Claude D. Pepper Older Americans Independence Center

Jay Magaziner, Ph.D., M.S.Hyg
Alice Ryan, Ph.D.
Les Katzel, M.D., Ph.D.
Anne Sullens, M.A
Program Administrator

The mission of the UM-OAIC is to address the process by which function is lost, and the multiple factors that affect the onset and progression of disability. Building on these important perspectives, the UMOAIC focuses on the restoration of function (i.e., enablement) in order to improve function in those with impairments, and prevent or delay further progression in those who are already disabled. This is accomplished by 1) conducting research that examines the mechanisms underlying the functional impairments associated with chronic diseases in older people, such as stroke, hip fracture, obesity, Type-2 diabetes, osteoarthritis, Parkinson's disease, and vascular disease; 2) designing novel, efficacious rehabilitation interventions that produce clinically relevant outcomes and study the mechanisms underlying these interventions; 3) translating interventions found to be efficacious in UM-OAIC clinical laboratories and other clinical centers for implementation and rigorous evaluation outside the clinic (e.g., home, senior center, gym); 4) supporting pilot and exploratory studies (PESs), UM-OAIC REC Scholar research, development projects (DPs), and externally funded projects (EP) that are consistent with the UM-OAIC theme; and 5) supporting the development of junior faculty and REC Scholars from multiple disciplines as they pursue careers as independent, academic scientists with expertise in the study of older persons with disabling diseases through mentor-based, didactic and experiential training in bench-to-bedside-to-community translational research.

The UM-OAIC has three resource cores (RC): Biostatistics and Informatics (RC1); Applied Physiology and  Mechanisms (RC-2); and Rehabilitation Science and Technologies (RC-3), that serve as resources for the conduct of innovative exercise and activity-based rehabilitation research. An enhanced Research Education Core (REC) will provide didactic and experiential, and leadership training under the guidance of an interdisciplinary mentoring teams to prepare the next generation of scientists committed to careers in aging research. A Pilot and Exploratory Studies Core (PESC) supports the development and execution of pilot and REC Scholar projects.  Center aims will be accomplished by: 1) advancing our understanding of the mechanisms by which exercise and activity-based and multi-modal rehabilitation interventions directed a specific impairments affect multiple body systems; 2) developing and testing interventions to restore function and minimize disability following acute disabling events and to prevent declines related to serious chronic diseases; and 3) training the next generation of investigators who will further the understanding of the aging process and develop interventions that help promote health and independence in older adults with disabling medical conditions.  

Leadership and Administrative Core (LAC)
Leader 1:    Jay Magaziner, PhD, MS Hyg.
Leader 2:    Leslie I. Katzel, MD
Leader 3:    Alice Ryan, PhD
The Leadership and Administrative Core (LAC) ensures that the UM-OAIC provides support for conducting novel research and training the next generation of scientists pursuing research careers in aging and oversight to the five UM-OAIC cores. Core leaders also foster maximal outreach and interaction with the rest of the University of Maryland, Baltimore (UMB) inter-professional campus, other OAICs, and research programs elsewhere pursuing work on areas relevant to the UM-OAIC’s enablement theme. The LAC will receive input and guidance, and discuss program operations in the Core Leadership Executive Committee (CLEC) meeting of core leaders; the UM-OAIC Research and Education Advisory Panel (REAP) charged with reviewing proposed Development and Pilot Exploratory Studies and progress of Scholars; a Community Advisory Board (CAB) that will provide input on issues that are most relevant for enabling function in older persons with disabling conditions in different communities and on the merit of research that is being proposed and conducted in the UM-OAIC; an Internal Advisory Committee (IAC) that evaluates UM-OAIC progress and accomplishments, and provides advice on ways to extend research on aging to other university centers and departments; and an External Advisory Board (EAB) that will provide guidance to the program and report progress annually to the NIA. In addition, the LAC receives advice from an Internal Data and Safety Monitoring Board (I-DSMB) that will review the conduct of clinical protocols to ensure patient safety and progress of projects, and an External Data and Safety Monitoring Board (E-DSMB) that will provide another layer of review by experienced, impartial scientists that will monitor study progress and data quality and safety, and report to the NIA annually.

Research Education Component (REC)
Leader 1:    Mary-Claire Roghmann, MD, MS
Leader 2:    Jack Guralnik, MD, PhD, MPH
The purpose of the Research Education Core (REC) is to support the development of junior faculty from multiple disciplines as they pursue careers as scientists with a focus on the restoration of function among older adults with impairments and on the prevention or delay of progression in those who are already disabled. The REC supports Scholars and affiliated faculty (who are former Scholars or junior faculty with career development awards related to our mission) in mentor-based research training and other career development activities in a supportive research environment. The REC will achieve the above with the following aims: 1) Recruit and retain REC Scholars and affiliated faculty committed to research careers congruent with the UM-OAIC mission; 2) train REC Scholars and affiliated faculty through mentored research projects and individualized training plans which use the resources of the UM-OAIC, the national OAIC network and other NIA supported programs; 3) Develop a Leadership Academy which will teach leadership skills and provide leadership experience for promising junior and mid-level scientists with demonstrated commitment and expertise to become the next leaders, in the UM-OAIC and nationally, in research aimed at improving function in older adults and 4) evaluate the UM-OAIC Research Education Core with the help of experts in the University of Maryland Baltimore (UMB) Faculty Center for Teaching and Learning and in the Research Education Advisory Panel (REAP).

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Stephen Seliger, MD, MS
Leader 2:    Marc Hochberg, MD, MPH, MACP, MACR
The purpose of the UM-OAIC Pilot and Exploratory Studies Core (PESC) is to provide critical initial funding for pilot and exploratory studies that are consistent with the UM-OAICs overall goal of advancing the study of enablement in older adults by: 1) identifying the deficits associated with specific disabling conditions; 2) investigating the mechanisms and pathophysiology responsible for these deficits; and 3) developing exercise, other activity-based interventions, and multi-modal rehabilitation strategies that target these mechanisms and deficits; 4) testing them in clinical laboratories/centers under carefully controlled conditions; and 5) adapting them for implementation and further testing in home and other settings outside the medical center. To meet this objective, the PESC will attract junior investigators (and established investigators new to aging research) across a broad range of disciplines to study rehabilitation and recovery in older adults and in relevant pre-clinical models, stimulate new studies in aging-related rehabilitation research through targeted funding, encourage new interdisciplinary collaborations, and translate efficacious therapies across the spectrum from bench to clinical laboratory to community practice. This will advance the UM-OAIC research goal of expanding therapies in the broadest context of rehabilitation that emphasizes restorative and preventive medicine to promote the recovery and enablement of older adults with disabling conditions.

Applied Physiology and Tissue Mechanisms
Leader 1:    Alice Ryan, PhD
Leader 2:    Leslie I. Katzel, MD
Leader 3:    Chris Ward, PhD
RC-2 provides UM-OAIC investigators comprehensive support for quantified physical activity, functional and metabolic phenotyping, and blood and tissue bioassays to advance clinical research. Research performed by UM-OAIC investigators demonstrates that various modes of exercise, and/or rehabilitation training, improve cardiovascular fitness, muscle endurance, strength, neuromotor control, and body composition in older people with chronic disease and disability such as those with stroke, peripheral arterial disease (PAD), congestive heart failure, obesity, diabetes, hip fracture, an intensive care unit stay, HIV and cancer. Collectively, these works inform our overarching hypothesis that exercise, activity-based, and multi-modal rehabilitation can improve multiple physiological systems in older mobility-limited individuals which in turn can improve functional performance, reduce cardiometabolic disease risk, and prevent further functional decline. To achieve this goal, RC2 implements specific aims that: 1) advance research focused on the mechanisms of functional decline in older persons with disability and the mitigation of decline with exercise or activity-based or multi-modal rehabilitation and 2) provide mentoring and training to REC Scholars, affiliated faculty, and UM-OAIC researchers in the performance of aging research relevant to exercise and rehabilitation-based restoration of function and the prevention of functional declines in older people with chronic disabling diseases.

Biostatistics and Informatics
Leader 1:    John D. Sorkin, MD, PhD
Leader 2:    Michael Terrin, MD, MPH
Leader 3:    Laurence Magder, PhD
The goal of the Biostatistics and Informatics Core (RC-1) plays a central role in UM-OAIC research helping investigators design, conduct, and report results of research studies. RC-1 plays a key role in the coordination and integration of UM-OAIC. Our informatics infrastructure facilitates UM-OAIC operation and oversight by tracking study progress, recording and reporting adverse events, monitoring core requests and use, and providing reports to PIs and Core leaders. RC-1 participates in REC organized education efforts and participates in other research training initiatives at the university. This core has 2 two major goals: 1) to support the conduct of studies that promote the independence of older adults with disabling conditions; 2) train the next generation of investigators who will conduct studies that promote health and independence in older adults. One-on-one training will take place as we help Scholars and other investigators design, execute, analyze and publish their results and as we participate in Research Design Studios, Project Initiation Support Groups and Research Working Groups. In addition, the RC-1 will help investigators find and enroll participants for their research projects, we are expanding our recruitment efforts by adding an investigator experienced in recruiting older persons. Finally, the core will also develop biostatistical methods and informatics resources that facilitate funded and supported projects of the UM-OAIC.

Neuromotor Mechanisms and Rehabilitation
Leader 1:    Richard Macko, MD
Leader 2:    Li-Qun (Larry) Zhang, PhD
Rehabilitation Science and Technologies Resource Core 3 (RC-3), aims to improve our ability to prevent and reverse these declines. We build on this core’s strengths in rehabilitation medicine and physical therapy with a focus on gait, balance and mobility research, by expanding to mechanistic studies of motor learning and activity-dependent plasticity. Incorporation of new bioengineering capacity has expanded the resources and mentoring needed by UM-OAIC investigators to design, test, and translate novel rehabilitative technologies and engineering-informed approaches into new services and products. Technology transfer processes and academic-private partnerships are introduced to accelerate translation into community practice and into products with public health impact. The central hypothesis of RC-3 is that rehabilitation science-based therapeutics that leverage activity-dependent plasticity and neuromotor learning (including balance, mobility training, and bioengineering-modelled rehabilitation robotics and other technologies) will improve recovery and enhance function in older adults with functional limitations and disability. The aims of RC-3 are as follows: 1) develop and support mechanistic investigations of physical activity and exercise-mediated central and peripheral neuromuscular adaptations that underlie the neuroplastic mediated improvements in functional performance produced by rehabilitative interventions and enabling technologies; 2) mentor and support REC Scholars and UM-OAIC researchers in the design, development and implementation of motor learning-based rehabilitation studies and enabling technologies and the underlying neuromuscular mechanisms to improve functional outcomes in older persons with functional limitations and 3) facilitate translation of UM-OAIC discoveries across the mechanistic, rehabilitation engineering, applied clinical testing, and technology transfer phases in order to catalyze transition of discoveries into evidence-based services, products, and tools for precision rehabilitation.

REC Scholar, Research & Grants Funded During Pepper Supported Time Years /
Jeanine Ursitti, PhD
Assistant Professor / Department of Orthopaedics
Cell Mechanics as a Biomarker of Osteosarcopenia”
Abstract: Previous work has identified increased cytoskeletal stiffness, driven by increased levels of microtubules post-translationally modified by detyrosination, as a common predictor of biological dysfunction across bone, skeletal muscle, and cardiac tissue. Our new preliminary evidence in aging mice (17-78 weeks) finds increasing microtubule detyrosination in muscle and bone and increased stiffness/mechanics in the muscle fiber. The goal of this pilot project is to determine whether microtubule dependent cytoskeletal stiffness is a novel biomarker of biological aging. Here we will extend our measures of cell mechanics (in isolated intact skeletal muscle fibers) and tubulin biochemistry (in skeletal muscle and bone), to circulating peripheral blood mononuclear cells (PBMCs), to test our hypothesis that the level of microtubule detyrosination, and microtubule dependent cytoskeletal stiffness, are biomarkers of biological age. Hypothesis/Aims: We hypothesize that age-related changes in microtubule (MT) structure and post-translational modifications in Peripheral Blood Mononuclear Cells (PBMCs) will track with changes in skeletal muscle fibers, bone osteocytes, and perhaps other tissues, making it a predictive, easily assessable biomarker. We further hypothesize that the cellular stiffness of PBMCs will track with deTyrosinated MTs (deTyr-MTs) in aging skeletal muscle. We have two specific aims: Aim 1: Define age dependent changes in cytoskeletal structure and properties across disparate tissues and blood monocytes. Aim 2. Determine age-related changes in PBMC mechanics as a biomarker of aging and treatment efficacy.
  • OAIC Coordinating Center: Early Career Faculty Flexible, High Value Award. Ursitti (PI). 07/2021-06/2022. $5,000

2021-2024 /
9 (total)
2 (1st/Sr)
Andrea Levine, MD
Assistant Professor / Department of Medicine
The Longevity of ARDS Inflammatory Subphenotypes and Their Role in Predicting Functional Recovery in Older Adults
Abstract: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening illness of severe hypoxemia. A hyper- and hypo-inflammatory subphenotype exist with a differential treatment effect. We aim to describe the longevity of the subphenotypes determine whether these subphenotypes can predict functional recovery in older adult patients. Hypothesis/Aims: Subphenotype longevity: To determine whether the ARDS subphenotype established on hospital admission is sustained during the inpatient hospitalization and post-acute recovery phase. Approach: We will utilize a parsimonious combination of validated plasma biomarkers (IL-8, HCO-3, and Protein C) to determine whether ARDS subphenotypes established at admission are maintained through the duration of the inpatient hospitalization and at post-acute follow-up three months after discharge in older adult patients. Aim 2: Correlation with longitudinal functional recovery: To determine whether ARDS subphenotype predicts the trajectory of functional recovery in older survivors of ARDS. Approach: In a pilot study, survivors of ARDS will be followed at three months after hospital discharge and assessed for pulmonary recovery via spirometry, neurocognitive function using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), psychiatric status using the Hospital Anxiety and Depression Survey (HADS) and PCL-5 and neuromuscular function using a six-minute walk test and short physical performance battery (SPPB). We will determine whether the inflammatory subphenotype assigned at hospital discharge predicts functional recovery at three-months after hospital discharge.
2022-2024 /
23 (total)
9 (1st/Sr)
Sarasijhaa Desikan, MD
Assistant Professor / Department of Surgery, University of Maryland School of Medicine
Asymptomatic Carotid Stenosis: Cognitive and Mobility Function after Exercise (ACCOF-Ex)
The purpose of her study is to determine the effect of a challenging aerobic and balance exercise intervention on cognitive and mobility function in patients with moderate (50-69%) asymptomatic carotid artery stenosis. In addition, the study evaluates functional near-infrared spectroscopy (fNIRS) as a novel modality to assess cerebral oxygenation during cognitive and mobility tasks.
  • Asymptomatic Carotid Stenosis: Cognitive Function and Plaque Correlates- Exercise Intervention. University of Maryland Institute for Clinical and Translational Research Voucher Support Grant, Desikan (PI). 1/2020-1/2021. $5,000
  • Asymptomatic Carotid Stenosis and Mobility Function with Exercise Intervention. RR&D CDA-2. Desikan (PI). 10/2022-09/2027. $2,029,681

2020-2023 /
10 (total)
2 (1st/Sr)

Past Scholars
F. Rainer von Coelln, Dr. med, Department of Neurology, University of Maryland School of Medicine (2017-2020)
Tasneem Khambaty, PhD, Department of Psychology, University of Maryland Baltimore County (2018-2021)
Jason Falvey, PT, DPT, PhD, Department of Physical Therapy and Rehabilitation Science (2021-2021)

1. Project Title: Relations of Glucose Variability with Cognitive Function and Functional Status among Older Adults at Risk for Diabetes
  Leader: Tasneem Khambaty, PhD
  Abstract: Type 2 diabetes (T2DM) is an independent risk factor for dementia and less severe forms of cognitive dysfunction and may compromise functional status. Metrics derived from continuous glucose monitoring (CGM) technology – i.e., glucose variability – may facilitate the detection of impaired glycemia much earlier than the conventional glycemic metrics. We propose a robust characterization of intra- and inter-day variability in glucose regulation and a deeper understanding of the extent to which this variability influences cognitive aging and functional decline in persons at risk for diabetes. Understanding this early aging trajectory is an important step towards discerning the mechanisms underlying various aspects of glycemia and neurocognition. Hypotheses: Our central hypothesis is that even before diabetes onset, glucose variability will be associated with worse cognitive function and lower functional status among older adults. Our specific aims are to examine the association of glucose variability derived from CGMS over a 10-day self-monitoring period with cognitive function, and functional status among individuals with prediabetes, aged 50 or older.
2. Project Title: Immune mechanisms responsible for the impaired B cell responses to new antigens in the elderly
  Leader: Franklin Toapanta, PhD
  Abstract: Development of humoral responses to new antigens are impaired in older adults (>65 years). Alterations at multiple levels of the immune system are likely implicated and, to date, there is little information about the intrinsic B cell factors responsible for the poor antibody responses in older adults. We have used Hepatitis B virus vaccination as a model to study potential alterations on B cell responses. We hypothesized that older adults, compared to young adults, have a reduced pool of circulating antigen-specific B cells to novel antigens. Furthermore, we hypothesized that in older adults, antigen-specific B memory cells induced by vaccination will have reduced antibody production capacity due to higher activation thresholds. These studies were proposed to be carried out in cryopreserved specimens (PBMC) of volunteers vaccinated with Recombivax-HB (HBV vaccine).
3. Project Title: Home Exercise (HEX) for Homebound Older Adults
  Leader: Alyssa Stookey, PhD

Abstract:Little is known about the feasibility and utility of pragmatic home-based exercise in older homebound adults with severe mobility disability. We propose a feasibility study to design and implement a pragmatic 12-week home exercise program (HEX) intervention program to improve physical functioning and quality of life in homebound older adults with mobility disability.

Hypothesis: Our general hypothesis is HEX will prove feasible and effective in maintaining and restoring physical functioning and perceived quality of life. Aim #1: We will work with providers and patients to develop a feasible and pragmatic, multi-component home exercise program targeting mobility, strength, and performance of task-oriented ADLs. Aim #2: Perform a small study to better assess feasibility and determine the effect(s) of the home-based intervention created in Aim 1 on functional outcomes and QOL(at baseline, 6 weeks, and 12 weeks) in older, homebound adults.

4. Project Title: Mobile Sensor Investigation of Gait Variability and Hip abductors
  Leader: Odessa Addison, DPT, PhD
  Abstract: Our work suggests that dysfunction of the hip abductors may contribute to balance and mobility limitations resulting in increased fall risk. We have previously shown that gait variability, defined as fluctuations between gait cycles, are an important assessment of mobility and balance function and related to muscle composition of the hip abductor muscles. Gait variability is traditionally assessed via a short 25-foot walk way. However, this distance is too short to account for the impact of fatigue. We propose examining changes in gait variability over a six-minute walk distance may allow for an earlier detection of fall risk by exposing impairments that occur under conditions of fatigue that would otherwise go undetected. The overall aim of our work is to study the use of technology-based assessments and interventions which impact enablement of older adults. Hypothesis/Aims: Aim 1: Examine changes in gait variability between the early and late phase of the six-minute walk. Aim 2: Compare how gait variability in the early and late phases of the six-minute walk relates to muscle size and composition of the hip abductors. Aim 3: Examine how changes in the hip abductors after a 12-week intervention relates to changes in gait variability during the early and late phases of the six-minute walk.
5. Project Title: Neural Mechanisms of Motor Recovery with Technology Assisted Training for Post-stroke Hemiparesis
  Leader: Robynne Braun, MD, PhD
  Abstract: Arm weakness persists chronically in 40% of stroke survivors and accounts for at least half of the decline in quality of life after stroke. Our preliminary work indicates that technology-assisted-training can provide clinically meaningful improvements in arm function for approximately 30% of patients with chronic post-stroke-hemiparesis. The goals of this proposal are: 1) to investigate brain network activity changes that occur during technology-assisted-training and 2) to determine the baseline residual brain network connectivity required for patients to respond to technology-assisted-training, The results of this study will lead to establishment of a personalized medicine algorithm for technology-assisted-training to the patients most likely to respond to it, shifting the delivery of therapy for chronic stroke-induced arm weakness towards individualized, evidence-based care. Hypothesis/Aims: Aim 1: Define cortical connectivity dynamics during technology-assisted-training. Hypothesis: Technology- assisted- training induced increases in cortical connectivity between bilateral primary motor areas and angular gyrus and parietal operculum will positively correlate with improvement in technology-assisted-assessments. Approach: Near infrared spectroscopy brain imaging will be used to measure cortical activity in motor and non-motor cortical areas real-time during 9 sessions of technology-assisted-training over 3 weeks in a cohort of 10 patients with chronic post-stroke-hemiparesis. The relationships between cortical connectivity and measures of movement and proprioception will be analyzed and compared between stroke survivors and 10 healthy controls. Aim 2: Identify baseline brain network connectivity predictors of technology-assisted-training impairment reductions. Hypothesis (a): Baseline connectivity of angular gyrus and parietal operculum to sensorimotor networks will predict reductions in impairment induced by technology-assisted-training. Approach: We have brain MRI baseline network functional connectivity data on 66 patients with chronic post-stroke hemiparesis who have undergone 3 months (~36 sessions) of technology-assisted-training of the upper extremity. This aim will analyze baseline brain functional connectivity prior to the onset of training to find correlates of training induced impairment reduction.
6. Project Title: Ryanodine Receptors as Novel Targets in Chronotropic Incompetence in the Aging Heart
  Leader: B. Maura Greiser, PhD
  Abstract: Chronotropic incompetence is the hallmark of the aging heart. This means that the heart’s pacemaker, the sino-atrial node (SAN), fails to produce a heart rate that is fast enough to match circulatory demand. This results in reduced left ventricular output over time in the aging heart compared to younger hearts. Hypothesis/Aims: The goal of this Pilot Project is to provide foundational evidence linking RyR2 dysfunction to chronotropic incompetence. We further want to test whether aging-mediated RyR2 dysfunction in SAN cells can be partially reversed by a) pharmaceutical agents that stabilize RyR2 function and b) by reducing the levels of intracellular reactive oxygen species (ROS).
7. Project Title: Engaging Community and Municipal Stakeholders to Improve High-Quality Aging in Place for Community Dwelling Older Hip Fracture Survivors with Alzheimer’s Disease or Related Dementias
  Leader: Jason Falvey, PT, DPT, PhD
  Abstract: This project will assess factors that most strongly impact the number of healthy days spent at home after hip fracture for patients with dementia, using Medicare claims data linked with social vulnerability data. Hypothesis/Aims: 1) Assess how socioeconomic disadvantage at individual and neighborhood level impacts healthy days at home for persons with dementia; 2) Assess high-quality aging in place phenotypes among older adults with dementia and determine pre and peri-operative factors associated with these phenotypes
8. Project Title: Persistence of Depression and Pain and Functional Outcomes in Knee Osteoarthritis
  Leader: Alan Rathbun, PhD, MPH
  Hypothesis/Aims: Aim 1: To assess how the persistence of depressive symptoms cumulatively affect functional outcomes among persons with or at risk for symptomatic knee OA. Hypothesis: Greater persistence of depressive symptoms is associated with worse function over time in a dose-dependent manner. Aim 2: To determine whether dynamic fluctuations in knee pain mediate the association between persistent depression and functional outcomes. Hypothesis: Higher pain severity will be associated with a stronger indirect (mediated) effect of depressive symptoms on functional outcomes.
9. Project Title: Cell Mechanics as a Biomarker of Osteosarcopenia
  Leader: Jeanine Ursitti, PhD
  Abstract: Previous work has identified increased cytoskeletal stiffness, driven by increased levels of microtubules post-translationally modified by detyrosination, as a common predictor of biological dysfunction across bone, skeletal muscle, and cardiac tissue. Our new preliminary evidence in aging mice (17-78 weeks) finds increasing microtubule detyrosination in muscle and bone and increased stiffness/mechanics in the muscle fiber. The goal of this pilot project is to determine whether microtubule dependent cytoskeletal stiffness is a novel biomarker of biological aging. Here we will extend our measures of cell mechanics (in isolated intact skeletal muscle fibers) and tubulin biochemistry (in skeletal muscle and bone), to circulating peripheral blood mononuclear cells (PBMCs), to test our hypothesis that the level of microtubule detyrosination, and microtubule dependent cytoskeletal stiffness, are biomarkers of biological age. Hypothesis/Aims: We hypothesize that age-related changes in microtubule (MT) structure and post-translational modifications in Peripheral Blood Mononuclear Cells (PBMCs) will track with changes in skeletal muscle fibers, bone osteocytes, and perhaps other tissues, making it a predictive, easily assessable biomarker. We further hypothesize that the cellular stiffness of PBMCs will track with deTyrosinated MTs (deTyr-MTs) in aging skeletal muscle. We have two specific aims: Aim 1: Define age dependent changes in cytoskeletal structure and properties across disparate tissues and blood monocytes. Aim 2. Determine age-related changes in PBMC mechanics as a biomarker of aging and treatment efficacy.
10. Project Title: The Longevity of ARDS Inflammatory Subphenotypes and Their Role in Predicting Functional Recovery in Older Adults
  Leader: Andrea Levine, MD
  Hypothesis/Aims: Subphenotype longevity: To determine whether the ARDS subphenotype established on hospital admission is sustained during the inpatient hospitalization and post-acute recovery phase. Approach: We will utilize a parsimonious combination of validated plasma biomarkers (IL-8, HCO-3, and Protein C) to determine whether ARDS subphenotypes established at admission are maintained through the duration of the inpatient hospitalization and at post-acute follow-up three months after discharge in older adult patients. Aim 2: Correlation with longitudinal functional recovery: To determine whether ARDS subphenotype predicts the trajectory of functional recovery in older survivors of ARDS. Approach: In a pilot study, survivors of ARDS will be followed at three months after hospital discharge and assessed for pulmonary recovery via spirometry, neurocognitive function using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), psychiatric status using the Hospital Anxiety and Depression Survey (HADS) and PCL-5 and neuromuscular function using a six-minute walk test and short physical performance battery (SPPB). We will determine whether the inflammatory subphenotype assigned at hospital discharge predicts functional recovery at three-months after hospital discharge.
DEVELOPMENT PROJECTS (0 Development Projects Listed)
  No development projects.
RESEARCH (23 Projects Listed)
1. Project Title: Resistive Training and Functional Genetic Mechanisms of Skeletal Muscle Recovery Post-stroke
  Leader(s): XU, HUICHIN
    American Heart Association (AHA) 19CDA34760258 / ( 2019 - 2022 )
  Stroke is the leading cause of long term disability in US with motor dysfunction being one of the most common deficit post-stroke. The purpose of this career award application is to facilitate my successful transition into an independent investigator in the field of molecular mechanisms of post-stroke muscle recovery as well as the development of therapy targets to promote post-stroke motor function recovery. The proposed research plan leverages the strengths of the mentee's expertise in functional genomics, and a mentor team's long-standing research program in muscle biology and exercise training for stroke participants to optimize skeletal muscle adaptation and recovery. Having already established a highly effective resistive exercise training (RT) protocol for stroke disability by my mentors, I am now well positioned to elucidate the molecular-genetic underpinnings of RT-hypertrophy in stroke survivors. A better understanding of the molecular mechanisms underlying the benefit of exercise intervention for post-stroke muscle atrophy and adaptation is central to developing pharmacological targets for prevention and treatment of post-stroke muscle atrophy and strength decline. This proposal uses a systems biology approach combined with candidate hypothesis to address the gap in knowledge by testing whether exercise-induced changes in muscle are mediated by functional genomics regulation of myoplasticity pathways. This career development award proposal will use banked muscle biopsy samples obtained from existing resistive exercise intervention trials led by my mentors to identify myoplasticity related gene expression and DNA methylation changes underlying the beneficial effect of RT. This project will enable me to have a deep understanding of muscle biology, clinical rehabilitation intervention and assessment. The results of this project and the skills acquired through the proposed training plan will set a solid foundation for me to launch a career delineating the signaling cascades and developing therapy targets to promote post-stroke muscle recovery and health.
2. Project Title: Rehabilitation Interventions Based on Accurate Assessments with Combined Home-Hospital Rehabilitation.
  Leader(s): Zhang, Li-Qun
    National Institute on Disability and Rehabilitation Research (NIDILRR) 90REMM0001 / ( 2020 - 2025 )
  The mission of this RERC is to champion innovative technologies/approaches for assessment-based rehabilitation with combined hospital-home rehabilitation that will improve therapeutic outcomes among individuals with neurologic disorders and older adults with disabilities. This RERC develops and tests devices and techniques to increase the volume and effectiveness of impairment-specific therapies. Stroke and other neurologic disorders often involve considerable sensorimotor impairments with complex pathological changes: these impairments involve multiple muscle groups, multiple joints, and thus many variables are involved. These impairments negatively affect mobility and manipulation in a large population of patients. Due to this complexity, it is often not feasible to assess complicated impairment accurately through current clinical examinations. Furthermore, the vast majority of therapies focus on in-clinic, one-on-one treatments with therapists, and there is a need for combining technology-enabled home therapies and accurate impairment assessments to augment clinic-based treatment. This RERC develops and tests devices and techniques that may increase the volume and effectiveness of impairment-specific therapies. Many rehabilitation technologies including rehabilitation robots have been developed and applied to rehabilitation successfully. However, there is a lack of combined accurate assessment and treatment protocols and devices that evaluate and treat specific impairments. The RERC objectives are to assess closely related impairments post-stroke or associated with older adults with high fall risks, including sensorimotor impairments across multi-joints, impaired balance and gait post-stroke, and reduced balance and increased risk of falls associated with aging. Outcomes include accurate assessments of mobility and manipulation impairments and improvements following combined hospital and home rehabilitation, ranging from muscles to joint, from single to multiple joints, from hand to arm, and from balance control to stepping. The project develops novel products, including assessment tools, wearable rehabilitation robots, multi-joint arm/hand robots, and sliding-stepping robots.
    VA I01CX001601 / ( 2018 - 2023 )
  Diabetes is common in the Veterans Health Administration (VHA) patient population with a prevalence of24% making it a priority clinical issue for Veterans. Between 10 and 25% of people with diabetes will develop afoot ulcer during their lifetime. Diabetic foot ulcers are a leading cause of hospitalization, as well as the primarycause of lower limb amputations. About 5% of patients with a foot ulcer require an amputation each year,typically due to the development of infection at the site of the foot ulcer. Because foot ulcers are a leadingcause of disability in people with diabetes, more effective prevention is needed. The role of the skin microbiotaon the development of chronic foot ulcers after minor trauma is unknown. Prior work has shown that the feet of diabetic Veterans had a higher load of S. aureus compared withnon-diabetic veterans. Our preliminary data suggest that there are higher loads of S. aureus and total bacteriaon the feet of diabetic Veterans at high risk for future foot ulcer compared to diabetic Veterans at low risk of afuture foot ulcer. If so, manipulating the skin microbiota of the feet could reduce the risk of foot complications.Thus, we propose the following aims to test our central hypotheses that the skin microbiota is part of the causalpathway in the development of chronic ulcers. Using a randomized, double-blind clinical trial, 200 adults with diabetes and a prior foot ulcer will berandomly assigned to chlorhexidine or placebo wipes for daily foot care over one year. Specific Aim 1A: Todetermine if chlorhexidine reduces the recurrence of foot complications including chronic foot ulcer, footinfection or foot amputation. We hypothesize that the chlorhexidine group will have a lower incidence of chronicfoot ulcer or foot infection or foot amputation than the placebo group. Specific Aim 1B: To determine ifchlorhexidine increases antibiotic resistance among ESKAPE [and diabetic foot infection] pathogens. Wehypothesize that a) the chlorhexidine group will not be colonized with E. cloacae, S. aureus, K. pneumoniae, A.baumannii, P. aeruginosa and E. faecium (ESKAPE) [and diabetic foot infection] pathogens with a higher MIC tochlorhexidine than the placebo group and b) the chlorhexidine group will not be colonized with ESKAPE [anddiabetic foot infection] pathogens with a higher MIC to key antibiotics than the placebo group. We expect to gain: 1) an assessment of the feasibility of chlorhexidine as a daily intervention to preventrecurrent foot ulcers in Veterans with diabetes, and 2) an understanding of the risk of antimicrobial resistancewith long term chlorhexidine use. Our long term goal is to test whether interventions which manipulate the skinmicrobiota prevent foot ulcers in a larger (adequately powered for a clinically relevant endpoint) clinical trial inorder to reduce the risk of amputation associated with diabetic foot ulcers.
  Leader(s): SPANAKIS, ILIAS
    VA I01CX001825 / ( 2018 - 2023 )
  More than 25% of patients admitted to general wards/non Intensive Care Unit (non-ICU) setting have a historyof Diabetes Mellitus (DM); and as for 2012, $125 billion dollars were costs associated with hospitalization ofdiabetics in the United States (US). Up to 30% of the hospitalized diabetics develop hypoglycemia, a conditionthat is associated with higher hospital charges, prolonged length of stay, and increased morbidity and mortality.Reducing hypoglycemic events in the inpatient setting has led hospitals to develop hypoglycemia preventionpolicies; policies which are however limited by the infrequent Point of Care (POC) capillary blood glucose testingin the general wards. Continuous Glucose Monitoring (CGM) devices represent additional ways to monitorblood glucose levels. Only a limited number of studies have examined the use of CGM devices in the non-ICUsetting. In all these studies, CGM use was found to be superior compared to POC in hypoglycemia detection.However, as the results of CGM were blinded (alarms were turned off) for both the investigators and theparticipants, interventions to prevent hypoglycemia were not performed. Additionally, one major limitation ofCGM technology is that CGM receiver/monitor needs to be located in the patient's room, due to BluetoothTechnology signal-strength restrictions, necessitating nurses to enter frequently the patient's room in order tocheck CGM glucose values. In the current award application, we describe the development of an innovativesystem that allows CGM glucose values to be transmitted from the patients' bedside to a monitoring device thatis located at a central nursing station- a system that we call Glucose Telemetry System (GTS).We propose the conduction of a prospective randomized clinical trial that will examine whether GTS combinedwith a hypoglycemia prevention protocol, can decrease hypoglycemia in the medical wards without resulting inhyperglycemia- resulting to better clinical outcomes. Specifically we hypothesize that: (1) Veterans who will berandomized to GTS will have less hypoglycemia than Veterans randomized to control group (standard of care);(2) Veterans who will be randomized to GTS will not experience more frequent hyperglycemia, as a result ofthe frequent application of the hypoglycemia prevention protocol, compared to Veterans randomized to thecontrol group; and (3) GTS use will reduce the frequency of hypoglycemia induced seizures during theirhospitalization decreasing length of stay and inpatient mortality. We will study 244 Veterans with DM2 whoare at a higher risk for hypoglycemia. Consenting Veterans will be stratified in two groups based on the numberof risk factors of hypoglycemia (=2 risk factors, =3 risk factors); and then further randomized in a 1:1randomization scheme (122 Veterans randomized to GTS and 122 randomized Veterans to standard of care-POC blood glucose monitoring). For the participants of the control group, retrospective CGM devices will beused in order to compare glycemic outcomes between the two groups. Our primary outcome is difference inhypoglycemic event rate between the two groups. Other outcomes of interest are times spent in hypoglycemia,normoglycemia, hyperglycemia and severe hyperglycemia, length of stay, seizure activity related tohypoglycemia and inpatient mortality.Discovering novel ways to monitor glucose values in the hospital setting could have a significant impact inpreventing hypoglycemia in the inpatient setting- a condition that is associated with adverse clinical outcomes.We believe that our proposal is highly innovative. The trial may lead to future wider use of CGM in hospitalizedpatients with DM who are at a higher risk for hypoglycemia, similar to the way that we use cardiac telemetry forpatients who are at an increased risk for developing arrhythmias.
    VA I01CX001965 / ( 2020 - 2025 )
  Over 70% of Veterans who receive health care at the VA are overweight or obese, and obesity rates of Veterans receiving care at the VA are higher compared to non-Veterans and Veterans who do not use the VA. Obesity contributes to loss of mobility which is a significant determinant of morbidity and loss of independence. Obesity also is associated with elevated cardiometabolic risk factors, including lipid profile, insulin resistance, hypertension, and inflammation. Though weight loss of as little as 3% improves physical functioning and reduces type 2 diabetes and cardiovascular risk factors, most subjects are unsuccessful at long-term weight maintenance, regaining almost half the weight lost within the following two years and return to baseline weight within the next 3-5 years. This clinical trial takes on the challenge of maintaining weight reduction by altering energy balance and possibly skeletal muscle substrate oxidation to mitigate weight regain in overweight and obese older Veterans with mobility limitations. The objective of this award proposal is to test in a randomized clinical trial the effectiveness of an intensive weight management program with and without intermittent fasting (IF) to combat weight regain and the obesity crisis in our Veterans. IF refers to short periods of intense energy restriction. We propose to enroll a total of 200 overweight and obese Veterans with mobility impairments into a 12 weeks weight loss program that incorporates a low calorie Heart Healthy (HH) diet and exercise at the Baltimore and Atlanta VAMCs. Following weight loss (WL), Veterans will be randomized to weight maintenance (WM: continuation of HH and exercise guidelines) program or weight maintenance with intermittent fasting (WM+IF) for 24 weeks. Our central hypothesis is that IF will provide the stimulus for prevention of weight regain at 36 weeks and will improve cardiometabolic and functional health factors. Further, we hypothesize that the ability to appropriately modify fuel utilization through skeletal muscle fatty acid oxidation enzymes is an important factor in weight maintenance and weight regain. This CSR&D Clinical Trial Merit Award introduces an innovative practice of IF to prevent weight relapse after clinically significant weight reduction and could provide evidence-based recommendations to promote this type of intervention in the Veteran population.
    VA I01RX002790 / ( 2019 - 2023 )
  The Veterans Health Administration (VHA) is the largest U.S. HIV health provider with 64% of these Veterans 50+ years of age. HIV infection in the setting of antiretroviral therapy represents a chronic disease with an advanced aging phenotype manifested as increased cardiovascular disease, sarcopenia, and frailty, primarily driven by systemic inflammation. We found a 42% reduction in VO2peak in older HIV+ adults that significantly improved with high-intensity aerobic (AEX) and resistance training (RT). Yet, durable strategies for high-intensity exercise in older adults remain a challenge and limited data are available in older HIV+ adults. There is an urgent need to address these knowledge gaps in order to prevent widespread disability in HIV+ Veterans. Our objective is to provide a high-intensity exercise program for older Veterans that can be widely disseminated and attenuates processes underlying aging. Epigenetic changes with increased age encapsulate the putative effects of biological aging and lifestyle factors. DNA methylation (DNAm) patterns are frequently modified in genes encoding pro-inflammatory cytokines, but can be reversed with exercise training. DNA methylation age (DNAm Age) is an epigenetic biomarker that is expressed in years and provides a concrete benchmark of advanced aging. We found that HIV+ adults have DNAm Age 11 years greater than age- matched adults without HIV. Further, in adults without HIV, increased DNAm Age is associated with physical inactivity, weakness and frailty. Our preliminary data in the Veterans Aging Cohort Study (VACS) show that DNAm Age correlates with the VACS Index, a measure of frailty in HIV+ adults. However, the impact of exercise training on DNAm Age has yet to be determined in any patient population. We propose to adapt our center-based high-intensity AEX+RT intervention in older HIV+ Veterans into a video telehealth (VTEL) delivered functional (no stationary equipment) exercise program that leverages epigenetic outcomes to demonstrate anti-aging effects of exercise. The overarching hypothesis is that VTEL high-intensity functional circuit exercise in older HIV+ Veterans will improve the advanced aging phenotype and attenuate DNAm epigenetic processes underlying aging. Our experimental approach includes a 12-week VTEL exercise intervention in 80 older HIV+ Veterans who are randomized to exercise or standard of care sedentary control groups. AIM 1 will determine the effect of VTEL exercise on VO2peak, sarcopenia, and frailty as phenotypic outcomes of advanced aging in HIV. AIM 2 will investigate the effect of VTEL exercise on DNAm Age as a biomarker of advanced aging. AIM 3 will determine the effect of VTEL exercise on DNA methylation of specific genes encoding specific pro-inflammatory cytokines in leukocytes. This approach will advance our understanding of effective and feasible exercise strategies to prevent and minimize disability in patient populations with advanced aging. Findings will provide an innovative approach to functional exercise in all older adults. DNAm Age could be used as a personalized benchmark for an individual s benefit from exercise to promote sustainable behavior change. Findings will also provide epigenetic risk profiles that can be used to generate a personalized exercise prescription, an important next step in the next decade of precision medicine. The proposal leverages our exercise training experience in HIV and VTEL, availability of 3,000 HIV+ Veterans at Atlanta and Baltimore VAMCs, and the VHA VTEL infrastructure. The capacity to disseminate VTEL exercise with minimal cost using existing infrastructure will facilitate large-scale dissemination and national impact. Deliverables include improved clinical outcomes and substantial cost savings from reduced hospitalization and institutionalization rates.
    VA I01RX003096 / ( 2020 - 2024 )
  Falls are by far the leading cause of accidental injury and death in older adults. The Veteran population is more severely affected by falls since it is significantly older than the overall population (45% over 65 years of age vs. 13%); and Veterans would benefit substantially more from an accurate diagnosis and treatment of fall propensity. Despite its importance, much is still unknown about the manner in which balance control is compromised by age and disease. Therapeutic interventions for people who are at risk of falling have proven to be of limited utility. Engineering methods are well suited to study and evaluate balance; but have to date been applied to overly simplified scenarios that lack the complexity to probe the musculoskeletal and neurophysiological bases for balance and falls. The long term objective of this research, which began with a VA Rehabilitation Research & Development (RR&D) Career Development Award (CDA-2), is to develop improved directives and protocols for the diagnosis and treatment of balance-related posture and movement coordination problems. This proposal significantly advances engineering methods to address existing gaps in the diagnosis and treatment of balance impairments through the development of a Balanced Reach Training Protocol (BRTP). The BRTP continuously challenges subjects to perform reaching tasks at the limits of their balance for an extended period of time, and increases these limits as subjects demonstrate improved performance. The goal of this tool is to quantitatively assess and improve at-risk individuals' ability to maintain balance when disturbed by volitional movements of the body and its parts an important class of balance disturbances integral to many activities of daily living that can precipitate falls. The BRTP focuses on performance at and just beyond the limits of balance, unlike most such tests and training protocols that do not challenge subjects in this way. The BRTP's most immediate and salient metric is the limiting boundary of standing reach; and we hypothesize that expanding this boundary, as the BRTP is designed to do, will improve balance and make individuals more resistant to falls (in the context of expected balance disturbances). Confirmation of this hypothesis could provide a new perspective on existing training protocols' modest success rates, and direction for the design of new protocols with the potential to significantly improve these rates. [Though the BRTP is a training platform, we also believe that the performance metrics and analytical results produced by it can form the basis for new diagnostic measures that more reliably and precisely quantify and explain balance performance problems; and track changes in them over time.] Such diagnostic and treatment protocols would be particularly beneficial to the VA Health Care System, as it would lead to improvements in: patient throughput, quality of care, and treatment costs. Though this proposal targets the aging Veteran population, the BRTP is a general tool that can aid in the diagnosis and treatment of balance disorders arising from conditions other than aging. These include obesity, diabetes (which often leads to lower extremity muscle degeneration and peripheral neuropathy), sarcopenia, vestibular disorders, and neurological disorders such as stroke. Veterans whose balance has been compromised by Traumatic Brain Injury (TBI) (whether combat-related or not) may also benefit from the BRTP.
    NIH K01AG064041 / ( 2019 - 2024 )
  Symptomatic knee osteoarthritis (OA) affects 10% of men and 13% of women 60 years or older, anddepressive symptoms are common, estimated to be prevalent in one-fifth of these patients. Depressivesymptoms worsen knee OA disease severity and are a barrier to pain management and engagement inphysical activity. Clinical care guidelines recommend depression treatment in older adults with knee OA butprovide no direction on how to simultaneously manage both conditions, and patients are often not treated fortheir depressive symptoms and receive interventions only for their chronic physical illness. This issue isexacerbated by the routine exclusion of individuals with chronic physical diseases and comorbid depressionfrom clinical trials and lack of protocols designed for these patients. Recent research advocates the use oftreatments that benefit both conditions simultaneously, or combined treatment using two interventions inparallel that are designed to work together, such that approaches enhance efficacy beyond that of an individualtherapy with a single disease target. Treatment guidelines advise exercise programs to manage pain anddisability and improve psychosocial health in those with knee OA, but compliance to physical activity protocolsis low in persons with chronic pain and disability and is only made worse by comorbid depression. Adherenceis critical to the efficacy of depression treatments using exercise training, and no such exercise program hasever been designed for and tested in OA patients with co-occurring depressive symptoms in a way to enhancecompliance. Duloxetine is the only antidepressant medication indicated for pain management in knee OApatients that has demonstrated efficacy and tolerability when treating depression in older adults, and therefore,is a viable pharmacological complement to exercise training. There are no protocols that combine treatmentsusing interventions that affect symptoms of both knee OA and depression, and a strategy focused on co-management of the two conditions could be disseminated to and implemented by generalist medicalpractitioners. Thus, the research goal of this K01 application is to evaluate the feasibility of and then pilot test aprotocol comprised of aerobic exercise training plus duloxetine for the treatment of symptomatic knee OA andcomorbid depression. The proposed research will be implemented with a period of close mentoring and careerdevelopment activities focused on learning 1) methods for qualitative data collection and analysis that can beused to understand patients perspectives and experiences and 2) strategies for the implementation andevaluation of interventions in clinical research. This proposal is aligned with the NIA Strategic Directions forResearch on Aging emphasizing older adults with multiple chronic conditions that complicate clinical care andis intended to lead to a research program that uses observational epidemiology evaluating the relationshipsand mechanisms between musculoskeletal disorders and comorbid depression in older adults to inform thedevelopment of protocols that are designed to manage symptoms of both the primary condition and sequalae.
9. Project Title: Gerofit - A Program Promoting Exercise and Health for Older Veterans
  Leader(s): KATZEL, LESLIE I
    VA N/A / ( 2018 - NA )
  Gerofit is a supervised exercise program for older Veterans that was developed at the VA Medical Center in Durham, North Carolina, in 1986. As a part of Gerofit, veterans are given a personal exercise program based on their physical profile and goals. Veterans are welcome to remain in the program as long as they wish. Gerofit can include individual and group based exercises such as Tai Chi, line dancing, balance, core coordination, and strengthening classes. The exercise program may include treadmills, elliptical machines, stair climbers, bicycles and a variety of strengthening machines. Guidance in carrying out the exercise program is provided by trained exercise staff such as a nurse or physical therapist. Participants in the program have demonstrated improved health, physical function and well-being. They have shown improvements in blood pressure, diabetes management, symptom management, well-being, quality of life, physical function, overall fitness, and longevity.
10. Project Title: Comparative effectiveness of pulmonary embolism prevention after hip and knee replacement (PEPPER): balancing safety and effectiveness
    PCORI PCS-1402-09328 / ( 2016 - 2024 )
  Nearly 1 million total hip (THR) and knee (TKR) replacements are performed each year in the United States, and comprise the largest single type of operation paid for by Medicare. Because disturbing the bone marrow cavity turns on the blood clotting system in humans, these operations are often complicated by formation of blood clots in the veins of the leg (deep vein thrombosis, DVT). Sometimes, these blood clots detach from the leg veins and travel to the lungs (pulmonary embolism, PE), where they interfere with the normal pumping of blood from the heart. When a large clot gets stuck in the lung, it can result in death; this happens in 0.1-0.5 percent of patients after hip or knee replacement, which means between 1,000 and 5,000 deaths each year. The use of blood thinners around the time of operation reduces the risk of pulmonary embolism and related death, but also increases the risk of bleeding from the raw bony surfaces that are created when the joint replacement is done. The ideal balance between use of blood thinners to prevent PE and the risk of bleeding associated with their use is not known. Nearly all surgeons and professional organizations agree that use of blood thinners is beneficial in this setting, but some clinical guidelines recommend the use of very strong blood thinners while others favor weaker blood thinners in order to reduce bleeding risk. These events are so uncommon that no clinical trial is large enough to provide an answer as to whether the strongest of blood thinners, or weaker medicines, are the best to use in this setting. Similarly, information that is available from billing records of large health care insurance companies, such as Medicare, is unable to provide an answer because this information also has shortcomings that limit its usefulness. Since 2012, no study, including the very detailed AHRQ Comparative Effectiveness Review, has been willing to recommend a specific blood thinner as the best to use after hip and knee replacement because there is so little information about the tradeoff between preventing pulmonary embolism and the risk of bleeding that occurs more frequently with the strongest of blood thinners. Objectives: Our purpose is to combine information about effectiveness in preventing blood clots in the lungs and legs, which is important to how patients do after total hip and knee replacement, with the opinions of patients about the safety of the most commonly employed blood thinners with respect to the chance of bleeding problems that each drug might cause after the operation. The patient's preferences for using blood thinners to decrease the risk of blood clots that might result in death will be balanced with the patient's concerns about how bleeding problems related to the blood thinners might reduce the success of the joint replacement by causing pain, stiffness, a need for another operation, or infection that might result in having to remove the joint replacement parts altogether. This work will therefore provide background information to help both patients and their surgeons in deciding which blood thinner would be best to use after hip and knee replacement. We expect that the choice of blood thinner will understandably be different for many patients and their surgeons, depending upon how much of a chance of a poor result after the joint replacement that each patient would be willing to accept in return for lowering the risk of a life-threatening blood clot. Because it is so uncommon for a patient to die from a blood clot in the lung after hip and knee replacement, it takes a very large number of patients to be able to see a real difference in the effects of these drugs on blood clots and bleeding in order to determine which drug is best. In fact, none of the previous studies about this issue have been large enough to see any real differences between drugs with respect to death from blood clots, but there have been differences in bleeding with the stronger blood thinners having as much as three to five times more bleeding problems than aspirin, which is a weak blood thinner that may be equally effective in preventing life-threatening blood clots. Methods: We propose a study that is large enough to compare real differences in rates of life-threatening blood clots between the three most commonly used blood thinners after hip and knee replacement, while also comparing different rates of bleeding with each drug that can make a repeat operation necessary and may ultimately make the joint replacement function less well. Approximately 25,000 patients undergoing elective THR or TKR will be enrolled at 25 centers over 2.5 years at a rate of 400 patients per site per year. The study will encompass four years, with six months startup for IRB approval, six months follow-up per patient, and six months for final data analysis. Together, the study centers account for 33,000 THR and TKR per year; each center will randomize patients to all three groups representative of current practice; aspirin plus pneumatic compression (least bleeding risk regimen), low-intensity warfarin (most popular North American regimen), and rivaroxaban (greatest effectiveness in preventing blood clots). A patient advisory board (PAB) has been established; each member has undergone THR or TKR and some have experienced PE or reoperation for wound complications. The PAB will attach a relative value to each event, the effort spent in its prevention, and its impact on function, risk of reoperation, and loss of the implant. Patient outcomes: Primary effectiveness outcomes will include clinically important PE/DVT resulting in readmission and death from all causes. Safety outcomes will include major bleeding and patient-reported wound and remote bleeding. Patients will attach relative importance to blood clots, bleeding, and death and consider this tradeoff in order to determine the relative risk tolerances for blood clots and bleeding to decide which blood thinner is most appropriate for which patients.
11. Project Title: A practical intervention to improve patient-centered outcomes after hip fractures among older adults (REGAIN Trial)
  Leader(s): NEUMAN, MARK
    PCORI PCS-1406-18876 / ( 2015 - 2023 )
  Hip fractures occur more than 300,000 times each year among older US adults; the vast majority of patients undergo surgery that requires anesthesia. One year after fracture, 50 percent of previously independent patients have died or require nursing home placement, and 40 percent of survivors who previously walked independently need help to walk 10 feet. The REGAIN trial (REgional versus General Anesthesia for promoting INdependence after hip fracture) will compare short- and long-term outcomes of two common approaches to anesthesia for hip fracture surgery. We hypothesize that patients treated with spinal (nerve block), versus general anesthesia, will experience fewer complications and less pain during hospitalization; be more likely to regain independence in walking by 60 days after surgery; be more likely to return home by 180 days; have better overall health, less disability, and less pain; and be more satisfied with their care. REGAIN will enroll 1,600 patients from 18 academic and community hospitals across the United States. Participants will be adults aged 50 and older undergoing surgery for hip fractures, who could walk independently before fracture, and who are eligible for spinal and general anesthesia. Patients will be centrally randomized to receive either spinal or general anesthesia. We received extensive input into the overall study question, the outcomes to be studied, and methods for outcome assessment from our lead patient partner (the Center for Advocacy for the Rights and Interests of the Elderly); stakeholders, including the Gerontological Society of America; and a community patient and caregiver advisory group. Patients and stakeholders also drafted key sections of the proposal, and we received additional input from leading medical professional societies in orthopedic surgery and anesthesia, and from major health care payers. By comparing two universally available, basic anesthetic approaches, the REGAIN trial will directly and immediately affect patient decision making, care, and outcomes for the more than 300,000 US patients who need surgery to treat hip fractures each year, as well as the more than 8.5 million older US adults who face decisions about anesthesia for other major surgeries each year.
    NIH R01AG050469 / ( 2017 - 2022 )
  DESCRIPTION (provided by applicant): Knee osteoarthritis (OA) is a major cause of pain, functional limitation and disability and among the most costly musculoskeletal conditions. A burgeoning population with knee OA and poor clinical outcomes in the absence of effective treatments are key drivers of the soaring rates and costs of knee replacement. Knee OA pathology and clinical outcomes typically unfold over decades and have a highly varied time course. It is a priority to understand the range of factors that contribute to poor and good outcomes in knee OA, but there are critical gaps in knowledge about the long-term course of the disease and its determinants. It is sensible to target prevention and treatment on those most at risk for poor outcomes. However, there is a paucity of longitudinal studies long enough (=10 years) with frequent assessment using standardized measures to capture the full trajectory, range and variability of outcomes and investigate their determinants. In addition, investigation ofthese questions is hampered by baseline heterogeneity in knee OA severity and impact, which can be a source of imprecision and bias in observational studies of disease prognosis. Started in 2002, the OAI is a unique cohort study of 4796 persons with or at risk for knee OA that has uniform, rich clinical and imaging data from annual assessments and has been followed comprehensively for up to 8 years with good retention. We now propose to continue assessment of outcomes of knee OA for up to 15 years after baseline, primarily by phone and mail, an efficient and less burdensome approach that will yield more complete follow-up than clinic visits alone in this aging cohort. A brief clinic visit in a subset of participants will enale us to study performance measures of function as a long-term outcome. Our goal is to take advantage of this unprecedented opportunity for long-term follow-up to describe the full trajectory and probability of outcomes at different stages of disease, to identify vulnerable and protected phenotypes in its long-term course and investigate potentially modifiable predictors of these outcomes. Outcomes will span a range of health domains, including: knee-OA related (pain, functional limitation and performance, OA global impact, knee replacement), disability/participation and general health. The extended follow-up provides the opportunity for an analysis design that reduces the risk of common sources of bias and imprecision in studies of disease prognosis by allowing the use of changes from baseline to year 4 to define 'inception events,' such as the transition to more advanced stages of knee pain or structural OA or the development of favorable and unfavorable trajectories of risk factors (knee OA-related, physical performance, general health and psychosocial variables). These changes will then be evaluated for their association with subsequent outcomes occurring from year 5 to year 15 in analyses conditioned on a range of baseline knee OA-related and other covariates with a minimal risk of collider stratification bias. Using this approach we will investigate questions that can inform emerging strategies for prevention and treatment that are focused on improving outcomes in persons with knee OA. These include describing the probabilities of both poor and good long-term outcomes at different stages of knee pain and structural OA, comparing outcomes in those with recent transitions to more advanced stages with those whose course has been stable, and identifying the modifiable determinants of long-term outcomes at different stages of disease and whether these differ by stage, thus suggesting the need for tailored interventions to improve outcomes.
    NIH R01AG051647 / ( 2017 - 2022 )
  Hip fractures are common among older women and can have a devastating impact on their ability toremain independent. A clinically important functional decline and failure to recover following a hip fracture hasbeen documented as much as a year after the fracture, even among individuals who were functioning at highlevels before the event. Age-associated androgen deficiency in women contributes to deficits in muscle mass,strength and power that are common in this patient population before the fracture, and are exacerbatedafterward. A pilot study of testosterone (T) supplementation in elderly female hip fracture patients hasdemonstrated the feasibility of T treatment in this population, and showed gains in lean body mass (LBM) andmuscle strength with active drug, compared to placebo. The benefits of exercise in restoring muscle strengthand physical function after a hip fracture have been documented. However, it remains unclear whether Ttreatment can augment the effects of exercise on mobility and patient-reported function, or whether anyobserved benefits are sustained beyond the period of active treatment. Proposed is a 3-group, multi-center,randomized, placebo-controlled, double-blinded, parallel group clinical trial in frail elderly female hip fracturepatients. 300 female hip fracture patients will be enrolled from 6 clinical sites, using objective screening criteriafor T deficiency (serum total testosterone level < 30 ng/dl) and physical frailty (Modified Physical PerformanceTest (PPT) Score < 28). The trial will compare the effects of supervised exercise training (EX) alone, EXcombined with T therapy (EX+T) and no EX with placebo T treatment (CON), to ascertain the incrementalimpact of adding T to ET in older adult women following hip fracture. The 6-month intervention will be followedby a 6-month no-treatment sustainability phase. The primary outcome measure is the Six Minute WalkDistance (6MWD). Secondary outcome measures include: 1) dual energy x-ray absorptiometry (DXA)measurements of whole body and appendicular LBM and bone mineral density of the unfractured proximalfemur; 2) maximal skeletal muscle strength (1-RM) for leg extension in both limbs; 3) objective physicalperformance measures; and 4) self-reported performance of activities of daily living and quality of life, includingthe Hip Rating Questionnaire (HRQ). We plan to carefully monitor testosterone levels, adverse events,biochemical parameters, and factors related to adherence to the interventions. Information from this study has the potential to alter treatment of hip fracture in older women, a problemthat contributes to significant morbidity and mortality, and has a large public health impact. The proposedstudy is highly aligned with NIA s mission of identifying interventions that target common geriatric conditions,and improve treatment options for older adults with multiple morbidities or risk factors.
  Leader(s): GRAY, VICKI L.
    NIH R01AG060051 / ( 2018 - 2023 )
  Project Summary/Abstract Falls and their consequences are among the major problems in the medical care of older individuals.The long-term goal of this research is to a mechanistically derived therapeutic intervention to enhance musclepower, weight-shifting capability, and lateral balance to prevent falls. When human balance is challenged,protective stepping is a vital strategy for preventing a fall during activities of daily life. Many older people at riskfor falls have particular difficulties with successfully stepping sideways as a protective response to loss ofbalance in the lateral direction. We propose that age-related declines in lateral balance function throughimpaired weight transfer and protective stepping linked with falls, result from neuromuscular and biomechanicallimitations in hip abductor-adductor (AB-AD) muscle power generation. Moreover, we hypothesize that thesefunctional and neuromotor impairments can be improved with high velocity muscle resistance power training.The specigic aims are: Aim 1. To determine the age-associated changes in neuromuscular and biomechanicalperformance of the hip joint AB-AD musculature by evaluating the isolated maximum torque and powerproduction and neuromuscular activation patterns. Aim 2. To determine the aging changes in neuromotorperformance of the hip AB-AD musculature during the pre-step weight transfer phase of waist-pull induced sidestepping and voluntary reaction time stepping. Aim 3. To establish a first line of evidence showing thathypothesized aging deficits in sidestepping caused by neuromotor impairments in hip AB-AD muscle powerproduction may be reversible, we will determine the effects of velocity dependent muscle resistance powertraining (3 x/week x 10 weeks) compared with strength training on neuromuscular, biomechanical, andfunctional performance outcomes. Overall, the studies will identify age-related neuromotor mechanisms ofabnormal hip AB-AD muscle power production that impair lateral weight transfer, balance stability, and mobilityfunction. Establishing a first line of support for the superiority of velocity dependent power training overstrength training on muscle performance and protective balance and functional mobility outcomes, will lead to afuture comparative intervention trial to enhance these functions and prevent falls in older adults.
    NIH R01AR071614 / ( 2018 - 2023 )
  PROJECT SUMMARYOsteoporosis and other diseases of skeletal fragility affect more than 200 million people worldwide andcontributes to ~9 million factures annually. Preventing bone loss and/or restoring lost bone mass in patients isof vital importance to limiting the personal and economic impact of diseases of skeletal fragility. A key target inthe stimulation of new bone formation is the protein sclerostin, an antagonist of the Wnt/beta-catenin signalingcascade, which is produced by bone embedded osteocytes. Numerous osteoanabolic cues, includingmechanical load, reduce expression of the sclerostin leading to de-repression of osteoblastogenesis andstimulation of de novo bone formation. However, key mechanistic details of how osteocytes sense mechanicalload, transduce these load signals to biologic effectors, the identity of these biological effectors and howsclerostin bioavailability is regulated are unclear. Our preliminary data have uncovered a number of novelmediators of how osteocytes sense and respond to mechanical cues. Specifically, we show that microtubule-dependent cytoskeletal stiffness regulates mechano-activated Ca2+ influx. Furthermore, we implicate TRPV4as a major mechano-dependent Ca2+ influx pathway that drives Ca2+ dependent activation ofcalcium/calmodulin-dependent kinase II (CamKII) to reduce sclerostin bioavailability in the osteocyte. In thepresent grant, we will use in vitro, ex vivo and in vivo models to determine the contribution of MT density andcytoskeletal crosslinking to osteocyte mechanosensing, define the contribution and mechanisms of osteocyteTRPV4 channel opening in response to mechanical stress and elucidate the mechanisms by which FFSS-dependent CamKII activation regulates sclerostin degradation and Sost gene transcription. This work will morefully explain the biological regulation of sclerostin, will mechanistically link several gaps in the knowledge ofhow osteocytes sense and respond to mechanical load, and will reveal novel targets to improve or preservebone mass in aging and disease.
    NIH R01HL142290 / ( 2019 - 2022 )
  Atrial myocyte cell biology will be examined in isolated single cells in vitro and mice in vivo tocharacterize quantitatively how chemo-mechanical signaling works in health and disease. This signalingpathway is activated by changes in myocyte shape as happens when the atria fill with blood, and myocytesstretch, during diastolic filling. Using extremely high temporal and spatial resolution imaging the PIs willexamine how chemo-mechanical signaling contributes to subcellular changes in Ca2+, excitation-contractioncoupling to influence both electrical and Ca2+ instability. Preliminary results suggest that newly identified largeaxial tubules in atrial myocytes (discovered by the PIs) along with Ca2+ release 'super-hubs' play a role in aunique Ca2+ signaling system found in atrial myocytes. Furthermore, the mechano-chemo X-ROS pathwaydiscovered by the PIs in ventricular myocytes is likely to have a special role to play in atrial myocytes. Thissignaling pathway links the mechanics of cellular stretch, transmitted through microtubules, to the generation oflocal subcellular reactive oxygen species (ROS) that likely target multiple Ca2+ signaling proteins such asCaMKII and RyR2. Preliminary results suggest this X-ROS signaling is very active in atrial myocytes and maybe linked to the novel structures described by the PIs. The proposed work will identify quantitatively thecontributions of the special structures, X-ROS signaling and chemo-mechanical signaling to the normalphysiology of atrial myocytes and the contributions to the development of atrial fibrillation (AF). Two verydifferent mouse models of AF will be used along with specific transgenic mice to quantitatively characterizeCa2+ signaling and cellular electrophysiology in atrial myocytes and determine how chemo-mechanicalsignaling contributes to cellular physiology and pathophysiology. This investigation will provide criticallyimportant new information on how atrial myocytes work and fail in health and disease. The likely newdiscoveries produced by the proposed work will broaden our understanding of atrial cell biology and lay thefoundation for innovative, effective and novel therapies for atrial dysfunction and AF.
  Leader(s): DAVIS, DERIK L
    NIH R03AG067927 / ( 2020 - 2022 )
  Mobility limitation is a major burden to public health, affecting one-third of adults 65 years and older. Mobility limitation is predictive of disability, hospitalization, falls and mortality in older populations. The contribution of lower limb dysfunction to mobility limitation is well established. The influence of upper-limb dysfunction on mobility performance is less well understood. Shoulder pain and rotator cuff tear are common in adults 65 years and older. Well-known manifestations of shoulder pain or rotator cuff tear include lower performance on subjective measures of activities of daily living and lower performance on objective measures of shoulder strength and range of motion. Recent studies suggest that impaired rhythmic interlimb coordination variability between shoulders is associated with mobility limitation in healthy older adult populations. We hypothesize that the presence of shoulder pain or rotator cuff tear alters the rhythmic interlimb coordination variability between shoulders in community-dwelling older adults. The first aim of the proposal investigates the association of rhythmic interlimb coordination variability between shoulders during overground walking with mobility performance in a population which includes community-dwelling older adults with shoulder pain or rotator cuff tear. The second aim of the proposal investigates the association of shoulder pain or rotator cuff tear with rhythmic interlimb coordination variability during overground walking. The knowledge gained from this proposal will inform future studies designed (1) to test novel strategies for identifying community-dwelling older adults who are vulnerable to develop mobility limitation and (2) to test novel interventions designed to slow functional declines in community-dwelling older adults with mobility limitation.
    NIH R24AG063728 / ( 2019 - 2022 )
  PROJECT SUMMARY/ABSTRACTAging Research focuses on aging processes, age-related diseases, and special problems andneeds of older adults. Aging Research helps us to understand the nature of aging and how bestto extend the healthy, active years of life. Greater diversity among the populations engaged inAging Research studies is essential in order to understand the complex relationships amonghealth status and age, race, physical functioning (and physical impairment), culture, andsocioeconomic status. The proposed project will foster a community-academic Aging Researchcollaborative that promotes trust and develops recruitment and retention methods to increasethe diversity of older adult participants in clinical studies of agingAchieving greater diversity in clinical research study populations involving older adults isdesirable and feasible, yet comes at a cost. Our proposed study of recruitment methods willhelp answer the question, Can we identify evidenced-based recruitment methods that are botheffective (successfully recruit populations underrepresented in clinical research) and efficient(provide a reasonable return on investment) in recruiting and retaining underrepresentedpopulations in clinical studies of aging We will accomplish this by building the infrastructurenecessary to support methodological research in partnership with community organizations withwhom we have worked on prior multiyear federal grants, including an R24 from the U.S.Department of Health and Human Services' Agency for Healthcare Research and Quality(AHRQ). The project aims are:Aim 1: Foster a community-academic Aging Research collaborative that promotes trust anddevelops recruitment and retention methods to increase the diversity of older adult participantsin clinical studies of agingAim 2: Engage diverse older adults, their community-based health care providers, andinvestigators in a manner that facilitates bi-directional learning for future Aging Research studiesAim 2a: Move older adults along the willingness to participate in research continuumAim 2b: Enhance the cultural competence of investigators studying aging and by doing sopromote trustworthiness of Aging Research studies by community membersAim 3: Guided by co-developed ethical principles, facilitate the enrollment of three difficult-to-recruit subpopulations: older African Americans, older adults with impairments (hearing, vision,mobility), and those who are homebound into a Registry
  Leader(s): GURWITZ, JERRY H
    NIH R33AG057806 / ( 2018 - 2023 )
  PROJECT SUMMARY / ABSTRACTThe Health Care Systems Research Network (HCSRN)-Older Americans Independence Centers (OAICs)AGING (Advancing Geriatrics Infrastructure and Network Growth) Initiative, funded under an R24 grantmechanism (R24 AG045050), was initiated in 2014 to foster collaborations between HCSRN and OAIC (akaPepper Centers) investigators in order to advance an interdisciplinary research agenda focused on advancingthe science of multiple chronic conditions (MCCs) in older adults. The AGING Initiative is a highly productive,collaborative, transdisciplinary endeavor involving scientists from 18 HCSRN research centers, embeddedwithin healthcare delivery systems caring for nearly 2 million persons aged 65 and older, in partnership withinvestigators from 15 premier, university-based centers established by the National Institute on Aging (theOAICs). Under the R24, efforts relevant to advancing MCCs science have centered around: (1) characterizingand sharing unique data resources; (2) supporting innovative, collaborative pilot projects; (3) mentoring newand early-stage investigators; and (4) disseminating research methods and findings. This collaboration hasidentified several understudied, high priority research domains, as well as an urgent need for formal careerdevelopment support for new and early-stage scientists committed to aging research on etiology, prevention,and treatment, relevant to the care of older persons with MCCs. The overarching aim of our expanded R33program, conceived and developed by the R24 HCSRN-OAICs AGING Initiative Steering Committee, and itsWorkgroups and External Advisory Committee, is to elaborate on the successful programs and infrastructure ofthe R24, while taking our AGING Initiative in new, more ambitious directions. We will create new coreresources, career development opportunities, and funding opportunities, aligning patients' interests with thoseof scientists. Our specific aims are: (1) to expand on and further develop innovative methods related tomeasurement and analytics, observational research, and pragmatic clinical trial design and implementation, toinform the development and testing of novel interventions that improve the care and outcomes of older personswith MCCs; (2) to foster the career development and success of new and early-stage investigators, includingunderrepresented minorities, and create a nation-wide cohort of MCCs scholars, who are prepared to establishproductive collaborations early in their careers to catalyze an expansion of interdisciplinary research relevant tothe science of MCCs; (3) to create a new core function as part of an elaborated infrastructure that promotespatient-centered research by engaging patients and care partners in all stages of the research process; and(4) to fund a series of P-2-R ( Pilot-to-R award ) grants that will advance the R33 research priorities relevantto the science of MCCs. The P-2-R grants will serve to promote the development and implementation oflarger, multi-disciplinary, multi-site studies laying a foundation upon which to continue to grow the AGINGInitiative.
20. Project Title: Elderly Oral Health: The relationship between oral health problems, dental care use, medical conditions, and provided medical care
  Leader(s): MANSKI, RICHARD J
    NIH R56AG064782 / ( 2019 - 2022 )
  The goal of this project is to focus on the relationship between dental use, overall health, comorbidity, and medical services use. The central hypothesis guiding this study is that dental care use is highly correlated with better-than-average general health and lower levels of comorbidity and utilization of medical services. We will test the hypothesis and conduct this study using secondary data available from the Medicare Beneficiary Survey (MCBS) and Chronic Conditions Warehouse (CCW), Area Health Resources File (AHRF) and the University of Michigan Institute for Social Research (ISR) Health and Retirement Study (HSR). We will also take advantage of a HRS dental specific module co-developed by members of this research team and the survey staff at the ISR. This proposed project builds upon and is an extension of several collaborative studies previously conducted by this research team. Results obtained from this study will have a high impact on the health and welfare of the Medicare eligible community population by describing which co-morbid states are associated with the presence of oral diseases, whether or not preventive treatments are associated with lower levels of those co-morbid states, and whether or not the use of corrective treatments are associated with amelioration of those co-morbid states in comparison to the frequency and severity of those co-morbid states among individuals whose oral diseases are not treated. Specifically we will: Aim 1. Estimate the relationship between utilization of dental care services by elderly persons and co- morbidities over time. The working hypothesis is that elderly persons not using dental care service are more likely to experience specific co-morbidities compared to those using dental services on a regular basis. Aim 2. Estimate the relationship between preventive dental care service use, oral health problems, and co- morbidities over time by elderly persons. The working hypothesis is that elderly persons with regular use of preventive dental care or without oral health care problems are less likely to experience specific co-morbidities over time than elderly persons not regularly using preventive dental care or with oral health care issues. Aim 3. Estimate the relationship between oral disease and co-morbidities over time for elderly persons. The working hypothesis is that elderly persons with oral disease are more likely over time to experience specific co- morbidities compared to elderly persons without oral disease.
  Leader(s): MAGAZINER, JAY
    NIH T32AG000262 / ( 1998 - 2023 )
  AbstractThe aging of the United States population highlights the need for increased interdisciplinary research on diseasesand disabilities that affect older persons. The objective of years 21 25 of this successful program is to continuetraining 5 pre- and 2 postdoctoral fellows to conduct independent and original research in the epidemiology ofaging, with an emphasis on the prevention of late life disability and functional decline and the maximization offunction in those with existing disabilities and disabling conditions. The program emphasizes four broadsubstantive areas in which program faculty have gerontologic research experience and are conducting ongoingprojects: musculoskeletal epidemiology; neuroepidemiology; genetic epidemiology; and pharmacoepidemiology.The program prepares trainees to: 1) contribute to an interdisciplinary research team under the supervision of aprimary mentor expert in the epidemiology of aging and secondary mentors expert in epidemiology methodsand/or biostatistics, gerontology and content areas relevant to trainee research; 2) develop a research question,articulate hypotheses, and design and perform an epidemiologic study to address hypotheses; 3) become expertin at least one substantive area relevant to functional decline and the maximization of function in those withdisabilities and disabling conditions; 4) demonstrate excellence in conducting independent, innovative research;5) gain experience presenting research results; 6) master a core curriculum in epidemiology and biostatistics; 7)be knowledgeable about basic biological and psychosocial processes of aging; 8) master principles ofresponsible conduct of research; and 9) be prepared for transition to a research career in academia,government, industry or non-profit sector using capabilities in the epidemiology of aging.The program is located within the Department of Epidemiology and Public Health (EPH) of the University ofMaryland School of Medicine. Major program strengths include: 1) availability of core epidemiology of agingfaculty, and faculty expert in gerontology, epidemiology, biostatistics, and substantive areas that are focus ofprogram; 2) interdisciplinary training and research opportunities in aging and related areas; 3) graduate trainingopportunities including advanced coursework through the Doctoral Programs in Epidemiology and HumanGenetics, Gerontology, and Pharmaceutical Health Services Research; and 4) ability to capitalize onBaltimore/Washington corridor to leverage resources across multiple domains (academia, government, industry,and non-profit). We expect the training program, with its team of dedicated faculty, will continue to serve traineesin launching successful careers as leaders in the epidemiology of aging. The program director is recognized forhis leadership nationally and within the University of Maryland; as such, he is in an excellent position to fosterthe development of trainees through participation in interdisciplinary research programs locally and nationally.Leaders of the Doctoral Programs Epidemiology and Human Genetics and in Gerontology will serve as programassociate directors.
    NIH U19AI150574 / ( 2020 - 2025 )
  The Inter-collaborative Radiation Countermeasures (INTERACT) Consortium was assembled for the overall goal of developing safe and effective medical countermeasures (MCM) to mitigate and/or treat the acute, delayed, and long-term consequences of radiation exposure for all subsets of the civilian population in the event of a radiological or nuclear (RadNuc) public health emergency. The biological complexity of multiorgan injury (MOI) and failure associated with acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE) requires a comprehensive, multidisciplinary approach to efficiently identify new targets for therapeutic intervention and to move promising MCMs from the research laboratory to advanced pharmaceutical development and approval under the U.S. Food and Drug Administration s (FDA) Animal Rule (AR) regulatory pathway. INTERACT, a newly formed University of Maryland School of Medicine (UMSOM)-based Center for Medical Countermeasures against Radiation (CMCR), is a partnership of internationally-recognized investigators from four U.S.-based universities who possess a broad depth of expertise in MCM development, a unique set of animal model platforms, and a common goal of sharing ideas and quality practices to advance the cutting-edge scientific discovery and translational development of MCMs. INTERACT projects are broadly designed around a common theme to promote tissue regeneration through targeting the biological processes involved in cellular degeneration that contribute to the clinical manifestation of ARS/DEARE after prompt exposure to high-doses of total body irradiation (TBI). Candidate MCMs under investigation target key biological mechanisms associated with a radiation-induced accelerated aging process including genomic instability, mitochondrial damage, cellular senescence, and inflammation that leads to the hematopoietic (Project 1) and gastrointestinal subsyndromes of ARS (Projects 2, 3), cutaneous radiation injury (Project 3), and DEARE (Projects 1 and 4). Preliminary datum for each of the MCMs under investigation in Projects 1-4 have shown a significant improvement in survival when administered at least 24 hours post- exposure and strong safety profiles in preclinical, and in some cases clinical trials. To advance MCM development within the framework of the AR regulatory pathway for all subsets of the population, projects are supported by two service cores (Core A- Administrative, Core B- Multispecies Efficacy and Pharmacometric Modeling Core) and two consortium cores (Coordinating Center Core, and the Opportunities Fund Management Core). Core B offers one of, if not the most, comprehensive animal model platforms available for MCM testing within the broader CMCR consortia, and includes rabbit, minipig, and non-human primate models of ARS and/or DEARE. INTERACT is synergistic with other potential Centers by offering capabilities and resources currently unavailable to other sites through data and resource sharing and technology transfer to advance and strengthen the National Institute of Allergy and Infectious Diseases (NIAID)/National Institute of Health (NIH) s mission to ensure the nation s preparedness to respond to a radiological or nuclear incident.
23. Project Title: Cooling to Help Injured Lungs (CHILL) Phase 2B Randomized Control Trial of Therapeutic Hypothermia in Patients with ARDS
  Leader(s): HASDAY, JEFFREY J
    Department of Defense W81XWH-20-1-0432 / ( 2019 - 2024 )
  Acute respiratory distress syndrome (ARDS) is a disease in which the lungs are injured and no longer are able to support the body s needs for absorbing oxygen and removing carbon dioxide. About 40% of patients with ARDS die. There are no medications available that are effective in patients with ARDS. The objective of the proposed study is to test whether reducing body temperature by 4 F-6 F for 48 hours while giving a paralytic medication to prevent shivering will reduce lung injury in patients with ARDS. The rationale for this study is based on (1) the known effect of cooling to reduce the need for oxygen thereby reducing the work required of the injured lungs and (2) the effect of cooling to inactivate certain molecules that cause the lung injury.
  1. Long-term sex differences in all-cause and infection-specific mortality post hip fracture.
    Bajracharya R, Guralnik JM, Shardell MD, Rathbun AM, Yamashita T, Hochberg MC, Gruber-Baldini AL, Magaziner JS, Orwig DL
    J Am Geriatr Soc, 2022 Apr 12, 70(7): 2107-2114 | PMID: 35415882 | PMCID: PMC9283265
    Citations: | AltScore: 4.85
  2. Test-retest reliability of the FALL FIT system for assessing and training protective arm reactions in response to a forward fall.
    Borrelli J, Creath R, Westlake K, Rogers MW
    MethodsX, 2022, 9: 101702 | PMID: 35518921 | PMCID: PMC9062354
    Citations: | AltScore: NA
  3. Age-related changes in protective arm reaction kinematics, kinetics, and neuromuscular activation during evoked forward falls.
    Borrelli J, Creath R, Westlake K, Rogers MW
    Hum Mov Sci, 2022 Feb, 81: 102914 | PMID: 34923206 | PMCID: PMC8895474
    Citations: 1 | AltScore: NA
  4. Prevalence and clinical outcomes of hospitalized patients with upper extremity deep vein thrombosis.
    Cires-Drouet RS, Durham F, Sharma J, Cheeka P, Strumpf Z, Cranston E, Xu C, Mayorga-Carlin M, Sorkin JD, Lal BK
    J Vasc Surg Venous Lymphat Disord, 2022 Jan, 10(1): 102-110 | PMID: 34089941 | PMCID: PMC9000923
    Citations: | AltScore: 8.25
  5. Gluteal muscle fatty infiltration, fall risk, and mobility limitation in older women with urinary incontinence: a pilot study.
    Davis DL, Roberts A, Calderon R, Kim S, Ryan AS, Sanses TVD
    Skeletal Radiol, 2022 Jul 27 | PMID: 35896734
    Citations: | AltScore: 0.5
  6. Stakeholders' views on priorities essential for establishing a supportive environment for clinical trials in nursing homes.
    Delude C, Abi-Elias IH, Quinn CC, Adams AS, Magaziner JS, Ito K, Jain P, Gurwitz JH, Mazor KM
    J Am Geriatr Soc, 2022 Apr, 70(4): 950-959 | PMID: 35188222 | PMCID: PMC8986625
    Citations: | AltScore: 4.3
  7. Baseline Predictors of Response to Repetitive Task Practice in Chronic Stroke.
    Dimyan MA, Harcum S, Ermer E, Boos AF, Conroy SS, Liu F, Horn LB, Xu H, Zhan M, Chen H, Whitall J, Wittenberg GF
    Neurorehabil Neural Repair, 2022 Jul, 36(7): 426-436 | PMID: 35616437 | PMCID: PMC9197874
    Citations: | AltScore: NA
  8. Impact of the COVID-19 pandemic on diagnosis of new cancers: A national multicenter study of the Veterans Affairs Healthcare System.
    Englum BR, Prasad NK, Lake RE, Mayorga-Carlin M, Turner DJ, Siddiqui T, Sorkin JD, Lal BK
    Cancer, 2022 Mar 1, 128(5): 1048-1056 | PMID: 34866184 | PMCID: PMC8837676
    Citations: 7 | AltScore: 403.33
  9. Association of Financial Strain With Mortality Among Older US Adults Recovering From an Acute Myocardial Infarction.
    Falvey JR, Hajduk AM, Keys CR, Chaudhry SI
    JAMA Intern Med, 2022 Apr 1, 182(4): 445-448 | PMID: 35188537 | PMCID: PMC8861896
    Citations: | AltScore: 194.25
  10. Neighborhood Socioeconomic Disadvantage and Disability After Critical Illness.
    Falvey JR, Murphy TE, Leo-Summers L, Gill TM, Ferrante LE
    Crit Care Med, 2022 May 1, 50(5): 733-741 | PMID: 34636807 | PMCID: PMC9001742
    Citations: 1 | AltScore: 32.95
  11. Telemedicine for Older Adult Nursing Home Residents to Avoid Emergency Department Visits: The Experience of the NHTeleED Project in Maryland.
    Gruber-Baldini AL, Quinn CC, Roggio AX, Browne BJ, Magaziner JS
    J Am Med Dir Assoc, 2022 Feb 26
    pii: S1525-8610(22)00101-3. | PMID: 35231439 | PMCID: PMC8881981
    Citations: | AltScore: NA
  12. Synergistic Associations of Depressive Symptoms and Executive Functions With Longitudinal Trajectories of Diabetes Biomarkers Among Urban-Dwelling Adults Without Diabetes.
    Khambaty T, Leibel DK, Katzel LI, Evans MK, Zonderman AB, Waldstein SR
    Psychosom Med, 2022 May 1, 84(4): 478-487 | PMID: 35311806 | PMCID: PMC9064939
    Citations: | AltScore: NA
  13. Association Between Foot Surgery Type and Subsequent Healing in Veterans With Moderate-to-Severe Diabetic Foot Infections.
    Kim JJ, Littman AJ, Sorkin JD, Roghmann MC
    Open Forum Infect Dis, 2022 Feb, 9(2): ofab650 | PMID: 35111873 | PMCID: PMC8802798
    Citations: | AltScore: 1
  14. Impact of Hospital-Based Rehabilitation Services on Discharge to the Community by Value-Based Payment Programs After Joint Replacement Surgery.
    Kumar A, Roy I, Warren M, Shaibi SD, Fabricant M, Falvey JR, Vashist A, Karmarkar AM
    Phys Ther, 2022 Apr 1, 102(4):
    pii: pzab313. | PMID: 35079829 | PMCID: PMC9190306
    Citations: | AltScore: 17.85
  15. Evaluating the optimal training paradigm for transcarotid artery revascularization based on worldwide experience.
    Lal BK, Cambria R, Moore W, Mayorga-Carlin M, Shutze W, Stout CL, Broussard H, Garrett HE Jr, Nelson W, Titus JM, Macdonald S, Lake R, Sorkin JD
    J Vasc Surg, 2022 Feb, 75(2): 581-589.e1 | PMID: 34562569 | PMCID: PMC8792193
    Citations: | AltScore: 19.25
  16. The effect of diabetes on abdominal aortic aneurysm growth over 2?years.
    Nordness MJ, Baxter BT, Matsumura J, Terrin M, Zhang K, Ye F, Webb NR, Dalman RL, Curci JA
    J Vasc Surg, 2022 Apr, 75(4): 1211-1222.e1 | PMID: 34695550 | PMCID: PMC8940607
    Citations: 2 | AltScore: 4.55
  17. Role of volume in small abdominal aortic aneurysm surveillance.
    Olson SL, Panthofer AM, Blackwelder W, Terrin ML, Curci JA, Baxter BT, Weaver FA, Matsumura JS, Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial Investigators.
    J Vasc Surg, 2022 Apr, 75(4): 1260-1267.e3 | PMID: 34655683 | PMCID: PMC8940629
    Citations: 1 | AltScore: NA
  18. Randomised comparative effectiveness trial of Pulmonary Embolism Prevention after hiP and kneE Replacement (PEPPER): the PEPPER trial protocol.
    Pellegrini VD Jr, Eikelboom JW, Evarts CM, Franklin PD, Garvin KL, Goldhaber SZ, Iorio R, Lambourne CA, Magaziner J, Magder L, Steering Committee of the PEPPER Trial and the PEPPER Trial Investigators, funded by PCORI.
    BMJ Open, 2022 Mar 8, 12(3): e060000 | PMID: 35260464 | PMCID: PMC8905949
    Citations: 1 | AltScore: NA
  19. COVID-19 Vaccination Associated With Reduced Postoperative SARS-CoV-2 Infection and Morbidity.
    Prasad NK, Lake R, Englum BR, Turner DJ, Siddiqui T, Mayorga-Carlin M, Sorkin JD, Lal BK
    Ann Surg, 2022 Jan 1, 275(1): 31-36 | PMID: 34417362 | PMCID: PMC8678152
    Citations: 6 | AltScore: 244.8
  20. Model Testing of the Factors That Influence Performance of Function Focused Care and Function Among Assisted Living Residents.
    Resnick B, Boltz M, Galik E, Fix S, Holmes S, Zhu S
    J Appl Gerontol, 2022 Feb, 41(2): 401-410 | PMID: 35067104 | PMCID: PMC8792441
    Citations: 1 | AltScore: NA
  21. Predictive Equations Overestimate Resting Metabolic Rate in Survivors of Chronic Stroke.
    Ryan AS, Novitskaya M, Treuth AL
    Arch Phys Med Rehabil, 2022 Feb 19, 103(7): 1352-1359
    pii: S0003-9993(22)00226-X. | PMID: 35192798 | PMCID: PMC9246861
    Citations: | AltScore: NA
  22. Impact of psychological resilience on walking capacity in older adults following hip fracture.
    Soliman G, Fortinsky RH, Mangione K, Beamer BA, Magder L, Binder EF, Craik R, Gruber-Baldini A, Orwig D, Resnick B, Wakefield DB, Magaziner J
    J Am Geriatr Soc, 2022 Jul 20 | PMID: 35856155
    Citations: | AltScore: 243.25
  23. Reply to Verhoef et al.
    Sorkin JD, Manary M, Smeets PAM, MacFarlane AJ, Astrup A, Prigeon RL, Hogans BB, Odle J, Davis TA, Tucker KL, Duggan CP, Tobias DK
    Am J Clin Nutr, 2022 Feb 9, 115(2): 598-600 | PMID: 35139165 | PMCID: PMC8827123
    Citations: | AltScore: NA
  1. Examining the influence of mental stress on balance perturbation responses in older adults.
    Akinlosotu RY, Alissa N, Waldstein SR, Creath RA, Wittenberg GF, Westlake KP
    Exp Gerontol, 2021 Oct 1, 153: 111495 | PMID: 34314843 | PMCID: PMC8919298
    Citations: | AltScore: 1.5
  2. Attenuating persistent sodium current-induced atrial myopathy and fibrillation by preventing mitochondrial oxidative stress.
    Avula UMR, Dridi H, Chen BX, Yuan Q, Katchman AN, Reiken SR, Desai AD, Parsons S, Baksh H, Ma E, Dasrat P, Ji R, Lin Y, Sison C, Lederer WJ, Joca HC, Ward CW, Greiser M, Marks AR, Marx SO, Wan EY
    JCI Insight, 2021 Oct 28, 6(23):
    pii: e147371. | PMID: 34710060 | PMCID: PMC8675199
    Citations: 1 | AltScore: 7.5
  3. Assessing calorie and protein recommendations for survivors of critical illness weaning from prolonged mechanical ventilation - can we find a proper balance?
    Balasubramanian S, Tran DH, Serra M, Parker EA, Diaz-Abad M, Deepak J, McCurdy MT, Verceles AC
    Clin Nutr ESPEN, 2021 Oct, 45: 449-453 | PMID: 34620353 | PMCID: PMC8925994
    Citations: | AltScore: NA
  4. Race and other sociodemographic categories are differentially linked to multiple dimensions of interpersonal-level discrimination: Implications for intersectional, health research.
    Beatty Moody DL, Waldstein SR, Leibel DK, Hoggard LS, Gee GC, Ashe JJ, Brondolo E, Al-Najjar E, Evans MK, Zonderman AB
    PLoS One, 2021, 16(5): e0251174 | PMID: 34010303 | PMCID: PMC8133471
    Citations: | AltScore: 4
  5. Red cell distribution width, anemia and their associations with white matter integrity among middle-aged urban adults.
    Beydoun MA, Shaked D, Hossain S, Weiss J, Beydoun HA, Maldonado AI, Katzel LI, Davatzikos C, Gullapalli RP, Seliger SL, Erus G, Evans MK, Zonderman AB, Waldstein SR
    Neurobiol Aging, 2021 Sep, 105: 229-240 | PMID: 34120091 | PMCID: PMC8338752
    Citations: | AltScore: 0.25
  6. Healthy Eating Index-2015 Is Associated with Grip Strength among the US Adult Population.
    Bigman G, Ryan AS
    Nutrients, 2021 Sep 25, 13(10):
    pii: 3358. | PMID: 34684359 | PMCID: PMC8540420
    Citations: 1 | AltScore: NA
  7. A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.
    Binder EF, Christensen JC, Stevens-Lapsley J, Bartley J, Berry SD, Dobs AS, Fortinsky RH, Hildreth KL, Kiel DP, Kuchel GA, Marcus RL, McDonough CM, Orwig D, Sinacore DR, Schwartz RS, Volpi E, Magaziner J, Schechtman KB
    Contemp Clin Trials, 2021 May, 104: 106356 | PMID: 33716173 | PMCID: PMC9119796
    Citations: 2 | AltScore: 1.6
  8. B and T Cell Immunity in Tissues and Across the Ages.
    Booth JS, Toapanta FR
    Vaccines (Basel), 2021 Jan 6, 9(1):
    pii: E24. | PMID: 33419014 | PMCID: PMC7825307
    Citations: 3 | AltScore: 2.85
  9. Untangling biomechanical differences in perturbation-induced stepping strategies for lateral balance stability in older individuals.
    Borrelli J, Creath R, Gray VL, Rogers MW
    J Biomech, 2021 Jan 4, 114: 110161 | PMID: 33316540 | PMCID: PMC7778461
    Citations: 1 | AltScore: NA
  10. Calcium influx through the mitochondrial calcium uniporter holocomplex, MCUcx.
    Boyman L, Greiser M, Lederer WJ
    J Mol Cell Cardiol, 2021 Feb, 151: 145-154 | PMID: 33147447 | PMCID: PMC7880866
    Citations: 8 | AltScore: 0.5
  11. Feasibility and effects of high-intensity interval training in older adults living with HIV.
    Briggs BC, Ryan AS, Sorkin JD, Oursler KK
    J Sports Sci, 2021 Feb, 39(3): 304-311 | PMID: 32962523 | PMCID: PMC8212165
    Citations: 6 | AltScore: 1
  12. What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
    Cawthon PM, Patel SM, Kritchevsky SB, Newman AB, Santanasto A, Kiel DP, Travison TG, Lane N, Cummings SR, Orwoll ES, Duchowny KA, Kwok T, Hirani V, Schousboe J, Karlsson MK, Mellstr?m D, Ohlsson C, Ljunggren ?, Xue QL, Shardell M, Jordan JM, Pencina KM, Fielding RA, Magaziner J, Correa-de-Araujo R, Bhasin S, Manini TM
    J Gerontol A Biol Sci Med Sci, 2021 Sep 13, 76(10): e321-e327 | PMID: 34166490 | PMCID: PMC8436986
    Citations: 1 | AltScore: 10.05
  13. Repetitive Traumatic Brain Injury Among Older Adults.
    Chauhan AV, Guralnik J, dosReis S, Sorkin JD, Badjatia N, Albrecht JS
    J Head Trauma Rehabil, 2021 Jul 26, 37(4): E242-E248 | PMID: 34320558 | PMCID: PMC8789954
    Citations: | AltScore: 1
  14. Catheter-based interventions versus medical and surgical approaches in acute pulmonary embolism.
    Cires-Drouet RS, Nagarsheth K, Kaczorowski DJ, Toursavadkohi S, Deatrick K, Madathil RJ, Jones KM, Liskov S, Fitch J, Sayad M, Pasrija C, Mayorga-Carlin M, Herr D, Sorkin JD, Griffith B, Lal BK, Gammie JS
    J Vasc Surg Venous Lymphat Disord, 2021 Nov, 9(6): 1382-1390 | PMID: 33965609 | PMCID: PMC9048149
    Citations: | AltScore: NA
  15. Correlation of Quantitative Versus Semiquantitative Measures of Supraspinatus Intramuscular Fatty Infiltration to Shoulder Range of Motion and Strength: A Pilot Study.
    Davis DL, Almardawi R, Henn RF 3rd, Zhuo J, Mulligan ME, Resnik CS, Abdullah SB, Al Khalifah H, Gilotra MN, Hasan SA, Gullapalli RP
    Curr Probl Diagn Radiol, 2021 Sep-Oct, 50(5): 629-636 | PMID: 32654835 | PMCID: PMC8565480
    Citations: 2 | AltScore: 0.25
  16. Reliability of supraspinatus intramuscular fatty infiltration estimates on T1-weighted MRI in potential candidates for rotator cuff repair surgery: full-thickness tear versus high-grade partial-thickness tear.
    Davis DL, Gilotra MN, Calderon R, Roberts A, Hasan SA
    Skeletal Radiol, 2021 Nov, 50(11): 2233-2243 | PMID: 33959799 | PMCID: PMC8565455
    Citations: | AltScore: NA
  17. Effects of exercise training with weight loss on skeletal muscle expression of angiogenic factors in overweight and obese older men.
    Evans WS, Blumenthal JB, Heilman JM, Ryan AS, Prior SJ
    J Appl Physiol (1985), 2021 May 20, 131(1): 56-63 | PMID: 34013746 | PMCID: PMC8325618
    Citations: 2 | AltScore: 6.3
  18. Implications of Race and Ethnicity in Sarcopenia US National Prevalence of Sarcopenia by Muscle Mass, Strength, and Function Indices.
    G B, As R
    Gerontol Geriatr Res, 2021, 4(1):
    pii: 126 | PMID: 35368515 | PMCID: PMC8970578
    Citations: | AltScore: 0.25
  19. Association between Physical Activity and Mortality in Patients with Claudication.
    Gardner AW, Addison O, Katzel LI, Montgomery PS, Prior SJ, Serra MC, Sorkin JD
    Med Sci Sports Exerc, 2021 Apr 1, 53(4): 732-739 | PMID: 32991346 | PMCID: PMC7969371
    Citations: 2 | AltScore: 34.3
  20. Cognitive decrement in older adults with symptomatic peripheral artery disease.
    Gardner AW, Montgomery PS, Wang M, Shen B, Casanegra AI, Silva-Palacios F, Ungvari Z, Yabluchanskiy A, Csiszar A, Waldstein SR
    Geroscience, 2021 Oct, 43(5): 2455-2465 | PMID: 34498199 | PMCID: PMC8599571
    Citations: 1 | AltScore: 0.5
  21. Revascularization for asymptomatic carotid artery stenosis improves balance and mobility.
    Gray VL, Desikan SK, Khan AA, Barth D, Sikdar S, Sorkin JD, Lal BK
    J Vasc Surg, 2021 Oct, 74(4): 1272-1280 | PMID: 34019991 | PMCID: PMC8958337
    Citations: | AltScore: 1.25
  22. IL-6 and Soluble Receptors in Overweight and Obese African American Women With and Without Breast Cancer.
    Griffith KA, Ryan AS
    Biol Res Nurs, 2021 Apr, 23(2): 218-222 | PMID: 32748635 | PMCID: PMC8264857
    Citations: | AltScore: NA
  23. Low Back Pain and Substance Use: Diagnostic and Administrative Coding for Opioid Use and Dependence Increased in U.S. Older Adults with Low Back Pain.
    Hogans BB, Siaton BC, Taylor MN, Katzel LI, Sorkin JD
    Pain Med, 2021 Apr 20, 22(4): 836-847 | PMID: 33594426 | PMCID: PMC8599750
    Citations: 1 | AltScore: 3.7
  24. In-Bed Sensorimotor Rehabilitation in Early and Late Subacute Stroke Using a Wearable Elbow Robot: A Pilot Study.
    Huang MZ, Yoon YS, Yang J, Yang CY, Zhang LQ
    Front Hum Neurosci, 2021, 15: 669059 | PMID: 34108868 | PMCID: PMC8180557
    Citations: | AltScore: NA
  25. Age-dependent changes in nuclear-cytoplasmic signaling in skeletal muscle.
    Iyer SR, Hsia RC, Folker ES, Lovering RM
    Exp Gerontol, 2021 Jul 15, 150: 111338 | PMID: 33862137 | PMCID: PMC8165001
    Citations: 4 | AltScore: 1.6
  26. Calcium Signaling Silencing in Atrial Fibrillation: Implications for Atrial Sodium Homeostasis.
    Kaplan AD, Joca HC, Boyman L, Greiser M
    Int J Mol Sci, 2021 Sep 29, 22(19):
    pii: 10513. | PMID: 34638854 | PMCID: PMC8508839
    Citations: 3 | AltScore: NA
  27. Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion.
    Khan AA, Patel J, Desikan S, Chrencik M, Martinez-Delcid J, Caraballo B, Yokemick J, Gray VL, Sorkin JD, Cebral J, Sikdar S, Lal BK
    J Vasc Surg, 2021 May, 73(5): 1611-1621.e2 | PMID: 33166609 | PMCID: PMC8209736
    Citations: 5 | AltScore: 0.25
  28. Depressive symptom heterogeneity among older adults after hip fracture.
    Kirk JM, Magaziner J, Shardell MD, Ryan AS, Gruber-Baldini AL, Orwig D, Hochberg MC, Rathbun AM
    Age Ageing, 2021 Nov 10, 50(6): 1943-1951 | PMID: 34405224 | PMCID: PMC8768453
    Citations: | AltScore: 4.75
  29. Periprocedural complications in patients with SARS-CoV-2 infection compared to those without infection: A nationwide propensity-matched analysis.
    Lal BK, Prasad NK, Englum BR, Turner DJ, Siddiqui T, Carlin MM, Lake R, Sorkin JD
    Am J Surg, 2021 Aug, 222(2): 431-437 | PMID: 33384154 | PMCID: PMC7836786
    Citations: 7 | AltScore: 9.75
  30. The Effect of Frailty on Walking Recovery after Hip Fracture: A Secondary Analysis of the Community Ambulation Project.
    Mangione KK, Craik RL, Kenny A, Memaj A, Miller MF, Chen M, Weingart M, Orwig D, Magaziner J
    J Gerontol A Biol Sci Med Sci, 2021 Feb 12, 76(11): e335-e339
    pii: glab044. | PMID: 33575796 | PMCID: PMC8514060
    Citations: | AltScore: NA
  31. Using Treatment Fidelity Measures to Understand Walking Recovery: A Secondary Analysis From the Community Ambulation Project.
    Mangione KK, Posner MA, Craik RL, Wolff EF, Fortinsky RH, Beamer BA, Binder EF, Orwig DL, Magaziner J, Resnick B
    Phys Ther, 2021 Aug 1, 101(8):
    pii: pzab109. | PMID: 33823028 | PMCID: PMC8520021
    Citations: | AltScore: 11.55
  32. Differential misclassification of cognitive impairment by sex among hip fracture patients.
    Mutchie HL, Albrecht JS, Orwig DL, Huang Y, Boscardin WJ, Hochberg MC, Magaziner JS, Gruber-Baldini AL
    J Am Geriatr Soc, 2021 Dec 10, 70(3): 838-845 | PMID: 34890469 | PMCID: PMC8904289
    Citations: | AltScore: 9.65
  33. Four Square Step Test Performance in Hip Fracture Patients.
    Mutchie HL, Orwig DL, Beamer B, Conroy V, Guralnik J, Magaziner J, Gruber-Baldini AL
    J Geriatr Phys Ther, 2021 Apr 28, 45(2): 81-89 | PMID: 33935219 | PMCID: PMC8551310
    Citations: | AltScore: 0.25
  34. Evaluating Growth Patterns of Abdominal Aortic Aneurysm Diameter With Serial Computed Tomography Surveillance.
    Olson SL, Wijesinha MA, Panthofer AM, Blackwelder WC, Upchurch GR Jr, Terrin ML, Curci JA, Baxter BT, Matsumura JS
    JAMA Surg, 2021 Apr 1, 156(4): 363-370 | PMID: 33595625 | PMCID: PMC7890454
    Citations: 5 | AltScore: 20.4
  35. Sex Differences in Recovery Across Multiple Domains among Older Adults with Hip Fracture.
    Orwig DL, Abraham DS, Hochberg MC, Gruber-Baldini A, Guralnik JM, Cappola AR, Golden J, Hicks GE, Miller RR, Resnick B, Shardell M, Sterling RS, Bajracharya R, Magaziner J
    J Gerontol A Biol Sci Med Sci, 2021 Sep 23, 77(7): 1463-1471
    pii: glab271. | PMID: 34555162 | PMCID: PMC9255694
    Citations: 1 | AltScore: 3.85
  36. Change in vertebral strength and bone mineral density in men and women over the year post-hip fracture: a subgroup analysis.
    Orwig DL, Kopperdahl D, Keaveny T, Magaziner J, Hochberg M
    Arch Osteoporos, 2021 Feb 22, 16(1): 37 | PMID: 33619589 | PMCID: PMC8183184
    Citations: | AltScore: NA
  37. Telehealth Exercise Intervention in Older Adults With HIV: Protocol of a Multisite Randomized Trial.
    Oursler KK, Marconi VC, Briggs BC, Sorkin JD, Ryan AS, FIT VET Project Team.
    J Assoc Nurses AIDS Care, 2021 Jan 20, 33(2): 168-177 | PMID: 33481463 | PMCID: PMC8289938
    Citations: | AltScore: 4.3
  38. A Nation-Wide Review of Elective Surgery and COVID-Surge Capacity.
    Prasad NK, Englum BR, Turner DJ, Lake R, Siddiqui T, Mayorga-Carlin M, Sorkin JD, Lal BK
    J Surg Res, 2021 Nov, 267: 211-216 | PMID: 34157490 | PMCID: PMC8213966
    Citations: 7 | AltScore: 446.08
  39. Increased complications in patients who test COVID-19 positive after elective surgery and implications for pre and postoperative screening.
    Prasad NK, Lake R, Englum BR, Turner DJ, Siddiqui T, Mayorga-Carlin M, Sorkin JD, Lal BK
    Am J Surg, 2021 Apr 14, 223(2): 380-387
    pii: S0002-9610(21)00234-8. | PMID: 33894979 | PMCID: PMC8045424
    Citations: 6 | AltScore: 7
  40. Coronavirus disease 2019 and clinical research in U.S. nursing homes.
    Quinn CC, Adams AS, Magaziner JS, Gurwitz JH
    J Am Geriatr Soc, 2021 Apr 19, 69(7): 1748-1751 | PMID: 33872385 | PMCID: PMC8250950
    Citations: 8 | AltScore: 7.8
  41. Effect of Stretching of Spastic Elbow Under Intelligent Control in Chronic Stroke Survivors-A Pilot Study.
    Rao S, Huang M, Chung SG, Zhang LQ
    Front Neurol, 2021, 12: 742260 | PMID: 34970204 | PMCID: PMC8713334
    Citations: | AltScore: NA
  42. Testing the Impact of FFC-AL-EIT on Psychosocial and Behavioral Outcomes in Assisted Living.
    Resnick B, Boltz M, Galik E, Fix S, Holmes S, Zhu S, Barr E
    J Am Geriatr Soc, 2021 Feb, 69(2): 459-466 | PMID: 33095469 | PMCID: PMC8116977
    Citations: 2 | AltScore: 3.25
  43. Comparison of Lateral Perturbation-Induced Step Training and Hip Muscle Strengthening Exercise on Balance and Falls in Community Dwelling Older Adults: A Blinded Randomized Controlled Trial.
    Rogers MW, Creath RA, Gray V, Abarro J, McCombe Waller S, Beamer BA, Sorkin JD
    J Gerontol A Biol Sci Med Sci, 2021 Jan 25, 76(9): e194-e202
    pii: glab017. | PMID: 33491052 | PMCID: PMC8361357
    Citations: 4 | AltScore: 4.6
  44. Effect of mupirocin for Staphylococcus aureus decolonization on the microbiome of the nose and throat in community and nursing home dwelling adults.
    Roghmann MC, Lydecker AD, Shardell M, DeBoy RT, Johnson JK, Zhao L, Hittle LL, Mongodin EF
    PLoS One, 2021, 16(6): e0252004 | PMID: 34101737 | PMCID: PMC8186807
    Citations: 1 | AltScore: 1
  45. Skeletal muscle myostatin gene expression and sarcopenia in overweight and obese middle-aged and older adults.
    Ryan AS, Li G
    JCSM Clin Rep, 2021 Oct, 6(4): 137-142 | PMID: 35311023 | PMCID: PMC8932637
    Citations: | AltScore: 0.25
  46. Pathways in Skeletal Muscle: Protein Signaling and Insulin Sensitivity after Exercise Training and Weight Loss Interventions in Middle-Aged and Older Adults.
    Ryan AS, Li G, McMillin S, Prior SJ, Blumenthal JB, Mastella L
    Cells, 2021 Dec 10, 10(12):
    pii: 3490. | PMID: 34943997 | PMCID: PMC8700073
    Citations: | AltScore: 2.25
  47. Bone Mineral Density Changes during Weight Regain following Weight Loss with and without Exercise.
    Serra MC, Ryan AS
    Nutrients, 2021 Aug 19, 13(8):
    pii: 2848. | PMID: 34445008 | PMCID: PMC8400683
    Citations: | AltScore: 5.9
  48. Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO).
    Shardell M, Cappola AR, Guralnik JM, Hicks GE, Kritchevsky SB, Simonsick EM, Ferrucci L, Semba RD, Shaffer NC, Harris T, Eiriksdottir G, Gudnason V, Cotch MF, Orwoll E, Ensrud KE, Cawthon PM
    Am J Clin Nutr, 2021 Jul 1, 114(1): 16-28 | PMID: 33826696 | PMCID: PMC8246604
    Citations: | AltScore: 6.5
  49. Association of Vaginal Microbiota With Signs and Symptoms of the Genitourinary Syndrome of Menopause Across Reproductive Stages.
    Shardell M, Gravitt PE, Burke AE, Ravel J, Brotman RM
    J Gerontol A Biol Sci Med Sci, 2021 Aug 13, 76(9): 1542-1550 | PMID: 33903897 | PMCID: PMC8361365
    Citations: 3 | AltScore: NA
  50. A guide for authors and readers of the American Society for Nutrition Journals on the proper use of P values and strategies that promote transparency and improve research reproducibility.
    Sorkin JD, Manary M, Smeets PAM, MacFarlane AJ, Astrup A, Prigeon RL, Hogans BB, Odle J, Davis TA, Tucker KL, Duggan CP, Tobias DK
    Am J Clin Nutr, 2021 Oct 4, 114(4): 1280-1285 | PMID: 34258613 | PMCID: PMC8488872
    Citations: 4 | AltScore: 61.75
  51. Excess Mortality in COVID-19-Positive Versus COVID-19-Negative Inpatients With Diabetes: A Nationwide Study.
    Spanakis EK, Yoo A, Ajayi ON, Siddiqui T, Khan MM, Seliger SL, Klonoff DC, Feng Z, Sorkin JD
    Diabetes Care, 2021 Sep, 44(9): e169-e170 | PMID: 34233926 | PMCID: PMC8740932
    Citations: 3 | AltScore: 1.5
  52. Augmented exercise pressor response during maximal treadmill exercise is not related to systemic inflammation in stroke survivors.
    Sprick JD, Serra MC, Ryan AS, Li Y, Park J
    Top Stroke Rehabil, 2021 May, 28(4): 251-257 | PMID: 32783602 | PMCID: PMC7878569
    Citations: | AltScore: 1.5
  53. Evaluating Test-Retest Reliability of Fatigability in Chronic Stroke.
    Stookey AD, Macko RF, Ivey FM, Katzel LI
    J Stroke Cerebrovasc Dis, 2021 Sep, 30(9): 105895 | PMID: 34242857 | PMCID: PMC8767492
    Citations: | AltScore: NA
  54. The Effect of High Protein and Mobility-Based Rehabilitation on Clinical Outcomes in Survivors of Critical Illness.
    Wappel S, Tran DH, Wells CL, Verceles AC
    Respir Care, 2021 Jan, 66(1): 73-78 | PMID: 32817444 | PMCID: PMC8208101
    Citations: 1 | AltScore: 25.15
  55. Effects of transcranial direct current stimulation (tDCS) on posture, movement planning, and execution during standing voluntary reach following stroke.
    Yang CL, Gad A, Creath RA, Magder L, Rogers MW, Waller SM
    J Neuroeng Rehabil, 2021 Jan 7, 18(1): 5 | PMID: 33413441 | PMCID: PMC7791870
    Citations: 2 | AltScore: NA
  56. Predictors of the start of declining eGFR in patients with systemic lupus erythematosus.
    Yip TC, Saria S, Petri M, Magder LS
    Lupus, 2021 Jan, 30(1): 15-24 | PMID: 33115373 | PMCID: PMC7770013
    Citations: | AltScore: 0.5
  57. Intensive In-Bed Sensorimotor Rehabilitation of Early Subacute Stroke Survivors With Severe Hemiplegia Using a Wearable Robot.
    Zhang C, Huang MZ, Kehs GJ, Braun RG, Cole JW, Zhang LQ
    IEEE Trans Neural Syst Rehabil Eng, 2021, 29: 2252-2259 | PMID: 34665733 | PMCID: PMC8843010
    Citations: 1 | AltScore: NA


Thomas M. Gill, MD
Yale University
Serving since 2006 (16 years)

Bret Goodpaster, PhD
Sanford Burnham Prebys Medical Discovery Institute
Serving since 2011 (11 years)

Karen Bandeen-Roche, PhD
Johns Hopkins University
Serving since 2011 (11 years)

Mark Redfern, PhD
University of Pittsburgh
Serving since 2011 (11 years)

Stephen Kritchevsky, PhD (chair)
Wake Forest University Baptist Medical Center
Serving since 2011 (11 years)

Cynthia Boyd, MD, MPH
Johns Hopkins University
Serving since 2016 (6 years)

LaDora Thompson, PhD, PT
Boston University
Serving since 2018 (4 years)

Julius Dewald, PT, PhD
Northwestern University
Serving since 2022 (0 years)

Alice Ryan, PhD (2022)
  • Federal Advisory Committee Appointment, Veterans Affairs Rehabilitation Research and Development Service
Alice Ryan, PhD (2021)
  • Federal Advisory Committee Appointment, Veterans Affairs Rehabilitation Research and Development Service
Andrea Levine, MD (2022)
  • Dean's Alumni Award for Diversity and Inclusion
Barbara Resnick, PhD, RN, CRNP, FAAN, FAANP (2021)
  • Ada Sue Hinshaw Award from the National Institute of Nursing Research
Barbara Resnick, PhD, RN, CRNP, FAAN, FAANP (2022)
  • University of Maryland Baltimore Distinguished University Professor: highest appointment bestowed on a faculty member at UMB. It is a recognition not just of excellence, but also of impact and significant contribution to the nominee’s field, knowledge, profession, and/or practice.
Jason Falvey, PT, DPT, PhD, GCS (2022)
  • Jack Walker Award: by the American Physical Therapy Association (APTA) National Honors and Awards program. The Jack Walker Award honors an author or team whose published study in Physical Therapy & Rehabilitation Journal presents novel and innovative research related to patient care and advance clinical science, as it pertains to the physical therapy profession. Dr. Falvey will be recognized and will receive his award, by APTA's Board of Directors, in August at the APTA Honors and Awards Ceremony, held during the APTA House of Delegates.
  • New Investigator Award: Health and Aging Foundation/American Geriatrics Society
  • Top Platform Presentation in Health Policy and Administration: American Physical Therapy Association Combined Sections Meeting, San Antonio, Texas
Jennifer Albrecht, PhD (2021)
  • University of Maryland School of Medicine, Department of Epidemiology and Public Health: Faculty Mentoring Award
Michelle Shardell, PhD (2021)
  • Elected Program Chair, American Statistical Association Statistics in Epidemiology Section
  • Elected to Board of Directors, American Statistical
  • Elected to Council of Sections Governing Board, American Statistical Association


General Brief Description of Minority Activities:
Not defined.

Minority Trainee(s):
  • Alan Rathbun, PhD, MPH, Assistant Professor of Epidemiology and Public Health, University of Maryland School of Medicine
    Dr. Rathbun is a musculoskeletal epidemiologist whose current research career is focused in musculoskeletal disorders, epidemiological theory, research study design, causal inference, and applied biostatistics. He currently has a K01 award and a UM-OAIC pilot award and is collaborating with OAIC investigators on both of these projects.
  • Bianka Onwumbiko, PhD Candidate, PhD Student, Psychology Department, University of Maryland Baltimore County
    Ms. Onwumbiko’s interests include the role of epigenetic modifications such as DNA methylation in the relations of structural discrimination to racial health disparities. Her master’s thesis project will examine the association between neighborhood disorder and DNA methylation based immunosenescence among African American and White women and men. Dr. Shari Waldstein currently serves as her mentor and master’s thesis chair.
  • Bisola Amodu, Clinical Research Coordinator and Pre-Med student, Department of Neurology, University of Maryland School of Medicine
    She is being mentored by Dr. Robynne Braun for training and education in the conduct of clinical trials and trained in the use of TMS for stroke recovery research.
  • Danielle Beatty Moody, PhD, Assistant Professor of Psychology, University of Maryland Baltimore County
    Dr. Beatty Moody’s area of interest includes relations of early life social disadvantage and perceived discrimination to cardiometabolic and brain health endpoints as a function of race, SES, gender and age. Dr. Shari Waldstein is her department mentor and primary mentor for Dr. Moody’s current K01. She continues to work on her diversity supplement “Early life social disadvantage, brain, frailty, and physical function: HANDLS” that is funded from NIA through the UM-OAIC.
  • Derik Davis, MD, Associate Professor of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine
    Dr. Davis’ current research career is focused in musculoskeletal radiology examining the effects of increased visceral adipose tissue (VAT) and reduced skeletal muscle (SMM) on cardiovascular disease (CVD), diabetes and functional outcomes in older adults. He collaborates with UM-OAIC studies performing radiology imaging and reading with Dr. Alice Ryan. He also has a R03 grant “Shoulder Pain, Rotator Cuff Tear, Coordination, and Mobility in Aging” funded by NIA.
  • Derrick Larkins, DPT, PhD Candidate, PhD Student in the Department of Physical Therapy and Rehabilitation Science, University of Maryland, School of Medicine
    Dr. Odessa Addison is his primary mentor, and he is interested in muscle quality and injury prevention.
  • Doyinsola Bailey, PhD, Post-Doctoral student, Department of Epidemiology and Public Health, University of Maryland School of Medicine
    Her research focus is long term outcomes of traumatic brain injury among older adults. In addition to her dissertation work, she worked on projects that used Medicare administrative claims data to assess the effects of adherence to continuous positive airway pressure therapy on cardiovascular (CV) and healthcare utilization outcomes among older adults with obstructive sleep apnea (OSA). She was awarded a diversity supplement from the American Association of Sleep Medicine Foundation to conduct additional work specifically related to older adults with comorbid OSA and CVD. Dr. Jennifer Albrecht served as the chair of her dissertation committee and her mentor.
  • Eduardo Alsina, PhD Candidate, PhD Student, Psychology Department, University of Maryland Baltimore County
    Mr. Alsina's interests include disparities in the relations of cardiovascular risk factors to cognitive function and magnetic resonance imaging assessed subclinical brain pathology as a function of self-identified race and socioeconomic status. His master's thesis examined interactive relations of left ventricular mass and sociodemographic factors on cognitive outcomes in urban-dwelling African American and White adults. His dissertation project examines whether interactive relations between the APOE polymorphism and race to memory function are mediated by brain atrophy patterns indicative of early risk for Alzheimer’s dementia. Dr. Shari Waldstein currently serves as his mentor and dissertation chair.
  • Frances Alfonzo, PhD Candidate, PhD Student, Psychology Department, University of Maryland Baltimore County
    Ms. Alfonzo’s interests include relations of diabetes and pre-diabetes status to neurocognitive function. Her master’s thesis project will examine potential interactive relations of prediabetes status and self-identified race to cognitive performance in midlife urban dwelling adults. Dr. Shari Waldstein currently serves as her mentor and master’s thesis chair.
  • Jason Ashe, PhD Candidate, PhD Student, Psychology Department, University of Maryland, Baltimore County
    Mr. Ashe’s interests include how religious participation protects against risk for cardiovascular disease and accelerated aging in the context of racial health disparities. His master’s thesis project examined the interactive relations of religious coping, self-identified race, and sex to telomere length in urban dwelling African American adults. His dissertation will determine whether religious coping buffers the negative relation of discrimination to cardiovascular risk profiles in African American women and men. Dr. Shari Waldstein currently serves as his mentor and dissertation chair.
  • Jennifer Kirk, BA, PhD Candidate, Gerontology PhD Student, Department of Epidemiology and Public Health, University of Maryland, School of Medicine
    Her research focus is disparities in bone health among older adults. She is currently conducting analyses using Medicare administrative claims data to estimate the impact of comorbid OSA on healthcare utilization among older adults with depression. Dr. Jennifer Albrecht served as the chair of her dissertation committee and her mentor.
  • Marcel Lanza, PhD, Research Associate of Physical Therapy and Rehabilitation Science, University of Maryland School of Medicine
    Dr. Lanza’s area of research interest includes falls and stepping recovery and its relationship to muscle. He was recently awarded a UM-OAIC pilot study "The Effects of Neuromuscular Activity and Muscle Structure on Stepping Performance in Older Adults". He is co-mentored by Drs. Odessa Addison, Vicki Gray and Alice Ryan.
  • Peter MacIver, PhD Candidate, PhD Student, Psychology Department, University of Maryland Baltimore County
    Mr. Maciver’s interests include disparities in relations of cardiovascular risk factors to cognitive function and MRI-assessed subclinical brain pathology as a function of race and socioeconomic status. His master’s thesis examined relations of arterial stiffening (assessed by pulse wave velocity) to cognitive function and associated socio-demographic variation. His dissertation will examine relations of anxiety to cerebral perfusion as a function of race and sex. Dr. Shari Waldstein currently serves as his mentor and dissertation chair.
  • Ruth Akinlosotu, PT, MPH, PhD Candidate, PhD student, Predoctoral Scholar, Department of Physical Therapy and Rehabilitation Science, University of Maryland School of Medicine
    She worked with Dr. Rainer von Coelln on the analysis of Dynaport data generated during his UM-OAIC pilot project. She was a co-author on a poster with Dr. von Coelln during a University of Maryland School of Medicine Center for Research on Aging: Aging Research Symposium and at a recent Department of Neurology Research Day. She is mentored by Dr. Kelly Westlake.
  • Shaline Escarfulleri, PhD Candidate, PhD Student, Psychology Department, University of Maryland, Baltimore County
    Ms. Escarfulleri’s interests include the role of emotion regulation in the relation of stress exposure and negative affect to cardiometabolic risk factors and neurocognition as a function of socioeconomic status. Her master’s thesis project will examine whether the relation of SES to carotid intimal medial thickening is partially mediated by negative affect. Dr. Shari Waldstein currently serves as her mentor and master’s thesis chair.
  • Von Homer, PhD, Assistant Professor of Biomechanics at Delaware State University
    Dr. Homer completed a post-doctoral award this past year. Dr. Homer is studies computational neuroscience and biomechanics-based methods to evaluate neuromuscular performance and fatigue within footwear to assess whether its construction is ergonomically fit to safeguard people from injury while helping footwear companies create superior products focused on comfort, fit, and performance biomechanics and neuroscience and developed, a method for predicting Injury Risk. Drs. Macko and Charlene Hafer-Macko served as his mentors.

Minority Grant(s):