Evaluating Tirzepatide's Therapeutic Potential In Mitigating Obesity-Associated Comorbidities, 2024 Nova Southeastern University
Evaluating Tirzepatide's Therapeutic Potential In Mitigating Obesity-Associated Comorbidities, Zaneh Kahook, Talaya Jones, Carina Bryan, Mayur Parmar
HCA-NSU MD Research Day
Objective: The study aims to explore the therapeutic potential of dual GIP/GLP-1 agonist tirzepatide in managing obesity and its associated manifestations, including obstructive sleep apnea (OSA), hidradenitis suppurativa (HS), and obesity-associated cancer (OAC) risks. Background: OSA and HS are the associated comorbidities noted in persons with obesity. Obesity has been associated with an increased risk of cancers, such as breast cancer. Reducing obesity could improve these conditions. Tirzepatide has demonstrated efficacy in reducing body weight, but its benefits in obesity-related conditions and cancer risk need further investigation. Methods: Data was synthesized from peer-reviewed literature on tirzepatide. Additional sources were identified …
A Rare Case Of Pulmonary Nocardiosis With Pseudomonas Aeruginosa Superinfection In An Immunocompromised Patient, 2024 Jefferson Health Northeast
A Rare Case Of Pulmonary Nocardiosis With Pseudomonas Aeruginosa Superinfection In An Immunocompromised Patient, Kevin Liu, Md, Samuel Shulimson, Do, Herbert Patrick, Md
Jefferson Health - Northeast Posters (formerly Aria Health Posters)
Introduction
Nocardiosis is an uncommon opportunistic infection with over two thirds occurring in those who are immunocompromised [1] or who have undergone solid organ transplants [2]. Here, we present a unique case of pulmonary Nocardiosis complicated by superimposed Pseudomonas infection.
Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, 2024 The Texas Medical Center Library
Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, Chenyang Li, Thinh T Nguyen, Jian-Rong Li, Xingzhi Song, Junya Fujimoto, Latasha Little, Curtis Gumb, Chi-Wan B Chow, Ignacio I Wistuba, Andrew P Futreal, Jianhua Zhang, Shawna M Hubert, John V Heymach, Jia Wu, Christopher I Amos, Jianjun Zhang, Chao Cheng
Faculty, Staff and Student Publications
Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with …
Multi-Ancestry Gwas Meta-Analyses Of Lung Cancer Reveal Susceptibility Loci And Elucidate Smoking-Independent Genetic Risk, 2024 The Texas Medical Center Library
Multi-Ancestry Gwas Meta-Analyses Of Lung Cancer Reveal Susceptibility Loci And Elucidate Smoking-Independent Genetic Risk, Bryan R Gorman, Sun-Gou Ji, Michael Francis, Anoop K Sendamarai, Yunling Shi, Poornima Devineni, Uma Saxena, Elizabeth Partan, Andrea K Devito, Jinyoung Byun, Younghun Han, Xiangjun Xiao, Don D Sin, Wim Timens, Jennifer Moser, Sumitra Muralidhar, Rachel Ramoni, Rayjean J Hung, James D Mckay, Yohan Bossé, Ryan Sun, Christopher I Amos, Va Million Veteran Program, Saiju Pyarajan
Faculty, Staff and Student Publications
Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 …
Issue 11: Pulmonary & Critical Care Insider, 2024 Parkview Health
Issue 11: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls, Dustin D. Linn Pharmd, Payal Shukla Md, Ms, Patricia Rich Md, Morgan Crites Np-C
Critical Care & Pulmonary
Pulmonary & Critical Care Insider Issue 11
Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.
The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.
---------
Topics:
VIEWPOINTS:
Blood Pressure Measurement
Home Noninvasive Ventilation
ORIGINAL STUDY SUMMARY
Acute Pulmonary Embolism
The PEXIVAS trial
Respiratory Failure in hemorrhagic shock
SNAPSHOTS:
RBC Transfusions
New Small cell lung cancer Treatment.
Molecular Landscape Of Erbb2 Alterations In 3000 Advanced Nsclc Patients, 2024 The Texas Medical Center Library
Molecular Landscape Of Erbb2 Alterations In 3000 Advanced Nsclc Patients, Lingzhi Hong, Sonia Patel, Leylah M Drusbosky, Yuanyuan Xiong, Rongrong Chen, Ruixuan Geng, Simon Heeke, Monique Nilsson, Jia Wu, John V Heymach, Yingyi Wang, Jianjun Zhang, Xiuning Le
Faculty, Staff and Student Publications
ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 …
Peran Pemeriksaan Penanda Tumor Cairan Pleura Dalam Diagnosis Efusi Pleura Maligna Akibat Kanker Paru Primer, 2024 Divisi Respirologi dan Penyakit Kritis, Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Indonesia/Rumah Sakit dr. Cipto Mangunkusumo, Jakarta
Peran Pemeriksaan Penanda Tumor Cairan Pleura Dalam Diagnosis Efusi Pleura Maligna Akibat Kanker Paru Primer, Cleopas M. Rumende, Noorwati Sutandyo, Arif R. Hanafi, Samuel K. Rumende, Erwin C. Susanto, Truely P. Sitorus
Jurnal Penyakit Dalam Indonesia
Introduction. Pleural effusion is a frequently acquired lung disorder and based on the type of cause it is divided into malignant and non-malignant pleural effusion. Cytological examination of pleural fluid to differentiate between malignant and non-malignant pleural effusion shows varying sensitivity. Research regarding the benefits of CEA and Cyfra 21-1 pleural fluid examination to detect malignant pleural effusion due to primary lung cancer in Indonesia is still very limited. The aims of this study is to determine the sensitivity and specificity of CEA and Cyfra 21-1 pleural fluid in diagnosing malignant pleural effusion due to primary lung camcer.
Methods …
Ventilasi Noninvasif Pada Obstructive Sleep Apnea Dan Obesity Hypoventilation Syndrome, 2024 Divisi Respirologi dan Penyakit Kritis, Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Universitas Indonesia/RSUPN Dr. Cipto Mangunkusumo, Jakarta
Ventilasi Noninvasif Pada Obstructive Sleep Apnea Dan Obesity Hypoventilation Syndrome, Herikurniawan Herikurniawan, Joanna Audrey, Firina Adelya
Jurnal Penyakit Dalam Indonesia
Chronic respiratory disease such as obstructive sleep apnea (OSA) and obesity-hypoventilation syndrome (OHS) remain are respiratory sleeping disorder that gradually affect quality of life. Comprehensive treatment such as the use of non-invasive ventilation (NIV) is a method adopted to improve the patient’s quality of life. The correct choice of NIV mode, mask and titration methods will provide optimal therapeutic effects to the patient. This article review lays out an update on the use of non-invasive ventilation as the treatment of OSA and OHS.
Comorbidity Of Mood Disorders And Upper Airway Resistance Syndrome: A Case Report, 2024 The University of Texas Rio Grande Valley School of Medicine
Comorbidity Of Mood Disorders And Upper Airway Resistance Syndrome: A Case Report, Abhishekh Pokhrel, Alexa Lissete Zarate, Alcides Amador
Research Colloquium
Background: The comorbidity of mood disorders and Upper Airway Resistance Syndrome (UARS) presents a significant challenge, especially in pediatric populations. UARS, characterized by increased upper airway resistance during sleep, often leads to disrupted sleep and daytime symptoms such as fatigue and cognitive impairment. Studies estimate UARS affects 15-30% of patients undergoing polysomnography for suspected sleep-disordered breathing. Mood & Anxiety Disorders are prevalent in patients with sleep-disordered breathing, with higher rates than in the general population.
Case Presentation: 16-year-old female, with psychiatric history of Bipolar II Disorder current episode depressed, ADHD, and Other Specified Anxiety Disorder presents for a follow-up. Since …
The Discover In-Hospital Cardiac Arrest (Discover Ihca) Study: An Investigation Of Hospital Practices After In-Hospital Cardiac Arrest, 2024 Montefiore Medical Center
The Discover In-Hospital Cardiac Arrest (Discover Ihca) Study: An Investigation Of Hospital Practices After In-Hospital Cardiac Arrest, Luke Andrea, Nathaniel S. Herman, Jacob Vine, Katherine M. Berg, Saiara Choudhury, Mariana Vaena, Jordan E. Nogle, Saleem M. Halablab, Aarthi Kaviyarasu, Jonathan Elmer, Gabriel Wardi, Alex K. Pearce, Conor Crowley, Micah T. Long, J. Taylor Herbert, Kipp Shipley, Brittany D. Bissell Turpin, Michael J. Lanspa, Adam Green, Shekhar A. Ghamande, Akram Khan, Siddharth Dugar, Aaron M. Joffe, Michael Baram, Cooper March, Nicholas J. Johnson, Alexander Reyes, Krassimir Denchev, Michael Loewe, Et Al
School of Medicine Faculty Publications
IMPORTANCE: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort. OBJECTIVES: Our study collects granular data on post-IHCA …
Pleural Effusions In Patients Diagnosed With Pneumonia In Urgent Care Clinics, 2024 Intermountain Health and the University of Utah School of Medicine
Pleural Effusions In Patients Diagnosed With Pneumonia In Urgent Care Clinics, Nathan C. Dean, Jacqueline R. Eve, Allison M. Butler, James H. Hart, Theadora Sakata, Karen E. Connor, Edward A. Stenehjem, Y.C.G. Lee
The University of Louisville Journal of Respiratory Infections
Introduction: Pleural effusions in patients with community-acquired pneumonia have been associated with worse outcomes in emergency department and hospital inpatient populations, but the incidence of effusions and their outcomes in outpatient urgent care clinics is unknown. This observational cohort study describes patients diagnosed with pneumonia and pleural effusions on upright 2-view chest X-rays performed in urgent care clinics.
Methods: We extracted electronic health record data from January 2019 through December 2020 on all patients over 12 years old with an International Statistical Classification of Diseases 10th revision diagnosis of pneumonia entered by the treating clinician, plus “possible” or “likely” …
Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement, 2024 The Texas Medical Center Library
Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith
Faculty, Staff and Student Publications
Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …
The Discover In-Hospital Cardiac Arrest (Discover Ihca) Study: An Investigation Of Hospital Practices After In-Hospital Cardiac Arrest, 2024 Thomas Jefferson University
The Discover In-Hospital Cardiac Arrest (Discover Ihca) Study: An Investigation Of Hospital Practices After In-Hospital Cardiac Arrest, Luke Andrea, Nathaniel S Herman, Jacob Vine, Katherine M Berg, Saiara Choudhury, Mariana Vaena, Jordan E Nogle, Saleem M Halablab, Aarthi Kaviyarasu, Jonathan Elmer, Gabriel Wardi, Alex K Pearce, Conor Crowley, Micah T Long, J Taylor Herbert, Kipp Shipley, Brittany D Bissell Turpin, Michael J Lanspa, Adam Green, Shekhar A Ghamande, Akram Khan, Siddharth Dugar, Aaron M Joffe, Michael Baram, Cooper March, Nicholas J Johnson, Alexander Reyes, Krassimir Denchev, Michael Loewe, Ari Moskowitz
Division of Pulmonary and Critical Care Medicine Faculty Papers
IMPORTANCE: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort.
OBJECTIVES: Our study collects granular data on post-IHCA …
Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, 2024 The Texas Medical Center Library
Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon
Faculty, Staff and Student Publications
Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …
A 72-Year-Old Man With Acute Lung Injury And Anti-Melanoma Differentiation-Associated Gene 5 Antibody: A Case Report, 2024 Jefferson Einstein Hospital
A 72-Year-Old Man With Acute Lung Injury And Anti-Melanoma Differentiation-Associated Gene 5 Antibody: A Case Report, Irakli Lemonjava, Jose Manuel Martinez Manzano, Sahar Sultan, Rekha Bhat, Corrado Minimo, Zurab Azmaiparashvili, Sadia Benzaquen
Einstein Health Papers
Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA-5 Ab) is associated with amyopathic dermatomyositis (DM). These patients are particularly at high-risk for developing acute and rapidly progressive interstitial lung disease (ILD). Given the lack of muscle-related symptoms, along with its sudden onset and rapid clinical progression, the diagnosis of anti-MDA-5 Ab + ILD represents a challenge for clinicians. Even after the diagnosis is established, prognosis remains dismal owing to a hyperinflammatory state, mimicking cytokine storm, commonly refractory to potent immunosuppressive therapy. Hence, we present an elderly African American man who developed acute and rapidly progressive ILD in the setting of positive anti-MDA5 …
Lung Cell Transplantation For Pulmonary Fibrosis, 2024 The Texas Medical Center Library
Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner
Faculty, Staff and Student Publications
Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …
Results Of A Prospective Trial To Evaluate Novel Lung Function Imaging For Lung Cancer Surgery, 2024 Thomas Jefferson University
Results Of A Prospective Trial To Evaluate Novel Lung Function Imaging For Lung Cancer Surgery, Lydia J. Wilson, Phd, Richard Castillo, Phd, Edward Castillo, Phd, Bernard Jones, Phd, Moyed Miften, Phd, Lindsey Olsen, Phd, Vikas Aragam, Phd, Robert A. Meguid, Md, Mph, Crystal J. Erickson, Md, Amanda Young, Msn, Matthew Blum, Md, Tyler Grenda, Md, Julie Barta, Md, Benjamin Leiby, Phd, Timothy Waxweiler, Md, Brian Kavanagh, Md, Mph, John D. Mitchell, Md, Yevgeniy Vinogradskiy, Phd
Department of Radiation Oncology Posters
Background
- Surgery is the primary form of definitive treatment for early-stage lung cancer.
- Poor lung function before surgery places patients at high risk of pulmonary complications after resection.
- Surgeons evaluate patient fitness for surgery using pulmonary function tests (PFTs) to calculate the predicted postoperative PFT (ppoPFT).
- Conventional ppoPFT calculations assume homogeneous lung function, which can be inaccurate.
- 4DCT-ventilation is a novel lung function imaging modality developed in radiation oncology that uses 4DCT data to calculate high-resolution ventilation maps.
A Follow-Up To Implementing A Sizing Chart For Nasal Cannula Placement To Decrease Associated Pressure Ulcers In Infants, 2024 Thomas Jefferson University Hospital
A Follow-Up To Implementing A Sizing Chart For Nasal Cannula Placement To Decrease Associated Pressure Ulcers In Infants, William F. Bucher, Rrt-Nps
Division of Pulmonary and Critical Care Medicine Posters
Background
The Joint commission definition of a “Pressure Ulcer” is a broader term that includes decubitus ulcers, but also includes any ulcerations associated with pressure. In 2015, over a three-month period, the Intensive Care Nursery (ICN) at Thomas Jefferson University Hospital had five patients who developed pressure ulcers due to placement of an improper size nasal cannula being used for that patient. Infant nasal cannulas are typically classified as being for micro premature, premature, neonate, infant, and intermediate infant size patients. To this day, there is no instruction by most manufactures for fitting a nasal cannula to the actual size …
Epigenome-Wide Association Study Of Prostate Cancer In African American Men Identified Differentially Methylated Genes, 2024 Moffitt Cancer Center
Epigenome-Wide Association Study Of Prostate Cancer In African American Men Identified Differentially Methylated Genes, Anders Berglund, Kosj Yamoah, Steven A. Eschrich, Rana Falahat, James J. Mulé, Sungjune Kim, Jaime Matta, Julie Dutil, Gilberto Ruiz-Deya, Carmen Ortiz Sanchez, Liang Wang, Hyun Park, Hirendra N. Banerjee, Tamara Lotan, Kathryn Hughes Barry, Ryan M. Putney, Seung Joon Kim, Clement Gwede, Jacob K. Kresovich, Youngchul Kim, Hui Yi Lin, Jasreman Dhillon, Ratna Chakrabarti, Jong Y. Park
School of Public Health Faculty Publications
Introduction: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results: Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected …
Effects Of E-Cigarettes On The Lung And Systemic Metabolome In People With Hiv, 2024 LSU Health Sciences Center - New Orleans
Effects Of E-Cigarettes On The Lung And Systemic Metabolome In People With Hiv, Aline Zaparte, Courtney J. Christopher, Connie Arnold, Lauren Richey, Adairre Castille, Kyle Mistretta, Christopher M. Taylor, Huiyi Lin, Steve Nelson, John P. Kirwan, John W. Apolzan, Shawn R. Campagna, David A. Welsh
School of Medicine Faculty Publications
The popularity of e-cigarettes (vaping) has soared, creating a public health crisis among teens and young adults. Chronic vaping can induce gut inflammation and reduce intestinal barrier function through the production of the proinflammatory molecule hydrogen sulfide (H2S). This is particularly concerning for people with HIV (PWH) as they already face impaired immune function and are at a higher risk for metabolic dysregulation, diabetes, and chronic liver disease. Furthermore, PWH experience unhealthy behaviors, making it crucial to understand the systemic metabolic dysregulation and pathophysiological mechanisms associated with vaping in this population. Here, we employed liquid chromatography–mass spectrometry (LC-MS)-based metabolomics to …