Medicine and Health Sciences Commons^™

Trim-Nhl Protein, Nhl-2, Modulates Cell Fate Choices In The C. Elegans Germ Line, John L. Brenner, Erin M. Jyo, Ariz Mohammad, Paul Fox, Vovanti Jones, Elaine Mardis, Tim Schedl, Eleanor M. Maine

2020-Current year OA Pubs

Many tissues contain multipotent stem cells that are critical for maintaining tissue function. In Caenorhabditis elegans, germline stem cells allow gamete production to continue in adulthood. In the gonad, GLP-1/Notch signaling from the distal tip cell niche to neighboring germ cells activates a complex regulatory network to maintain a stem cell population. GLP-1/Notch signaling positively regulates production of LST-1 and SYGL-1 proteins that, in turn, interact with a set of PUF/FBF proteins to positively regulate the stem cell fate. We previously described sog (suppressor of glp-1 loss of function) and teg (tumorous enhancer of glp-1 gain of function) genes that …

Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al.

2020-Current year OA Pubs

A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty-four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid-study from the original to …

Facial Paresis As The First Sign In Atypical Facioscapulohumeral Muscular Dystrophy, Nneoma S. Wamkpah, John J. Chi

2020-Current year OA Pubs

No abstract provided.

Comparison Of Plasma And Csf Biomarkers In Predicting Cognitive Decline, Andrew J Aschenbrenner, Yan Li, Rachel L Henson, Katherine Volluz, Jason Hassenstab, Philip Verghese, Tim West, Matthew R Meyer, Kristopher M Kirmess, Anne M Fagan, Chengjie Xiong, David Holtzman, John C Morris, Randall J Bateman, Suzanne E Schindler

2020-Current year OA Pubs

OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer's disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.

METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over …

Diagnosis And Management Of Functional Tic-Like Phenomena, Irene A Malaty, Seonaid Anderson, Shannon M Bennett, Cathy L Budman, Barbara J Coffey, Keith A Coffman, Erica Greenberg, Joseph F Mcguire, Kirsten R Müller-Vahl, Michael S Okun, Julio Quezada, Amy Robichaux-Viehoever, Kevin J. Black

2020-Current year OA Pubs

Over the past 3 years, a global phenomenon has emerged characterized by the sudden onset and frequently rapid escalation of tics and tic-like movements and phonations. These symptoms have occurred not only in youth known to have tics or Tourette syndrome (TS), but also, and more notably, in youth with no prior history of tics. The Tourette Association of America (TAA) convened an international, multidisciplinary working group to better understand this apparent presentation of functional neurological disorder (FND) and its relationship to TS. Here, we review and summarize the literature relevant to distinguish the two, with recommendations to clinicians for …

Identification Of Novel Genes And Proteoforms In Angiostrongylus Costaricensis Through A Proteogenomic Approach, Esdras Matheus Gomes Da Silva, Karina Mastropasqua Rebello, Young-Jun Choi, Vitor Gregorio, Alexandre Rossi Paschoal, Makedonka Mitreva, James H Mckerrow, Ana Gisele Da Costa Neves-Ferreira, Fabio Passetti

2020-Current year OA Pubs

RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions.

High-Speed, Scanned Laser Structuring Of Multi-Layered Eco/Bioresorbable Materials For Advanced Electronic Systems, Quansan Yang, Yameng Xu, Ying Yan, Wilson Z Ray, Mitchell A Pet, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin …

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden In Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility, Wei-Yi Lei, Shu-Wei Liang, Taher Omari, Wei-Chuan Chang, Ming-Wun Wong, Jui-Sheng Hung, Chih-Hsun Yi, Tso-Tsai Liu, Lin Lin, C Prakash Gyawali, Chien-Lin Chen

2020-Current year OA Pubs

BACKGROUND/AIMS: Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients.

METHODS: Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR.

RESULTS: Of 85 (56.3% female, mean age: 46.7 …

Defining Cellular Complexity In Human Autosomal Dominant Polycystic Kidney Disease By Multimodal Single Cell Analysis, Yoshiharu Muto, Eryn E Dixon, Yasuhiro Yoshimura, Haojia Wu, Kohei Omachi, Nicolas Ledru, Parker C Wilson, Jeffrey H Miner, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease characterized by progressive expansion of kidney cysts. To better understand the cell types and states driving ADPKD progression, we analyze eight ADPKD and five healthy human kidney samples, generating single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. Activation of proinflammatory, profibrotic signaling pathways are driven by proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts and collecting duct cells. We identify GPRC5A as a marker for cyst-lining collecting duct cells that exhibits increased transcription factor …

"We Start Where We Are": A Qualitative Study Of Barriers And Pragmatic Solutions To The Assessment And Reporting Of Implementation Strategy Fidelity, Christopher F Akiba, Byron J Powell, Brian W Pence, Kate Muessig, Carol E Golin, Vivian Go

2020-Current year OA Pubs

BACKGROUND: Fidelity measurement of implementation strategies is underdeveloped and underreported, and the level of reporting is decreasing over time. Failing to properly measure the factors that affect the delivery of an implementation strategy may obscure the link between a strategy and its outcomes. Barriers to assessing and reporting implementation strategy fidelity among researchers are not well understood. The aims of this qualitative study were to identify barriers to fidelity measurement and pragmatic pathways towards improvement.

METHODS: We conducted in-depth interviews among researchers conducting implementation trials. We utilized a theory-informed interview approach to elicit the barriers and possible solutions to implementation …

Myocardial Infarction Size As An Independent Predictor Of Intramyocardial Haemorrhage In Acute Reperfused Myocardial Ischaemic Rats, Rui Xia, Tong Zhu, Yu Zhang, Bo He, Yushu Chen, Lei Wang, Yang Zhou, Jichun Liao, Jie Zheng, Yongmei Li, Fajin Lv, Fabao Gao

2020-Current year OA Pubs

BACKGROUND: In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner.

METHODS: Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1-3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were …

Mindfulness Training For Depressed Older Adults Using Smartphone Technology: Protocol For A Fully Remote Precision Clinical Trial, Abigail Schweiger, Thomas L Rodebaugh, Eric J Lenze, Katie Keenoy, Jason Hassenstab, Jeanne Kloeckner, Torie R Gettinger, Ginger E Nicol

2020-Current year OA Pubs

BACKGROUND: Precision medicine, optimized interventions, and access to care are catchphrases for the future of behavioral treatments. Progress has been slow due to the dearth of clinical trials that optimize interventions' benefits, individually tailor interventions to meet individual needs and preferences, and lead to rapid implementation after effectiveness is demonstrated. Two innovations have emerged to meet these challenges: fully remote trials and precision clinical trials.

OBJECTIVE: This paper provides a detailed description of Mindful MyWay, a study designed to test online mindfulness training in older adults with depression. Consistent with the concept of fully remote trials using a smartphone app, …

Risk Factors And Treatment Strategy For Retinal Vascular Occlusive Diseases, Ryo Terao, Ryosuke Fujino, Tazbir Ahmed

2020-Current year OA Pubs

Retinal occlusive diseases are common diseases that can lead to visual impairment. Retinal artery occlusion and retinal vein occlusion are included in the clinical entity, but they have quite different pathophysiologies. Retinal artery occlusion is an emergent eye disorder. Retinal artery occlusion is mainly caused by thromboembolism, which frequently occurs in conjunction with life-threatening stroke and cardiovascular diseases. Therefore, prompt examinations and interventions for systemic vascular diseases are often necessary for these patients. Retinal vein occlusion is characterized by retinal hemorrhage and ischemia, which may impair visual function via several complications such as macular edema, macular ischemia, vitreous hemorrhage, and …

Genetic Addiction Risk And Psychological Profiling Analyses For "Preaddiction" Severity Index, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the

Discovery And Characterization Of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors And Preclinical Safety Assessment Of Ucb7362, Martin A Lowe, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life (

Strategies For De-Implementation Of Low-Value Care-A Scoping Review, Sara Ingvarsson, Henna Hasson, Ulrica Von Thiele Schwarz, Per Nilsen, Byron J Powell, Clara Lindberg, Hanna Augustsson

2020-Current year OA Pubs

BACKGROUND: The use of low-value care (LVC) is a persistent problem that calls for knowledge about strategies for de-implementation. However, studies are dispersed across many clinical fields, and there is no overview of strategies that can be used to support the de-implementation of LVC. The extent to which strategies used for implementation are also used in de-implementing LVC is unknown. The aim of this scoping review is to (1) identify strategies for the de-implementation of LVC described in the scientific literature and (2) compare de-implementation strategies to implementation strategies as specified in the Expert Recommendation for Implementing Change (ERIC) and …

Epidemiology Of Plasmid Lineages Mediating The Spread Of Extended-Spectrum Beta-Lactamases Among Clinical Escherichia Coli, Bejan Mahmud, Meghan A Wallace, Kimberly A Reske, Kelly Alvarado, Carol E Muenks, David A Rasmussen, Carey-Ann D Burnham, Cristina Lanzas, Erik R Dubberke, Gautam Dantas

2020-Current year OA Pubs

The prevalence of extended-spectrum beta-lactamases (ESBLs) among clinical isolates of Escherichia coli has been increasing, with this spread driven by ESBL-encoding plasmids. However, the epidemiology of ESBL-disseminating plasmids remains understudied, obscuring the roles of individual plasmid lineages in ESBL spread. To address this, we performed an in-depth genomic investigation of 149 clinical ESBL-like E. coli isolates from a tertiary care hospital. We obtained high-quality assemblies for 446 plasmids, revealing an extensive map of plasmid sharing that crosses time, space, and bacterial sequence type boundaries. Through a sequence-based network, we identified specific plasmid lineages that are responsible for the dissemination of …

Comparison Of Metagenomic Sequencing And The Nanostring Ncounter Analysis System For The Characterization Of Bacterial And Viral Communities In Vaginal Samples, Todd N Wylie, Jane Schrimpf, Haley Gula, Brandi N Herter, Kristine M Wylie

2020-Current year OA Pubs

DNA sequencing assays have been used to characterize the vaginal microbiome and to identify associations with clinical outcomes. The purpose of this study was to evaluate the utility of the NanoString nCounter platform, a more efficient assay compared to sequencing, for the characterization of vaginal microbial communities. A panel of NanoString nCounter probes was designed to detect common vaginal bacteria and viruses with relevance to reproductive health. A defined synthetic community of microbes and 43 clinical samples were interrogated with NanoString nCounter assays and compared to known compositions or metagenomic shotgun sequencing (MSS) results. The NanoString nCounter platform and MSS …

Enteric Pathogen Testing Importance For Children With Acute Gastroenteritis: A Modified Delphi Study, Gillian A M Tarr, Drew J Persson, Phillip I Tarr, Stephen B Freedman

2020-Current year OA Pubs

The application of clinical diagnostics for gastroenteritis in children has implications for a broad collection of stakeholders, impacting clinical care, communicable disease control, and laboratory utilization. To support diagnostic stewardship as gastroenteritis testing options continue to advance, it is critical to understand which enteropathogens constitute priorities for testing across stakeholder groups. Using a modified Delphi technique, we elicited opinions of subject matter experts to determine clinical and public health testing priorities. There was a high level of overall agreement (≥80%) among stakeholders (final round

Emergence Of Compensatory Mutations Reveals The Importance Of Electrostatic Interactions Between Hiv-1 Integrase And Genomic Rna, Christian Shema Mugisha, Tung Dinh, Abhishek Kumar, Kasyap Tenneti, Jenna E Eschbach, Keanu Davis, Robert Gifford, Mamuka Kvaratskhelia, Sebla B Kutluay

2020-Current year OA Pubs

HIV-1 integrase (IN) has a noncatalytic function in virion maturation through its binding to the viral RNA genome (gRNA). Class II IN substitutions inhibit IN-gRNA binding and result in the formation of virions with aberrant morphologies marked by mislocalization of the gRNA between the capsid lattice and the lipid envelope. These viruses are noninfectious due to a block at an early reverse transcription stage in target cells. HIV-1 IN utilizes basic residues within its C-terminal domain (CTD) to bind to the gRNA; however, the molecular nature of how these residues mediate gRNA binding and whether other regions of IN are …

Marijuana Use And Dna Methylation-Based Biological Age In Young Adults, Drew R Nannini, Yinan Zheng, Brian T Joyce, Tao Gao, Lei Liu, David R Jacobs Jr, Pamela Schreiner, Chunyu Liu, Steve Horvath, Ake T Lu, Kristine Yaffe, Stephen Sidney, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana's effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.

RESULTS: A random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with …

Self-Renewal Of Macrophages: Tumor-Released Factors And Signaling Pathways, Serena Filiberti, Mariapia Russo, Silvia Lonardi, Mattia Bugatti, William Vermi, Cathy Tournier, Emanuele Giurisato

2020-Current year OA Pubs

Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. During tumor growth, both tissue-resident macrophages and newly recruited monocyte-derived macrophages can give rise to tumor-associated macrophages (TAMs), which have been associated with poor prognosis in most cancers. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating …

Pooled Image-Base Screening Of Mitochondria With Microraft Isolation Distinguishes Pathogenic Mitofusin 2 Mutations, Alex L Yenkin, John C Bramley, Colin L Kremitzki, Jason E Waligorski, Mariel J Liebeskind, Xinyuan E Xu, Vinay D Chandrasekaran, Maria A Vakaki, Graham W Bachman, Robi D Mitra, Jeffrey D Milbrandt, William J Buchser

2020-Current year OA Pubs

Most human genetic variation is classified as variants of uncertain significance. While advances in genome editing have allowed innovation in pooled screening platforms, many screens deal with relatively simple readouts (viability, fluorescence) and cannot identify the complex cellular phenotypes that underlie most human diseases. In this paper, we present a generalizable functional genomics platform that combines high-content imaging, machine learning, and microraft isolation in a method termed "Raft-Seq". We highlight the efficacy of our platform by showing its ability to distinguish pathogenic point mutations of the mitochondrial regulator Mitofusin 2, even when the cellular phenotype is subtle. We also show …

Human Neutrophil Development And Functionality Are Enabled In A Humanized Mouse Model, Yunjiang Zheng, Esen Sefik, John Astle, Kutay Karatepe, Hasan H Öz, Angel G Solis, Ruaidhrí Jackson, Hongbo R Luo, Emanuela M Bruscia, Stephanie Halene, Liang Shan, Richard A Flavell

2020-Current year OA Pubs

Mice with a functional human immune system serve as an invaluable tool to study the development and function of the human immune system in vivo. A major technological limitation of all current humanized mouse models is the lack of mature and functional human neutrophils in circulation and tissues. To overcome this, we generated a humanized mouse model named MISTRGGR, in which the mouse granulocyte colony-stimulating factor (G-CSF) was replaced with human G-CSF and the mouse G-CSF receptor gene was deleted in existing MISTRG mice. By targeting the G-CSF cytokine-receptor axis, we dramatically improved the reconstitution of mature circulating and tissue-infiltrating …

Ring-Fused 2-Pyridones Effective Against Multidrug-Resistant Gram-Positive Pathogens And Synergistic With Standard-Of-Care Antibiotics, Taylor M Nye, Hasan Tükenmez, Pardeep Singh, Ana L Flores-Mireles, Chloe L P Obernuefemann, Jerome S Pinkner, Souvik Sarkar, Mari Bonde, Anders E G Lindgren, Karen W Dodson, Jörgen Johansson, Fredrik Almqvist, Michael G Caparon, Scott J Hultgren

2020-Current year OA Pubs

The alarming rise of multidrug-resistant Gram-positive bacteria has precipitated a healthcare crisis, necessitating the development of new antimicrobial therapies. Here we describe a new class of antibiotics based on a ring-fused 2-pyridone backbone, which are active against vancomycin-resistant enterococci (VRE), a serious threat as classified by the Centers for Disease Control and Prevention, and other multidrug-resistant Gram-positive bacteria. Ring-fused 2-pyridone antibiotics have bacteriostatic activity against actively dividing exponential phase enterococcal cells and bactericidal activity against nondividing stationary phase enterococcal cells. The molecular mechanism of drug-induced killing of stationary phase cells mimics aspects of fratricide observed in enterococcal biofilms, where both …

Discovery Of A Novel Genomic Alteration That Renders Leukemic Cells Resistant To Cd19-Targeted Immunotherapies, Armin Ghobadi, Jack H Landmann, Alun Carter, Matthew L Cooper, Mehmet Emrah Selli, Jufang Chang, Christopher A Miller, Francesca Ferraro, David Y Chen, Amanda M Smith, Taylor A Lavalle, Eric J Duncavage, Nathan Singh, Et Al.

2020-Current year OA Pubs

No abstract provided.

Novel Chelating Agents For Zirconium-89-Positron Emission Tomography (Pet) Imaging: Synthesis, Dft Calculation, Radiolabeling, And In Vitro And In Vivo Complex Stability, Chi Soo Kang, Shuyuan Zhang, Haixing Wang, Yujie Liu, Siyuan Ren, Yanda Chen, Jingbai Li, Nilantha Bandara, Andrey Yu Rogachev, Buck E Rogers, Hyun-Soon Chong

2020-Current year OA Pubs

We report the synthesis and evaluation of novel chelating agents for zirconium-89 (

The Impact Of Tsc-1 And -2 Mutations On Response To Therapy In Malignant Pecoma: A Multicenter Retrospective Analysis, Lawrence Liu, Nikhil Grandhi, Yang Lyu, Xiao Zhang, Jingqin Luo, Mia Weiss, Brian Van Tine, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

METHODS: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations. …

Somatic Mutations In Fat Cadherin Family Members Constitute An Underrecognized Subtype Of Colorectal Adenocarcinoma With Unique Clinicopathologic Features, Liang-Li Wang, Wei Zheng, Xiu-Li Liu, Feng Yin

2020-Current year OA Pubs

BACKGROUND: The FAT cadherin family members (FAT1, FAT2, FAT3 and FAT4) are conserved tumor suppressors that are recurrently mutated in several types of human cancers, including colorectal carcinoma (CRC).

AIM: To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.

METHODS: We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset. CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in

RESULTS: This CRC study cohort had frequent mutations in the

CONCLUSION:

The Mechanics Of Implementation Strategies And Measures: Advancing The Study Of Implementation Mechanisms, Cara C Lewis, Predrag Klasnja, Aaron R Lyon, Byron J Powell, Rebecca Lengnick-Hall, Gretchen Buchanan, Rosemary D Meza, Michelle C Chan, Marcella H Boynton, Bryan J Weiner

2020-Current year OA Pubs

BACKGROUND: There is a fundamental gap in understanding the causal mechanisms by which strategies for implementing evidence-based practices address local barriers to effective, appropriate service delivery. Until this gap is addressed, scientific knowledge and practical guidance about which implementation strategies to use in which contexts will remain elusive. This research project aims to identify plausible strategy-mechanism linkages, develop causal models for mechanism evaluation, produce measures needed to evaluate such linkages, and make these models, methods, and measures available in a user-friendly website. The specific aims are as follows: (1) build a database of strategy-mechanism linkages and associated causal pathway diagrams, …