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Biomedical Engineering and Bioengineering Commons™
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Articles 1 - 30 of 101
Full-Text Articles in Biomedical Engineering and Bioengineering
Evaluating Tissue Morphology In The Context Of Varied Initial Fabrication Conditions, Cassidy Caffin
Evaluating Tissue Morphology In The Context Of Varied Initial Fabrication Conditions, Cassidy Caffin
Biomedical Engineering Undergraduate Honors Theses
Cardiovascular diseases have been the leading cause of death for years. This includes myocardial infarctions (MI) where blood flow to the myocardium is restricted. This causes damage to cardiac muscle due to insufficient oxygen. There are multiple ways to treat patients following an MI with the most common involving assorted medication. However, there are limited medications that can be used for treating patients following MIs, and the FDA’s decreasing approval rate for new cardiac drugs will not dramatically improve the range of options. The lead-up to drug candidate rejection by the FDA can involve drugs exhibiting promising preliminary research that …
Dorsal Root Ganglia Neurite Outgrowth Following Traumatic Spinal Cord Injury Repair: A Review, Adrienne Vaughan
Dorsal Root Ganglia Neurite Outgrowth Following Traumatic Spinal Cord Injury Repair: A Review, Adrienne Vaughan
Biomedical Engineering Undergraduate Honors Theses
Traumatic spinal cord injury (tSCI) can cause partial sensorimotor deficiency or total dysfunction, rendering patients unable to perform necessary tasks and dramatically decreasing their quality of life. tSCI is a very prevalent issue. In the United States alone, there are approximately 54 new cases of SCI per one million people each year, or 18,000 new cases annually. tSCI creates a lesion gap filled with axon-inhibiting fibrotic scar tissue. Comprehensive functional recovery following traumatic spinal cord injury (tSCI) requires axonal regeneration across wound site lesions. Dorsal root ganglia (DRG) neurite outgrowth is often evaluated in PNI therapeutic research since it can …
Analyzing Diverse Student Experiences: The Intersection Of Equity, Inclusivity, And Biomedical Engineering Education Through A Clinical Observations And Needs Finding Course, Jacquelynn Horsey
Biomedical Engineering Undergraduate Honors Theses
In the field of biomedical engineering, needs identification and solution development are an important element of the design process. In our undergraduate curriculum, a course was designed to allow clinical observation and provide an opportunity for students to learn about engineering design and engage with clinicians via completing rotations in medical facilities near our campus. While this type of course is not unique, evaluating its efficacy is not simple. Given the broad range of institutional resources available- such as proximity to a medical school, or residency programs- reporting the quality of such courses within the context of such available resources …
Restoring An Iso:5840-Compliant Pulse Duplicator Device For Hydrodynamic Performance Characterization Of Artificial Cardiac Valves, Denver Eagar
Biomedical Engineering Undergraduate Honors Theses
During the summer of 2021, I was employed as an intern at Dynatek Labs, an implantable prosthetics testing company located in southern Missouri. My primary project was to modernize an abandoned pulse duplicator device and protocol to allow the company to re-enter a market area which they left nearly 15 years prior: heart valve testing. The company halted this initiative due to changes in international testing standards in previous years. The International Standards Organization Cardiac Valves Working Group released the latest version of standards concerning artificial heart valve testing (ISO 5840) in January of 2021. Accordingly, my project required that …
Virtual Reality As An Education Tool In Biomedical Engineering, Megan Wilkerson
Virtual Reality As An Education Tool In Biomedical Engineering, Megan Wilkerson
Biomedical Engineering Undergraduate Honors Theses
Virtual Reality (VR) has become more accessible in recent years, both to experience and to create. Various studies have shown that incorporating VR in an educational setting can yield positive results. Virtual reality videos created using course-specific content could prove to be a beneficial educational tool. VR videos were implemented in a remote biomolecular engineering laboratory course. 180° VR videos of lab procedures were recorded and viewed by students using a Google Cardboard headset and their smartphones. After viewing all the VR lab videos, students were given a survey to report their experiences. The survey contained questions used to measure …
Localized Intra-Arterial Drug Delivery Device For Stroke Treatment, Benjamin Yip
Localized Intra-Arterial Drug Delivery Device For Stroke Treatment, Benjamin Yip
Biomedical Engineering Undergraduate Honors Theses
Strokes are one of the leading causes of death and long-term disability in the United States, and according to the Centers for Disease Control and Prevention more than 795,000 people experience a stroke every year. Around 87% of all strokes are ischemic strokes making it the most common form of stroke. While ischemic strokes are treatable, current devices and methods still result in high mortality rates and high risks of hemorrhaging after treatment. The aim of this study is to design and test a prototype of a novel device for the localized delivery of thrombolytics to treat ischemic strokes. The …
Disparities In Response, Motivations, And Self-Efficacy To Entrepreneurially Minded Learning Within Underrepresented Students' Groups, Kaitlin Hall
Biomedical Engineering Undergraduate Honors Theses
Systemic racism in the United States is embedded within the policies that have created oppression for certain groups. Women, people of color, and those from low-income families have less access to entrepreneurial knowledge due to the education gap. It has been determined that less than 20 percent of US patents entail a female inventor. Black and Hispanic college graduates also lack this access as fewer than half as many individuals hold patents. Ensuring that these populations are educated in inventor knowledge can facilitate greater inclusion. The historical Brown vs the Board of Education intended to end unequal public schooling. It …
Erythrocyte Deformability In Response To Glucose Using Liquid Crystals, Jayden Goff
Erythrocyte Deformability In Response To Glucose Using Liquid Crystals, Jayden Goff
Biomedical Engineering Undergraduate Honors Theses
The worldwide prevalence of diabetes mellitus is rapidly increasing with about 9.3% of the adult population living with the disease. People with diabetes have trouble regulating their blood glucose levels which typically leads to hyperglycemia. Under normal physiological conditions, erythrocytes can undergo deformations in response to shear stress when passing through capillaries with a smaller diameter. Poorly managed hyperglycemia can lead to the glycosylation of erythrocyte membrane proteins and hemoglobin. This glycosylation leads to increased rigidity of the cells along with decreased deformability in response to mechanical stress; therefore, these cells have a higher susceptibility of getting stuck in the …
3d Volumetric Mapping Of Tissue Properties Via A Catheter-Scale Microendoscope Imaging System, Andrew Stark
3d Volumetric Mapping Of Tissue Properties Via A Catheter-Scale Microendoscope Imaging System, Andrew Stark
Biomedical Engineering Undergraduate Honors Theses
The study of tumor microvasculature is an important area of interest for research and clinical communities; however, there are significant limitations in the clinical characterization of the tumor microenvironment. Optical methods offer quantitative real-time measurement of tissue structure and perfusion and can be miniaturized for deployment endoscopically into previously inaccessible locations. However, conventional optical methods (i.e., optical coherence tomography, white light endoscopy, etc.) gives limited information about tissue perfusion while the diameter of various optical probes along with the complexity of scanning mechanisms make it difficult to access certain areas. In this study, a new technique for characterizing the tumor …
Developing A Semester-Long Project In A Biomechanical Engineering Course To Instill The Entrepreneurial Mindset In The Next-Generation Biomedical Engineering Students, Loren Hedgecock
Biomedical Engineering Undergraduate Honors Theses
Entrepreneurial-Minded Learning (EML) is an emerging pedagogy progressively gaining popularity in the engineering education community. Coincided with project-based learning (PBL), EML illustrates an essential dimension to the instruction of next-generation engineers, equipping them with various perspectives and approaches to relate societal challenges with technical concepts. Nationwide initiatives, such as the Kern Entrepreneurial Engineering Network (KEEN), have developed a learning framework specifically designed to create engineers such as these. The implementation of EML aims to stimulate connections, create value, and ignite curiosity. This study introduced a semester-long project based on these EML skillsets in a sophomore-level biomechanical engineering course. To evaluate …
The Influence Of Mmp14 On Angiogenesis In Chemotherapy-Treated Tumors, Abdussaboor Muhammad
The Influence Of Mmp14 On Angiogenesis In Chemotherapy-Treated Tumors, Abdussaboor Muhammad
Biomedical Engineering Undergraduate Honors Theses
Colorectal cancer is the third most common cancer in the world, and it is the fourth most common cause of cancer related death (1). There have been many significant advancements regarding the treatment of cancer which aim to shrink the size of tumors in patients. However, there is still more that needs to be understood about the many different factors that play a role in colorectal cancer development.
Angiogenesis is the process of forming new blood vessels from existing ones and it requires breaking down and remodeling of the extracellular matrix (ECM) in order to allow endothelial cells to migrate …
Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier
Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier
Biomedical Engineering Undergraduate Honors Theses
Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …
Determination Of Tissue-Level Changes In Tumors That Are Indicative Of Metastasis Using Optical Spectroscopy, Sanidhya D. Tripathi
Determination Of Tissue-Level Changes In Tumors That Are Indicative Of Metastasis Using Optical Spectroscopy, Sanidhya D. Tripathi
Biomedical Engineering Undergraduate Honors Theses
Breast cancer, accounting for 12% of all new cancer cases, is one of the leading causes of death in women worldwide. Although patient survival has improved over the years, metastatic spread to other organ sites and not due to the primary tumor is the most common form of tumor recurrence, accounting for 90% deaths. Hypoxia is a common hallmark of solid tumors and is linked with metastasis, therapeutic resistance, and poor patient survival. Defined as a state of decreased oxygen availability, cells under hypoxia have an increased rate of genetic mutation, local invasion, and resistance to treatment such as radiation …
Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake
Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake
Biomedical Engineering Undergraduate Honors Theses
When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …
Clot Analogs For The Development Of Improved Treatment Methods In Ischemic Stroke, Charles A. Rieth
Clot Analogs For The Development Of Improved Treatment Methods In Ischemic Stroke, Charles A. Rieth
Biomedical Engineering Undergraduate Honors Theses
According to the CDC, nearly 800,000 individuals experience stroke each year in the United States [1]. Greater than 70% of strokes are of ischemic etiology and involve the occlusion of key arteries in the cardiovascular system [2]. Tissue plasminogen activator (IV-tPA) is the current gold standard for thrombolytic approaches [3]; however, this therapeutic is only effective between 3 and 4.5 hours from the patient’s last know well [4]. As a result, less than 5% of acute ischemic stroke patients receive IV-tPA. In order to increase the viability of AIS treatment as a whole, it is essential that thrombolytic techniques are …
Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales
Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales
Biomedical Engineering Undergraduate Honors Theses
Venous valve failure allows for the retrograde, or backward, flow of blood into the lower extremities, which leads to Chronic Venous Insufficiency (CVI). CVI infringes upon quality of life through ulceration and can result in death due to Deep Vein Thrombosis (DVT), or blood clots, causing pulmonary embolism. A successful treatment of CVI restores valve function and prevents retrograde blood flow; however, current bioprosthetic venous valves exhibit low patency and high calcification. To improve upon bioprosthetic venous valves and CVI treatment, the University of Arkansas’s Cardiovascular Biomechanics Lab conducts studies with the purpose of comparing the properties and performance of …
Modifications Of A Machine To Produce Clinically-Sized Angioplasty Balloons For Bifurcations, Natalie Smith
Modifications Of A Machine To Produce Clinically-Sized Angioplasty Balloons For Bifurcations, Natalie Smith
Biomedical Engineering Undergraduate Honors Theses
Coronary artery disease is the most common form of heart disease and the leading cause of death in the U.S. ("Heart Disease Facts | cdc.gov", 2021). Typically, coronary artery disease is a result of coronary stenosis, constriction of the coronary artery, which can cause heart failure, arrhythmia, or heart attack ("Coronary Artery Disease: Prevention, Treatment and Research", 2021). Angioplasty balloons are a common treatment method for coronary stenosis and work by placing a stent at the lesion site to widen the vessel and promote blood flow. A type of lesion which remains particularly difficult and relatively common to treat is …
Characterizing The Expression Pattern And Function Of Tartan During Drosophila Development, Alaina Baggett
Characterizing The Expression Pattern And Function Of Tartan During Drosophila Development, Alaina Baggett
Biomedical Engineering Undergraduate Honors Theses
The development of complex structures and organs by multicellular organisms relies on the ability of epithelial cells to self-organize. Epithelia are sheets of connected cells, and compartment boundaries are formed between certain epithelial cells to create distinct tissue compartments. Compartment boundaries are specialized cell-cell interfaces that are enriched for the cytoskeletal proteins actin and myosin, leading to straight cell edges under relatively high tension that act as fences keep cells from moving between compartments. In the model organism Drosophila melanogaster (fruit fly), compartment boundaries in the early embryo are established in response to the non-uniform striped expression of the cell-surface …
Pulse Rate Variability Analysis During Hemorrhage In An Experimental Porcine Model, Gabbie Bonvillain, Lauren Crimmins, Md Abul Hayat, Adria Abella Villafranca, Sam Stephens, Hanna K. Jensen, Joseph A. Sanford, Jingxian Wu, Kevin W. Sexton, Morten Jensen
Pulse Rate Variability Analysis During Hemorrhage In An Experimental Porcine Model, Gabbie Bonvillain, Lauren Crimmins, Md Abul Hayat, Adria Abella Villafranca, Sam Stephens, Hanna K. Jensen, Joseph A. Sanford, Jingxian Wu, Kevin W. Sexton, Morten Jensen
Biomedical Engineering Undergraduate Honors Theses
During the acute phase of hemorrhage, heart rate and peripheral resistance increases to maintain proper oxygen delivery to vital organs. This response is mediated by the autonomic nervous system. Heart rate variability (HRV) has become a widely utilized measure to determine the autonomic nervous system control over the heart. Recently, pulse rate variability (PRV) has been suggested to serve as a surrogate for HRV. This study evaluates the ability of PRV obtained from peripheral arterial pressure waveforms as a method for detecting hemorrhage. Time domain and frequency domain metrics were evaluated for 5-minute and 15-minute arterial pressure waveform signals prior …
Effects Of Il-10 On Local Cell Populations And Functional Recovery Following Vml Injury, Zain Blackwell
Effects Of Il-10 On Local Cell Populations And Functional Recovery Following Vml Injury, Zain Blackwell
Biomedical Engineering Undergraduate Honors Theses
Volumetric muscle loss (VML) injuries are prevalent in both military personnel suffering from battlefield related incidents, and civilians following severe motor accidents. Despite its prevalence, VML has no pro-regenerative clinical treatments in place to recover some of the functional capabilities of the damaged muscle. Free flap grafting, debridement of damaged tissue, and physical therapy are the only clinical standards available that offer little functional recovery benefits, even after years of consistent treatment. In this study, anti-inflammatory cytokine interleukin-10 in conjunction with autologous minced muscle was assessed as a possible treatment for VML injuries and its influences on cellular behavior within …
Quantifying Blood Flow Patterns In The Pediatric Heart Using Blood Speckle Imaging, Harrison Dean
Quantifying Blood Flow Patterns In The Pediatric Heart Using Blood Speckle Imaging, Harrison Dean
Biomedical Engineering Undergraduate Honors Theses
Congenital Heart Disease (CHD) is the most common type of congenital disease worldwide. Echocardiography using Doppler ultrasound is typically used to diagnose and monitor CHD; however, it is angle-dependent in nature and as a result is limited in its ability to accurately evaluate ventricular function. Blood Speckle Imaging (BSI) is a novel, angle-independent imaging modality that provides detailed blood flow information and visualization within a given area using speckle-tracking. In this study, velocity-field information obtained from BSI was used to calculate flow parameters such as kinetic energy (KE) and circulation using a custom created MATLAB program. BSI was performed on …
Quantification Of Superoxide Production In Cells Treated With L-Buthionine Sulfoximine, Rebekah Townsley
Quantification Of Superoxide Production In Cells Treated With L-Buthionine Sulfoximine, Rebekah Townsley
Biomedical Engineering Undergraduate Honors Theses
Hydroxyl radicals, superoxides, and hydrogen peroxides are common reactive oxygen species (ROS) that are produced by the mitochondria during cellular respiration [1]. Signal transduction pathways in the mitochondria are used to maintain the balance of ROS. However, when these mechanisms fail to regulate ROS properly, it causes oxidative damage and can lead to the development of various diseases such as cancer, respiratory, neurodegenerative, and cardiovascular diseases. L-buthionine sulfoximine (BSO) has been used previously to induce oxidative stress by inhibiting the γ-GCS enzyme used to synthesize glutathione, an antioxidant used to convert ROS to water [3]. BSO reduces glutathione production, thus …
Mapping The Domain Of Rna Helicase Ddx1 That Interacts With The Ns1 Of Influenza A Viruses, Elise Wyatt
Mapping The Domain Of Rna Helicase Ddx1 That Interacts With The Ns1 Of Influenza A Viruses, Elise Wyatt
Biomedical Engineering Undergraduate Honors Theses
Of the known influenza virus strains, influenza A viruses (IAVs) are the most catastrophic due to their highly contagious nature and possibly life-threatening symptoms. IAVs invade a host cell and enter the nucleus where they use the cell’s nuclear machinery for replication of their viral RNA genome which is then exported to neighboring cells to establish a productive infection. Host pathogen recognition receptors (PRRs) respond to viral infection by signaling the cell to produce type I interferons (IFNs) to fight the foreign invader. Non-structural protein 1 (NS1) of IAVs, a major component in the regulation of viral replication, opposes host …
Evaluating Cellular Response Of Different Valve Interstitial Cell (Vic) Phenotypes To Angiotensin I, Smit Patel
Evaluating Cellular Response Of Different Valve Interstitial Cell (Vic) Phenotypes To Angiotensin I, Smit Patel
Biomedical Engineering Undergraduate Honors Theses
Calcific Aortic Valve Disease (CAVD), one of the leading causes of death in the United States, is characterized by diminished functioning and limited movement of the aortic valve (AV) due to increased thickening, disorganized extracellular matrix elastin fibers, increased collagen content, and abnormal deposition and formation of calcium nodules on the AV [1, 2]. There are two types of CAVD: i) Aortic valve sclerosis (AVS), in which patients suffer from tissue hardening, fibrosis, and early calcification, and ii) calcific aortic stenosis (CAS), representative by excessive calcification on the AV and reduced AV opening, are the two main forms of CAVD …
The Linear And Non-Linear Relationships Between Peripheral Venous Pressure, Arterial Circulation, And Patient Factors, Lauren Crimmins
The Linear And Non-Linear Relationships Between Peripheral Venous Pressure, Arterial Circulation, And Patient Factors, Lauren Crimmins
Biomedical Engineering Undergraduate Honors Theses
Peripheral venous pressure (PVP) can be used to measure blood volume status with a minimally invasive procedure. The pediatric cohort undergoing surgery for pyloric stenosis was studied to determine how arterial circulation and patient factors linearly impact PVP. The relationship between PVP and these confounding factors can provide valuable information for future PVP researchers.
To investigate the linear relationship between PVP and electrocardiogram (ECG) the waveforms were transformed into the frequency domain. A power spectral density was plotted, and the Pearson correlation coefficients were calculated for both preoperative and intraoperative settings. Linear regression models were computed for PVP and varying …
Metabolic Profiling Of Radiation Resistance In Head And Neck Squamous Cell Carcinoma, Natalie Curry
Metabolic Profiling Of Radiation Resistance In Head And Neck Squamous Cell Carcinoma, Natalie Curry
Biomedical Engineering Undergraduate Honors Theses
Abstract
Head and neck squamous cell carcinoma is the sixth most common cancer worldwide. Radiation therapy is one of the most common treatments for HNSCC, however, many patients do not respond to radiation therapy. Currently, it takes about a month for clinicians to definitively determine whether a tumor is responsive to radiation therapy. Current studies have identified that the prevention of mitochondrial oxidative stress caused by reactive oxygen species can prevent DNA damage and lead to a decrease in apoptosis in radiation resistant cells Measuring the oxygen consumption rate through Seahorse metabolic assays allows us to quantify basal respiration, maximal …
Expanding Image Datasets For Deep Learning By Evaluating Independence Through Coefficient Correlation And Mean-Squared Error, Ayman Yousef
Expanding Image Datasets For Deep Learning By Evaluating Independence Through Coefficient Correlation And Mean-Squared Error, Ayman Yousef
Biomedical Engineering Undergraduate Honors Theses
With deep learning being leveraged more regularly in the field of image classification, particularly in medical imaging, network optimizations have become a field in and of itself. With open source, comprehensive medical image datasets few and far, computational dataset expansion has become a useful tool for researchers without the ability to further manually collect data. However, with the rich amount of data that imaging modalities like multi-photon microscopy collect at a time, there is potential to expand datasets through proper utilization of this data that often time goes unused. Previous deep learning studies have shown that improper expansion can conflate …
Monitoring Fgf1-Treated Skin Wounds With Label-Free Multiphoton Microscopy, Gianna Busch
Monitoring Fgf1-Treated Skin Wounds With Label-Free Multiphoton Microscopy, Gianna Busch
Biomedical Engineering Undergraduate Honors Theses
Chronic skin wounds pose a significant threat to public health, affecting as many as 5.5 million people in the United States every year and costing the healthcare system $10 billion annually1,2. These wounds are associated with prolonged inflammation, poor vascularization, increased infection risk, and high mortality rates3,4. There is significant interest in developing and testing a variety of biologics to promote wound healing. However, quantitative evaluations of healing are typically limited to measurements of wound size, and there is a critical need to develop quantitative biomarkers sensitive to different aspects of the healing process. Label-free multiphoton …
Developing Aligned Nerve Scaffolds In A 3d Type-I Collagen Gel, Gabriel David
Developing Aligned Nerve Scaffolds In A 3d Type-I Collagen Gel, Gabriel David
Biomedical Engineering Undergraduate Honors Theses
Despite significant progress in the field of peripheral nerve repair, clinical success is still limited, leaving millions to suffer from peripheral neuropathy with billions spent every year for treatment. Nerve repair methods that are capable of maximizing the regenerative properties of peripheral nerves are greatly desired in the field of medical science. This research aims to fill the gap between modern methods and the future of nerve repair by creating type-I collagen scaffolds with aligned degradation pores that will assist and nurture nerves growing through them. This is achieved by incorporating adipose stem cells into type-I collagen hydrogels and aligning …
Quantifying Mucosal Hemodynamics In A Murine Model Of Ulcerative Colitis With Diffuse Reflectance Spectroscopy, Elizabeth A. Bullard, Ariel I. Mundo, Shelby N. Bess, Kathryn P. Miller
Quantifying Mucosal Hemodynamics In A Murine Model Of Ulcerative Colitis With Diffuse Reflectance Spectroscopy, Elizabeth A. Bullard, Ariel I. Mundo, Shelby N. Bess, Kathryn P. Miller
Biomedical Engineering Undergraduate Honors Theses
Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence 10 out of every 100,000 people in North America and Western Europe. Though the exact etiology is uncertain, a number of studies have shown that inflammatory cells along with environmental factors, genetics, and lifestyle habits can contribute to the sustained inflammatory response. In order to determine the cellular mechanism behind relapse and remission of UC, researchers have frequently employed immunohistochemistry, western blotting and gene sequencing, but these destructive analysis methods require the removal of a sample, necessarily limiting these methods to …