Article
Genetics & Heredity
Yuliya Voskobiynyk, Gopal Battu, Stephanie A. Felker, J. Nicholas Cochran, Megan P. Newton, Laura J. Lambert, Robert A. Kesterson, Richard M. Myers, Gregory M. Cooper, Erik D. Roberson, Gregory S. Barsh
Summary: Dravet syndrome is a neurological disorder caused by mutations in the SCN1A gene, leading to decreased expression of the Na(v)1.1 sodium channel. Studies suggest that these mutations may disrupt normal splicing patterns, resulting in reduced channel expression and epilepsy-related pathophysiology.
Editorial Material
Medicine, Research & Experimental
Stephen C. Cannon
Summary: Loss-of-function mutations in SCN1A gene can cause Dravet syndrome (DS) by affecting Na(V)1.1 sodium channel subunit. This study demonstrates that deficiency of NEDD8 neddylation in inhibitory interneurons leads to a DS-like phenotype, suggesting a new pathomechanism for epileptic sodium channelopathy involving stabilization of Na(V)1.1 subunits by NEDD8.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Cell Biology
Eric Shao, Che-Wei Chang, Zhiyong Li, Xinxing Yu, Kaitlyn Ho, Michelle Zhang, Xin Wang, Jeffrey Simms, Iris Lo, Jessica Speckart, Julia Holtzman, Gui-Qiu Yu, Erik D. Roberson, Lennart Mucke
Summary: This study found that reducing TAU in excitatory neurons can alleviate various brain dysfunctions, including epilepsy and overactivation of the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway, in a mouse model of Dravet syndrome. Additionally, treatment with a TAU-lowering antisense oligonucleotide had similar therapeutic effects.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Clinical Neurology
Jiangwei Ding, Lei Wang, Zhe Jin, Yuanyuan Qiang, Wenchao Li, Yangyang Wang, Changliang Zhu, Shucai Jiang, Lifei Xiao, Xiaoyan Hao, Xulei Hu, Xinxiao Li, Feng Wang, Tao Sun
Summary: This study aimed to identify genes other than SCN1A that may cause DS or DS-like phenotypes. A comprehensive search of relevant studies was conducted, and a total of 29 studies met the inclusion criteria. The results suggest that various genes including PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, and STXBP1 may be involved in DS or DS-like phenotypes.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer A. Kearney, Letonia D. Copeland-Hardin, Samantha Duarte, Nicole A. Zachwieja, Isaiah K. Eckart-Frank, Nicole A. Hawkins
Summary: Pathogenic variants in SCN1A gene can result in different clinical phenotypes, and the severity is influenced by other genetic modifiers. The study found that disease severity is associated with the type of mutation, mode of inheritance, and genetic modifier factors.
Article
Medicine, General & Internal
Yongning Jiang, Xiangqin Zhou
Summary: This study analyzed the onset, clinical features, and EEG characteristics of myoclonic epilepsy in infancy (MEI). The study found that the onset of MEI can manifest as either atypical or typical seizures, but there were no significant differences in clinical or EEG features between the two groups. All patients were successfully treated with valproic acid monotherapy, and had normal psychomotor development at the end of the follow-up period.
Article
Neurosciences
Chunhong Chen, Fang Fang, Xu Wang, Junlan Lv, Xiaohui Wang, Hong Jin
Summary: This study aims to explore the phenotypic characteristics of SCN1A-associated seizure diseases and establish genotype-phenotype correlations. The clinical data of 41 patients carrying SCN1A variants were retrospectively analyzed. The study found that SCN1A variants result in diverse phenotypes, with both commonalities and individualistic differences. Factors such as age of seizure onset, type of seizures, duration, and variant location contribute to the phenotypic variations.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Saja Fadila, Bertrand Beucher, Iria Gonzalez Dopeso-Reyes, Anat Mavashov, Marina Brusel, Karen Anderson, Caroline Ismeurt, Ethan M. Goldberg, Ana Ricobaraza, Ruben Hernandez-Alcoceba, Eric J. Kremer, Moran Rubinstein
Summary: DS, a severe childhood epileptic encephalopathy caused by SCN1A mutations, has limited pharmaceutical treatment options. Delivery of a modified SCN1A gene into the brain improved DS comorbidities and showed potential as a therapeutic approach for infants and adolescents with DS-associated comorbidities.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Clinical Neurology
Phoebe Makiello, Tony Feng, Benjamin Dunwoody, Felix Steckler, Joseph Symonds, Sameer M. Zuberi, Liam Dorris, Andreas Brunklaus
Summary: This study investigated long-term predictors of health-related quality of life (HRQOL) in patients with Dravet syndrome (DS) and found that younger patients showed a significant decline in HRQOL and the use of sodium channel blockers negatively impacted long-term HRQOL.
Article
Medicine, Research & Experimental
Wenbing Chen, Bin Luo, Nannan Gao, Haiwen Li, Hongsheng Wang, Lei Li, Wanpeng Cui, Lei Zhang, Dong Sun, Fang Liu, Zhaoqi Dong, Xiao Ren, Hongsheng Zhang, Huabo Su, Wen-Cheng Xiong, Lin Mei
Summary: The study reveals that neddylation is critical for the stability of Na(v)1.1 in interneurons, impacting their excitability and potentially contributing to epilepsy. Deletion of Nae1 reduces Na(v)1.1 stability and increases network excitability, leading to seizures in mice. The findings highlight a new mechanism in the pathogenesis of epilepsy involving neddylation of Na(v)1.1.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Behavioral Sciences
Ellie Chilcott, Juan Antinao Diaz, Cori Bertram, Margherita Berti, Rajvinder Karda
Summary: Dravet Syndrome is a genetic epileptic syndrome characterized by severe seizures and cognitive impairments. Genetic therapy is considered a promising alternative for treatment, including gene supplementation, CRISPR-mediated transcriptional activation, and the use of antisense oligonucleotides.
EPILEPSY & BEHAVIOR
(2022)
Article
Multidisciplinary Sciences
Salima El Chehadeh, Kyung Ah Han, Dongwook Kim, Gyubin Jang, Somayeh Bakhtiari, Dongseok Lim, Hee Young Kim, Jinhu Kim, Hyeonho Kim, Julia Wynn, Wendy K. Chung, Giuseppina Vitiello, Ioana Cutcutache, Matthew Page, Jozef Gecz, Kelly Harper, Ah-Reum Han, Ho Min Kim, Marja Wessels, Allan Bayat, Alberto Fernandez Jaen, Angelo Selicorni, Silvia Maitz, Arjan P. M. de Brouwer, Anneke Vulto-van Silfhout, Martin Armstrong, Joseph Symonds, Sebastien Kury, Bertrand Isidor, Benjamin Cogne, Mathilde Nizon, Claire Feger, Jean Muller, Erin Torti, Dorothy K. Grange, Marjolaine Willems, Michael C. Kruer, Jaewon Ko, Amelie Piton, Ji Won Um
Summary: This study demonstrates the importance of SLITRK2 protein in synaptic communication and identifies X-linked variants of SLITRK2 that lead to neurodevelopmental disorders by impairing excitatory synapses.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ieva Keraite, Philipp Becker, Davide Canevazzi, Cristina Frias-Lopez, Marc Dabad, Raul Tonda-Hernandez, Ida Paramonov, Matthew John Ingham, Isabelle Brun-Heath, Jordi Leno, Anna Abuli, Elena Garcia-Arumi, Simon Charles Heath, Marta Gut, Ivo Glynne Gut
Summary: Accurate analysis of mitochondrial DNA is crucial for clinical research and diagnostics of mitochondrial diseases. This study presents a method that utilizes Cas9 cleavage, nanopore sequencing, and a custom pipeline to identify pathogenic variants and accurately quantify heteroplasmy. The authors demonstrate that their method is capable of detecting complex deletions, determining the phase of variants, and achieving high coverage of the mitochondrial genome, overcoming the limitations of short-read sequencing. The developed workflow provides a powerful tool for studying mtDNA variation and will greatly accelerate mitochondrial research.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
George A. Zographos, Sophie J. Russ-Hall, Ingrid E. Scheffer
Summary: Although anti-seizure medications that block sodium channels are generally not recommended for Dravet syndrome, there is ongoing debate about the use of the sodium-channel blocker phenytoin, which is commonly used to treat status epilepticus in Dravet syndrome patients. This study reports four cases of Dravet syndrome patients who experienced a reduction in seizure frequency and duration with long-term phenytoin therapy. In two patients, phenytoin resulted in prolonged periods without status epilepticus for the first time. Attempts to discontinue phenytoin in all patients after 1 to 20 years of use led to worsened seizure control. Reintroducing phenytoin improved seizure control, suggesting its potential benefits in certain Dravet syndrome patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Clinical Neurology
Katherine B. Howell, Jeremy L. Freeman, Mark T. Mackay, Michael C. Fahey, John Archer, Samuel F. Berkovic, Eunice Chan, Gabriel Dabscheck, Stefanie Eggers, Michael Hayman, James Holberton, Rodney W. Hunt, Susan E. Jacobs, Andrew J. Kornberg, Richard J. Leventer, Simone Mandelstam, Jacinta M. McMahon, Heather C. Mefford, Julie Panetta, Jessica Riseley, Victoria Rodriguez-Casero, Monique M. Ryan, Amy L. Schneider, Lindsay J. Smith, Zornitza Stark, Flora Wong, Eppie M. Yiu, Ingrid E. Scheffer, A. Simon Harvey
Summary: The study found that West syndrome and West syndrome-like epilepsy are the most common epilepsy syndromes among severe epilepsies of infancy, while the incidence of epilepsy of infancy and early infantile epileptic encephalopathy is lower. Most infants showed delayed or borderline development before the age of 2, with a small percentage of infants dying before the age of 2.
Article
Radiology, Nuclear Medicine & Medical Imaging
Andrew Thornton, Francesco Fraioli, Simon Wan, Helen S. Garthwaite, Balaji Ganeshan, Robert I. Shortman, Raymond Endozo, Stefan Voo, Irfan Kayani, Deena Neriman, Leon Menezes, Jamshed Bomanji, Toby Hilllman, Melissa Heightman, Joanna C. Porter, Ashley M. Groves
Summary: This study aimed to assess the temporal evolution of pulmonary F-18-FDG uptake in patients with COVID-19 and PCLD. The findings indicated that in acute COVID-19, pulmonary F-18-FDG uptake increased with time after infection, while in PCLD patients treated with steroids showed lower uptake.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Editorial Material
Respiratory System
Emma K. Denneny, Joanna C. Porter
Article
Immunology
Deborah L. W. Chong, Carine Rebeyrol, Ricardo J. Jose, Andrew E. Williams, Jeremy S. Brown, Chris J. Scotton, Joanna C. Porter
Summary: Neutrophil migration into the lung is mediated by cell adhesion molecules such as ICAM-1 and ICAM-2, which are upregulated during inflammatory stimulation. While beta(2) integrins interacting with ICAMs may regulate neutrophil traffic in healthy lung, these interactions may become redundant later in inflammation when epithelial junctions are disrupted.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Respiratory System
Jim M. Wild, Joanna C. Porter, Philip L. Molyneaux, Peter M. George, Iain Stewart, Richard James Allen, Raminder Aul, John Kenneth Baillie, Shaney L. Barratt, Paul Beirne, Stephen M. Bianchi, John F. Blaikley, Jonathan Brooke, Nazia Chaudhuri, Guilhem Collier, Emma K. Denneny, Annemarie Docherty, Laura Fabbri, Michael A. Gibbons, Fergus Gleeson, Bibek Gooptu, Ian P. Hall, Neil A. Hanley, Melissa Heightman, Toby E. Hillman, Simon R. Johnson, Mark G. Jones, Fasihul Khan, Rod Lawson, Puja Mehta, Jane A. Mitchell, Manuela Plate, Krisnah Poinasamy, Jennifer K. Quint, Pilar Rivera-Ortega, Malcolm Semple, A. John Simpson, D. J. F. Smith, Mark Spears, Lisa G. Spencer, Stefan C. Stanel, David R. Thickett, A. A. Roger Thompson, Simon L. F. Walsh, Nicholas D. Weatherley, Mark Everard Weeks, Dan G. Wootton, Chris E. Brightling, Rachel C. Chambers, Ling-Pei Ho, Joseph Jacob, Karen Piper Hanley, Louise Wain, R. Gisli Jenkins
Summary: The study will conduct longitudinal observational studies on patients with suspected ILD following COVID-19 to determine the prevalence of ILD at 12 months post-infection. Additional studies will focus on factors that determine the trajectory of recovery or progression of ILD. The results will be disseminated through peer-reviewed journals to establish the extent and consequences of LC-ILD and enable strategies to mitigate progression.
BMJ OPEN RESPIRATORY RESEARCH
(2021)
Letter
Respiratory System
Joanna C. Porter, Thida Win, Kjell Erlandsson, Kris Thielemans, Ashley M. Groves
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Critical Care Medicine
Benjamin A. Fisher, Tonny Veenith, Daniel Slade, Charlotte Gaskell, Matthew Rowland, Tony Whitehouse, James Scriven, Dhruv Parekh, Madhu S. Balasubramaniam, Graham Cooke, Nick Morley, Zoe Gabriel, Matthew P. Wise, Joanna Porter, Helen McShane, Ling-Pei Ho, Philip N. Newsome, Anna Rowe, Rowena Sharpe, David R. Thickett, Julian Bion, Simon Gates, Duncan Richards, Pamela Kearns
Summary: This study aimed to evaluate the efficacy of two drugs in hospitalized patients with COVID-19. The results showed that namilumab was able to reduce the inflammatory response, while infliximab did not show significant efficacy compared to usual care. Although there were some differences in adverse events and mortality rates, these differences were not significant.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Critical Care Medicine
Rachael A. Evans, Hamish McAuley, Ewen M. Harrison, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Omer Elneima, Annemarie B. Docherty, Nazir Lone, Olivia C. Leavy, Luke Daines, J. Kenneth Baillie, Jeremy S. Brown, Trudie Chalder, Anthony De Soyza, Nawar Diar Bakerly, Nicholas Easom, John R. Geddes, Neil J. Greening, Nick Hart, Liam G. Heaney, Simon Heller, Luke Howard, John R. Hurst, Joseph Jacob, R. Gisli Jenkins, Caroline Jolley, Steven Kerr, Onn M. Kon, Keir Lewis, Janet M. Lord, Gerry P. McCann, Stefan Neubauer, Peter J. M. Openshaw, Dhruv Parekh, Paul Pfeffer, Najib M. Rahman, Betty Raman, Matthew Richardson, Matthew Rowland, Malcolm G. Semple, Ajay M. Shah, Sally J. Singh, Aziz Sheikh, David Thomas, Mark Toshner, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Louise Wain, Christopher E. Brightling
Summary: The study aimed to understand the impact of COVID-19-related hospitalization on health and employment, identify factors associated with recovery, and describe recovery phenotypes. Findings revealed that some patients did not fully recover six months after discharge, with factors such as female sex, middle age, comorbidities, and severe illness contributing to difficulties in recovery. The study also identified four different recovery phenotypes.
LANCET RESPIRATORY MEDICINE
(2021)
Article
Critical Care Medicine
Iain Stewart, Joseph Jacob, Peter M. George, Philip L. Molyneaux, Joanna C. Porter, Richard J. Allen, Shahab Aslani, J. Kenneth Baillie, Shaney L. Barratt, Paul Beirne, Stephen M. Bianchi, John F. Blaikley, James D. Chalmers, Rachel C. Chambers, Nazia Chadhuri, Christopher Coleman, Guilhem Collier, Emma K. Denneny, Annemarie Docherty, Omer Elneima, Rachael A. Evans, Laura Fabbri, Michael A. Gibbons, Fergus Gleeson, Bibek Gooptu, Neil J. Greening, Beatriz Guillen Guio, Ian P. Hall, Neil A. Hanley, Victoria Harris, Ewen M. Harrison, Melissa Heightman, Toby E. Hillman, Alex Horsley, Linzy Houchen-Wolloff, Ian Jarrold, Simon R. Johnson, Mark G. Jones, Fasihul Khan, Rod Lawson, Olivia Leavy, Nazir Lone, Michael Marks, Hamish McAuley, Puja Mehta, Dhruv Parekh, Karen Piper Hanley, Manuela Plate, John Pearl, Krisnah Poinasamy, Jennifer K. Quint, Betty Raman, Matthew Richardson, Pilar Rivera-Ortega, Laura Saunders, Ruth Saunders, Malcolm G. Semple, Marco Sereno, Aarti Shikotra, A. John Simpson, Amisha Singapuri, David J. F. Smith, Mark Spears, Lisa G. Spencer, Stefan Stanel, David R. Thickett, A. A. Roger Thompson, Mathew Thorpe, Simon L. F. Walsh, Samantha Walker, Nicholas David Weatherley, Mark E. Weeks, Jim M. Wild, Dan G. Wootton, Chris E. Brightling, Ling-Pei Ho, Louise Wain, Gisli R. Jenkins
Summary: This study analyzed the data from the UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study to estimate the prevalence of residual lung abnormalities in hospitalized COVID-19 patients. The results showed that approximately 11% of recovered COVID-19 patients had residual lung abnormalities, highlighting the need for long-term monitoring.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Physiology
Deborah L. W. Chong, Theresia A. Mikolasch, Jagdeep Sahota, Carine Rebeyrol, Helen S. Garthwaite, Helen L. Booth, Melissa Heightman, Emma K. Denneny, Ricardo J. Jose, Akif A. Khawaja, Anna Duckworth, Myriam Labelle, Chris J. Scotton, Joanna C. Porter
Summary: This study investigates the role of platelets and platelet-derived TGF beta 1 in idiopathic pulmonary fibrosis (IPF). The study found that elevated platelet counts are associated with increased mortality in IPF patients, but this observation was not confirmed in a validation cohort. Additionally, platelet-derived TGF beta 1 does not significantly mediate inflammation or fibrosis in a bleomycin-induced pulmonary fibrosis animal model.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Letter
Critical Care Medicine
Christopher E. Brightling, Rachael A. Evans, Amisha Singapuri, Nikki Smith, Louise Wain
LANCET RESPIRATORY MEDICINE
(2023)
Article
Critical Care Medicine
Betty Raman, Celeste McCracken, Mark P. Cassar, Alastair J. Moss, Lucy Finnigan, Azlan Helmy A. Samat, Godwin Ogbole, Elizabeth M. Tunnicliffe, Fidel Alfaro-Almagro, Ricarda Menke, Cheng Xie, Fergus Gleeson, Elena Lukaschuk, Hanan Lamlum, Kevin McGlynn, Iulia A. Popescu, Zeena-Britt Sanders, Laura Saunders, Stefan K. Piechnik, Vanessa M. Ferreira, Chrysovalantou Nikolaidou, Najib M. Rahman, Ling-Pei Ho, Victoria C. Harris, Aarti Shikotra, Amisha Singapuri, Paul Pfeffer, Charlotte Manisty, Onn Min Kon, Mark Beggs, Declan P. O'Regan, Jonathan Fuld, Jonathan R. Weir-McCall, Dhruv Parekh, Rick Steeds, Krisnah Poinasamy, Dan J. Cuthbertson, Graham J. Kemp, Malcolm G. Semple, Alexander Horsley, Christopher A. Miller, Caitlin O'Brien, Ajay M. Shah, Amedeo Chiribiri, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish J. C. McAuley, Marco Sereno, Ruth M. Saunders, Linzy Houchen-Wolloff, Neil J. Greening, Charlotte E. Bolton, Jeremy S. Brown, Gourab Choudhury, Nawar Diar Bakerly, Nicholas Easom, Carlos Echevarria, Michael Marks, John R. Hurst, Mark G. Jones, Daniel G. Wootton, Trudie Chalder, Melanie J. Davies, Anthony De Soyza, John R. Geddes, William Greenhalf, Luke S. Howard, Joseph Jacob, William D-C Man, Peter J. M. Openshaw, Joanna C. Porter, Matthew J. Rowland, Janet T. Scott, Sally J. Singh, David C. Thomas, Mark Toshner, Keir Lewis, Liam G. Heaney, Ewen M. Harrison, Steven Kerr, Annemarie B. Docherty, Nazir I. Lone, Jennifer K. Quint, Aziz Sheikh, Bang Zheng, Gisli Jenkins, Eleanor F. Cox, Susan Francis, Mark Halling-Brown, James D. Chalmers, John P. Greenwood, Sven Plein, Paul J. C. Hughes, A. A. Roger Thompson, Sarah Rowland-Jones, James M. Wild, Matthew Kelly, Thomas A. Treibel, Steven Bandula, Raminder Aul, Karla Miller, Peter Jezzard, Stephen Smith, Thomas E. Nichols, Gerry P. McCann, Rachael A. Evans, Louise V. Wain, Christopher E. Brightling, Stefan Neubauer
Summary: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. This study aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. The findings highlight the need for proactive multidisciplinary care pathways with imaging playing a potential role in guiding surveillance and treatment strategies.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Health Care Sciences & Services
Malik A. Althobiani, Yatharth Ranjan, Joseph Jacob, Michele Orini, Richard James Butler Dobson, Joanna C. Porter, John R. Hurst, Amos A. Folarin
Summary: This study investigated the feasibility and acceptability of remote monitoring for patients with chronic respiratory diseases using wearable technology, home-based spirometers, finger pulse oximeters, and smartphone apps. The results showed that low-burden passive data collection methods had better adherence, engagement, and retention compared to active data collection methods. The study provides valuable insights for long-term remote monitoring in respiratory disease management.
JMIR FORMATIVE RESEARCH
(2023)
Letter
Respiratory System
Emma K. Denneny, Helen S. Garthwaite, Melissa J. Heightman, Joanna C. Porter
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2021)
Article
Medicine, General & Internal
Peter W. Horby, Martin J. Landray
Summary: Tocilizumab improved survival and other clinical outcomes in hospitalized COVID-19 patients with hypoxia and systemic inflammation, regardless of the level of respiratory support, and provided additional benefits on top of systemic corticosteroid therapy.
Article
Respiratory System
Swapna Mandal, Joseph Barnett, Simon E. Brill, Jeremy S. Brown, Emma K. Denneny, Samanjit S. Hare, Melissa Heightman, Toby E. Hillman, Joseph Jacob, Hannah C. Jarvis, Marc C. Lipman, Sindhu B. Naidu, Arjun Nair, Joanna C. Porter, Gillian S. Tomlinson, John R. Hurst
Summary: Following discharge from hospital, a significant number of COVID-19 patients continue to experience persistent symptoms such as breathlessness, cough, fatigue, and depression. Some patients also show elevated levels of biomarkers indicating ongoing health issues. Chest radiographs reveal abnormalities in a considerable portion of patients, with a small percentage showing deterioration.