@article {11845, title = {Changes in the Hierarchy of Functional Impairment from Middle Age to Older Age.}, journal = {The Journals of Gerontology, Series A }, volume = {77}, year = {2022}, pages = {1577-1584}, abstract = {

BACKGROUND: Understanding the hierarchy of functional impairment in older adults has helped illuminate mechanisms of impairment and inform interventions, but little is known about whether hierarchies vary by age. We compared the pattern of new-onset impairments in activities of daily living (ADLs) and instrumental ADLs (IADLs) from middle age through older age.

METHODS: We conducted a cohort study using nationally representative data from 32486 individuals enrolled in the Health and Retirement Study. The outcomes were new-onset impairment in each ADL and IADL, defined as self-reported difficulty performing each task, assessed yearly for 9 years. We used multi-state models and competing risks survival analysis to estimate the cumulative incidence of impairment in each task by age group (ages 50-64, 65-74, 75-84, and 85 or older).

RESULTS: The pattern of incident ADL impairments differed by age group. Among individuals ages 50-64 and 65-74 who were independent at baseline, over 9 years{\textquoteright} follow-up, difficulties dressing and transferring were the most common impairments to develop. In individuals ages 75-84 and 85 or older who were independent at baseline, difficulties bathing, dressing, and walking were most common. For IADLs, the pattern of impairments was similar across age groups; difficulty shopping was most common followed by difficulty managing money and preparing meals. Complementary analyses demonstrated a similar pattern.

CONCLUSIONS: These findings suggest that the hierarchy of ADL impairment differs by age. These findings have implications for the development of age-specific interventions to prevent or delay functional impairment.

}, keywords = {Activities of Daily Living, functional impairment}, issn = {1758-535X}, doi = {10.1093/gerona/glab250}, author = {Brown, Rebecca T and L Grisell Diaz-Ramirez and W John Boscardin and Anne Cappola and Lee, Sei J and Michael A Steinman} } @article {13027, title = {WHICH NEIGHBORHOOD FEATURES MATTER MOST FOR MUSCLE STRENGTH? FINDINGS FROM THE HEALTH AND RETIREMENT STUDY}, journal = {Innovation in Aging}, volume = {6}, year = {2022}, pages = {254{\textendash}255}, abstract = {Linking data from the National Neighborhood Data Archive (NaNDA) to the 2006-2018 Health and Retirement Study (N=22,245), we fit linear mixed models to assess which of 22 built and social neighborhood environment variables predicted grip strength, a measure of total-body muscle strength. Among 22,245 respondents (mean age=63 years, SD=9.2) with up to 4 grip strength measures, neighborhood physical disorder (B= -0.25 kg, 95\% CI= -0.37,-0.13), number of parks (B= 0.05 kg, 95\% CI= 0.01, 0.10), number of gyms/fitness centers (B=-0.44 kg, 95\% CI= -0.82, -0.07), proportion of highly developed land (B=-2.06 kg, 95\% CI=-4.06, -0.07), and \% urban (B=-0.66 kg, 95\% CI=-1.27, -0.05) were associated with grip strength level after adjustment. No social neighborhood variables were associated with grip strength. Although preliminary, findings suggest that highly developed urbanized land may be a barrier to maintaining muscle strength in later life, but resources such as parks are associated with better outcomes.}, keywords = {Grip strength, Muscle Strength, Neighborhood characteristics}, doi = {10.1093/geroni/igac059.1010}, author = {Kate A Duchowny and L Grisell Diaz-Ramirez and W John Boscardin and Peggy Cawthon and Maria Glymour and Scarlett Lin Gomez} } @article {11622, title = {Association of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention With Memory Decline in Older Adults Undergoing Coronary Revascularization}, journal = {JAMA}, volume = {325}, year = {2021}, pages = {1955-1964}, abstract = {It is uncertain whether coronary artery bypass grafting (CABG) is associated with cognitive decline in older adults compared with a nonsurgical method of coronary revascularization (percutaneous coronary intervention [PCI]).To compare the change in the rate of memory decline after CABG vs PCI.Retrospective cohort study of community-dwelling participants in the Health and Retirement Study, who underwent CABG or PCI between 1998 and 2015 at age 65 years or older. Data were modeled for up to 5 years preceding and 10 years following revascularization or until death, drop out, or the 2016-2017 interview wave. The date of final follow-up was November 2017.CABG (including on and off pump) or PCI, ascertained from Medicare fee-for-service billing records.The primary outcome was a summary measure of cognitive test scores and proxy cognition reports that were performed biennially in the Health and Retirement Study, referred to as memory score, normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged >=72 years). Memory score was analyzed using multivariable linear mixed-effects models, with a prespecified subgroup analysis of on-pump and off-pump CABG. The minimum clinically important difference was a change of 1 SD of the population-level rate of memory decline (0.048 memory units/y).Of 1680 participants (mean age at procedure, 75 years; 41\% female), 665 underwent CABG (168 off pump) and 1015 underwent PCI. In the PCI group, the mean rate of memory decline was 0.064 memory units/y (95\% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95\% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95\% CI, -0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95\% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95\% CI, 0.047 to 0.072) after the procedure (within-group change, -0.011 memory units/y [95\% CI, -0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95\% CI, -0.008 to 0.038; P = .21). There was statistically significant increase in the rate of memory decline after off-pump CABG compared with after PCI (difference-in-differences: mean increase in the rate of decline of 0.046 memory units/y [95\% CI, 0.008 to 0.084] after off-pump CABG), but not after on-pump CABG compared with PCI (difference-in-differences: mean slowing of decline of 0.003 memory units/y [95\% CI, -0.024 to 0.031] after on-pump CABG).Among older adults undergoing coronary revascularization with CABG or PCI, the type of revascularization procedure was not significantly associated with differences in the change of rate of memory decline.}, keywords = {cardiology, cardiothoracic surgery, ischemic heart disease}, isbn = {0098-7484}, doi = {10.1001/jama.2021.5150}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and Alexander K Smith and W John Boscardin and Kenneth E Covinsky and Michael S. Avidan and M. Maria Glymour} } @article {11579, title = {A Novel Method for Identifying a Parsimonious and Accurate Predictive Model for Multiple Clinical Outcomes.}, journal = {Computer Methods and Programs in Biomedicine}, volume = {204}, year = {2021}, pages = {106073}, abstract = {

BACKGROUND AND OBJECTIVE: Most methods for developing clinical prognostic models focus on identifying parsimonious and accurate models to predict a single outcome; however, patients and providers often want to predict multiple outcomes simultaneously. As an example, for older adults one is often interested in predicting nursing home admission as well as mortality. We propose and evaluate a novel predictor-selection computing method for multiple outcomes and provide the code for its implementation.

METHODS: Our proposed algorithm selected the best subset of common predictors based on the minimum average normalized Bayesian Information Criterion (BIC) across outcomes: the Best Average BIC (baBIC) method. We compared the predictive accuracy (Harrell{\textquoteright}s C-statistic) and parsimony (number of predictors) of the model obtained using the baBIC method with: 1) a subset of common predictors obtained from the union of optimal models for each outcome (Union method), 2) a subset obtained from the intersection of optimal models for each outcome (Intersection method), and 3) a model with no variable selection (Full method). We used a case-study data from the Health and Retirement Study (HRS) to demonstrate our method and conducted a simulation study to investigate performance.

RESULTS: In the case-study data and simulations, the average Harrell{\textquoteright}s C-statistics across outcomes of the models obtained with the baBIC and Union methods were comparable. Despite the similar discrimination, the baBIC method produced more parsimonious models than the Union method. In contrast, the models selected with the Intersection method were the most parsimonious, but with worst predictive accuracy, and the opposite was true in the Full method. In the simulations, the baBIC method performed well by identifying many of the predictors selected in the baBIC model of the case-study data most of the time and excluding those not selected in the majority of the simulations.

CONCLUSIONS: Our method identified a common subset of variables to predict multiple clinical outcomes with superior balance between parsimony and predictive accuracy to current methods.

}, keywords = {backward elimination, Bayesian Information Criterion, prognostic models, Survival Analysis, variable selection}, issn = {1872-7565}, doi = {10.1016/j.cmpb.2021.106073}, author = {L Grisell Diaz-Ramirez and Lee, Sei J and Alexander K Smith and Gan, Siqi and W John Boscardin} } @article {10028, title = {Association of functional impairment in middle age with hospitalization, nursing home admission, and death}, journal = {JAMA Internal Medicine}, year = {2019}, month = {Aug-04-2019}, abstract = {Importance Difficulty performing daily activities such as bathing and dressing ({\textquotedblleft}functional impairment{\textquotedblright}) affects nearly 15\% of middle-aged adults. Older adults who develop such difficulties, often because of frailty and other age-related conditions, are at increased risk of acute care use, nursing home admission, and death. However, it is unknown if functional impairments that develop among middle-aged people, which may have different antecedents, have similar prognostic significance. Objective To determine whether middle-aged individuals who develop functional impairment are at increased risk for hospitalization, nursing home admission, and death. Design, Setting, and Participants This matched cohort study analyzed longitudinal data from the Health and Retirement Study, a nationally representative prospective cohort study of US adults. The study population included 5540 adults aged 50 to 56 years who did not have functional impairment at study entry in 1992, 1998, or 2004. Participants were followed biennially through 2014. Individuals who developed functional impairment between 50 and 64 years were matched by age, sex, and survey wave with individuals without impairment as of that age and survey wave. Statistical analysis was conducted from March 15, 2017, to December 11, 2018. Exposures Impairment in activities of daily living (ADLs), defined as self-reported difficulty performing 1 or more ADLs, and impairment in instrumental ADLs (IADLs), defined similarly. Main Outcomes and Measures The 3 primary outcomes were time from the first episode of functional impairment (or matched survey wave, in controls) to hospitalization, nursing home admission, and death. Follow-up assessments occurred every 2 years until 2014. Competing risks survival analysis was used to assess the association of functional impairment with hospitalization and nursing home admission and Cox proportional hazards regression analysis was used to assess the association with death. Results Of the 5540 study participants (2739 women and 2801 men; median age, 53.7 years [interquartile range, 52.3-55.2 years]), 1097 (19.8\%) developed ADL impairment between 50 and 64 years, and 857 (15.5\%) developed IADL impairment. Individuals with ADL impairment had an increased risk of each adverse outcome compared with those without impairment, including hospitalization (subhazard ratio, 1.97; 95\% CI, 1.77-2.19), nursing home admission (subhazard ratio, 2.62; 95\% CI, 1.99-3.45), and death (hazard ratio, 2.06; 95\% CI, 1.74-2.45). After multivariable adjustment, the risks of hospitalization (subhazard ratio, 1.54; 95\% CI, 1.36-1.75) and nursing home admission (subhazard ratio, 1.73; 95\% CI, 1.24-2.43) remained significantly higher among individuals with ADL impairment, but the risk of death was not statistically significant (hazard ratio, 1.06; 95\% CI, 0.85-1.32). Individuals with IADL impairment had an increased risk of all 3 outcomes in adjusted and unadjusted analyses. Conclusions and Relevance Similar to older adults, middle-aged adults who develop functional impairment appear to be at increased risk for adverse outcomes. Even among relatively young people, functional impairment has important clinical implications.}, keywords = {Functional limitations, Hospitalization, Mortality, Nursing homes}, issn = {2168-6106}, doi = {10.1001/jamainternmed.2019.0008}, url = {http://archinte.jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2019.0008http:///jamainternalmedicine/article-pdf/doi/10.1001/jamainternmed.2019.0008/17440339/jamainternal_brown_2019_oi_190001.pdf}, author = {Rebecca T Brown and L Grisell Diaz-Ramirez and W John Boscardin and Sei J. Lee and Brie A Williams and Michael A Steinman} } @article {9916, title = {Cognitive Change After Cardiac Surgery Versus Cardiac Catheterization: A Population-Based Study.}, journal = {The Annals of Thoracic Surgergy}, volume = {107}, year = {2019}, pages = {1119-1125}, abstract = {

BACKGROUND: Despite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery.

METHODS: Participants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently.

RESULTS: Of 3,105 participants, 1,921 (62\%) underwent catheterization and 1,184 (38\%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95\% confidence interval:~-0.046 to 0.005 memory units, p~= 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26\% or 0.19\% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95\% confidence interval: 0.74 to 1.18).

CONCLUSIONS: In this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.

}, keywords = {Cardiac surgery, Cardiovascular disease, Cognition \& Reasoning, Memory}, issn = {1552-6259}, doi = {10.1016/j.athoracsur.2018.10.021}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and Alexander K Smith and W John Boscardin and Michael S. Avidan and M. Maria Glymour} } @article {9857, title = {{\textquoteleft}Til Death Do Us Part: End-of-Life Experiences of Married Couples in a Nationally Representative Survey}, journal = {Journal of the American Geriatrics Society}, year = {2018}, month = {Jan-09-2020}, abstract = {Objectives: To determine whether end-of-life (EOL) experiences in the first spouse in a marriage are associated with EOL experiences in the other spouse. Design: Nationally representative, longitudinal survey. Setting: Health and Retirement Study, Waves 1992{\textendash}2012 linked to Medicare claims. Participants: Community-dwelling older adults who died (N=4,558), representing 2,279 married heterosexual couples. Measurements: We examined 3 EOL experiences: enrollment in hospice for >3 days before death, lack of advance care planning (ACP) before death, and intensive care unit (ICU) use during the last 30 days of life. We used multiple logistic regression to determine whether the EOL experience of the first spouse was a significant predictor of the EOL experience of the second spouse after adjusting for demographic characteristics, socioeconomic status, health status, and time between the first and second spouses{\textquoteright} deaths. Results: First spouses who died were on average 80 years old, and 62\% were male; second spouses were on average 85 years old, and 62\% were female. After adjustment, second spouses were more likely to use hospice if the first spouse used hospice (odds ratio (OR)=1.68, 95\% confidence interval (CI)=1.29{\textendash}2.20). Second spouses were less likely to have ACP when the first spouse did not have ACP (OR=2.91, 95\% CI=2.02{\textendash}4.21). Hospice and ACP associations were stronger when deaths were closer in time to one another (p-value for interaction <.05). Second spouses were more likely to use ICU services if the first spouse did (OR=1.80, 95\% CI=1.27{\textendash}2.55). Conclusions: The EOL experiences of older spouses are strongly associated, which may be relevant when framing ACP discussions. {\textcopyright} 2018, Copyright the Author Journal compilation {\textcopyright} 2018, The American Geriatrics Society }, keywords = {End of life decisions, End-of-life care, Hospice, Marriage}, doi = {10.1111/jgs.15573}, url = {http://doi.wiley.com/10.1111/jgs.15573http://onlinelibrary.wiley.com/wol1/doi/10.1111/jgs.15573/fullpdfhttps://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111\%2Fjgs.15573}, author = {Ashwin A Kotwal and Abdoler, Emily and L Grisell Diaz-Ramirez and Amy Kelley and Katherine A Ornstein and W John Boscardin and Alexander K Smith} } @article {9116, title = {Association between persistent pain and memory decline and dementia in a longitudinal cohort of elders}, journal = {JAMA Internal Medicine}, volume = {177}, year = {2017}, chapter = {1146-1153}, abstract = {Importance: Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. Objective: To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Design, Setting, and Participants: Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. Exposures: {\textquotedblleft}Persistent pain,{\textquotedblright} defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Main Outcomes and Measures: Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Results: Of the 10,065 eligible HRS sample members, 60\% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9\% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate adjustment, persistent pain was associated with 9.2\% (95\% CI, 2.8\%-15.0\%) more rapid memory decline compared with those without persistent pain. After 10 years, this accelerated memory decline implied a 15.9\% higher relative risk of inability to manage medications and an 11.8\% higher relative risk of inability to manage finances independently. Adjusted dementia probability increased 7.7\% faster (95\% CI, 0.55\%-14.2\%); after 10 years, this translates to an absolute 2.2\% increase in dementia probability for those with persistent pain. Conclusions and Relevance: Persistent pain was associated with accelerated memory decline and increased probability of dementia.}, keywords = {Chronic pain, Cognitive Ability, Memory}, doi = {10.1001/jamainternmed.2017.1622}, url = {https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2629448}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and M. Maria Glymour and W John Boscardin and Kenneth E Covinsky} } @article {9471, title = {Functional Impairment and Decline in Middle Age: A Cohort Study.}, journal = {Annals of Internal Medicine}, volume = {167}, year = {2017}, pages = {761-768}, abstract = {

Background: Difficulties with daily functioning are common in middle-aged adults. However, little is known about the epidemiology or clinical course of these problems, including the extent to which they share common features with functional impairment in older adults.

Objective: To determine the epidemiology and clinical course of functional impairment and decline in middle age.

Design: Cohort study.

Setting: The Health and Retirement Study.

Participants: 6874 community-dwelling adults aged 50 to 56 years who did not have functional impairment at enrollment.

Measurements: Impairment in activities of daily living (ADLs), defined as self-reported difficulty performing 1 or more ADLs, assessed every 2 years for a maximum follow-up of 20 years, and impairment in instrumental ADLs (IADLs), defined similarly. Data were analyzed by using multistate models that estimate probabilities of different outcomes.

Results: Impairment in ADLs developed in 22\% of participants aged 50 to 64 years, in whom further functional transitions were common. Two years after the initial impairment, 4\% (95\% CI, 3\% to 5\%) of participants had died, 9\% (CI, 8\% to 11\%) had further ADL decline, 50\% (CI, 48\% to 52\%) had persistent impairment, and 37\% (CI, 35\% to 39\%) had recovered independence. In the 10 years after the initial impairment, 16\% (CI, 14\% to 18\%) had 1 or more episodes of functional decline and 28\% (CI, 26\% to 30\%) recovered from their initial impairment and remained independent throughout this period. The pattern of findings was similar for IADLs.

Limitation: Functional status was self-reported.

Conclusion: Functional impairment and decline are common in middle age, as are transitions from impairment to independence and back again. Because functional decline in older adults has similar features, current interventions used for prevention in older adults may hold promise for those in middle age.

Primary Funding Source: National Institute on Aging and National Center for Advancing Translational Sciences through the University of California, San Francisco, Clinical and Translational Sciences Institute.

}, keywords = {Activities of Daily Living, Functional limitations, Memory, Older Adults}, issn = {1539-3704}, doi = {10.7326/M17-0496}, author = {Rebecca T Brown and L Grisell Diaz-Ramirez and W John Boscardin and Sei J. Lee and Michael A Steinman} } @article {9344, title = {Wealth-Associated Disparities in Death and Disability in the United States and England.}, journal = {JAMA Internal Medicine}, volume = {177}, year = {2017}, pages = {1745-1753}, abstract = {

Importance: Low income has been associated with poor health outcomes. Owing to retirement, wealth may be a better marker of financial resources among older adults.

Objective: To determine the association of wealth with mortality and disability among older adults in the United States and England.

Design, Setting, and Participants: The US Health and Retirement Study (HRS) and English Longitudinal Study of Aging (ELSA) are nationally representative cohorts of community-dwelling older adults. We examined 12 173 participants enrolled in HRS and 7599 enrolled in ELSA in 2002. Analyses were stratified by age (54-64 years vs 66-76 years) because many safety-net programs commence around age 65 years. Participants were followed until 2012 for mortality and disability.

Exposures: Wealth quintile, based on total net worth in 2002.

Main Outcomes and Measures: Mortality and disability, defined as difficulty performing an activity of daily living.

Results: A total of 6233 US respondents and 4325 English respondents aged 54 to 64 years (younger cohort) and 5940 US respondents and 3274 English respondents aged 66 to 76 years (older cohort) were analyzed for the mortality outcome. Slightly over half of respondents were women (HRS: 6570, 54\%; ELSA: 3974, 52\%). A higher proportion of respondents from HRS were nonwhite compared with ELSA in both the younger (14\% vs 3\%) and the older (13\% vs 3\%) age cohorts. We found increased risk of death and disability as wealth decreased. In the United States, participants aged 54 to 64 years in the lowest wealth quintile (Q1) (<=$39 000) had a 17\% mortality risk and 48\% disability risk over 10 years, whereas in the highest wealth quintile (Q5) (>$560 000) participants had a 5\% mortality risk and 15\% disability risk (mortality hazard ratio [HR], 3.3; 95\% CI, 2.0-5.6; P < .001; disability subhazard ratio [sHR], 4.0; 95\% CI, 2.9-5.6; P < .001). In England, participants aged 54 to 64 years in Q1 (<={\textsterling}34,000) had a 16\% mortality risk and 42\% disability risk over 10 years, whereas Q5 participants (>{\textsterling}310,550) had a 4\% mortality risk and 17\% disability risk (mortality HR, 4.4; 95\% CI, 2.7-7.0; P < .001; disability sHR, 3.0; 95\% CI, 2.1-4.2; P < .001). In 66- to 76-year-old participants, the absolute risks of mortality and disability were higher, but risk gradients across wealth quintiles were similar. When adjusted for sex, age, race, income, and education, HR for mortality and sHR for disability were attenuated but remained statistically significant.

Conclusions and Relevance: Low wealth was associated with death and disability in both the United States and England. This relationship was apparent from age 54 years and continued into later life. Access to health care may not attenuate wealth-associated disparities in older adults.

}, keywords = {Cross-National, Disabilities, Mortality, Wealth Inequality}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2017.3903}, author = {Lena K Makaroun and Rebecca T Brown and L Grisell Diaz-Ramirez and Cyrus Ahalt and W John Boscardin and Lang-Brown, Sean and Sei J. Lee} }