Medicine and Health Sciences Commons^™

Efficacy And Safety Of Approved Cellular Therapies And Bispecific Antibodies In Solid Tumors: The Current State, Rabab Zehra Jafry, Saba Bilal Qamar, Sohaib Irfan, Muhammad Abbas Abid, Virginia Mohlere, Neha Maithel, Syed Hassan Jafri, Sanjay Awasthi, Samer Srour, Irfan A Vaziri, Muhammad Bilal Abid

Faculty, Staff and Student Publications

Cancer immunotherapy is a broad term including naked antibodies, bispecific antibodies (BsAbs), immune-checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapy, cancer vaccines, activated immune cells, and allogeneic hematopoietic cell transplantation. Recent advances in immune-engaging T-cell therapies have led to significant progress in novel treatments across various cancer types, resulting in prolonged patient survival, mainly in patients with hematologic malignancies. Several CAR T-cell constructs and BsAbs have been approved by regulatory authorities worldwide for relapsed, refractory leukemia, non-Hodgkin lymphoma, and multiple myeloma. Solid tumors are characterized by an immunosuppressive, fibroinflammatory tumor microenvironment (TME) and immune-suppressive cells, such as regulatory T-cells …

Dexmedetomidine On Supraventricular Tachycardia In Critical Illness: A Time-Dependent Propensity Score Matching Study, Qiaonan Zhong, Marin H Kollef, Patrick G Lyons, Andrew P Michelson

2020-Current year OA Pubs

BACKGROUND: Supraventricular tachycardia affects many critically ill patients. Dexmedetomidine, a commonly used sedative, has sympatholytic and vagotonic effects that may alter atrioventricular nodal conduction and contribute to SVT. We aim to determine the association between dexmedetomidine exposure and clinically significant supraventricular tachycardia in a heterogeneous cohort of mechanically ventilated, critically ill adults. METHODS: This retrospective cohort study included critically ill patients from 11 hospitals admitted between July 2018 and October 2022, who were intubated within 48 h of admission. The primary exposure was intravenous dexmedetomidine. The primary outcome was occurrence of clinically significant supraventricular tachycardia, defined as heart rate > 100 …

Effectiveness Of Updated 2023-2024 (Monovalent Xbb.1.5) Covid-19 Vaccination Against Sars-Cov-2 Omicron Xbb And Ba.2.86/Jn.1 Lineage Hospitalization And A Comparison Of Clinical Severity-Ivy Network, 26 Hospitals, 18 October 2023-9 March 2024, Kevin C Ma, Jennie H Kwon, Bijal Parikh, Et Al.

2020-Current year OA Pubs

BACKGROUND: Assessing variant-specific coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages.

METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 US states admitted 18 October 2023-9 March 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including …

Multimorbidity Profiles And Severe In-Hospital Outcomes In Adults With Respiratory Syncytial Virus, Kevin C Ma, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults hospitalized with acute respiratory infections, including respiratory syncytial virus (RSV), often have multiple underlying conditions. Few data are available on the combined effect of conditions on risk of severe outcomes from RSV disease.

METHODS: We enrolled adults hospitalized with RSV at 26 hospitals in 20 US states admitted January 2022-July 2024. Seventeen underlying conditions were selected after excluding those with rare prevalence (≤1%) or high pairwise correlation (≥0.7). We applied Bayesian profile regression to identify profiles of conditions associated with increased risk of RSV severe outcomes, stratifying among adults aged 18-59 and ≥60 years.

RESULTS: We analyzed data …

Multimodal Imaging Reveals A Lysosomal Drug Reservoir That Drives Heterogeneous Distribution Of Parp Inhibitors, Carmen R Moncayo, Lauren Pendergast, Priyanka Verma, Et Al.

2020-Current year OA Pubs

For all drugs, effective target engagement requires sufficient intracellular concentrations of drug to be reached, but whether tumour heterogeneity impacts drug distribution and efficacy is poorly studied. Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed treatment opportunities for women with high-grade serous ovarian carcinoma, but resistance remains a clinical hurdle in this highly heterogeneous tumour type. Here, we present a patient-derived explant multi-modal imaging pipeline, which demonstrates that cell-intrinsic PARP inhibitor accumulation is highly variable, both between patients and within tumours. Spatial transcriptomics reveals enrichment of apoptotic and lysosomal signatures in high-drug regions. Rucaparib, an intrinsically fluorescent PARP inhibitor, accumulates heterogeneously …

Factors Associated With Telemedicine Use By Cardiologists For Medicare Beneficiaries In 2022 To 2023: An Observational Study, Samantha Harris, R J Waken, Fengxian Wang, Khavya C Avula, Rishi K Wadhera, Jose F Figueroa, E John Orav, Uchenna Ofoma, Karen E Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, the Centers for Medicare and Medicaid Services created a waiver to reimburse telemedicine services. It is important to understand factors that facilitate incorporation of telemedicine into ongoing cardiovascular practice.

METHODS: This was a retrospective cohort study of telemedicine and office visits delivered by cardiologists between January 1, 2022, and December 31, 2023, for Medicare beneficiaries. We calculated the adjusted incidence rate ratio (aIRR) of telemedicine visits, representing the proportion of a physician's visits delivered by telemedicine, to identify factors associated with telemedicine use.

RESULTS: There were 23 334 physicians in our cohort; they were predominantly …

Avian Influenza Preparedness In Ghana: A Cross-Sectional Assessment Of Knowledge, Attitudes, And Practices Among Residents Of Nsawam-Adoagyiri Municipality, Eastern Region, Christopher Yaw Dumevi, George Boateng Kyei, Et Al.

2020-Current year OA Pubs

BACKGROUND: Avian influenza (AI) represents a persistent threat to public health, food security, and livelihoods in Ghana, where outbreaks of H5N1 and H9N2 have occurred. This cross-sectional study evaluated the knowledge, attitudes, and practices (KAP) related to avian influenza among residents of the Nsawam-Adoagyiri Municipality; an area characterized by intensive poultry production with the aim of delineating deficits in community-level preparedness and guiding evidence-based public health interventions. METHODS: A community-based cross-sectional study was conducted from May to July 2025 using a four-stage sampling technique. We surveyed 321 adults via structured questionnaires, evaluating socio-demographics and KAP related to AI. Scale reliability …

03-17-26 Bor Hsc Committee Meeting Agenda, Patricia Serna

HSC Committee (A subcommittee of the UNM Board of Regents)

03-17-26 BOR HSC Committee Meeting Agenda

Nursing Interventions To Reduce Anxiety And Psychological Distress In Breast Cancer Patients In The Us, Alexis Abboud, Al Araydeh Mifleh

The Cardinal Edge

Background Breast cancer patients frequently experience psychological challenges, such as anxiety, distress, and diminished quality of life (QoL). Nursing interventions show promise in addressing these issues; however, a comprehensive synthesis of their impact is lacking. This review evaluates the effectiveness of nursing interventions in reducing anxiety and psychological distress while improving QoL.

Research Question What nursing interventions effectively reduce anxiety and psychological distress and improve QoL among breast cancer patients in the United States?

Methods A systematic review was conducted following PRISMA 2020 guidelines. Searches of CINAHL, APA PsycInfo, and Medline identified studies published in the last five years in …

Evolving Solutions For Red Blood Cell Preservation, Ali Alkafaji, Charles A. Elder, Mohammad Zaidi, Kavin Parthiv, Michael A. Menze

The Cardinal Edge

In emergencies such as natural disasters, armed conflicts, or during outer space missions, the availability of transfusable blood can mean the difference between life and death. Red blood cells (RBCs) must be stored at +4 ± 2 °C and have a shelf life of just 42 days, which makes maintaining a stable blood supply during adverse conditions extraordinarily challenging. This challenge was especially apparent during the COVID-19 pandemic when hospitals faced severe blood shortages. Freeze-drying, or lyophilization, offers a promising avenue to extend the shelf life of RBCs for transfusion during crises. However, a significant hurdle in dry preservation is …

Filifactor Alocis Disrupts Efferocytosis To Sustain Inflammation In Periodontitis, Ella Dye, Silvia Uriarte, Ruth Idowu

The Cardinal Edge

Background: Filifactor alocis is a Gram-positive, obligate anaerobe that has emerged as a diagnostic marker of periodontitis. Neutrophils and macrophages are key players in oral immune homeostasis. Neutrophils are short-lived cells and constitutively undergo apoptosis. This apoptotic program can be accelerated or delayed by bacterial interactions. Macrophages clear apoptotic neutrophils via “efferocytosis,” a crucial mechanism for resolving inflammation and preventing tissue damage. The efferocytic process downregulates the expression and release of proinflammatory cytokines such as interleukin (IL)-6 and IL-23 while promoting anti-inflammatory responses. Our previous findings demonstrated that F. alocis delays neutrophil apoptosis, with fewer apoptotic cells observed after 18 …

Patient Presentation Affects Medical Student Comfort During Sexual Health Encounters, Harshith Jella, Emily J. Noonan, Laura Weingartner

The Cardinal Edge

BACKGROUND

Previous research has identified some disparities between the care that masculine- and feminine-presenting patients experience with regards to sexual health. These disparities could cause feelings of unease and also difficulty with patient-physician communication. In medical education, standardized patients can help students identify and address implicit biases that could propagate as providers.

METHODS

The study population consisted of second year medical students (n=100) from the University of Louisville who completed sexual history-taking during a standardized patient encounter. Coders evaluated the phrases used, perceived comfort levels, and SP feedback among masculine- and feminine-presenting standardized patients.

RESULTS

While the patient presentation did …

Egf Enhances Re-Epithelization In Our Ex-Vivo Pig Eye Model, Andrew D. Le, Lisandra Plana-Ramos, Kate Tarvestad, Brian Ceresa

The Cardinal Edge

The cornea, the foremost anterior portion of the eye, plays a critical role in vision by refracting light and serving as a protective barrier. Its three distinct layers—the outermost epithelial layer, the thick stromal layer, and the innermost endothelial layer work together to maintain corneal transparency and function. The epithelial layer is particularly susceptible to damage, which can compromise the eye’s defense against foreign particles such as bacteria and viruses, potentially leading to infection and blindness. In this study, we established an ex vivo porcine corneal model to quantitatively and qualitatively investigate corneal re-epithelialization. Using adult pig eyes sourced from …

Exploring The Impact Of Perceived Patient Age And Gender On Medical Students' Comfort And Confidence With Sexual History-Taking, Haven Gabrielle V. Romero, Laura Weingartner

The Cardinal Edge

BACKGROUND

Many medical students lack confidence when navigating a patient sexual history. Discomfort may stem from a lack of experience, societal taboos surrounding sexual health discussions, or concerns about maintaining professionalism while addressing sensitive topics. We aimed to investigate comfort and confidence among student genders and patient age.

METHODS

We analyzed 107 standardized patient (SP) encounters of second-year students across three sexual health cases with different presenting complaints. Perceived comfort and confidence were inferred from student body language, language, and conversational tone, which were categorized as: comfortable/confident, fairly comfortable/confident, not comfortable/confident.

RESULTS

Across cases, students were comfortable/confident in half (50%). …

Hsp90 Inhibitor In Reducing Integrated Stress Response In An Experimental Mouse Model Of Spinal Cord Injury, Yousef Abozaid, Aditya Sarkar, Lukasz P. Slomnicki, Michal Hetman

The Cardinal Edge

Spinal cord injury (SCI) initiates a complex cascade of molecular events, including protein misfolding and neuroinflammation, contributing to neural damage and impaired functional recovery. Heat Shock Protein 90 (HSP90), a critical molecular chaperone involved in cellular stress responses, emerges as a promising therapeutic target to mitigate secondary damage after SCI. This study was designed to validate the in-vivo effects of different doses of HSP90 inhibitor, HSP990-i, administered acutely after moderate T9 SCI mouse model. The level of HSP70 protein level is measured through western blot from the injury epicenter. Adult mice underwent experimental contusive SCI at the T9 level, followed …

Hallucinogens For Mood And Anxiety Disorders: A Critical Review Of Psychedelic-Assisted Therapies, Georgia Chlebek

The Cardinal Edge

In quite a few people worldwide, there are several mental disorders that prevent the brain from operating in the “proper” way, depression, anxiety, and post-traumatic stress disorder (PTSD) being among the most common. Luckily, there are several medications that are produced and used to treat these disorders, but some medications are hard to access, and others simply don’t help the patient. Firstly, these medications take time to study and prove safe for public use, though in some cases time is not readily available. In other cases, these medications are going through shortages and becoming increasingly difficult for patients to access …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

Lamin A/C And Linc Complex Expression Affects Nuclei's Mechanical Properties And Functions In Osteosarcoma, Shridha Rajeswar

The Cardinal Edge

The nucleus has long been simplified in the field of biology, despite being an important organelle. Until recently, it has been commonly depicted as a simple sphere located at the center of a cell, responsible mainly for regulating protein synthesis. However, current research indicates that the linkers of the nucleoskeleton and cytoskeleton (LINC) complexes, the pillars of nuclear architecture, play a critical role in maintaining nuclear integrity and function. These complexes interact with proteins, such as Lamins, that modulate responses to biomechanical stimuli through the regulation of gene expression. As such, when these structures are downregulated, they can contribute to …

Targeting Glioblastoma: Mechanistic And Clinical Perspectives From Uofl Research, Swetha Senthil Nathan

The Cardinal Edge

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with median survival lingering at 12–15 months despite surgery, radiation, and chemotherapy. This article explores cutting-edge research and clinical efforts at the University of Louisville aimed at improving GBM treatment outcomes. Dr. Joseph Chen investigates the tumor microenvironment, revealing how physical properties such as stiffness and porosity drive GBM cell proliferation, migration, and resistance to apoptosis. His lab’s findings suggest that porosity, rather than stiffness alone, may be a more accurate predictor of tumor invasion and progression-free survival. Additionally, his research highlights the role of hyaluronic acid and …

Sound, Speech, And Synapses: Rebuilding The Brain Through Neuroplasticity, Sireen Khader

The Cardinal Edge

No abstract provided.

Evaluating Assistive Technology-Mediated Hepatitis B Education On At-Risk Behaviours Among In-School Adolescents With Hearing Impairment In Oyo State, Nigeria, Suen. E. Olalekanmi, J. O. Odelola, O. O. Isaiah

The 2026 Assistive Technology for Persons with Intellectual and Physical Disabilities Conference

Background: Adolescents with hearing impairment experience heightened vulnerability to health risks, largely due to limited access to accurate, accessible, and comprehensible health information. Communication barriers often restrict their understanding of disease prevention, resulting in inadequate health literacy and increased engagement in behaviours that may expose them to preventable infections such as HB. Despite the availability of effective vaccines and preventive measures, HB remains a significant public health concern in Nigeria. This situation underscores the urgent need for researchers, educators, and healthcare professionals to develop and prioritise inclusive health education strategies that address the unique communication needs of adolescents with hearing …

Nonlinear Bivariate Associations And Mononuclear Cell‐Type‐Specific Expression Level Differences In The Sting Signalling Pathway, David Kaplan

Faculty Scholarship

Understanding intracellular signalling pathways is crucial since they regulate essential functional activities. Bivariate relationships have been useful in delineating these pathways in clinical samples. In our previous studies, we have found many linear associations between pathway components, and we have interpreted these correlations as rheostatic regulators. Increases in an upstream component are correlated with a commensurate downstream increase. Here, we report a quantitative analysis of molecules in the STING pathway by assessing the variance in human peripheral blood mononuclear cell-type-specific molecular expression from patients with atherosclerotic coronary artery disease. The induction of the type I interferon track by this pathway …

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Pleural Fluid Drainage Versus Observation, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Mark I Neuman, Samir S Shah

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for pleural fluid drainage in children (3 months to 18 years) with parapneumonic effusion and empyema. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Label-Free Microfluidic Modulation Spectroscopy Monitors Rna Origami Structure And Stability, Phoebe S Tsoi, Lathan Lucas, Allan Chris M Ferreon, Ewan K S Mcrae, Josephine C Ferreon

Faculty, Staff and Students Publications

RNA origami enables genetically encoded, single-stranded RNA nanostructures that can self-assemble through co-transcriptional folding and are increasingly deployed as scaffolds for biosensing, synthetic biology, and nanomedicine. A recurring practical bottleneck is scalable, solution-phase readout of whether a designed scaffold has reached its intended base-paired architecture, whether it undergoes slow maturation or kinetic trapping, and how its stability is distributed across motifs. Here, we adapt microfluidic modulation spectroscopy (MMS) as a label-free structural biosensor for RNA folding by exploiting the rich 1760–1600 cm−1 vibrational fingerprints of RNA bases and base pairs. MMS alternates between sample and composition-matched buffer measurements in a …

Anti-Diabetic Medication Adherence Among Adults With Type 2 Diabetes In Eastern Uganda: Prevalence, Associated Factors, Barriers, Facilitators, And Strategies For Improvement: A Mixed-Methods Study, Brenda Lalam, Lucy Ezatiru, John Michael Okusa, Safina Akello, Ronald Opito, Patrick Lubogo, Simon Eleku, Shamim Nabidda, Samuel Kabwigu, Samuel Okello

School of Nursing & Midwifery, East Africa

Background:  Type 2 diabetes mellitus (T2DM) is the most common type of endocrine disorder among adults, accounting for 90%-95% of diabetes mellitus globally. In Uganda, non-adherence to anti-diabetic medication remains high at 38.1%. This results in complications like diabetic ketoacidosis, hyperglycemia and microvascular complications.

Objective:  To determine the prevalence of adherence to anti-diabetic medication, its associated factors, and to explore barriers, facilitators, and strategies for improving adherence among adults with T2DM attending the diabetic clinic at Soroti Regional Referral Hospital (SRRH).

Methods: An explanatory sequential mixed-methods design was employed, consisting of a cross-sectional quantitative study followed by a descriptive qualitative …

Quality Improvement Project: Implementation Of A Screening Tool For Postpartum Depression, Yaminah Johnson

Doctor of Nursing Practice Projects

Postpartum depression (PPD) remains underrecognized in clinical practice, with many cases going undiagnosed due to inconsistent or absent screening processes. At the project site, only 60% of postpartum patients reported that their mental health needs were adequately addressed, highlight-ing a critical gap in care. The purpose of this quality improvement project was to implement an evidence-based PPD screening tool and evaluate its impact on provider confidence and patient outcomes. Guided by Lewin’s Theory of Planned Change and Orem’s Self-Care Deficit Theory, the project aimed to improve physician and nursing staff confidence in screening and increase appropriate interventions for patients who …

Lifestyle Intervention Therapy Modulates Global Dna Methylation And Adipogenic Gene Expression In Severely Obese Hypogonadal Men, Siresha Bathina, Virginia Fuenmayor Lopez, Mia Prado, Salina Biene Teo, Dennis T Villareal, Rui Chen, Clifford Qualls, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Background/Objectives: Previous studies have suggested that lifestyle intervention (LSI) therapies involving diet and exercise can modulate DNA methylation; however, whether this occurs in severely obese hypogonadal men undergoing weight loss from diet and exercise remains unclear.

Methods: In this study, we investigated the effects of weight loss from diet and exercise on global DNA methylation as well as on the mRNA expression of specific demethylation enzymes, DNMT1, DNMT3A, and DNMT3B—in peripheral blood mononuclear cells (PBMCs) and DNA methylation markers in DNA of severely obese hypogonadal men. This is a secondary analysis of samples of severely obese (body …

Clinical Practice Guideline By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society: 2026 Guideline Update On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Mark I Neuman, Samir S Shah

Faculty, Staff and Students Publications

As the first part of an update to the clinical practice guideline on the management of community-acquired pneumonia in infants and children older than 3 months of age, we present six updated recommendations. The updated recommendations span the characterization and management of pneumonia with parapneumonic effusion. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Pleural Fluid Drainage Compared To Surgical Debridement, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Samir S Shah, Mark I Neuman

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations on the choice of pleural fluid drainage by chest tube with fibrinolysis versus mechanical debridement. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Chest Ultrasound In Children With Parapneumonic Effusion, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Samir S Shah, Mark I Neuman

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. In this paper, the panel provides recommendations for the role of chest ultrasound to evaluate parapneumonic effusion and empyema. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.