Medicine and Health Sciences Commons^™

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In India: A Convergent Parallel Mixed Methods Study, Anubha Agarwal, Raji Devarajan, Salva Balbale, Aashima Chopra, Dorairaj Prabhakaran, Mark D Huffman, Lisa R Hirschhorn, Padinhare P Mohanan

2020-Current year OA Pubs

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally.

METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

2020-Current year OA Pubs

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in

Mapping Neural Correlates Of Biological Motion Perception In Autistic Children Using High-Density Diffuse Optical Tomography, Dalin Yang, Alexandra M Svoboda, Tessa G George, Patricia K Mansfield, Muriah D Wheelock, Mariel L Schroeder, Sean M Rafferty, Arefeh Sherafati, Kalyan Tripathy, Tracy Burns-Yocum, Elizabeth Forsen, John R Pruett, Natasha M Marrus, Joseph P Culver, John N Constantino, Adam T Eggebrecht

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. …

A Brief Alcohol Intervention (Bai) To Reduce Alcohol Use And Improve Prep Outcomes Among Men Who Have Sex With Men In Vietnam: Study Protocol For A Randomized Controlled Trial, Hao T M Bui, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes.

METHODS: Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion …

Association Between Tumor-Infiltrating Lymphocytes And Survival In Patients With Metastatic Breast Cancer Receiving First-Line Chemotherapy: Analysis Of Calgb 40502, Daniel G Stover, Mark Watson, Et Al.

2020-Current year OA Pubs

Association of stromal tumor-infiltrating lymphocytes (sTILs) with survival outcomes among patients with metastatic breast cancer (MBC) remains unclear. The primary objective was to evaluate the association of sTILs with progression-free survival in randomized phase III trial CALGB 40502. sTILs were associated with progression-free and overall survival in chemotherapy-treated MBC when controlling for treatment arm; however, this effect did not remain significant after additional adjustment for hormone receptor status. CALGB is now part of the Alliance for Clinical Trials in Oncology. Trial Registration: ClinicalTrials.gov: NCT00785291.

Using Deepsignalingflow To Mine Signaling Flows Interpreting Mechanism Of Synergy Of Cocktails, Heming Zhang, Yixin Chen, Philip Payne, Fuhai Li

2020-Current year OA Pubs

Complex signaling pathways are believed to be responsible for drug resistance. Drug combinations perturbing multiple signaling targets have the potential to reduce drug resistance. The large-scale multi-omic datasets and experimental drug combination synergistic score data are valuable resources to study mechanisms of synergy (MoS) to guide the development of precision drug combinations. However, signaling patterns of MoS are complex and remain unclear, and thus it is challenging to identify synergistic drug combinations in clinical. Herein, we proposed a novel integrative and interpretable graph AI model, DeepSignalingFlow, to uncover the MoS by integrating and mining multi-omic data. The major innovation is …

Mice Lacking Astn2 Have Asd-Like Behaviors And Altered Cerebellar Circuit Properties, Michalina Hanzel, Kayla Fernando, Susan E Maloney, Zachi Horn, Shiaoching Gong, Kärt Mätlik, Jiajia Zhao, H Amalia Pasolli, Søren Heissel, Joseph D Dougherty, Court Hull, Mary E Hatten

2020-Current year OA Pubs

Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with

Parent Attitudes Towards Predictive Testing For Autism In The First Year Of Life, Aurora M Washington, Amanda H Mercer, Catherine A Burrows, Stephen R Dager, Jed T Elison, Annette M Estes, Rebecca Grzadzinski, Chimei Lee, Joseph Piven, John R Pruett Jr, Mark D Shen, Benjamin Wilfond, Jason Wolff, Lonnie Zwaigenbaum, Katherine E Macduffie

2020-Current year OA Pubs

BACKGROUND: Emerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life. We investigated the perspectives of parents about the anticipated utility and impact of predicting later autism diagnosis from a biomarker-based test in infancy.

METHODS: Parents of infants were interviewed to ascertain receptiveness and perspectives on early (6-12 months) prediction of autism using emerging biomarker technologies. One group had experience parenting an older autistic child (n=30), and the other had no prior autism parenting experience (n=25). Parent responses were analyzed using inductive qualitative coding methods.

RESULTS: Almost …

Newborn Screening For Spinal Muscular Atrophy: Variations In Practice And Early Management Of Infants With Spinal Muscular Atrophy In The United States, Craig M Zaidman, Cameron D Crockett, Ethan Wedge, Grace Tabatabai, Natalie Goedeker

2020-Current year OA Pubs

In the United States (U.S.), newborn screening (NBS) for spinal muscular atrophy (SMA) is implemented by individual states. There is likely variation in the practice patterns of state NBS programs and among the providers caring for newborns with SMA. This is a prospective, descriptive, observational study that seeks to quantify and describe practice patterns and heterogeneities in state NBS programs and provider practices in the U.S. We surveyed U.S. state NBS programs and care providers of newborns with SMA. Thirty states and 41 practitioners responded. NBS program practices vary by state. Most (74%) state programs provide results to both primary …

The Role Of Brown Adipose Tissue In Branched-Chain Amino Acid Clearance In People, Yasser G Abdelhafez, Guobao Wang, Siqi Li, Vanessa Pellegrinelli, Abhijit J Chaudhari, Anthony Ramirez, Fatma Sen, Antonio Vidal-Puig, Labros S Sidossis, Samuel Klein, Ramsey D Badawi, Maria Chondronikola

2020-Current year OA Pubs

Brown adipose tissue (BAT) in rodents appears to be an important tissue for the clearance of plasma branched-chain amino acids (BCAAs) contributing to improved metabolic health. However, the role of human BAT in plasma BCAA clearance is poorly understood. Here, we evaluate patients with prostate cancer who underwent positron emission tomography-computed tomography imaging after an injection of

Single-Cell Analysis Of Innate Spinal Cord Regeneration Identifies Intersecting Modes Of Neuronal Repair, Vishnu Muraleedharan Saraswathy, Lili Zhou, Mayssa H Mokalled

2020-Current year OA Pubs

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an …

Complexity Organization Of Resting-State Functional-Mri Networks, Gabriel Trevino, John J Lee, Joshua S Shimony, Patrick H Luckett, Eric C Leuthardt

2020-Current year OA Pubs

Entropy measures are increasingly being used to analyze the structure of neural activity observed by functional magnetic resonance imaging (fMRI), with resting-state networks (RSNs) being of interest for their reproducible descriptions of the brain's functional architecture. Temporal correlations have shown a dichotomy among these networks: those that engage with the environment, known as extrinsic, which include the visual and sensorimotor networks; and those associated with executive control and self-referencing, known as intrinsic, which include the default mode network and the frontoparietal control network. While these inter-voxel temporal correlations enable the assessment of synchrony among the components of individual networks, entropic …

Sac1 Links Phosphoinositide Turnover To Cryptococcal Virulence, Elizabeth A Gaylord, Hau Lam Choy, Guohua Chen, Sydney L Briner, Tamara L Doering

2020-Current year OA Pubs

No abstract provided.

Development Of Vla4 And Cxcr4 Antagonists For The Mobilization Of Hematopoietic Stem And Progenitor Cells, Peter G Ruminski, Michael P Rettig, John F Dipersio

2020-Current year OA Pubs

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and …

Dominance Analysis To Assess Solute Contributions To Multicomponent Phase Equilibria, Daoyuan Qian, Hannes Ausserwoger, Tomas Sneideris, Mina Farag, Rohit V Pappu, Tuomas P J Knowles

2020-Current year OA Pubs

Phase separation in aqueous solutions of macromolecules underlies the generation of biomolecular condensates in cells. Condensates are membraneless bodies, representing dense, macromolecule-rich phases that coexist with the dilute, macromolecule-deficient phases. In cells, condensates comprise hundreds of different macromolecular and small molecule solutes. How do different solutes contribute to the driving forces for phase separation? To answer this question, we introduce a formalism we term energy dominance analysis. This approach rests on analysis of shapes of the dilute phase boundaries, slopes of tie lines, and changes to dilute phase concentrations in response to perturbations of concentrations of different solutes. The framework …

A Simplified G-Csf-Free Procedure Allows For In Vivo Hsc Gene Therapy Of Sickle Cell Disease In A Mouse Model, Chang Li, Anna K Anderson, Peter Ruminski, Michael Rettig, Darja Karpova, Hans-Peter Kiem, John F Dipersio, André Lieber

2020-Current year OA Pubs

We have reported the direct repair of the sickle cell mutation in vivo in a disease model using vectorized prime editors after hematopoietic stem cell (HSC) mobilization with granulocyte colony-stimulating factor (G-CSF)/AMD3100. The use of G-CSF for HSC mobilization is a hurdle for the clinical translation of this approach. Here, we tested a G-CSF-free mobilization regimen using WU-106, an inhibitor of integrin α4β1, plus AMD3100 for in vivo HSC prime editing in sickle cell disease (SCD) mice. Mobilization with WU-106 + AMD3100 in SCD mice was rapid and efficient. In contrast to the G-CSF/AMD3100 approach, mobilization of activated granulocytes and …

Infection Prevention And Control In 2030: A First Qualitative Survey By The Crystal Ball Initiative, Hugo Sax, Jonas Marschall, Crystal Ball Initiative

2020-Current year OA Pubs

BACKGROUND: Healthcare delivery is undergoing radical changes that influence effective infection prevention and control (IPC). Futures research (short: Futures), the science of deliberating on multiple potential future states, is increasingly employed in many core societal fields. Futures might also be helpful in IPC to facilitate current education and organisational decisions. Hence, we conducted an initial survey as part of the IPC Crystal Ball Initiative.

METHODS: In 2019, international IPC experts were invited to answer a 10-item online questionnaire, including demographics, housekeeping, and open-ended core questions (Q) on the "status of IPC in 2030" (Q1), "people in charge of IPC" (Q2), …

Dual Role Of Neuroplastin In Pancreatic Β Cells: Regulating Insulin Secretion And Promoting Islet Inflammation, Rie Asada Kitamura, Devynn Hummel, Alessandro Ustione, David W. Piston, Fumihiko Urano

2020-Current year OA Pubs

No abstract provided.

Neoantigen Landscape Supports Feasibility Of Personalized Cancer Vaccine For Follicular Lymphoma, Cody A Ramirez, Michelle Becker-Hapak, Kartik Singhal, David A Russler-Germain, Erica K Barnell, Ethan D Mcclain, Sweta Desai, Timothy Schappe, Onyinyechi C Onyeador, Susanna Kiwala, Jasreet Hundal, Zachary L Skidmore, Marcus P Watkins, Thomas B Mooney, Jason R Walker, Kilannin Krysiak, Felicia Gomez, Catrina C Fronick, Robert S Fulton, Robert D Schreiber, Neha Mehta-Shah, Amanda F Cashen, Brad S Kahl, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR …

Multimodal Mechanisms Of Pathogenic Variants In The Signal Peptide Of Fix Leading To Hemophilia B, Meng Gao, Long Chen, Jinlong Yang, Shixia Dong, Qing Cao, Zihan Cui, Yanyan Dong, Hongli Liu, Yan Shen, Haiping Yang, Zhenyu Hao, Lei Zhang, Weikai Li, Jian-Ke Tie, Guomin Shen

2020-Current year OA Pubs

Signal peptide (SP) is essential for protein secretion, and pathogenic variants in the SP of factor IX (FIX) have been identified in hemophilia B (HB). However, the underlying mechanism for the genotype-phenotype correlation of these variants has not been well studied. Here, we systematically examined the effects of 13 pathogenic point variants in the SP of FIX using different approaches. Our results showed that these point variants lead to HB by missense variants and/or aberrant premessenger RNA (pre-mRNA) splicing. The missense variants in a hydrophobic core (h-region) mainly affected the cotranslational translocation function of the SP, and those in C-terminal …

Signaling By A Bacterial Phytochrome Histidine Kinase Involves A Conformational Cascade Reorganizing The Dimeric Photoreceptor, E Sethe Burgie, Katherine Basore, Michael J Rau, Brock Summers, Alayna J Mickles, Vadim Grigura, James A J Fitzpatrick, Richard D Vierstra

2020-Current year OA Pubs

Phytochromes (Phys) are a divergent cohort of bili-proteins that detect light through reversible interconversion between dark-adapted Pr and photoactivated Pfr states. While our understandings of downstream events are emerging, it remains unclear how Phys translate light into an interpretable conformational signal. Here, we present models of both states for a dimeric Phy with histidine kinase (HK) activity from the proteobacterium Pseudomonas syringae, which were built from high-resolution cryo-EM maps (2.8-3.4-Å) of the photosensory module (PSM) and its following signaling (S) helix together with lower resolution maps for the downstream output region augmented by RoseTTAFold and AlphaFold structural predictions. The head-to-head …

Kat2a And Kat2b Prevent Double-Stranded Rna Accumulation And Interferon Signaling To Maintain Intestinal Stem Cell Renewal, Mai-Uyen Nguyen, Angela Halstead, José B Sáenz, Et Al.

2020-Current year OA Pubs

Histone acetyltransferases

Epigenetic Reprogramming Driving Successful And Failed Repair In Acute Kidney Injury, Yoshiharu Muto, Eryn E Dixon, Yasuhiro Yoshimura, Nicolas Ledru, Yuhei Kirita, Haojia Wu, Benjamin D Humphreys

2020-Current year OA Pubs

Acute kidney injury (AKI) causes epithelial damage followed by subsequent repair. While successful repair restores kidney function, this process is often incomplete and can lead to chronic kidney disease (CKD) in a process called failed repair. To better understand the epigenetic reprogramming driving this AKI-to-CKD transition, we generated a single-nucleus multiomic atlas for the full mouse AKI time course, consisting of ~280,000 single-nucleus transcriptomes and epigenomes. We reveal cell-specific dynamic alterations in gene regulatory landscapes reflecting, especially, activation of proinflammatory pathways. We further generated single-nucleus multiomic data from four human AKI samples including validation by genome-wide identification of nuclear factor …

Untargeted Lipidomics Reveals Racial Differences In Lipid Species Among Women, Ghazaleh Pourali, Liang Li, Kayla R Getz, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

Understanding the biological mechanisms underlying racial differences in diseases is crucial to developing targeted prevention and treatment. There is, however, limited knowledge of the impact of race on lipids. To address this, we performed comprehensive lipidomics analyses to evaluate racial differences in lipid species among 506 non-Hispanic White (NHW) and 163 non-Hispanic Black (NHB) women. Plasma lipidomic profiling quantified 982 lipid species. We used multivariable linear regression models, adjusted for confounders, to identify racial differences in lipid species and corrected for multiple testing using a Bonferroni-adjusted p-value <  10

Multi-Omic Analysis Of Huntington's Disease Reveals A Compensatory Astrocyte State, Fahad Paryani, Ji-Sun Kwon, Andrew S Yoo, Et Al.

2020-Current year OA Pubs

The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death. Because astrocytes play essential roles in lipid metabolism, we explored the heterogeneity of astrocytic states in both protoplasmic and fibrous-like (CD44+) astrocytes. Significantly, …

Postacute Sequelae Of Sars-Cov-2 Infection In The Pre-Delta, Delta, And Omicron Eras, Yan Xie, Taeyoung Choi, Ziyad Al-Aly

2020-Current year OA Pubs

BACKGROUND: Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the coronavirus disease 2019 (Covid-19) pandemic, including the evolution of SARS-CoV-2, may have affected the risk and burden of PASC. Whether the risk and burden of PASC have changed over the course of the pandemic is unclear.

METHODS: We used health records of the Department of Veterans Affairs to build a study population of 441,583 veterans with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and 4,748,504 noninfected contemporaneous controls. We estimated the cumulative incidence of …

The Neonatal Fc Receptor (Fcrn) Is A Pan-Arterivirus Receptor, Teressa M Shaw, Meagan E Sullender, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Arteriviruses infect a variety of mammalian hosts, but the receptors used by these viruses to enter cells are poorly understood. We identified the neonatal Fc receptor (FcRn) as an important pro-viral host factor via comparative genome-wide CRISPR-knockout screens with multiple arteriviruses. Using a panel of cell lines and divergent arteriviruses, we demonstrate that FcRn is required for the entry step of arterivirus infection and serves as a molecular barrier to arterivirus cross-species infection. We also show that FcRn synergizes with another known arterivirus entry factor, CD163, to mediate arterivirus entry. Overexpression of FcRn and CD163 sensitizes non-permissive cells to infection …

Deltex Family E3 Ligases Specifically Ubiquitinate The Terminal Adp-Ribose Of Poly(Adp-Ribosyl)Ation, Matthew Kelly, Chase Dietz, Samuel Kasson, Yong Zhang, Michael J Holtzman, In-Kwon Kim

2020-Current year OA Pubs

Poly(ADP-ribose) polymerases (PARPs) are critical to regulating cellular activities, such as the response to DNA damage and cell death. PARPs catalyze a reversible post-translational modification (PTM) in the form of mono- or poly(ADP-ribosyl)ation. This type of modification is known to form a ubiquitin-ADP-ribose (Ub-ADPR) conjugate that depends on the actions of Deltex family of E3 ubiquitin ligases (DTXs). In particular, DTXs add ubiquitin to the 3'-OH of adenosine ribose' in ADP-ribose, which effectively sequesters ubiquitin and impedes ubiquitin-dependent signaling. Previous work demonstrates DTX function for ubiquitination of protein-free ADPR, mono-ADP-ribosylated peptides, and ADP-ribosylated nucleic acids. However, the dynamics of DTX-mediated …

Tracking The Prevalence And Emergence Of Sars-Cov-2 Variants Of Concern Using A Regional Genomic Surveillance Program, Ana Jung, Lindsay Droit, Binita Febles, Catarina Fronick, Lisa Cook, Scott A Handley, Bijal A Parikh, David Wang

2020-Current year OA Pubs

UNLABELLED: SARS-CoV-2 molecular testing coupled with whole-genome sequencing is instrumental for real-time genomic surveillance. Genomic surveillance is critical for monitoring the spread of variants of concern (VOCs) as well as discovery of novel variants. Since the beginning of the pandemic, millions of SARS-CoV-2 genomes have been deposited into public sequence databases. This is the result of efforts of both national and regional diagnostic laboratories. In this study, we describe the results of SARS-CoV-2 genomic surveillance from February 2021 to June 2022 at a metropolitan hospital in the United States. We demonstrate that consistent daily sampling is sufficient to track the …

Stroke Severity, Caregiver Feedback, And Cognition In The Regards-Cares Study, Jason A Blake, D Leann Long, Amy J Knight, Burel R Goodin, Michael Crowe, Suzanne E Judd, J David Rhodes, David L Roth, Olivio J Clay

2020-Current year OA Pubs

BACKGROUND: Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver-report of poststroke functioning with longitudinal cognitive outcomes.

METHODS AND RESULTS: One hundred fifty-seven caregivers and stroke survivor dyads participated in the CARES (Caring for Adults Recovering From the Effects of Stroke) project, an ancillary study of the REGARDS (Reasons for Geographic and Racial Differences in …