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Articles 3931 - 3960 of 325679
Full-Text Articles in Entire DC Network
Cardiac Resynchronization Therapy: A Review, Caique M Ternes, Jitae A Kim, Anirban Basu, Kenneth A Ellenbogen, Mihail G Chelu
Cardiac Resynchronization Therapy: A Review, Caique M Ternes, Jitae A Kim, Anirban Basu, Kenneth A Ellenbogen, Mihail G Chelu
Faculty, Staff and Students Publications
Importance: Heart failure (HF) affects more than 64 million individuals worldwide, and acute HF is associated with 1-year mortality rates of 23.6% in North America and Europe. Cardiac dyssynchrony from conduction system disease may cause HF progression, particularly in patients with left ventricular (LV) systolic dysfunction.
Observations: Electrical dyssynchrony in HF most commonly presents as left bundle-branch block and affects 20% to 30% of patients with reduced LV ejection fraction (LVEF). Cardiac resynchronization therapy, which includes biventricular pacing and conduction system pacing, restores synchronous ventricular contraction and is recommended for patients with symptomatic HF despite optimal medical therapy, LVEF of …
Inflammaging In Aged Tissues Drives Remodeling Of The Cd8+ T Cell Compartment, Irina Shchukina, Carlos J Rodriguez-Hernandez, Heather S Ruiz, Maksim Kleverov, Rachel L Mintz, Katsutaka Mineura, Subhadra C Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A Mogilenko, Rachael L Field, Tran H Nguyen, Quazim A Alayo, Christopher G Huckstep, Barbora Vander Wielen, Jonathan R Brestoff, Sheila A Stewart, David W Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J Randolph, Maxim N Artyomov
Inflammaging In Aged Tissues Drives Remodeling Of The Cd8+ T Cell Compartment, Irina Shchukina, Carlos J Rodriguez-Hernandez, Heather S Ruiz, Maksim Kleverov, Rachel L Mintz, Katsutaka Mineura, Subhadra C Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A Mogilenko, Rachael L Field, Tran H Nguyen, Quazim A Alayo, Christopher G Huckstep, Barbora Vander Wielen, Jonathan R Brestoff, Sheila A Stewart, David W Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J Randolph, Maxim N Artyomov
2020-Current year OA Pubs
Aging strongly impacts CD8
Regulation Of Pfh1 Helicase Activity By Nucleic Acid Interactions And Mitochondrial Ssb, María Ortiz-Rodríguez, Saurabh P Singh, Francisco J Cao-García, Roberto Galletto, Borja Ibarra
Regulation Of Pfh1 Helicase Activity By Nucleic Acid Interactions And Mitochondrial Ssb, María Ortiz-Rodríguez, Saurabh P Singh, Francisco J Cao-García, Roberto Galletto, Borja Ibarra
2020-Current year OA Pubs
Pif1-family helicases are essential for proper nuclear and mitochondrial genome maintenance, yet the regulation of their activities remains incompletely understood. Here, we use single-molecule manipulation and visualization techniques to dissect the real-time mechanochemical behavior of Pfh1, the sole Pif1-family helicase in
Comprehensive Mass Spectrometry Screening-Derived Atlas Of Hdac Inhibitors Reveals Histone-Specific Acetylation Changes, Rashmi Karki, Francisca N De Luna Vitorino, Richard M Searfoss, Joanna K Lempiäinen, Cheryl H Arrowsmith, Benjamin A Garcia
Comprehensive Mass Spectrometry Screening-Derived Atlas Of Hdac Inhibitors Reveals Histone-Specific Acetylation Changes, Rashmi Karki, Francisca N De Luna Vitorino, Richard M Searfoss, Joanna K Lempiäinen, Cheryl H Arrowsmith, Benjamin A Garcia
2020-Current year OA Pubs
Histone deacetylase inhibitors (HDACis) have emerged as valuable therapeutics for cancer and other diseases; however, their effects on histone post-translational modification remain poorly characterized. Here, we applied quantitative mass spectrometry and high-throughput sequencing to systematically profile site-specific changes in histone modifications in response to a panel of HDACis. This platform enabled mapping of histone modification changes across hundreds of sites, including low-abundance histone marks. Furthermore, an integrative analysis of chromatin immunoprecipitation followed by sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data identified genome-wide binding sites for the low-abundance histone modification of H2A.Z acetylation in HeLa and MDA-MB-231 breast cancer cells, highlighting the …
Patterns Of Care And Clinical Outcomes In Systemic Peripheral T-Cell Lymphoma: The Leo-Mer Prospective Cohort Study, Jia Ruan, Neha Mehta-Shah, Brad Kahl, Et Al.
Patterns Of Care And Clinical Outcomes In Systemic Peripheral T-Cell Lymphoma: The Leo-Mer Prospective Cohort Study, Jia Ruan, Neha Mehta-Shah, Brad Kahl, Et Al.
2020-Current year OA Pubs
Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for peripheral T-cell lymphoma (PTCL). We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in 2 related prospective cohort studies, Lymphoma Epidemiology of Outcomes (LEO) from 2015 to 2020 and Molecular Epidemiology Resource (MER) from 2002 to 2015, both followed to 2024. The primary end points were event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimator and Cox regression model. Secondary end points included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP (cyclophosphamide, …
Real-World Evidence For Pembrolizumab Gemcitabine Vinorelbine And Liposomal Doxorubicin In Classical Hodgkin Lymphoma, Grace Baek, Nancy L Bartlett, Marcus Watkins, Et Al.
Real-World Evidence For Pembrolizumab Gemcitabine Vinorelbine And Liposomal Doxorubicin In Classical Hodgkin Lymphoma, Grace Baek, Nancy L Bartlett, Marcus Watkins, Et Al.
2020-Current year OA Pubs
No abstract provided.
Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: 4-Year Follow-Up Of The Pathfinder Study, Jason Gotlib, Stephen T Oh, Et Al.
Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: 4-Year Follow-Up Of The Pathfinder Study, Jason Gotlib, Stephen T Oh, Et Al.
2020-Current year OA Pubs
Advanced systemic mastocytosis (AdvSM), a clonal hematologic neoplasm driven predominantly by D816V-mutant KIT, is often characterized by organ damage. Associated hematologic neoplasms (AHNs; usually myeloid) are often present, leading to poor survival. We report on the oral, highly selective, potent KIT D816V inhibitor avapritinib (200 mg once daily, starting dose) with >4 years follow-up from the fully enrolled PATHFINDER study. End points included overall response rate (ORR; primary), duration of response (DOR), progression-free survival (PFS), overall survival (OS), changes in objective biomarkers of disease, and safety (all secondary). Of 107 patients with AdvSM (including 71 [66%] with SM-AHN; overall population …
Staff Education To Improve Treatment Adherence Among Young Adults With Mental Health And Substance Use Disorders In An Outpatient Behavioral Health Clinic, Nkechinyere Eririma Nwachukwu
Staff Education To Improve Treatment Adherence Among Young Adults With Mental Health And Substance Use Disorders In An Outpatient Behavioral Health Clinic, Nkechinyere Eririma Nwachukwu
Walden Dissertations and Doctoral Studies
No abstract provided.
Improving Antihypertensive Medication Adherence Through Patient-Centered Assessment In Rural Primary Care, Tiesha Keoni Mathis
Improving Antihypertensive Medication Adherence Through Patient-Centered Assessment In Rural Primary Care, Tiesha Keoni Mathis
Walden Dissertations and Doctoral Studies
No abstract provided.
An Emotional Intelligence Staff Education Program For Patient-Aligned Care Team (Pact) Members, Linda Rogers
An Emotional Intelligence Staff Education Program For Patient-Aligned Care Team (Pact) Members, Linda Rogers
Walden Dissertations and Doctoral Studies
No abstract provided.
Trends In The Management Of Acute Pyogenic Flexor Tenosynovitis Of The Hand: A Comprehensive Analysis., Michael Anderson, Taylor J Manes, Davis Hedbany, Sylvester Okoro, Nithin Gupta, Morgan Turnow, Stephen Berling
Trends In The Management Of Acute Pyogenic Flexor Tenosynovitis Of The Hand: A Comprehensive Analysis., Michael Anderson, Taylor J Manes, Davis Hedbany, Sylvester Okoro, Nithin Gupta, Morgan Turnow, Stephen Berling
Ambulatory and Primary Care Articles
Background Acute pyogenic flexor tenosynovitis (APFT) is typically managed operatively, but there is growing interest in nonoperative treatments using intravenous (IV) antibiotics to reduce surgical complications. Timely intervention is essential, as delayed treatment increases the risk of systemic, life-threatening infections. This study aimed to characterize national trends in the operative management of APFT and to compare mortality and amputation outcomes between operatively and nonoperatively managed patients. Methods A retrospective analysis was conducted using data from the TriNetX United States Collaborative Network from 2015 to 2023. Patients were identified using ICD-10 and CPT codes and categorized into operative and nonoperative cohorts, …
Epileptic Seizure Prediction From Eeg Using Continual Learning With Cnns, Adnan Amin, Ammar Bathich, Feras Al-Obeidat, Safa Naes, Maria Jose Sousa
Epileptic Seizure Prediction From Eeg Using Continual Learning With Cnns, Adnan Amin, Ammar Bathich, Feras Al-Obeidat, Safa Naes, Maria Jose Sousa
All Works
Epilepsy is a persistent neurological disorder that affects over 50 million people worldwide, with nearly one-third of patients remaining unresponsive to conventional therapeutic treatments. This study introduces a progressively adaptive seizure prediction framework designed to enhance early detection and clinical decision-making. The proposed model employs a deep learning strategy grounded in continual learning (CL) principles, using Convolutional Neural Networks (CNNs) in combination with knowledge distillation techniques. This enables the model to assimilate new data while retaining previously learned information. The approach was evaluated on the publicly available Bonn University EEG dataset, following a sequential learning process in which each successive …
Staff Education To Improve Fall Prevention Knowledge In A Transitional Care Unit, David M. Ogato
Staff Education To Improve Fall Prevention Knowledge In A Transitional Care Unit, David M. Ogato
Walden Dissertations and Doctoral Studies
No abstract provided.
A Disorder-Aware Computational Framework To Identify Structurally Tractable Targets In Proliferative Vitreoretinopathy, Mak B. Djulbegovic, Nedym Hadzijahic, David J. Taylor Gonzalez, Michael Antonietti, Sidra Zafar, Ajay E. Kuriyan
A Disorder-Aware Computational Framework To Identify Structurally Tractable Targets In Proliferative Vitreoretinopathy, Mak B. Djulbegovic, Nedym Hadzijahic, David J. Taylor Gonzalez, Michael Antonietti, Sidra Zafar, Ajay E. Kuriyan
Wills Eye Hospital Papers
OBJECTIVE: Proliferative vitreoretinopathy (PVR) remains a major cause of failure after rhegmatogenous retinal detachment repair and lacks effective pharmacologic therapies. Although epithelial-mesenchymal transition (EMT) is central to PVR pathogenesis, the structural determinants governing the tractability of EMT regulators, particularly those involving intrinsic disorder, remain poorly defined. We developed a disorder-aware, artificial intelligence-enabled computational framework to evaluate EMT-associated proteins in PVR and prioritize structurally tractable regulators for structure-based targeting.
DESIGN: A computational, hypothesis-generating study employing an in silico screening and structural modeling pipeline.
SUBJECTS: No human subjects or biological specimens were included. The dataset comprised 25 EMT-associated proteins implicated in PVR, …
Probiotic Intake Related To Hemoglobin A1c Among U.S. Veterans With Type 2 Diabetes Mellitus, Maryann Martin
Probiotic Intake Related To Hemoglobin A1c Among U.S. Veterans With Type 2 Diabetes Mellitus, Maryann Martin
Walden Dissertations and Doctoral Studies
No abstract provided.
Staff Education To Improve Icu Nurses’ Knowledge And Confidence In End-Of-Life Care Through A Structured Education Intervention, Alyssia Lee Wright
Staff Education To Improve Icu Nurses’ Knowledge And Confidence In End-Of-Life Care Through A Structured Education Intervention, Alyssia Lee Wright
Walden Dissertations and Doctoral Studies
No abstract provided.
Staff Education On Reducing Falls In Psychiatric Inpatient Care Through A Nurse-Led Multifactorial Education And Prevention Program, Marceline Nkwenti
Staff Education On Reducing Falls In Psychiatric Inpatient Care Through A Nurse-Led Multifactorial Education And Prevention Program, Marceline Nkwenti
Walden Dissertations and Doctoral Studies
No abstract provided.
Staff Education To Reduce The Incidence Of Pressure Injury In Medical-Surgical Inpatients, Francis Omelu
Staff Education To Reduce The Incidence Of Pressure Injury In Medical-Surgical Inpatients, Francis Omelu
Walden Dissertations and Doctoral Studies
No abstract provided.
Experiences Of First-Generation Immigrant Parents In Caring For Children With Type 1 Diabetes, Nahel Kibreab
Experiences Of First-Generation Immigrant Parents In Caring For Children With Type 1 Diabetes, Nahel Kibreab
Walden Dissertations and Doctoral Studies
No abstract provided.
A Multi-Agent Large Language Model Framework To Automatically Assess Performance Of A Clinical Ai Triage Tool, Adam Flanders, Yifan Peng, Luciano Prevedello, Robyn Ball, Errol Colak, Prahlad Menon, George Shih, Hui-Ming Lin, Paras Lakhani
A Multi-Agent Large Language Model Framework To Automatically Assess Performance Of A Clinical Ai Triage Tool, Adam Flanders, Yifan Peng, Luciano Prevedello, Robyn Ball, Errol Colak, Prahlad Menon, George Shih, Hui-Ming Lin, Paras Lakhani
Department of Radiology Faculty Papers
Radiology reports can be used as a surrogate for performance of clinical AI tools. Radiology reports were analyzed by an ensemble of eight open-source LLM models and a internal version of GPT-4o using a single multi-shot prompt that assessed for presence of ICH. Performance of the open-source models, consensus of models and GPT-4o were compared to human report review. Three ideal consensus LLM ensembles were tested for rating the performance of the triage tool. The capability of each LLM varied. The highest AUC performance was achieved with llama3.3:70b and GPT-4o. Using MCC the ideal combination of LLMs were: Full-9 Ensemble, …
Successful Laparoscopic-Assisted Management Of A Rare Purely Cystic Type Iv Sacrococcygeal Teratoma In Neonate: A Case Report, Alghalya Khalid Almaawali, Ahmed Alwahaibi, Yousuf Al-Shaqsi, Farman Laghari, Bashar Dawud, Marwa Al-Riyami
Successful Laparoscopic-Assisted Management Of A Rare Purely Cystic Type Iv Sacrococcygeal Teratoma In Neonate: A Case Report, Alghalya Khalid Almaawali, Ahmed Alwahaibi, Yousuf Al-Shaqsi, Farman Laghari, Bashar Dawud, Marwa Al-Riyami
Sultan Qaboos University Medical Journal
Type IV sacrococcygeal teratomas (SCTs) are the rarest subtype of SCTs. We report a 2-week-old female who presented to a tertiary care centre in Muscat, Oman, in 2024 with abdominal distension and feeding intolerance. Imaging revealed a purely cystic presacral lesion, managed with successful laparoscopic-assisted cyst excision and coccygectomy. Histopathology confirmed a mature cystic SCT and the patient was diagnosed with a purely cystic Altman type IV SCT. The postoperative course was uneventful apart from minor wound dehiscence, which resolved with conservative management. Follow-up showed complete wound healing and no recurrence. Purely cystic Type IV SCTs are extremely rare and …
Smaller Right Ventricle Results In Poorer Exercise Performance In Young Patients With Repaired Tetralogy Of Fallot, Christiane Mhanna, Katerina Kourpas, Takeshi Tsuda
Smaller Right Ventricle Results In Poorer Exercise Performance In Young Patients With Repaired Tetralogy Of Fallot, Christiane Mhanna, Katerina Kourpas, Takeshi Tsuda
Department of Pediatrics Faculty Papers
BACKGROUND: Severe right ventricular (RV) dilatation and exercise intolerance are considered indications for pulmonary valve replacement in surgically repaired tetralogy of Fallot (rTOF).
METHODS AND RESULTS: Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were performed in rTOF patients with pulmonary insufficiency (PI). Oxygen pulse (OP), calculated as oxygen consumption (V̇O
CONCLUSIONS: A smaller RV was associated with worse exercise performance, indicating exercise intolerance is independent of RV dilatation in young rTOF with PI and represents a unique pathological entity responsible for reduced exercise performance.
Lessons Learned In Providing Infant And Early Childhood Mental Health Consultation During The Covid-19 Pandemic, Rashele Wade
Lessons Learned In Providing Infant And Early Childhood Mental Health Consultation During The Covid-19 Pandemic, Rashele Wade
Journal of Global Awareness
Access to quality childcare is a protective factor from lifelong issues such as school failure, school drop-out, and incarceration. Conversely, preschool suspension and expulsion are significant risk factors. Evidence-based interventions, such as Infant and Early Childhood Mental Health Consultation, aim to reduce and eliminate the incidence of preschool suspensions and expulsions. The COVID-19 pandemic disrupted access to quality childcare for many children across the country and globally. This study utilized a qualitative action research approach and generic qualitative inquiry to examine the research question, “How can we improve Infant and Early Childhood Mental Health Consultation through lessons learned during the …
Caring For The Carers: Exploring The Mental Wellbeing Of Informal Palliative Caregivers Of Cancer Patients In Kenya, James Kariuki, Rose Njiraini
Caring For The Carers: Exploring The Mental Wellbeing Of Informal Palliative Caregivers Of Cancer Patients In Kenya, James Kariuki, Rose Njiraini
Journal of Global Awareness
Cancer cases have been on the increase globally, and this has led to economic burden on the affected households. One way of reducing the cost of care is through home-based care by informal palliative caregivers who include family members, friends, and other people assigned by the family members to take care of the patient. The objectives of this study were to assess the status of the mental wellbeing of palliative caregivers of cancer patients; to examine the relationship between the ability of the patient to cope with cancer diagnosis and the mental wellbeing of the caregiver; and to investigate the …
Navigating Burnout: The Role Of Workplace Support For Social Work Clinicians, Melanie Fulton
Navigating Burnout: The Role Of Workplace Support For Social Work Clinicians, Melanie Fulton
Journal of Global Awareness
The shortage of mental health workers is a growing concern in the United States, and social workers a substantial portion of employees who work with individuals with mental health concerns. This shortage stresses the importance of studying factors that impact burnout for mental health clinicians, particularly social work clinicians. While burnout among social workers in some settings have been documented in the literature, less research has focused on independently licensed clinical social workers in private practice. This study had participants complete a survey to examine the relationship between workplace support, burnout, and professional fulfillment among this population (N = 57). …
Exploring The Role Of Magnesium Deficiency In Inflammatory Bowel Disease, Victor A. Bob-Yellowe, Shaunte Hadnot, Sonya Bhatia, Anesu K. Murambadoro
Exploring The Role Of Magnesium Deficiency In Inflammatory Bowel Disease, Victor A. Bob-Yellowe, Shaunte Hadnot, Sonya Bhatia, Anesu K. Murambadoro
MEDI 9331 Scholarly Activities Clinical Years
Inflammatory Bowel Disease (IBD) is a group of chronic gastrointestinal disorders, including Ulcerative Colitis and Crohn’s disease. As of 2020, it was estimated that IBD significantly impacts the lives of approximately 2.39 million Americans. Magnesium (Mg) is an essential mineral involved in many bodily functions, including immune response and gut health. Recent studies suggest that Magnesium levels may be linked to IBD. Therefore, this review aims to explain how Magnesium might play a role in the development or progression of IBD. Additionally, this article discusses the overall role that Magnesium’s plays in gut health and whether Magnesium supplementation could be …
Five Corridors: A Community Health Needs Assessment Of Horry County, Stephen Borders, Hayley Bilko, Molly Craig, Olivia Guthrie, Ashley Mcconnell, Emily Mcgowan, Anna Quick, Abigail Rike, Makayla Wilson
Five Corridors: A Community Health Needs Assessment Of Horry County, Stephen Borders, Hayley Bilko, Molly Craig, Olivia Guthrie, Ashley Mcconnell, Emily Mcgowan, Anna Quick, Abigail Rike, Makayla Wilson
Public Health
This report presents a Community Health Needs Assessment (CHNA) of Horry County, South Carolina. Its central analytical contribution is a five-corridor framework derived from k-means cluster analysis of the county's 76 residential census tracts, drawing on social and economic indicators from the American Community Survey and health estimates from the CDC PLACES program. The analysis organizes the county into five distinct community types — Affluent Coastal Retirement, Moderate Coastal Retirement, Inland Rural/Suburban Transitional, Concentrated Disadvantage, and Hispanic Hospitality Worker — each with a characteristic profile of social and health conditions.
Within this framework, the assessment examines a range of social …
Brain Age Prediction In Generalized Anxiety Disorder Using A Convolutional Neural Network, Corey Richier, André Zugman, Anita Harrewijn, Elise M. Cardinale, Parmis Khosravi, Moji Aghajani, Willem B. Bruin, Kevin Hilbert, Narcis Cardoner, Anderson M. Winkler
Brain Age Prediction In Generalized Anxiety Disorder Using A Convolutional Neural Network, Corey Richier, André Zugman, Anita Harrewijn, Elise M. Cardinale, Parmis Khosravi, Moji Aghajani, Willem B. Bruin, Kevin Hilbert, Narcis Cardoner, Anderson M. Winkler
Human Genetics Publications
Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The …
Improving Nursing Compliance With Pressure Injury Prevention In Postoperative Patients In The Cardiovascular Intensive Care Unit, Chingyi Lam
Doctor of Nursing Practice Final Project Abstract
Pressure injuries acquired in the hospital continue to be a major concern in patient safety among critically ill populations. The purpose of the quality improvement project was to improve nursing compliance with pressure injury prevention strategies among postoperative patients in a cardiovascular intensive care unit (CVICU). Patients who undergo cardiovascular surgery are at a high risk of developing pressure injuries due to immobility, sedation, vasopressors, and prolonged positioning on their backs. The quality improvement project was carried out in a 37-bed CVICU using the Institute for Healthcare Improvement (IHI) Model for Improvement and Plan–Do–Study–Act (PDSA) cycles. Data on nursing repositioning …
Influence Of Polyvinyl Alcohol Content On Starch-Based Bioplastic Reinforced With Chitosan And Microcrystalline Cellulose, Bagus Kharisma Putra, Andoko Andoko, Mochamad Viky Afandy, Muhammad Faizullah Pasha, Riduwan Prasetya
Influence Of Polyvinyl Alcohol Content On Starch-Based Bioplastic Reinforced With Chitosan And Microcrystalline Cellulose, Bagus Kharisma Putra, Andoko Andoko, Mochamad Viky Afandy, Muhammad Faizullah Pasha, Riduwan Prasetya
Chimica et Natura Acta
Starch-based bioplastics are promising sustainable alternatives to petroleum-based plastics; however, their limited mechanical strength and stability restrict broader packaging applications. This study investigates the influence of polyvinyl alcohol (PVA) content on the structural and functional properties of starch-based bioplastic films reinforced with chitosan and microcrystalline cellulose (MCC). Films prepared by solution casting with varying PVA compositions were characterized in terms of density, mechanical properties, thermal stability, biodegradation behavior, antibacterial activity, and structural features. Increasing PVA content produced denser film structures with improved tensile strength and thermal stability, while elongation at break reached its maximum at the intermediate formulation, indicating a …