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A Novel Interaction Between Extracellular Vimentin And Fibrinogen In Fibrin Formation, Marina Martinez-Vargas, Adrian Cebula, Lisa S Brubaker, Nitin Seshadri, Fong W Lam, Michele Loor, Todd K Rosengart, Andrew Yee, Rolando E Rumbaut, Miguel A Cruz

Faculty, Staff and Students Publications

INTRODUCTION: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis and COVID-19. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. Because elevated levels of vimentin have been detected in sepsis, we sought to investigate the relationship between vimentin and the increased fibrin formation potential observed in these patients.

MATERIALS AND METHODS: This hypothesis was examined by using recombinant human vimentin, anti-vimentin antibodies, plasma derived from healthy and critically ill patients, confocal microscopy, co-immunoprecipitation assays, and size exclusion chromatography.

RESULTS: The level of vimentin in plasma derived from critically ill …

Peptidylarginine Deiminase 2 Citrullinates Mzb1 And Promotes The Secretion Of Igm And Iga, Benjamin Geary, Bo Sun, Ronak R Tilvawala, Leonard Barasa, Konstantin Tsoyi, Ivan O Rosas, Paul R Thompson, I-Cheng Ho

Faculty, Staff and Students Publications

INTRODUCTION: MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T …

Cell-Type-Specific Aging Clocks To Quantify Aging And Rejuvenation In Neurogenic Regions Of The Brain, Matthew T Buckley, Eric D Sun, Benson M George, Ling Liu, Nicholas Schaum, Lucy Xu, Jaime M Reyes, Margaret A Goodell, Irving L Weissman, Tony Wyss-Coray, Thomas A Rando, Anne Brunet

Faculty, Staff and Students Publications

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic …

Multiomics In Primary And Metastatic Breast Tumors From The Aurora Us Network Finds Microenvironment And Epigenetic Drivers Of Metastasis, Susana Garcia-Recio, Toshinori Hinoue, Gregory L Wheeler, Benjamin J Kelly, Ana C Garrido-Castro, Tomas Pascual, Aguirre A De Cubas, Youli Xia, Brooke M Felsheim, Marni B Mcclure, Andrei Rajkovic, Ezgi Karaesmen, Markia A Smith, Cheng Fan, Paula I Gonzalez Ericsson, Melinda E Sanders, Chad J Creighton, Jay Bowen, Kristen Leraas, Robyn T Burns, Sara Coppens, Amy Wheless, Salma Rezk, Amy L Garrett, Joel S Parker, Kelly K Foy, Hui Shen, Ben H Park, Ian Krop, Carey Anders, Julie Gastier-Foster, Mothaffar F Rimawi, Rita Nanda, Nancy U Lin, Claudine Isaacs, P Kelly Marcom, Anna Maria Storniolo, Fergus J Couch, Uma Chandran, Michael Davis, Jonathan Silverstein, Alexander Ropelewski, Minetta C Liu, Susan G Hilsenbeck, Larry Norton, Andrea L Richardson, W Fraser Symmans, Antonio C Wolff, Nancy E Davidson, Lisa A Carey, Adrian V Lee, Justin M Balko, Katherine A Hoadley, Peter W Laird, Elaine R Mardis, Tari A King, Charles M Perou

Faculty, Staff and Students Publications

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER

Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Alveolar macrophages (AMs) are critical components of the innate defense mechanism in the lung. Nestled tightly within the alveoli, AMs, derived from the yolk-sac or bone marrow, can phagocytose foreign particles, defend the host against pathogens, recycle surfactant, and promptly respond to inhaled noxious stimuli. The behavior of AMs is tightly dependent on the environmental cues whereby infection, chronic inflammation, and associated metabolic changes can repolarize their effector functions in the lungs. Several factors within the tumor microenvironment can re-educate AMs, resulting in tumor growth, and reducing immune checkpoint inhibitors (ICIs) efficacy in patients treated for non-small cell lung cancer …

Covid-19 And Pregnancy: Clinical Outcomes; Mechanisms, And Vaccine Efficacy, Deepak Kumar, Sonam Verma, Indira U Mysorekar

Faculty, Staff and Students Publications

As the COVID-19 pandemic continues into its third year, emerging data indicates increased risks associated with SARS-CoV-2 infection during pregnancy, including pre-eclampsia, intrauterine growth restriction, preterm birth, stillbirth, and risk of developmental defects in neonates. Here, we review clinical reports to date that address different COVID-19 pregnancy complications. We also document placental pathologies induced by SARS-CoV-2 infection, entry mechanisms in placental cells, and immune responses at the maternal-fetal interface. Since new variants of SARS-CoV-2 are emerging with characteristics of higher transmissibility and more effective immune escape strategies, we also briefly highlight the genomic and proteomic features of SARS-CoV-2 investigated to …

Combining Charlson Comorbidity And Vacs Indices Improves Prognostic Accuracy For All-Cause Mortality For Patients With And Without Hiv In The Veterans Health Administration, Kathleen A Mcginnis, Amy C Justice, Vincent C Marconi, Maria C Rodriguez-Barradas, Ronald G Hauser, Krisann K Oursler, Sheldon T Brown, Kendall J Bryant, Janet P Tate, Veterans Aging Cohort Study Affiliations

Faculty, Staff and Students Publications

INTRODUCTION: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index.

METHODS: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components …

The Pathway To The Natural Gas Industry: Financial Development, Coal Consumption, And Carbon Dioxide Emissions In Pr China, Teng Tong, Jaime Ortiz, Haibo Wang

Faculty, Staff and Students Publications

This paper revisits the causal links between financial development, coal consumption, and CO2 emissions in P.R. China over the 1977–2017 period to validate the development of its natural gas industry. It uses a Bootstrap ARDL bound test with structural breaks to establish stationarity, short- and long-run dynamics, and causality of the series. The results show there are no long-run relationships among these three variables, but a Granger causality test does indicate the presence of both a two-way Granger causality between coal consumption and CO2 emissions, and a one-way Granger causality running from financial development to both coal consumption and CO2 …

Corrigendum: Alveolar Macrophages In Lung Cancer: Opportunities And Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

In the published article, there was an error in the article title. Instead of “Alveolar Macrophages in Lung Cancer: Opportunities Challenges”, it should be “Alveolar Macrophages in Lung Cancer: Opportunities and Challenges”.

The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Guidelines For Evaluating Safety Using Traffic Encounters: Proactive Crash Estimation On Roadways With Conventional And Autonomous Vehicle Scenarios, Andrew P. Tarko, Mario A. Romero, Vamsi Krishna Bandaru, Xueqian Shi

JTRP Technical Reports

With the expected arrival of autonomous vehicles, and the ever-increasing levels of automation in today’s human driven vehicles, road safety is changing at a rapid pace. This project aimed to address the need for an efficient and rapid method of safety evaluation and countermeasure identification via traffic encounters, specifically traffic conflicts that are considered useful surrogates of crashes. Recent research-delivered methods for estimating crash frequencies based on these events were observed in the field. In this project we developed a method for observing traffic encounters with two LiDAR-based traffic monitoring units, called TScan, which were recently developed in JTRP-funded projects …

Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah

Faculty, Staff and Students Publications

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive …

Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro

Faculty, Staff and Students Publications

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such …

Nourishing The Brain On Deep Space Missions: Nutritional Psychiatry In Promoting Resilience, Nihar N Pathare, Flavia Fayet-Moore, Jennifer A Fogarty, Felice N Jacka, Philip Strandwitz, Gary E Strangman, Dorit B Donoviel

Faculty, Staff and Students Publications

The grueling psychological demands of a journey into deep space coupled with ever-increasing distances away from home pose a unique problem: how can we best take advantage of the benefits of fresh foods in a place that has none? Here, we consider the biggest challenges associated with our current spaceflight food system, highlight the importance of supporting optimal brain health on missions into deep space, and discuss evidence about food components that impact brain health. We propose a future food system that leverages the gut microbiota that can be individually tailored to best support the brain and mental health of …

Photoplethysmography-New Applications For An Old Technology: A Sleep Technology Review, Scott Ryals, Ambrose Chiang, Sharon Schutte-Rodin, Arvind Chandrakantan, Nitun Verma, Steven Holfinger, Fariha Abbasi-Feinberg, Anuja Bandyopadhyay, Kelly Baron, Sumit Bhargava, Ken He, Joseph Kern, Jennifer Miller, Ruchir Patel, Dulip Ratnasoma, Maryann C Deak

Faculty, Staff and Students Publications

Education is integral to the American Academy of Sleep Medicine (AASM) mission. The AASM Emerging Technology Committee identified an important and evolving piece of technology that is present in many of the consumer and clinical technologies that we review on the AASM #SleepTechnology (https://aasm.org/consumer-clinical-sleep-technology/) resource—photoplethysmography. As more patients with sleep tracking devices ask clinicians to view their data, it is important for sleep providers to have a general understanding of the technology, its sensors, how it works, targeted users, evidence for the claimed uses, and its strengths and weaknesses. The focus in this review is photoplethysmography—a sensor type …

A Strategic Assessment Of Needs And Opportunities For The Wider Adoption Of Electric Vehicles In Indiana, Ha Kyun Ju, Tae Rim Kim, Kyubyung Kang, Dan Daehyun Koo, Konstantina Gkritza, Samuel Labi

JTRP Technical Reports

INDOT plans to invest nearly $100 million to build a statewide electric vehicle (EV) charging network as part of the National Electric Vehicle Infrastructure Formula Program. SPR-4509 Phase-I identified energy EV charging deserts in Indiana for long-distance trips. SPR-4509 Phase-II further examines the charging stations' impact on EV long-distance trips in Indiana. Using an agent-based simulation model, the number of charges, vehicle miles traveled, energy used during the trip, and energy used during charging were estimated for nine different cases. High EV daily charging demand areas in Indiana were shown in ArcGIS based on multiple scenarios of different charging station …

Implementing Epoxy Injection In Concrete Overlaid Bridge Decks, Prince Baah

JTRP Technical Reports

Concrete overlays have proven to be an effective maintenance treatment as they slow de-icing chemical and water penetration into the original deck surface. Typically, due to vibration, structural flexibility, and weak bond between the concrete overlay and deck concrete potentially due to poor construction, de-bonding develops at the boundary between the original deck and overlay. This de-bonding creates voids, providing reservoir for chloride laden water to fill after it penetrates cracks in the surface. Displacing this liquid solution and filling these cracks with epoxy helps reduce freeze/thaw cycling and reduces spalling. The epoxy material protects the bridge deck from moisture …

Speed Management On Freeways In Transition Zones Between Rural And Urban Conditions, Raul A. Pineda-Mendez, Xueqian Shi, Andrew P. Tarko, Mario A. Romero

JTRP Technical Reports

Drivers’ noncompliance with the posted speed limit reductions on rural-to-urban freeway transition zones is a recurrent problem in Indiana and other states. Speed-reduction treatments, such as pavement markings and active signing, aim to solve this issue. Optical speed bars, longitudinal speed reduction markings, and speed feedback signs were identified as the most promising speed-reduction treatments for experimental implementation in Indiana. Probe-vehicle-based speed data for 1 year was acquired on selected freeway segments to measure the speed effect. A set of fixed-effects linear regression models were used to estimate the effect of speed-reduction treatments on three key speed behavior characteristics—average speed, …

Determining Optimal Traffic Opening Time Through Concrete Strength Monitoring: Wireless Sensing, Zhihao Kong, Na Lu

JTRP Technical Reports

Construction and concrete production are time-sensitive and fast-paced; as such, it is crucial to monitor the in-place strength development of concrete structures in real-time. Existing concrete strength testing methods, such as the traditional hydraulic compression method specified by ASTM C 39 and the maturity method specified by ASTM C 1074, are labor-intensive, time consuming, and difficult to implement in the field. INDOT’s previous research (SPR-4210) on the electromechanical impedance (EMI) technique has established its feasibility for monitoring in-situ concrete strength to determine the optimal traffic opening time. However, limitations of the data acquisition and communication systems have significantly hindered the …

Development Of A Multiple Water Course Joint Probability Analysis Procedure For Indiana Watersheds, Ankit Ghanghas, Sayan Dey, Venkatesh Merwade

JTRP Technical Reports

The design of hydraulic structures located near a confluence of two streams must take into consideration the flows from both of the streams. A hydraulic structure located on a small tributary that drains into a large river immediately downstream is not just affected by the flow in the tributary, but also by the backwater flow from the downstream river. Currently INDOT uses a tabular summary (Table 1.1 and Table 7.3 in the HEC-22 manual) of joint probabilities of coincident flows in designing hydraulic structures at confluences. However, the source of the table is unknown, and the tabular summary provides coincidental …

Developing Customized Nrcs Unit Hydrographs (Finley Uhs) For Ungauged Watersheds In Indiana, Tao Huang, Venkatesh Merwade

JTRP Technical Reports

The Natural Resources Conservation Service (NRCS, formerly the Soil Conservation Service, SCS) unit hydrograph (UH) is one of the most commonly used synthetic UH methods for hydrologic modeling and engineering design all over the world. However, previous studies have shown that the application of the NRCS UH method for some ungauged watersheds in the state of Indiana produced unrealistic flood predictions for both the peak discharge and the time to peak. The objective of this work is to customize the NRCS UH by analyzing the role of its two key parameters, namely, the peak rate factor (PRF) and …

Assessment Of Pipe Fill Heights, Luz María Agudelo Urrego, Chatuphat Savigamin, Devansh Gandhi, Ghadir Haikal, Antonio Bobet

JTRP Technical Reports

The design of buried pipes, in terms of the allowable minimum and maximum cover heights, requires the use of both geotechnical and structural design procedures. The geotechnical procedure focuses on estimating the load on the pipe and the compressibility of the foundation soil. The focus of the structural design is choosing the correct cross-section details of the pipe under consideration. The uncertainties of the input parameters and installation procedures are significant. Because of that, the Load Resistance Factor Design (LRFD) method is considered to be suitable for the design of buried pipes. Furthermore, the interaction between the pipe structure and …

Predictive Analytics For Quantifying The Long-Term Costs Of Defects During Bridge Construction, Nichole Marie Criner, Manuel Salmeron, Xin Zhang, Shirley J. Dyke, Julio A. Ramirez, Benjamin Eric Wogen

JTRP Technical Reports

During the lifecycle of a bridge, deterioration of the concrete deck originates from many sources, e.g., corrosion due to water infiltration in conjunction with chlorides from the use of de-icing salts. Such deterioration may be affected by any one of the following six actions relevant to a bridge from conception to demolition: design, construction, in-service conditions, maintenance, repair and rehabilitation, and replacement. Many researchers have studied the relationships between these sources and their consequences. However, the relationship between construction defects and inspection practices, and its impact on the deterioration process has not yet been identified. This project focuses on the …

Gis-Based Geotechnical Database For Collaborative Gis, Rameez Ali Raja, Vidushi Toshniwal, Rodrigo Salgado

JTRP Technical Reports

INDOT spends at least 8 million dollars annually on geotechnical site investigations, not including the amounts spent by contractors. The laborious and costly job of data collection in geotechnical practice requires the efficient storing and organizing of this valuable data to develop correlations and trends in spatially varying geotechnical data. INDOT currently uses gINT software for managing geotechnical data and ArcGIS for storing boring logs and geotechnical reports. The INDOT geotechnical office is pursuing means to improve the efficiency of their operations by developing a GIS-based geotechnical database for secure storage, easy retrieval, and flexible sharing of geotechnical data to …

Speed Enforcement In Work Zones And Synthesis On Cost-Benefit Assessment Of Installing Speed Enforcement Cameras On Indot Road Network, Jijo K. Mathew, Jairaj C. Desai, Howell Li, Darcy M. Bullock

JTRP Technical Reports

Work zone safety is a high priority for transportation agencies across the United States. High speeds in construction zones are a well-documented risk factor that increases the frequency and severity of crashes. It is therefore important to understand the extent and severity of high-speed vehicles in and around construction work zones. This study uses CV trajectory data to evaluate the impact of several work zone speed compliance measures, such as posted speed limit signs, radar-based speed feedback displays, and automated speed enforcement on controlling speeds inside the work zone. This study also presents several methodologies to characterize both the spatial …

Shear And Bearing Capacity Of Corroded Steel Beam Bridges And The Effects On Load Rating, Deven Kanakamedala, Jungil Seo, Amit H. Varma, Robert J. Connor, Anna Tarasova

JTRP Technical Reports

Corrosion in the girders of steel girder bridges often occurs due to the deicing salts, water, and other debris that leak through the deck joints into the web and bottom flange at the girder ends. Corrosion causes loss of cross-sectional area leading to a reduction in section properties of the member, which eventually results in a reduction in structural resistance against shear and bearing. In this study, seven full-scale tests were performed on decommissioned steel girders acquired from bridges scheduled for demolition in Indiana. Two of the four girders had severe corrosion with cracks and holes in the bottom of …

Salt Monitoring And Reporting Technology (Smart) For Salt Stockpile Inventory Reporting, Justin A. Mahlberg, Raja Manish, Yerassyl Koshan, Mina Joseph, Jidong Liu, Haydn A. Malackowski, Zechariah Deloach, Timothy Wells, Jeremy Mcguffey, Ayman Habib, Darcy M. Bullock

JTRP Technical Reports

Transportation agencies in northern environments spend a considerable amount of their budget on salt for winter operations. For example, in the state of Indiana, there are approximately 120 salt storage facilities distributed throughout the state and the state expends between 30 M USD and 60 M USD on inventory and delivery each year. Historical techniques of relying on visual estimates of salt stockpiles can be inaccurate and unhelpful for managing the supply chain during the winter or planning for re-supply during the summer months. This project report describes the implementation of a portable and permanent LiDAR system that can be …

Bim Standards For Roads And Related Transportation Assets, Hang Li, Hosam Hegazy, Xiaorui Xue, Jiansong Zhang, Yunfeng Chen

JTRP Technical Reports

With the industry foundation classes (IFC) building information modeling (BIM) standard (ISO 16739) being adopted by AASHTO as the national standard for modeling bridge and road infrastructure projects, there comes a great opportunity to upgrade the INDOT model development standard of roads and related assets to 2D+3D BIM. This upgrade complies with the national standard and creates a solid foundation for preserving accurate asset information for lifecycle data needs. This study reviewed the current modeling standards for drainage and pavement at different state DOTs and investigated the interoperability between state-of-the-art design modeling software and IFC. It was found that while …

Implementation Of Enhanced Probe Data (Canbus) For Tactical Workzone And Winter Operations Management, Jairaj Desai, Rahul Suryakant Sakhare, Justin Mahlberg, Jijo K. Mathew, Howell Li, Darcy M. Bullock

JTRP Technical Reports

For over a decade, segment-based probe data has been extensively used by transportation stakeholders for monitoring mobility on Indiana roadways. However, enhanced probe data from connected vehicles includes a richer dataset that can provide more detailed real-time and after-action reviews. This enhanced data includes detailed vehicle trajectories, at 3s resolution, and “event data.” This event data is near real-time and includes hard-braking events, hard-acceleration events, weather-related data, including wiper activations and some seat belt usage data. This project developed a set of methodologies and resulting visualizations that enables the use of emerging connected vehicle data in operational decision-making on work …

Crowdsourcing/Winter Operations Dashboard Upgrade, Justin A. Mahlberg, Jairaj Desai, Haydn Malackowski, Howell Li, Jijo K. Mathew, Rahul Suryakant Sakhare, Timothy Wells, Darcy M. Bullock

JTRP Technical Reports

INDOT has recently completed the deployment of Parsons telematics-based dash-cameras, automatic vehicle locator (AVL) positions, and spreader rate monitoring across their winter operations fleet. The motivation of this study was to develop dashboards that integrate connected vehicle data into the real-time monitoring and after-action review of winter storms. Each month approximately 13 billion connected vehicle records are ingested for the state of Indiana and almost 99 billion weather data records are ingested nationwide in 15-minute intervals. This study developed techniques to utilize this connected vehicle data and weather data to monitor real-time mobility of interstates and post storm after-action assessments …

Indot Research Program Benefit Cost Analysis—Return On Investment For Projects Completed In Fy 2022, Bob Mccullouch

JTRP Technical Reports

To demonstrate the value of research and its implementation, the Governor’s Office initially requested an annual financial analysis of the INDOT Research Program to determine the return on the research investment (ROI). The INDOT Research & Development (R&D) has continued to publish an annual Return on Investment report. The current financial analysis is for research projects that completed in FY 2022. Analyses on previous year’s projects is necessary primarily due to the time it takes some project outcomes to be implemented and verifiable data generated, extending into the following year. Therefore, the FY 2023 analysis is completed research projects in …