tbuckley/cabot-search huggingface dataset:
TREATMENT PATTERNS IN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE PATIENTS WITH HYPERCHOLESTEROLEMIA (ASCVD-H) AND PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA (FH), A RETROSPECTIVE DATABASE COHORT STUDY IN THE US
Authors: Raquel Lahoz, Divyagiri Seshagiri, Assya Achouba, Batul Electriwala, Yingjie Ding, Ji Haeng Heo, Rachel Studer
Journal: Journal of the American College of Cardiology (2021)
SIGNIFICANT ETHNIC DIFFERENCES IN PREVALENCE, CARDIAC MANIFESTATIONS AND MORTALITY IN PATIENTS WITH MODERATE TO SEVERE COVID-19 BETWEEN MIDDLE EASTERN ARABS AND SOUTH ASIAN ETHNICITY
Authors: Fahad Alkindi, Maather Alabri, Maryam Alissaii, Shihab Alkindi, Tasneem Alrashdi, Salma Alharthi, Muzna Alfarsi, Khalid Alsaidi, Adil Alghafri, Sultan Allawati, Shabib Alasmi, Khamis Alhashmi, Sathiya Murthui, Sunil K Nadar, Hilal Alsabti
Journal: Journal of the American College of Cardiology (2021)
Relationship between heart failure and the risk of acute exacerbation of COPD
Authors: Eleanor L Axson, Alex Bottle, Martin R Cowie, Jennifer K Quint
Journal: Thorax (2021)

Rationale Heart failure (HF) management in chronic obstructive pulmonary disease (COPD) is often delayed or suboptimal. Objectives To examine the effect of HF and HF medication use on moderate-to-severe COPD exacerbations. Methods and measurements Retrospective cohort studies from 2006 to 2016 using nationally representative English primary care electronic healthcare records linked to national hospital and mortality data. Patients with COPD with diagnosed and possible HF were identified. Possible HF was defined as continuous loop diuretic use in the absence of a non-cardiac indication. Incident exposure to HF medications was defined as ≥2 prescriptions within 90 days with no gaps &gt;90 days during ≤6 months of continuous use; prevalent exposure as 6+ months of continuous use. HF medications investigated were angiotensin receptor blockers, ACE inhibitors, beta-blockers, loop diuretics and mineralocorticoid receptor antagonists. Cox regression, stratified by sex and age, further adjusted for patient characteristics, was used to determine the association of HF with exacerbation risk. Main results 86 795 patients with COPD were categorised as no evidence of HF (n=60 047), possible HF (n=8476) and newly diagnosed HF (n=2066). Newly diagnosed HF (adjusted HR (aHR): 1.45, 95% CI: 1.30 to 1.62) and possible HF (aHR: 1.65, 95% CI: 1.58 to 1.72) similarly increased exacerbation risk. Incident and prevalent use of all HF medications were associated with increased exacerbation risk. Prevalent use was associated with reduced exacerbation risk compared with incident use. Conclusions Earlier opportunities to improve the diagnosis and management of HF in the COPD population are missed. Managing HF may reduce exacerbation risk in the long term.
Abstract 13367: Hemodynamic Determinants of Tricuspid Annular Pulmonary Systolic Excursion (tapse)/ Systolic Pulmonary Arterial Pressure (spap) Ratio in Heart Failure With Reduced Ejection Fraction
Authors: Francesco Bandera, Greta Ghizzardi, Mauro Agnifili, Samuele Pizzocri, Sara Boveri, Eleonora Alfonzetti, Massimo Saviano, Giacomo D’Alesio, Francesco Badogni, Marco Guazzi
Journal: Circulation (2019)

Introduction: The TAPSE/SPAP ratio has gained a role as an easy-to-use surrogate of right ventricle-to-pulmonary circulation (RV-PC) coupling, showing a strong prognostic significance in heart fail...
Flexible Wearable Sensors for Cardiovascular Health Monitoring
Authors: Shuwen Chen, Jiaming Qi, Shicheng Fan, Zheng Qiao, Joo Chuan Yeo, Chwee Teck Lim
Journal: Advanced Healthcare Materials (2021)

Abstract Cardiovascular diseases account for the highest mortality globally, but recent advances in wearable technologies may potentially change how these illnesses are diagnosed and managed. In particular, continuous monitoring of cardiovascular vital signs for early intervention is highly desired. To this end, flexible wearable sensors that can be comfortably worn over long durations are gaining significant attention. In this review, advanced flexible wearable sensors for monitoring cardiovascular vital signals are outlined and discussed. Specifically, the functional materials, configurations, mechanisms, and recent advances of these flexible sensors for heart rate, blood pressure, blood oxygen saturation, and blood glucose monitoring are highlighted. Different mechanisms in bioelectric, mechano‐electric, optoelectric, and ultrasonic wearable sensors are presented to monitor cardiovascular vital signs from different body locations. Present challenges, possible strategies, and future directions of these wearable sensors are also discussed. With rapid development, these flexible wearable sensors will potentially be applicable for both medical diagnosis and daily healthcare use in tackling cardiovascular diseases.
Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length
Authors: Claire F McGroder, David Zhang, Mohammad A Choudhury, Mary M Salvatore, Belinda M D'Souza, Eric A Hoffman, Ying Wei, Matthew R Baldwin, Christine Kim Garcia
Journal: Thorax (2021)

The risk factors for development of fibrotic-like radiographic abnormalities after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalisation remains unclear. At 4 months after hospitalisation, fibrotic-like patterns were more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission and leucocyte telomere length are independent risk factors for fibrotic-like radiographic abnormalities. These fibrotic-like changes correlate with lung function, cough and measures of frailty, but not with dyspnoea.
Hepatic Small Ubiquitin‐Related Modifier (SUMO)–Specific Protease 2 Controls Systemic Metabolism Through SUMOylation‐Dependent Regulation of Liver–Adipose Tissue Crosstalk
Authors: Yang Liu, Xin Dou, Wei‐yu Zhou, Meng Ding, Ling Liu, Ruo‐qi Du, Liang Guo, Shu‐wen Qian, Yan Tang, Qi‐qi Yang, Dong‐ning Pan, Xiao‐ying Li, Yan Lu, Jin‐ke Cheng, Qi‐qun Tang
Journal: Hepatology (2021)

Background and Aims NAFLD, characterized by aberrant triglyceride accumulation in liver, affects the metabolic remodeling of hepatic and nonhepatic tissues by secreting altered hepatokines. Small ubiquitin‐related modifier (SUMO)–specific protease 2 (SENP2) is responsible for de‐SUMOylation of target protein, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic metabolism remains unclear. Approach and Results We found that SENP2 was the most dramatically increased SENP in the fatty liver and that its level was modulated by fed/fasted conditions. To define the role of hepatic SENP2 in metabolic regulation, we generated liver‐specific SENP2 knockout (Senp2‐LKO) mice. Senp2‐LKO mice exhibited resistance to high‐fat diet–induced hepatic steatosis and obesity. RNA‐sequencing analysis showed that Senp2 deficiency up‐regulated genes involved in fatty acid oxidation and down‐regulated genes in lipogenesis in the liver. Additionally, ablation of hepatic SENP2 activated thermogenesis of adipose tissues. Improved energy homeostasis of both the liver and adipose tissues by SENP2 disruption prompted us to detect the hepatokines, with FGF21 identified as a key factor markedly elevated in Senp2‐LKO mice that maintained metabolic homeostasis. Loss of FGF21 obviously reversed the positive effects of SENP2 deficiency on metabolism. Mechanistically, by screening transcriptional factors of FGF21, peroxisome proliferator–activated receptor alpha (PPARα) was defined as the mediator for SENP2 and FGF21. SENP2 interacted with PPARα and deSUMOylated it, thereby promoting ubiquitylation and subsequent degradation of PPARα, which in turn inhibited FGF21 expression and fatty acid oxidation. Consistently, SENP2 overexpression in liver facilitated development of metabolic disorders. Conclusions Our finding demonstrated a key role of hepatic SENP2 in governing metabolic balance by regulating liver–adipose tissue crosstalk, linking the SUMOylation process to metabolic regulation.
Classifying Motion Intention of Step Length and Synchronous Walking Speed by Functional Near-Infrared Spectroscopy
Authors: Yufei Zhu, Chunguang Li, Hedian Jin, Lining Sun
Journal: Cyborg and Bionic Systems (2021)

In some patients who have suffered an amputation or spinal cord injury, walking ability may be degraded or deteriorated. Helping these patients walk independently on their own initiative is of great significance. This paper proposes a method to identify subjects’ motion intention under different levels of step length and synchronous walking speed by using functional near-infrared spectroscopy technology. Thirty-one healthy subjects were recruited to walk under six given sets of gait parameters (small step with low/midspeed, midstep with low/mid/high speed, and large step with midspeed). The channels were subdivided into more regions. More frequency bands (6 subbands on average in the range of 0-0.18 Hz) were decomposed by applying the wavelet packet method. Further, a genetic algorithm and a library for support vector machine algorithm were applied for selecting typical feature vectors, which were represented by important regions with partial important channels mentioned above. The walking speed recognition rate was 71.21% in different step length states, and the step length recognition rate was 71.21% in different walking speed states. This study explores the method of identifying motion intention in two-dimensional multivariate states. It lays the foundation for controlling walking-assistance equipment adaptively based on cerebral hemoglobin information.
LOW-HARM score predicted mortality in patients hospitalized with COVID-19 in Mexico
Authors: Michelle D. Kelsey, Christopher B. Granger
Journal: Annals of Internal Medicine (2021)

Source CitationSoto-Mota A, Marfil-Garza BA, Martinez Rodriguez E, et al. The low-harm score for predicting mortality in patients diagnosed with COVID-19: a multicentric validation study. J Am Coll Emerg Physicians Open. 2020;1:1436-43. https://pubmed.ncbi.nlm.nih.gov/33230506/AbstractClinical Impact RatingsHospitalists: Infectious Disease: Critical Care:
LEFT ATRIAL APPENDAGE CLOSURE IN PATIENTS WITH PRIOR FAILED ATTEMPT AT WATCHMAN 2.5 OR PROHIBITIVE APPENDAGE ANATOMY: INSIGHTS FROM THE PINNACLE FLX TRIAL
Authors: Gregory Jackson, Christopher Ellis, Arvindh Kanagasundram, Moussa Mansour, Brad Sutton, Vicki Houle, Saibal Kar, Shephal Doshi, Jose Osorio
Journal: Journal of the American College of Cardiology (2021)
CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope
Authors: Ania Skowera, Richard J. Ellis, Ruben Varela-Calviño, Sefina Arif, Guo Cai Huang, Cassie Van-Krinks, Anna Zaremba, Chloe Rackham, Jennifer S. Allen, Timothy I.M. Tree, Min Zhao, Colin M. Dayan, Andrew K. Sewell, Wendy W. Unger, Jan W. Drijfhout, Ferry Ossendorp, Bart O. Roep, Mark Peakman
Journal: Journal of Clinical Investigation (2009)
Identification and Molecular Characterization of Endothelial Cells Associated with Hematopoietic Niche Formation in Humans Identifies IL-33 As an Anabolic Niche Factor
Authors: Keane Jared Guillaume Kenswil, Christopher Adrian Jaramillo, Zhen Ping, Si Chen, Remco Michiel Hoogenboezem, Maria Athina Mylona, Maria Niken Adisty, Eric Moniqué Johannes Bindels, Hans Stoop, King Hong Lam, Pieter Koen Bos, Bram van Eerden, Tom Cupedo, Marc Hermanus Gerardus Petrus Raaijmakers
Journal: Blood (2017)
Anisotropic scaffolds for peripheral nerve and spinal cord regeneration
Authors: Wen Xue, Wen Shi, Yunfan Kong, Mitchell Kuss, Bin Duan
Journal: Bioactive Materials (2021)

The treatment of long-gap (>10 mm) peripheral nerve injury (PNI) and spinal cord injury (SCI) remains a continuous challenge due to limited native tissue regeneration capabilities. The current clinical strategy of using autografts for PNI suffers from a source shortage, while the pharmacological treatment for SCI presents dissatisfactory results. Tissue engineering, as an alternative, is a promising approach for regenerating peripheral nerves and spinal cords. Through providing a beneficial environment, a scaffold is the primary element in tissue engineering. In particular, scaffolds with anisotropic structures resembling the native extracellular matrix (ECM) can effectively guide neural outgrowth and reconnection. In this review, the anatomy of peripheral nerves and spinal cords, as well as current clinical treatments for PNI and SCI, is first summarized. An overview of the critical components in peripheral nerve and spinal cord tissue engineering and the current status of regeneration approaches are also discussed. Recent advances in the fabrication of anisotropic surface patterns, aligned fibrous substrates, and 3D hydrogel scaffolds, as well as their in vitro and in vivo effects are highlighted. Finally, we summarize potential mechanisms underlying the anisotropic architectures in orienting axonal and glial cell growth, along with their challenges and prospects.
Determination of complete chromosomal haplotypes by bulk DNA sequencing
Authors: Richard W. Tourdot, Gregory J. Brunette, Ricardo A. Pinto, Cheng-Zhong Zhang
Journal: Genome biology (2021)

Haplotype phase represents the collective genetic variation between homologous chromosomes and is an essential feature of non-haploid genomes. Here we describe a computational strategy to reliably determine complete whole-chromosome haplotypes using a combination of bulk long-range sequencing and Hi-C sequencing. We demonstrate that this strategy can resolve the haplotypes of parental chromosomes in diploid human genomes with high precision (>99%) and completeness (>98%) and assemble the syntenic structure of rearranged chromosomes in aneuploid cancer genomes at base pair level resolution. Our work enables direct interrogation of chromosome-specific alterations and chromatin reorganization using bulk DNA sequencing.
UTILIZATION AND COST OF GUIDELINE DIRECTED MEDICAL THERAPY (GDMT) FOR HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF) AMONG MEDICARE BENEFICIARIES: A MODEL-BASED ANALYSIS
Authors: Sonu Abraham, Yee Soo Kim, Anu Mariam Saji, Sachin Shah, Guy Kulbak, Sarju Ganatra, Sourbha Dani
Journal: Journal of the American College of Cardiology (2021)
Association Between Age at Diabetes Onset and Subsequent Risk of Dementia
Authors: Claudio Barbiellini Amidei, Aurore Fayosse, Julien Dumurgier, Marcos D. Machado-Fragua, Adam G. Tabak, Thomas van Sloten, Mika Kivimäki, Aline Dugravot, Séverine Sabia, Archana Singh-Manoux
Journal: JAMA (2021)

<h3>Importance</h3> Trends in type 2 diabetes show an increase in prevalence along with younger age of onset. While vascular complications of early-onset type 2 diabetes are known, the associations with dementia remains unclear. <h3>Objective</h3> To determine whether younger age at diabetes onset is more strongly associated with incidence of dementia. <h3>Design, Setting, and Participants</h3> Population-based study in the UK, the Whitehall II prospective cohort study, established in 1985-1988, with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013, and 2015-2016, and linkage to electronic health records until March 2019. The date of final follow-up was March 31, 2019. <h3>Exposures</h3> Type 2 diabetes, defined as a fasting blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed type 2 diabetes, use of diabetes medication, or hospital record of diabetes between 1985 and 2019. <h3>Main Outcomes and Measures</h3> Incident dementia ascertained through linkage to electronic health records. <h3>Results</h3> Among 10 095 participants (67.3% men; aged 35-55 years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.7 years. Dementia rates per 1000 person-years were 8.9 in participants without diabetes at age 70 years, and rates were 10.0 per 1000 person-years for participants with diabetes onset up to 5 years earlier, 13.0 for 6 to 10 years earlier, and 18.3 for more than 10 years earlier. In multivariable-adjusted analyses, compared with participants without diabetes at age 70, the hazard ratio (HR) of dementia in participants with diabetes onset more than 10 years earlier was 2.12 (95% CI, 1.50-3.00), 1.49 (95% CI, 0.95-2.32) for diabetes onset 6 to 10 years earlier, and 1.11 (95% CI, 0.70-1.76) for diabetes onset 5 years earlier or less; linear trend test (<i>P</i> &lt; .001) indicated a graded association between age at onset of type 2 diabetes and dementia. At age 70, every 5-year younger age at onset of type 2 diabetes was significantly associated with an HR of dementia of 1.24 (95% CI, 1.06-1.46) in analyses adjusted for sociodemographic factors, health behaviors, and health-related measures. <h3>Conclusions and Relevance</h3> In this longitudinal cohort study with a median follow-up of 31.7 years, younger age at onset of diabetes was significantly associated with higher risk of subsequent dementia.
The role of microRNAs in the osteogenic and chondrogenic differentiation of mesenchymal stem cells and bone pathologies
Authors: Maria Rosa Iaquinta, Carmen Lanzillotti, Chiara Mazziotta, Ilaria Bononi, Francesca Frontini, Elisa Mazzoni, Lucia Oton-Gonzalez, John Charles Rotondo, Elena Torreggiani, Mauro Tognon, Fernanda Martini
Journal: Theranostics (2021)

Mesenchymal stem cells (MSCs) have been identified in many adult tissues.MSCs can regenerate through cell division or differentiate into adipocytes, osteoblasts and chondrocytes.As a result, MSCs have become an important source of cells in tissue engineering and regenerative medicine for bone tissue and cartilage.Several epigenetic factors are believed to play a role in MSCs differentiation.Among these, microRNA (miRNA) regulation is involved in the fine modulation of gene expression during osteogenic/ chondrogenic differentiation.It has been reported that miRNAs are involved in bone homeostasis by modulating osteoblast gene expression.In addition, countless evidence has demonstrated that miRNAs dysregulation is involved in the development of osteoporosis and bone fractures.The deregulation of miRNAs expression has also been associated with several malignancies including bone cancer.In this context, bone-associated circulating miRNAs may be useful biomarkers for determining the predisposition, onset and development of osteoporosis, as well as in clinical applications to improve the diagnosis, follow-up and treatment of cancer and metastases.Overall, this review will provide an overview of how miRNAs activities participate in osteogenic/chondrogenic differentiation, while addressing the role of miRNA regulatory effects on target genes.Finally, the role of miRNAs in pathologies and therapies will be presented.
AGGRESSIVE MALIGNANT PERIPHERAL NERVE SHEATH TUMOR WITH METASTASIS TO THE RIGHT VENTRICLE
Authors: Saikrishna Patibandla, Ahmed Elwidaa, Dipesh Ludhwani, Brock Lindsey, Miklos Auber, Sudarshan Balla, Yasmin Hamirani
Journal: Journal of the American College of Cardiology (2021)
Abstract 11936: Red Blood Cell Distribution Width Predicts Near-Term Mortality in Patients With Atherosclerotic Cardiovascular Disease
Authors: Ozan Dikilitas, Baosheng He, Iftikhar Kullo
Journal: Circulation (2018)

Introduction: Red blood cell distribution width (RDW), a measure of heterogeneity in the size of circulating red blood cells, is predictive of adverse outcomes in a variety of diseases. We assessed...
Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
Authors: Sarra Smati, Arnaud Polizzi, Anne Fougerat, Sandrine Ellero-Simatos, Yuna Blum, Yannick Lippi, Marion Régnier, Alexia Laroyenne, Marine Huillet, Muhammad Arif, Cheng Zhang, Frederic Lasserre, Alain Marrot, Talal Al Saati, JingHong Wan, Caroline Sommer, Claire Naylies, Aurelie Batut, Celine Lukowicz, Tiffany Fougeray, Blandine Tramunt, Patricia Dubot, Lorraine Smith, Justine Bertrand-Michel, Nathalie Hennuyer, Jean-Philippe Pradere, Bart Staels, Remy Burcelin, Françoise Lenfant, Jean-François Arnal, Thierry Levade, Laurence Gamet-Payrastre, Sandrine Lagarrigue, Nicolas Loiseau, Sophie Lotersztajn, Catherine Postic, Walter Wahli, Christophe Bureau, Maeva Guillaume, Adil Mardinoglu, Alexandra Montagner, Pierre Gourdy, Hervé Guillou
Journal: Gut (2021)

Objective We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans. Design Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver. Results The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα. Conclusions These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target. Trial registration number NCT02390232 .
THE VALUE OF ZERO BEYOND THE CORONARIES
Authors: Ruby Havistin, Khadije Ahmad, Samantha Hartnett, April Kinninger, Ahmed Ghanem, Francesca Calicchio, Venkat Sanjay Manubolu, Vahid Rezvanizadeh, Suraj Dahal, Suvasini Lakshmanan, Matthew Budoff
Journal: Journal of the American College of Cardiology (2021)
TYPES OF SYNCOPE AND OUTCOMES IN BRUGADA SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Pattara Rattanawong, Jakrin Kewcharoen, Chanavuth Kanitsoraphan, Wasawat Vutthikraivit, Narut Prasitlumkum, Masihullah Barat, Eugene Chung, Win-Kuang Shen
Journal: Journal of the American College of Cardiology (2021)
日本人労働人口における喫煙,禁煙,および死亡リスク-日本の労働衛生研究に関する疫学協力-
Authors: Akter Shamima, Nakagawa Tohru, Honda Toru, Yamamoto Shuichiro, Kuwahara Keisuke, Okazaki Hiroko, Hu Huanhuan, Imai Teppei, Nishihara Akiko, Miyamoto Toshiaki, Sasaki Naoko, Ogasawara Takayuki, Uehara Akihiko, Yamamoto Makoto, Murakami Taizo, Shimizu Makiko, Eguchi Masafumi, Kochi Takeshi, Hori Ai, Nagahama Satsue, Tomita Kentaro, Konishi Maki, Kashino Ikuko, Nanri Akiko, Kabe Isamu, Mizoue Tetsuya, Kunugita Naoki, Dohi Seitaro
Journal: Circulation (2018)
Abstract 19255: A Risk Model to Predict One-Year Ischemic Stroke and Thromboembolism in Atrial Fibrillation: The China Atrial Fibrillation Registry Study
Authors: Xin Du, Xiang Li, Shanshuai Chang, Haifeng Liu, Xueyuan Guo, Shijing Guo, Tiange Chen, Jianzeng Dong, Guotong Xie, Changsheng Ma
Journal: Circulation (2017)

Introduction: Accurate prediction of ischemic stroke is highly needed in anticoagulation decision making for patients with atrial fibrillation (AF). We aim to develop a new risk model with improved...