Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis.

Human aging is marked by the emergence of a tapestry of clonal expansions in dividing tissues, particularly evident in blood as clonal hematopoiesis (CH). CH, linked to cancer risk and aging-related phenotypes, often stems from somatic mutations in a set of established genes. However, the majority of clones lack known drivers. Here we infer gene-level positive selection in whole blood exomes from 200,618 individuals in UK Biobank. We identify 17 additional genes, ZBTB33, ZNF318, ZNF234, SPRED2, SH2B3, SRCAP, SIK3, SRSF1, CHEK2, CCDC115, CCL22, BAX, YLPM1, MYD88, MTA2, MAGEC3 and IGLL5, under positive selection at a population level, and validate this selection pattern in 10,837 whole genomes from single-cell-derived hematopoietic colonies. Clones with mutations in these genes grow in frequency and size with age, comparable to classical CH drivers. They correlate with heightened risk of infection, death and hematological malignancy, highlighting the significance of these additional genes in the aging process.

Ediacaran marine animal forests and the ventilation of the oceans.

The rise of animals across the Ediacaran-Cambrian transition marked a step-change in the history of life, from a microbially dominated world to the complex macroscopic biosphere we see today.1,2,3 While the importance of bioturbation and swimming in altering the structure and function of Earth systems is well established,4,5,6 the influence of epifaunal animals on the hydrodynamics of marine environments is not well understood. Of particular interest are the oldest "marine animal forests,"7 which comprise a diversity of sessile soft-bodied organisms dominated by the fractally branching rangeomorphs.8,9 Typified by fossil assemblages from the Ediacaran of Mistaken Point, Newfoundland,8,10,11 these ancient communities might have played a pivotal role in structuring marine environments, similar to modern ecosystems,7,12,13 but our understanding of how they impacted fluid flow in the water column is limited. Here, we use ecological modeling and computational flow simulations to explore how Ediacaran marine animal forests influenced their surrounding environment. Our results reveal how organism morphology and community structure and composition combined to impact vertical mixing of the surrounding water. We find that Mistaken Point communities were capable of generating high-mixing conditions, thereby likely promoting gas and nutrient transport within the "canopy." This mixing could have served to enhance local-scale oxygen concentrations and redistribute resources like dissolved organic carbon. Our work suggests that Ediacaran marine animal forests may have contributed to the ventilation of the oceans over 560 million years ago, well before the Cambrian explosion of animals.

Telemedicine care coordination and visit frequency in pediatric patients with type 1 diabetes in Oregon.

Introduction: Children with type 1 diabetes require close monitoring with visits every 3-4 months. COVID-19-induced telemedicine expansion may alleviate the challenge of high visit frequency that children with type 1 diabetes face. However, telemedicine's impact on access to care may be limited if patients lack adequate support for telemedicine. The purpose of this study was to evaluate the impact of telemedicine care coordination services on visit frequency in an urban medical center without care coordination services versus a rural outreach program with established care coordination services serviced by the same providers. Methods: We evaluated EHR data from 790 children receiving care between July 2018 and December 2021 at a single academic center in Oregon. We estimated differences in likelihood of adequately timed monitoring care over time by patient care coordination services status using Generalized Estimating Equations. Results: Just prior to telemedicine expansion, patients receiving care coordination services were 25.6 % less likely to receive adequately timed monitoring care (95 % CI: 51.6 %, 114 %). Following telemedicine expansion, likelihood of adequately timed monitoring care increased from 28.8 % to 58.2 % among those receiving care coordination services and decreased from 38.7 % to 22.0 % among those not receiving care coordination services; increases in adequately timed monitoring care were 3.55 times greater in patients receiving care coordination services relative to those not (95 % CI: 2.10, 6.01). Discussion: For pediatric patients with type 1 diabetes, telemedicine care coordination may be an important factor for increasing visit adherence and may increase the number of patients meeting goal visit frequency beyond levels seen prior to widespread telemedicine availability.

A novel whole-team training programme for adult eating disorder services in England: rationale, development and preliminary evaluation.

AIMS AND METHOD: In response to recommendations for improving the quality and coordination of care delivered by eating disorder services, a whole-team training programme was commissioned by Health Education England in 2020. This paper describes the development and evaluation of the Eating Disorder Services for Adults (EDSA) whole-team training course, delivered to National Health Service adult eating disorder community teams in England. Course participants (n = 561) in the first two EDSA training cohorts (2021 and 2022) were asked to complete questionnaires at intake and after each session, asking about their views on the training. RESULTS: All course aspects were rated as highly enjoyable, meeting participants' training needs and fostering reflective practice. Thematic analysis identified themes relating to key innovative features of the course and suggestions for improvements. CLINICAL IMPLICATIONS: Preliminary evaluation suggests that EDSA is valued by clinicians to enhance their knowledge, skills and ability to improve eating disorder patient care.

Mapping awareness-raising and capacity-building materials on developmental disabilities for non-specialists: a review of the academic and grey literature.

Most children with developmental disabilities (DD), such as intellectual disabilities and autism, live in low- and middle-income countries (LMICs), where services are usually limited. Various governmental, non-governmental and research organisations in LMICs have developed awareness-raising campaigns and training and education resources on DD in childhood relevant to LMICs. This study aimed to comprehensively search and review freely available materials in the academic and grey literature, aimed at awareness raising, training and education on DD among non-specialist professionals and community members in LMICs. We consulted 183 experts, conducted key-word searches in five academic databases, four grey-literature databases and seventeen customised Google search engines. Following initial screening, we manually searched relevant systematic reviews and lists of resources and conducted forwards and backwards citation checks of included articles. We identified 7327 articles and resources after deduplication. We then used a rigorous multi-step screening process to select 78 training resources on DD relevant to LMICs, of which 43 aimed at informing and/or raising awareness DD, 16 highlighted specific strategies for staff in health settings and 19 in education settings. Our mapping analysis revealed that a wealth of materials is available for both global and local use, including comics, children's books, flyers, posters, fact sheets, blogs, videos, websites pages, social media channels, handbooks and self-education guides, and training programmes or sessions. Twelve resources were developed for cross-continental or global use in LMICs, 19 were developed for and/or used in Africa, 23 in Asia, 24 in Latin America. Most resources were developed within the context where they were intended to be used. Identified gaps included a limited range of resources on intellectual disabilities, manuals for actively delivering training to staff in education settings and resources targeted at eastern European LMICs: future intervention development and adaptation efforts should address such gaps, to ensure capacity building materials exist for a sufficient variety of DD, settings and geographical areas. Beyond identifying these gaps, the value of the review lies in the compilation of summary tables of information on all freely available resources found, to support their selection and use in wider contexts. Information on the resource content, country of original development and copyright is provided to facilitate resource sharing and uptake.

Cotinuous precision separation of gold using a metal-organic framework/polymer composite.

Critical metals of environmental and economic relevance can be found within complex mixtures, such as mine tailings, electronic waste and wastewater, at trace amounts. Specifically, gold is a critical metal that carries desired redox active properties in various applications, including modern electronics, medicine and chemical catalysis. Here we report the structuring of sub-micron Fe-BTC/PpPDA crystallites into larger 250µm or 500µm granules for continuous packed bed experiments for the precision separation of gold. The Structured Fe-BTC/PpPDA is highly crystalline and porous with a BET surface area of 750 m2g-1. Further, the hybrid nanocomposite material maintains its selectivity for gold ions over common inorganic interferents. The structuring approach reported prevents excessive pressure drop and ensures stability over time and operation in a packed bed column. Further, we demonstrate that the Structured Fe-BTC/PpPDA can concentrate at least 42 wt% of gold under a dynamic continuous flow operation. These findings highlight the potential of Structured Fe-BTC/PpPDA for practical applications in industry, particularly in the selective capture of gold from complex mixtures.

Evaluating the Impact of Telemedicine Expansion on Visit Frequency for Children with Type 1 Diabetes at a Single Academic Center in Oregon.

Objective: The telemedicine expansion (TE) that accompanied the COVID-19 pandemic presents a novel opportunity to increase access to care for rural-residing children with type 1 diabetes (T1D) who may live a great distance from their provider. The study objective was to compare trends in visit frequency among the pediatric T1D population at a single academic center in Oregon before and after TE by those living <100 miles versus ≥100 miles from clinic (MFC) and those residing in urban versus rural areas. Research Design and Methods: We evaluated electronic health record data from 790 children receiving care between July 2018 and December 2021. We estimated differences in likelihood of adequately timed monitoring care (ATMC) over time by patient residence using Generalized Estimating Equations. Results: Just before TE, 37.3% of children were receiving ATMC and those living ≥100 MFC were 20.6% less likely to receive ATMC compared with those living <100 MFC (relative risk [RR] 0.79; confidence interval [95% CI]: 0.57-1.11). Following TE, decreases in ATMC for those living ≥100 MFC were less than for those living <100 MFC (RR of interaction: 1.17; 95% CI: 0.68-2.00). Just before TE, those living in rural areas were as likely to receive ATMC compared with those living in urban areas (RR 1.00; 95% CI: 0.61-1.63). Following TE, decreases in ATMC were greater for those living in rural areas versus urban areas (RR of interaction: 0.79; 95% CI: 0.31-2.01). Conclusions: Between July 2020 and December 2021, the likelihood of ATMC decreased across the entire pediatric T1D population. Decreases in ATMC during this period were more substantial for those living <100 MFC and/or in rural areas, however, these discrepancies were not statistically significant.

Cognitive emotion regulation strategies among emerging adults with different self-harm histories.

Background: Self-injurious behaviors have a high prevalence in emerging adulthood. People who engage in self-injury report more emotion regulation difficulties than their peers without self-injury. However, there is little research on how use of emotion regulation strategies varies over brief periods among emerging adults with differing self-harm histories. The current study examined variability in cognitive emotion regulation strategies between emerging adults with no self-harm, previous suicide attempts, or non-suicidal self-injury (NSSI). Methods: Forty-one racially and ethnically diverse participants, ages 18-27, completed measures of cognitive emotion regulation once daily for one week. Results: Data collected from 5 of these days were analyzed due to missing data on days 6 and 7. Growth curve analyses revealed differences in trajectories of rumination, acceptance, and catastrophizing, depending on self-harm histories. Specifically, participants with previous NSSI displayed increases in rumination, acceptance, and catastrophizing over time, compared to peers with a previous suicide attempt. Limitations: The study design was limited by lack of assessment of self-harm during the daily diary, a limited assessment period of only one week, and distal time period of group classification. Conclusions: These findings suggest that while emerging adults with NSSI histories use more emotion regulation strategies, they may need assistance in selecting when and how to use specific strategies.

Cutaneous apocrine gland neoplasia in 16 captive African wild dogs (Lycaon pictus).

This retrospective study documents the occurrence of single and multiple cutaneous apocrine gland tumours (CATs) on the dorsal midline of 16 captive African wild dogs (AWDs, Lycaon pictus) derived from 161 submissions to diagnostic laboratories in South Africa, France and Germany between 1997 and 2022. Animals included in the study came from zoological institutions in South Africa (n = 2), France (n = 5) and Germany (n = 1) and ranged from 5 to 14 years of age. Fifteen affected animals were female (94%) and one was male. CATs presented as raised, hairless, multilobular, grey firm masses, consistently located along the dorsal midline. Apart from a single cutaneous apocrine adenoma and a cystadenoma occurring concurrently with two non-cystic adenocarcinomas, neoplasms were consistent with malignant cutaneous apocrine adenocarcinomas with lymphatic spread and visceral metastases. Advanced age and female sex were identified as risk factors. A genetic component or association with the increasing use of GnRH agonist contraceptives was suspected but could not be established. This study highlights the need for close clinical monitoring of AWDs over the age of 5 years for the development of CATs along the dorsal midline and supports early surgical intervention. More research is needed to determine the role of inbreeding, endocrine changes and husbandry factors that may play a role in the development of CATs on the dorsal midline of AWDs.

Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.

Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified among gene-modified or unmodified cells; however, an increased frequency of potential driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) was observed in both genetically modified and unmodified cells, suggesting positive selection of mutant clones during GT. This work sheds light on HSC clonal dynamics and the mutational landscape after GT in SCD, highlighting the enhanced fitness of some HSCs harboring pre-existing driver mutations. Future studies should define the long-term fate of mutant clones, including any contribution to expansions associated with myeloid neoplasms.

Cost comparison of in-person and telehealth modalities for a suicide safety planning group intervention: interim results from the "Project Life Force" randomized clinical trial.

Suicide prevention is a clinical priority for the US Veterans Health Administration. Evidence-based interventions, including developing a suicide safety plan, are recommended practices and are becoming more widespread. Adaptations to further augment safety planning include a manualized group intervention (Project Life Force, PLF) that combines safety planning with the teaching of skills to maximize use of the plan. A multi-year randomized controlled trial to test efficacy of PLF compared to treatment as usual is currently in progress. However, approximately a year into the study, in-person groups were converted to telehealth groups due to the COVID-19 pandemic. This study compares the per-veteran cost of PLF when delivered in-person versus by telehealth using preliminary trial data from the first 2.5 years of the trial. Cost to deliver PLF was obtained from the Veterans Health Administration's Managerial Cost Accounting data, which relies on activity-based costing. We found no significant differences in the average number of sessions or average group size between in-person and telehealth. However, the cost per group session was lower for the telehealth modality and this led to significant overall per-veteran savings. While efficacy data comparing from the two arms is still underway and we await the ongoing RCT results, our interim cost analysis highlights potential savings with the telehealth modality.

A pilot genome-wide association study meta-analysis of gastroparesis.

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. OBJECTIVE: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. METHODS: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. RESULTS: While no SNP associations were detected at strict significance (p ≤ 5 × 10-8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10-5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls). CONCLUSION: We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Convergent somatic evolution commences in utero in a germline ribosomopathy.

Clonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution.

Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy.

Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias1-4 remains unresolved. Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence. Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment.

Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.

Aged hematopoietic stem cells (HSCs) display diminished self-renewal and a myeloid differentiation bias. However, the drivers and mechanisms that underpin this fundamental switch are not understood. HSCs produce genotoxic formaldehyde that requires protection by the detoxification enzymes ALDH2 and ADH5 and the Fanconi anemia (FA) DNA repair pathway. We find that the HSCs in young Aldh2-/-Fancd2-/- mice harbor a transcriptomic signature equivalent to aged wild-type HSCs, along with increased epigenetic age, telomere attrition, and myeloid-biased differentiation quantified by single HSC transplantation. In addition, the p53 response is vigorously activated in Aldh2-/-Fancd2-/- HSCs, while p53 deletion rescued this aged HSC phenotype. To further define the origins of the myeloid differentiation bias, we use a GFP genetic reporter to find a striking enrichment of Vwf+ myeloid and megakaryocyte-lineage-biased HSCs. These results indicate that metabolism-derived formaldehyde-DNA damage stimulates the p53 response in HSCs to drive accelerated aging.

An open trial of VA CONNECT: Caring for Our Nation's Needs Electronically during the COVID-19 Transition.

The COVID-19 pandemic impacted emotional well-being due to safety concerns, grief, employment impacts, and social interaction limitations. Face-to-face mental health treatment restrictions were especially impactful to veterans who often gain social enrichment from Veterans Health Administration (VHA) care. We present results from a novel group-based telehealth intervention, VA Caring for Our Nation's Needs Electronically during the COVID-19 Transition (VA CONNECT), which integrates skills training and social support to develop a COVID-19 Safety & Resilience Plan. Veterans (n â€‹= â€‹29) experiencing COVID-related stress participated in an open trial of this 10-session, manualized group VHA telehealth intervention. We examined whether COVID-19-related stress, adjustment disorder symptoms, and loneliness decreased, and coping strategy use increased after participation in VA CONNECT. Between baseline and two-month follow-up, participants reported a significant reduction in perceived stress and adjustment disorder symptoms, and an increase in planning coping skills use. Significant changes were not observed in loneliness or other specific coping strategies. Findings may support the utility of VA CONNECT as an intervention for pandemic-related stress and improving certain coping skills. Future research should explore group-based telehealth interventions like VA CONNECT with other populations within and outside of the VA, which have value during major disruptions to face-to-face mental healthcare access.

The rangeomorph Pectinifrons abyssalis: Hydrodynamic function at the dawn of animal life.

Rangeomorphs are among the oldest putative eumetazoans known from the fossil record. Establishing how they fed is thus key to understanding the structure and function of the earliest animal ecosystems. Here, we use computational fluid dynamics to test hypothesized feeding modes for the fence-like rangeomorph Pectinifrons abyssalis, comparing this to the morphologically similar extant carnivorous sponge Chondrocladia lyra. Our results reveal complex patterns of flow around P. abyssalis unlike those previously reconstructed for any other Ediacaran taxon. Comparisons with C. lyra reveal substantial differences between the two organisms, suggesting they converged on a similar fence-like morphology for different functions. We argue that the flow patterns recovered for P. abyssalis do not support either a suspension feeding or osmotrophic feeding habit. Instead, our results indicate that rangeomorph fronds may represent organs adapted for gas exchange. If correct, this interpretation could require a dramatic reinterpretation of the oldest macroscopic animals.

Qualitative Study of Telehealth Delivery of Suicide-Specific Group Treatment "Project Life Force".

Minimal evidence exists for suicide-specific group treatment for high-risk patients offered over telehealth. This qualitative study assessed the acceptability, feasibility, and impact of a telehealth suicide safety planning intervention (SPI) multi-session group. High-risk suicidal Veterans (n = 17) participating in "Project Life Force-telehealth" (PLF-T); a manualized, 10-session SPI video group completed semi-structured qualitative interviews including measures of acceptability, appropriateness, and feasibility. We also interviewed the PLF-T coordinator and PLF-T group facilitators to identify adaptations to deliver PLF-T and learn about barriers and facilitators to implementation. A summary template and matrix analysis approach was used to analyze qualitative data. Veteran group participants were mostly male (88%), age 50 (SD = 15.6), ethnically diverse, and either divorced or separated (54%). Suicide symptoms upon study entry included past month ideation with methods (100%); and past year aborted, interrupted, or actual suicide attempt (59%). Participant interviews revealed an overall positive endorsement of PLF-telehealth with enhanced suicidal disclosure, and improved ability to manage urges and mitigate loneliness. On scales from 1 to 20, PLF-T was rated as highly acceptable (M = 17.50; SD = 2.92), appropriate (M = 17.25; SD = 3.59), and feasible (M = 18; SD = 2.45) by participants. Adaptations to deliver PLF-T included using a communications coordinator to conduct assertive outreach and engagement, adding a telehealth orientation session, restructuring sessions to review suicide severity, and screen-sharing safety plans to maximize learning. PLF-T enhanced convenience and access without compromising safety. Concerns included privacy and technological limitations including connectivity. Project Life Force-telehealth is acceptable and feasible to deliver via telehealth. This opens the possibility of delivery to hard-to-reach high-risk populations. ClinicalTrials.gov Identifier: NCT0365363.

Using machine-learning algorithms to improve imputation in the medical expenditure panel survey.

OBJECTIVE: To assess the feasibility of applying machine learning (ML) methods to imputation in the Medical Expenditure Panel Survey (MEPS). DATA SOURCES: All data come from the 2016-2017 MEPS. STUDY DESIGN: Currently, expenditures for medical encounters in the MEPS are imputed with a predictive mean matching (PMM) algorithm in which a linear regression model is used to predict expenditures for events with (donors) and without (recipients) data. Recipient events and donor events are then matched based on the smallest distance between predicted expenditures, and the donor event's expenditures are used as the recipient event's imputation. We replace linear regression algorithm in the PMM framework with ML methods to predict expenditures. We examine five alternatives to linear regression: Gradient Boosting, Random Forests, Extreme Random Forests, Deep Neural Networks, and a Stacked Ensemble approach. Additionally, we introduce an alternative matching scheme, which matches on a vector of predicted expenditures by sources of payment instead of a single total expenditure prediction to generate potentially superior matches. DATA COLLECTION: Study data is derived from a large federal survey. PRINCIPAL FINDINGS: ML algorithms perform better at both prediction and matching imputation than Ordinary Least Squares (OLS), the most common prediction algorithm used in PMM. On average, the Stacked Ensemble approach that combines all the ML algorithms performs best, improving expenditure prediction R2 by 108% (0.156 points) and final imputation R2 by 227% (0.397 points). Matching on a prediction vector also improves alignment of sources of payments between donor and recipient events. CONCLUSIONS: ML algorithms and an alternative matching scheme improve the overall quality of expenditure PMM imputation in the MEPS. These methods may have additional value in other national surveys that currently rely on PMM or similar methods for imputation.