B and -J, respectively, and showed no cross-reactivity with irrelevant pathogens, suggesting the excellent specificity of the assay. The constructed standard DNA templates were used to estimate the limit of detection. As shown by the results, the detection limit of the nanoPCR assay was nearly 10 copies/µL. To further evaluate the detection ability of the assay, 186 clinical samples were detected using the nanoPCR assay, among which, 14 samples were confirmed as ALV positive; the results were further confirmed by sequencing. In conclusion, a highly specific and sensitive nanoPCR assay was successfully developed, which could be a useful tool for clinical diagnosis as well as for the discrimination of ALV-A, -B and -J.

Control of Grain Weight and Size in Rice (Oryza sativa L.) by OsPUB3 Encoding a U-Box E3 Ubiquitin Ligase.

Grain weight and size, mostly determined by grain length, width and thickness, are crucial traits affecting grain quality and yield in rice. A quantitative trait locus controlling grain length and width in rice, qGS1-35.2, was previously fine-mapped in a 57.7-kb region on the long arm of chromosome 1. In this study, OsPUB3, a gene encoding a U-box E3 ubiquitin ligase, was validated as the causal gene for qGS1-35.2. The effects were confirmed firstly by using CRISPR/Cas9-based mutagenesis and then through transgenic complementation of a Cas9-free knock-out (KO) mutant. Two homozygous KO lines were produced, each having a 1-bp insertion in OsPUB3 which caused frameshift mutation and premature termination. Compared with the recipient and a transgenic-negative control, both mutants showed significant decreases in grain weight and size. In transgenic complementation populations derived from four independent T0 plants, grain weight of transgenic-positive plants was significantly higher than transgenic-negative plants, coming with increased grain length and a less significant decrease in grain width. Based on data documented in RiceVarMap V2.0, eight haplotypes were classified according to six single-nucleotide polymorphisms (SNPs) found in the OsPUB3 coding region of 4695 rice accessions. Significant differences on grain size traits were detected between the three major haplotypes, Hap1, Hap2 and Hap3 that jointly occupy 98.6% of the accessions. Hap3 having the largest grain weight and grain length but intermediate grain width exhibits a potential for simultaneously improving grain yield and quality. In another set of 257 indica rice cultivars tested in our study, Hap1 and Hap2 remained to be the two largest groups. Their differences on grain weight and size were significant in the background of non-functional gse5, but non-significant in the background of functional GSE5, indicating a genetic interaction between OsPUB3 and GSE5. Cloning of OsPUB3 provides a new gene resource for investigating the regulation of grain weight and size.

Control of Grain Shape and Size in Rice by Two Functional Alleles of OsPUB3 in Varied Genetic Background.

Grain shape and size are key determinants of grain appearance quality and yield in rice. In our previous study, a grain shape QTL, qGS1-35.2, was fine-mapped using near-isogenic lines (NILs) derived from a cross between Zhenshan 97 (ZS97) and Milyang 46 (MY46). One annotated gene, OsPUB3, was found to be the most likely candidate gene. Here, knockout and overexpression experiments were performed to investigate the effects of OsPUB3 on grain shape and size. Four traits were tested, including grain length, grain width, grain weight, and the ratio of grain length to width. Knockout of OsPUB3 in NILZS97, NILMY46, and another rice cultivar carrying the OsPUB3MY46 allele all caused decreases in grain width and weight and increases in the ratio of grain length to width. Results also showed that the magnitude of the mutational effects varied depending on the target allele and the genetic background. Moreover, it was found that NILZS97 and NILMY46 carried different functional alleles of OsPUB3, causing differences in grain shape rather than grain weight. In the overexpression experiment, significant differences between transgenic-positive and transgenic-negative plants were detected in all four traits. These results indicate that OsPUB3 regulates grain shape and size through a complex mechanism and is a good target for deciphering the regulatory network of grain shape. This gene could be used to improve grain appearance quality through molecular breeding as well.

Establishment of a recombinase polymerase amplification (RPA) fluorescence assay for the detection of swine acute diarrhea syndrome coronavirus (SADS-CoV).

BACKGROUND: Swine acute diarrhea syndrome coronavirus (SADS-CoV) causes acute vomiting and diarrhea in piglets, leading to significant financial losses for the pig industry. Recombinase polymerase amplification (RPA) is a rapid nucleic acid amplification technology used under constant temperature conditions. The study established a real-time reverse transcription (RT)-RPA assay for early diagnosis of SADS-CoV.  RESULTS: The detection limit of the real-time RT-RPA was 74 copies/µL of SADS-CoV genomic standard recombinant plasmid in 95% of cases. The assay was performed in less than 30 min and no cross-reactions were observed with eight other common viruses that affect swine, including classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), pseudo rabies virus (PRV), swine influenza virus (SIV), seneca valley virus (SVA), transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV). The coefficient of variation (C.V.) values of the two standards dilutions and three positive clinical sample ranged from 2.95% to 4.71%. A total of 72 clinical fecal samples from swine with diarrheal symptoms were analyzed with the developed RT-RPA and quantitative RT-PCR. There was 98.61% agreement between the RT-RPA and the quantitative real-time PCR results. CONCLUSIONS: These results indicated that the developed RT-RPA assay had good specificity, sensitivity, stability and repeatability. The study successfully established a broadly reactive RT-RPA assay for SADS-CoV detection.

Association between osteoporosis or osteopenia and taking antiplatelet agents in general US population of NHANES.

Background: Osteoporosis (OP) and osteopenia are common bone disorders in old age, and lots of patients suffering from OP or osteopenia need to take antiplatelet agents to treat basic diseases. However, clinical data on the link between osteopenia or OP and antiplatelet agents are limited. Methods: Data in this study were collected and screened from the NHANES from 2013 to 2014 and 2017 to 2018. The variables were extracted from interviews and compared between OP or osteopenia participants and normal. The relationship between OP or osteopenia and taking antiplatelet drugs was analyzed by weighted multivariate logistic regression. Results: After excluding individuals who were not eligible and had invalid data, we finally identified 894 participants for inclusion in the study. We found a negative association between OP or osteopenia and taking antiplatelet agents (OR = 0.53; 95% CI, 0.33-0.84; p < 0.05). These results did not change on multiple imputations (OR = 0.32, 95% CI, 0.19-0.56; p <0.01). In the subgroup analyses, the associations were more significant in women (OR = 0.18, 95% CI, 0.05-0.62; p <0.05). Conclusion: This study demonstrated that the association between OP or osteopenia and taking antiplatelet agents was significant. Therefore, it is necessary to confirm the result by extending further research.

Improving selective hydrogenation of carbonyls bond in α, ß-unsaturated aldehydes over Pt nanoparticles encaged within the amines-functionalized MIL-101-NH2.

The high selectivity in the hydrogenation reactions of α, ß-unsaturated aldehydes is always a demanding task. Precious Pt-based catalysts play a pivotal role in selective catalytic hydrogenation of α, ß-unsaturated aldehydes, but controlling the selectivity is still a great challenge. Herein, the Pt nanoparticles were encaged within the mesopores of amines (-NH2) functionalized MOFs via polyol reduction method as an efficient approach to enhance the selectivity of desired carbonyls bond reduction. The as-prepared 3-Pt/MOF-NH2(x) catalysts retained the inherent properties of MOF-NH2(x) supports such as crystallinity, surface area, pore texture, and surface acidity. Remarkably, the amines modified MOFs supported Pt-based catalysts (3-Pt/MOF-NH2(x)) improved the selective hydrogenation of carbonyls (CO) bond in cinnamaldehyde (CAL) and Furfural (FFL) with a higher selectivity (≥80 %) under mild conditions as compared to other reported catalysts. The improved catalytic performance for the selective hydrogenation of carbonyls (CO) bond is credited to the nitrogen (N) heteroatom of the amines group existing in the skeleton of MOFs and somewhat to the steric effect induced by mesopores of MOFs. The N heteroatom not only helps in the high uniform dispersion and stabilization of small-sized Pt nanoparticles (≈2nm) but also adjust the electron movement (electronic density) via synergistic effect resulting from the N to the vacant d-orbital of active Pt nanoparticles confined within MOFs, leading to more new interfacial electrophilic and nucleophilic sites, which are beneficial for selective hydrogenation of CO bond. Besides, the steric effect induced by mesopores of MOFs, encaging Pt nanoparticles, can also enhance the selective adsorption of the CO bond to interact with the catalyst active sites, resulting in higher selective hydrogenation of CO bond.

Advance directives completion and hospital out-of-pocket expenditures.

INTRODUCTION: Health care costs remain high at the end of life. It is not known if there is a relationship between advance directive (AD) completion and hospital out-of-pocket costs. This analysis investigated whether AD completion was associated with lower hospital out-of-pocket costs at end of life. METHODS: We used Health and Retirement Study participants who died between 2000 and 2014 (N = 9228) to examine the association between AD completion status and hospital out-of-pocket spending in the last 2 years of life through the use of a two-part model controlling for socioeconomic status, death-related characteristics and health insurance coverage. RESULTS: About 44% of decedents had completed ADs. Having an AD was significantly associated with $673 lower hospital out-of-pocket costs, with a higher magnitude of savings among younger decedents. Decedents who completed ADs 3 months or less before death had higher out-of-pocket costs ($1854 on average) than those who completed ADs more than 3 months before death ($1176 on average). CONCLUSIONS: AD completion was significantly associated with lower hospital out-of-pocket costs, with greater out-of-pocket savings among younger decedents. Early AD completers experienced lower costs than decedents who completed ADs closer to death.