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1. Glucodensity Functional Profiles Outperform Traditional Continuous Glucose Monitoring Metrics

Author

Matabuena, Marcos, Ghosal, Rahul, Aguilar, Javier Enrique, Wagner, Robert, Merino, Carmen Fernández, Castro, Juan Sánchez, Zipunnikov, Vadim, Onnela, Jukka-Pekka, and Gude, Francisco

Subjects
Statistics - Applications
Abstract

Continuous glucose monitoring (CGM) data has revolutionized the management of type 1 diabetes, particularly when integrated with insulin pumps to mitigate clinical events such as hypoglycemia. Recently, there has been growing interest in utilizing CGM devices in clinical studies involving healthy and diabetes populations. However, efficiently exploiting the high temporal resolution of CGM profiles remains a significant challenge. Numerous indices -- such as time-in-range metrics and glucose variability measures -- have been proposed, but evidence suggests these metrics overlook critical aspects of glucose dynamic homeostasis. As an alternative method, this paper explores the clinical value of glucodensity metrics in capturing glucose dynamics -- specifically the speed and acceleration of CGM time series -- as new biomarkers for predicting long-term glucose outcomes. Our results demonstrate significant information gains, exceeding 20\% in terms of adjusted $R^2$, in forecasting glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) at five and eight years from baseline AEGIS data, compared to traditional non-CGM and CGM glucose biomarkers. These findings underscore the importance of incorporating more complex CGM functional metrics, such as the glucodensity approach, to fully capture continuous glucose fluctuations across different time-scale resolutions.

Published
2024

2. MoistNet: Machine Vision-based Deep Learning Models for Wood Chip Moisture Content Measurement

Author

Rahman, Abdur, Street, Jason, Wooten, James, Marufuzzaman, Mohammad, Gude, Veera G., Buchanan, Randy, and Wang, Haifeng

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Quick and reliable measurement of wood chip moisture content is an everlasting problem for numerous forest-reliant industries such as biofuel, pulp and paper, and bio-refineries. Moisture content is a critical attribute of wood chips due to its direct relationship with the final product quality. Conventional techniques for determining moisture content, such as oven-drying, possess some drawbacks in terms of their time-consuming nature, potential sample damage, and lack of real-time feasibility. Furthermore, alternative techniques, including NIR spectroscopy, electrical capacitance, X-rays, and microwaves, have demonstrated potential; nevertheless, they are still constrained by issues related to portability, precision, and the expense of the required equipment. Hence, there is a need for a moisture content determination method that is instant, portable, non-destructive, inexpensive, and precise. This study explores the use of deep learning and machine vision to predict moisture content classes from RGB images of wood chips. A large-scale image dataset comprising 1,600 RGB images of wood chips has been collected and annotated with ground truth labels, utilizing the results of the oven-drying technique. Two high-performing neural networks, MoistNetLite and MoistNetMax, have been developed leveraging Neural Architecture Search (NAS) and hyperparameter optimization. The developed models are evaluated and compared with state-of-the-art deep learning models. Results demonstrate that MoistNetLite achieves 87% accuracy with minimal computational overhead, while MoistNetMax exhibits exceptional precision with a 91% accuracy in wood chip moisture content class prediction. With improved accuracy and faster prediction speed, our proposed MoistNet models hold great promise for the wood chip processing industry.

Published
2024
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3. From Glucose Patterns to Health Outcomes: A Generalizable Foundation Model for Continuous Glucose Monitor Data Analysis

Author

Lutsker, Guy, Sapir, Gal, Shilo, Smadar, Merino, Jordi, Godneva, Anastasia, Greenfield, Jerry R, Samocha-Bonet, Dorit, Dhir, Raja, Gude, Francisco, Mannor, Shie, Meirom, Eli, Chechik, Gal, Rossman, Hagai, and Segal, Eran

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

Recent advances in SSL enabled novel medical AI models, known as foundation models, offer great potential for better characterizing health from diverse biomedical data. CGM provides rich, temporal data on glycemic patterns, but its full potential for predicting broader health outcomes remains underutilized. Here, we present GluFormer, a generative foundation model for CGM data that learns nuanced glycemic patterns and translates them into predictive representations of metabolic health. Trained on over 10 million CGM measurements from 10,812 adults, primarily without diabetes, GluFormer uses autoregressive token prediction to capture longitudinal glucose dynamics. We show that GluFormer generalizes to 19 external cohorts (n=6,044) spanning different ethnicities and ages, 5 countries, 8 CGM devices, and diverse pathophysiological states. GluFormers representations exceed the performance of current CGM metrics, such as the Glucose Management Indicator (GMI), for forecasting clinical measures. In a longitudinal study of 580 adults with CGM data and 12-year follow-up, GluFormer identifies individuals at elevated risk of developing diabetes more effectively than blood HbA1C%, capturing 66% of all new-onset diabetes diagnoses in the top quartile versus 7% in the bottom quartile. Similarly, 69% of cardiovascular-death events occurred in the top quartile with none in the bottom quartile, demonstrating powerful risk stratification beyond traditional glycemic metrics. We also show that CGM representations from pre-intervention periods in Randomized Clinical Trials outperform other methods in predicting primary and secondary outcomes. When integrating dietary data into GluFormer, we show that the multi-modal version of the model can accurately generate CGM data based on dietary intake data, simulate outcomes of dietary interventions, and predict individual responses to specific foods.

Published
2024

4. Perceived Views on the Best Behavior Change Communication Approach to Eradicating Girls' Education Issues

Author

Patrick Gatsinzi, Korso Gude Butucha, and Paul Samuel Francis

Abstract

Girls' education is affected by forms of violence and teenage pregnancy, resulting in school dropouts. Governments have established Behavior Change Communication (BCC) approaches to address these issues, but with limited success. This study assessed teenage girls' perceived views on the best BCC strategies for eradicating these education issues. It explored their understanding of current approaches, identified the most effective methods, and suggested improvements for girls' education. Using an exploratory design, data were collected through interview guides and Focus Group Discussions (FGDs) involving 105 teenage girls, 10 parents, and 5 key informants. Various sampling techniques were employed, and data were analyzed thematically. Results on current approaches indicated strategies such as economic empowerment, parental involvement, media campaigns, counseling centers, reproductive health education, and disciplinary measures. The best and most effective approaches identified included testimony-telling, community committees for reproductive health education, access to educational materials, parental support, fostering self-dignity, and appropriate disciplinary actions. Suggestions for improving girls' education encompassed enhanced monitoring and evaluation, promotion of respectful language use, involvement of religious and community leaders, peer support systems, and fair disciplinary measures. The study contributes to a deeper understanding of effective approaches to addressing girls' education challenges and concludes that a well-coordinated, multi-stakeholder implementation of these strategies is essential for success.

Published
2024

5. Multilevel functional data analysis modeling of human glucose response to meal intake

Author

Matabuena, Marcos, Sartini, Joe, and Gude, Francisco

Subjects
Quantitative Biology - Quantitative Methods, Statistics - Applications
Abstract

Glucose meal response information collected via Continuous Glucose Monitoring (CGM) is relevant to the assessment of individual metabolic status and the support of personalized diet prescriptions. However, the complexity of the data produced by CGM monitors pushes the limits of existing analytic methods. CGM data often exhibits substantial within-person variability and has a natural multilevel structure. This research is motivated by the analysis of CGM data from individuals without diabetes in the AEGIS study. The dataset includes detailed information on meal timing and nutrition for each individual over different days. The primary focus of this study is to examine CGM glucose responses following patients' meals and explore the time-dependent associations with dietary and patient characteristics. Motivated by this problem, we propose a new analytical framework based on multilevel functional models, including a new functional mixed R-square coefficient. The use of these models illustrates 3 key points: (i) The importance of analyzing glucose responses across the entire functional domain when making diet recommendations; (ii) The differential metabolic responses between normoglycemic and prediabetic patients, particularly with regards to lipid intake; (iii) The importance of including random, person-level effects when modelling this scientific problem.

Published
2024

6. Robust Nonparametric Regression for Compositional Data: the Simplicial--Real case

Author

Bianco, Ana M., Boente, Graciela, González--Manteiga, Wenceslao, Sampedro, Francisco Gude, and Pérez--González, Ana

Subjects
Statistics - Methodology
Abstract

Statistical analysis on compositional data has gained a lot of attention due to their great potential of applications. A feature of these data is that they are multivariate vectors that lie in the simplex, that is, the components of each vector are positive and sum up a constant value. This fact poses a challenge to the analyst due to the internal dependency of the components which exhibit a spurious negative correlation. Since classical multivariate techniques are not appropriate in this scenario, it is necessary to endow the simplex of a suitable algebraic-geometrical structure, which is a starting point to develop adequate methodology and strategies to handle compositions. We centered our attention on regression problems with real responses and compositional covariates and we adopt a nonparametric approach due to the flexibility it provides. Aware of the potential damage that outliers may produce, we introduce a robust estimator in the framework of nonparametric regression for compositional data. The performance of the estimators is investigated by means of a numerical study where different contamination schemes are simulated. Through a real data analysis the advantages of using a robust procedure is illustrated.

Published
2024

9. Optimal Cut-Point Estimation for functional digital biomarkers: Application to Continuous Glucose Monitoring

Author

Lado-Baleato, Oscar, Matabuena, Marcos, Díaz-Louzao, Carla, and Gude, Francisco

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Establish optimal cut points plays a crucial role in epidemiology and biomarker discovery, enabling the development of effective and practical clinical decision criteria. While there is extensive literature to define optimal cut off over scalar biomarkers, there is a notable lack of general methodologies for analyzing statistical objects in more complex spaces of functions and graphs, which are increasingly relevant in digital health applications. This paper proposes a new general methodology to define optimal cut points for random objects in separable Hilbert spaces. The paper is motivated by the need for creating new clinical rules for diabetes mellitus disease, exploiting the functional information of a continuous diabetes monitor (CGM) as a digital biomarker. More specifically, we provide the functional cut off to identify diabetes cases with CGM information based on glucose distributional functional representations.

Published
2024

10. Personalized Imputation in metric spaces via conformal prediction: Applications in Predicting Diabetes Development with Continuous Glucose Monitoring Information

Author

Matabuena, Marcos, Díaz-Louzao, Carla, Ghosal, Rahul, and Gude, Francisco

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

The challenge of handling missing data is widespread in modern data analysis, particularly during the preprocessing phase and in various inferential modeling tasks. Although numerous algorithms exist for imputing missing data, the assessment of imputation quality at the patient level often lacks personalized statistical approaches. Moreover, there is a scarcity of imputation methods for metric space based statistical objects. The aim of this paper is to introduce a novel two-step framework that comprises: (i) a imputation methods for statistical objects taking values in metrics spaces, and (ii) a criterion for personalizing imputation using conformal inference techniques. This work is motivated by the need to impute distributional functional representations of continuous glucose monitoring (CGM) data within the context of a longitudinal study on diabetes, where a significant fraction of patients do not have available CGM profiles. The importance of these methods is illustrated by evaluating the effectiveness of CGM data as new digital biomarkers to predict the time to diabetes onset in healthy populations. To address these scientific challenges, we propose: (i) a new regression algorithm for missing responses; (ii) novel conformal prediction algorithms tailored for metric spaces with a focus on density responses within the 2-Wasserstein geometry; (iii) a broadly applicable personalized imputation method criterion, designed to enhance both of the aforementioned strategies, yet valid across any statistical model and data structure. Our findings reveal that incorporating CGM data into diabetes time-to-event analysis, augmented with a novel personalization phase of imputation, significantly enhances predictive accuracy by over ten percent compared to traditional predictive models for time to diabetes.

Published
2024

12. Genetic connectivity of wolverines in western North America

Author

Day, Casey C., Landguth, Erin L., Sawaya, Michael A., Clevenger, Anthony P, Long, Robert A., Holden, Zachary A., Akins, Jocelyn R., Anderson, Robert B., Aubry, Keith B., Barrueto, Mirjam, Bjornlie, Nichole L., Copeland, Jeffrey P., Fisher, Jason T., Forshner, Anne, Gude, Justin A., Hausleitner, Doris, Heim, Nichole A., Heinemeyer, Kimberly S., Hubbs, Anne, Inman, Robert M., Jackson, Scott, Jokinen, Michael, Kluge, Nathan P., Kortello, Andrea, Lacroix, Deborah L., Lamar, Luke, Larson, Lisa I., Lewis, Jeffrey C., Lockman, Dave, Lucid, Michael K., MacKay, Paula, Magoun, Audrey J., McLellan, Michelle L., Moriarty, Katie M., Mosby, Cory E., Mowat, Garth, Nietvelt, Clifford G., Paetkau, David, Palm, Eric C., Paul, Kylie J.S., Pilgrim, Kristine L., Raley, Catherine M., Schwartz, Michael K., Scrafford, Matthew A., Squires, John R., Walker, Zachary J., Waller, John S., Weir, Richard D., and Zeller, Katherine A.

Published
2024
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15. Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation

Author

Khan, Faraz H., Zhao, Debbie, Ha, Jong-Won, Nagueh, Sherif F., Voigt, Jens-Uwe, Klein, Allan L., Gude, Einar, Broch, Kaspar, Chan, Nicholas, Quill, Gina M., Doughty, Robert N., Young, Alistair, Seo, Ji-Won, García-Izquierdo, Eusebio, Moñivas-Palomero, Vanessa, Mingo-Santos, Susana, Wang, Tom Kai Ming, Bezy, Stephanie, Ohte, Nobuyuki, Skulstad, Helge, Beladan, Carmen C., Popescu, Bogdan A., Kikuchi, Shohei, Panis, Vasileios, Donal, Erwan, Remme, Espen W., Nash, Martyn P., and Smiseth, Otto A.

Published
2024
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16. Need for operational simplicity and timely disbursal of benefits—a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India

Author

Mohan, Malu, Thangaraj, Jeromie W. V., Pandey, Sumit, Sri Lakshmi Priya, G., Arunachalam, Sivavallinathan, Sharma, Rahul, Shewade, Hemant Deepak, Aishwarya, B., Afeeq, K., Khatoon, Afsana, Gokulvijay, B., Sireesha, Gude, Chandra, Kavita, Nandhakumar, S., Samuel, Prince, Nanditha Viswanathan, C., Shanmugasundaram, Devika, Rao, Raghuram, Murhekar, Manoj V., and Jeyashree, Kathiresan

Published
2024
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17. Genetic connectivity of wolverines in western North America

Author

Casey C. Day, Erin L. Landguth, Michael A. Sawaya, Anthony P Clevenger, Robert A. Long, Zachary A. Holden, Jocelyn R. Akins, Robert B. Anderson, Keith B. Aubry, Mirjam Barrueto, Nichole L. Bjornlie, Jeffrey P. Copeland, Jason T. Fisher, Anne Forshner, Justin A. Gude, Doris Hausleitner, Nichole A. Heim, Kimberly S. Heinemeyer, Anne Hubbs, Robert M. Inman, Scott Jackson, Michael Jokinen, Nathan P. Kluge, Andrea Kortello, Deborah L. Lacroix, Luke Lamar, Lisa I. Larson, Jeffrey C. Lewis, Dave Lockman, Michael K. Lucid, Paula MacKay, Audrey J. Magoun, Michelle L. McLellan, Katie M. Moriarty, Cory E. Mosby, Garth Mowat, Clifford G. Nietvelt, David Paetkau, Eric C. Palm, Kylie J.S. Paul, Kristine L. Pilgrim, Catherine M. Raley, Michael K. Schwartz, Matthew A. Scrafford, John R. Squires, Zachary J. Walker, John S. Waller, Richard D. Weir, and Katherine A. Zeller

Subjects
Medicine, Science
Abstract

Abstract Wolverine distribution contracted along the southern periphery of its range in North America during the 19th and 20th centuries due primarily to human influences. This history, along with low densities, sensitivity to climate change, and concerns about connectivity among fragmented habitats spurred the recent US federal listing of threatened status and special concern status in Canada. To help inform large scale landscape connectivity, we collected 882 genetic samples genotyped at 19 microsatellite loci. We employed multiple statistical models to assess the landscape factors (terrain complexity, human disturbance, forest configuration, and climate) associated with wolverine genetic connectivity across 2.2 million km2 of southwestern Canada and the northwestern contiguous United States. Genetic similarity (positive spatial autocorrelation) of wolverines was detected up to 555 km and a high-to-low gradient of genetic diversity occurred from north-to-south. Landscape genetics analyses confirmed that wolverine genetic connectivity has been negatively influenced by human disturbance at broad scales and positively influenced by forest cover and snow persistence at fine- and broad–scales, respectively. This information applied across large landscapes can be used to guide management actions with the goal of maintaining or restoring population connectivity.

Published
2024
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19. The pro-atherogenic enzyme PAPP-A is active in eluates from human carotid and femoral atherosclerotic plaques

Author

Mette Faurholdt Gude, Rikke Hjortebjerg, Mette Bjerre, Anne Kathrine Nissen Pedersen, Claus Oxvig, Lars Melholt Rasmussen, Jan Frystyk, and Lasse Steffensen

Subjects
IGF1, IGFBP4, PAPP-A, STC2, Atherosclerosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Pregnancy-associated plasma protein-A (PAPP-A) regulates bioavailability of insulin-like growth factor 1 (IGF1) in various tissues by proteolytic cleavage of a subset of IGF-binding proteins (IGFBPs). Pre-clinical studies have established a role of PAPP-A in atherosclerosis and proposed that targeting the proteolytic activity of PAPP-A has therapeutic value.This study aimed to investigate whether human atherosclerotic plaques contain proteolytically active PAPP-A, a prerequisite for further considering PAPP-A as a therapeutic target in patients. Methods: We obtained carotid (n = 9) and femoral (n = 11) atherosclerotic plaques from patients undergoing vascular surgery and incubated freshly harvested plaque tissue in culture media for 24 h. Subsequently, conditioned media were assayed for PAPP-A, STC2, IGFBP4, and IGF1 using immunoassays. Enzymatic activity of PAPP-A was assessed by its ability to process recombinant IGFBP4-IGF1 complexes - a specific substrate of PAPP-A - by Western blotting. Results: PAPP-A and STC2 were detectable in conditioned media from both carotid and femoral plaques, with higher STC2 concentrations in eluates from carotid plaque incubations (p = 0.02). IGFBP4 and IGF1 were undetectable. Conditioned media from all 20 plaques exhibited PAPP-A proteolytic activity. However, no correlation between PAPP-A concentration and its proteolytic activity was observed, whereas the PAPP-A: STC2 molar ratio correlated with PAPP-A activity (R2 = 0.25, p = 0.03). Conclusion: This study provides evidence for the presence of enzymatically active PAPP-A in atherosclerotic plaques and underscores the need for further investigating potential beneficial effects associated with targeting PAPP-A in atherosclerotic cardiovascular disease.

Published
2024
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20. Structural integrity of aging steel bridges by 3D laser scanning and convolutional neural networks

Author

Georgios Tzortzinis, Angelos Filippatos, Jan Wittig, Maik Gude, Aidan Provost, Chengbo Ai, and Simos Gerasimidis

Subjects
Engineering (General). Civil engineering (General), TA1-2040
Abstract

Abstract For steel bridges, corrosion has historically led to bridge failures, resulting in fatalities and injuries. To enhance public safety and prevent such incidents, authorities mandate in-situ evaluation and reporting of corroded members. The current inspection and evaluation protocol is characterized by intense labor, traffic delays, and poor capacity predictions. Here we combine full-scale experimental testing of a decommissioned girder, 3D laser scanning, and convolutional neural networks (CNNs) to introduce a continuous inspection and evaluation framework. Classification and regression CNNs are trained on a databank of 1,421 naturally inspired corrosion scenarios, generated computationally based on point clouds of three corroded girders collected in lab conditions. Results indicate low errors of up to 2.0% and 3.3%, respectively. The methodology is validated on eight real corroded ends and implemented for the evaluation of an in-service bridge. This framework promises significant advancements in assessing aging bridge infrastructure with higher accuracy and efficiency compared to analytical or semi-analytical approaches.

Published
2024
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21. Dapagliflozin in Post-Myocardial Infarction Acute Decompensated Heart Failure: Daffodil Study

Author

Pankaj Jariwala, Gururaj Pramod Kulkarni, Arshad Punjani, Kishan Hari, Dilip Babu Madhawar, Babu Dilip, and Dilip Gude

Subjects
acute decompensated heart failure, acute myocardial infarction, dapagliflozin, sodium–glucose cotransporter 2 inhibitor, Medicine, Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Dapagliflozin and sodium–glucose cotransporter 2 inhibitors reduce the risk of cardiac death and hospitalization for heart failure (HF), regardless of the patient’s status with type 2 diabetes mellitus (T2D). Further investigation is required to ascertain the impact of these drugs on patients suffering from acute myocardial infarction (AMI) complicated by acute decompensated heart failure (ADHF). Methods: In retrospective research comprising 371 patients with AMI complicated by ADHF of Killip class II–IV and left ventricular ejection fraction ≤40%, the effectiveness of dapagliflozin at a dosage of 10 mg once a day was compared to standard of care alone. The main results consisted of a primary composite outcome, which encompassed either cardiovascular (CV) mortality or hospitalization due to HF. Additional clinical outcomes assessed were CV mortality, hospitalization due to HF, and changes in laboratory measurements, including glycosylated hemoglobin, N-terminal prohormone B-type natriuretic peptide, and estimated glomerular filtration rate (eGFR). Results: In the group that received dapagliflozin, 10.7% of patients experienced a primary composite outcome event, while in the group that did not receive dapagliflozin, 24.9% of patients experienced one. The median follow-up period was 12.4 months, and the hazard ratio for CV death or hospitalization for HF was 0.67 (95% confidence interval [CI], 0.65–0.86; P < 0.001). Hazard ratio, 0.68; 95% CI, 0.55–0.69; P < 0.001), the group given dapagliflozin had fewer HF hospitalizations overall than the group given a placebo. Dapagliflozin decreased the likelihood of serious kidney outcomes and decelerated the yearly decline in the eGFR (2.1% vs. 7.6%; P < 0.001). Conclusions: Patients with AMI complicated by ADHF who received dapagliflozin had a lower risk of CV death or HF hospitalization, regardless of their T2D status.

Published
2024
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22. Correcting Model Misspecification via Generative Adversarial Networks

Author

Banerjee, Pronoma, Gude, Manasi V, Sampat, Rajvi J, Hedaoo, Sharvari M, Dhavala, Soma, and Saha, Snehanshu

Subjects
Computer Science - Machine Learning
Abstract

Machine learning models are often misspecified in the likelihood, which leads to a lack of robustness in the predictions. In this paper, we introduce a framework for correcting likelihood misspecifications in several paradigm agnostic noisy prior models and test the model's ability to remove the misspecification. The "ABC-GAN" framework introduced is a novel generative modeling paradigm, which combines Generative Adversarial Networks (GANs) and Approximate Bayesian Computation (ABC). This new paradigm assists the existing GANs by incorporating any subjective knowledge available about the modeling process via ABC, as a regularizer, resulting in a partially interpretable model that operates well under low data regimes. At the same time, unlike any Bayesian analysis, the explicit knowledge need not be perfect, since the generator in the GAN can be made arbitrarily complex. ABC-GAN eliminates the need for summary statistics and distance metrics as the discriminator implicitly learns them and enables simultaneous specification of multiple generative models. The model misspecification is simulated in our experiments by introducing noise of various biases and variances. The correction term is learnt via the ABC-GAN, with skip connections, referred to as skipGAN. The strength of the skip connection indicates the amount of correction needed or how misspecified the prior model is. Based on a simple experimental setup, we show that the ABC-GAN models not only correct the misspecification of the prior, but also perform as well as or better than the respective priors under noisier conditions. In this proposal, we show that ABC-GANs get the best of both worlds.

Published
2023

24. Investigation of the mechanical, absorption, flammability and swelling properties of graphene filled sisal/glass fiber reinforced polymer hybrid nanocomposites

Author

Bodduru Kamesh, Ravali Gude, Amrita Maddamsetty, Mesfin Kebede Kassa, Lavish Kumar Singh, and Ananda Babu Arumugam

Subjects
Graphene, sisal/glass hybrid composite, tensile and flexural properties, water absorption, flammability, Ian Phillip Jones, University of Birmingham, United Kingdom of Great Britain and Northern Ireland, Engineering (General). Civil engineering (General), TA1-2040
Abstract

AbstractHybrid graphene filled glass/sisal fiber-reinforced epoxy nanocomposites were successfully synthesized with different weight percentages (0%, 0.25%, 0.5%, 0.75% and 1%) of graphene nanoplatelets. The objective of this study was to investigate the effect of weight fraction of graphene on the mechanical and physical properties of the hybrid glass/sisal fiber-reinforced epoxy nanocomposites such as tensile, flexural, hardness, density, void content, flammability, water absorption and thickness swelling. The hybrid nanocomposites were fabricated using the vacuum bag-assisted hand lay-up technique. Different layup sequences were achieved by changing the position of the glass/sisal fiber layers, maintaining a total of five layers in each composite. The obtained results suggested that the addition of 1% graphene nano filler into the sisal/glass hybrid composite enhanced the tensile strength by 49.7% and Young’s modulus by 60%. Among GNP reinforced hybrid composites, highest value of toughness (16 J) was found in case of the composite containing 1 wt.% GNP. However, when 0.5% of GNPs were added in the composite, the flexural strength and modulus reached a maximum of 306 MPa and 25 GPa, respectively, which are 228% and 362% greater than sisal/glass hybrid composites. The water absorption of the composite sample containing 0.5% GNPs was 4.62% lower than those of other hybrid glass/sisal fiber reinforced epoxy composite. Furthermore, addition of 0.5 wt% GNP resulted in a decrease in the burning rate of the hybrid composite from 11.22 mm/min to 7.6 mm/min and from 23.13 mm/min to 20.18 mm/min, respectively.

Published
2024
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25. Sliding mode control design using a generalized reduced-order fractional model for chemical processes

Author

Juan J. Gude, Antonio Di Teodoro, D'hamar Agudelo, Marco Herrera, Luis Rincón, and Oscar Camacho

Subjects
Sliding mode control, Fractional-order model, Generalization procedure, Technology
Abstract

This article presents a comprehensive study that evaluates the potential advantages of adopting a unified, systematic, and organized general fractional model within the Sliding Mode Control (SMC) design framework. The exploration extends to the model's applicability in a variety of disciplines. Although prior research has utilized SMC and fractional-order systems independently, no previous work has established a mathematical framework that integrates a generic fractional-order SMC model. The study addresses this gap and highlights potential implications for control design and applications in a variety of fields, particularly for chemical processes.

Published
2024
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26. Improving the joint strength of thermoplastic composites joined by press joining using laser-based surface treatment

Author

Alexander Liebsch, Daniel Wohlfahrt, Thomas Kuntze, Levin Schilling, Jana Gebauer, Robert Kupfer, Niels Modler, Andrés Fabián Lasagni, and Maik Gude

Subjects
Thermoplastic composite, Laser treatment, Compression moulding, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Fibre-reinforced thermoplastic composites (TPC) provide an automated and cost-effective solution for their use in lightweight structures in series production. The combination of different material configurations allows the design of highly stress tolerant components. Previous studies demonstrated that the combination of TPC sheets, TPC hollow profiles and injection moulding compounds is even suitable for crash-relevant automotive parts. All three components are combined during the injection moulding process. To prevent collapse, the part must remain in a consolidated state and cannot be preheated. However, this results in poor adhesion between the hollow profile, the bulk material, and the TPC sheet. Previous studies have shown that the bonding strength between the hollow profile and the injection moulding compound can be increased by surface pre-treatment using laser structuring and plasma technology. In this work, laser structuring is employed to enhance the bonding strength between the hollow profile and the TPC sheet. Microscopy analysis is used to investigate the resulting surface morphology. Subsequently, single-lap-shear (SLS) specimens are produced by pressing the TPC sheets onto the flat part. The resulting bonding strengths are then evaluated by tensile shear tests. The study analyses the impact of various pre-treatment parameters on the bonding strength. Furthermore, it investigates the effect of sheet temperature on the bonding strength, including specimens without pre-treatment. Finally, the results of the surface treatment of hollow composite profiles are discussed.

Published
2024
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27. Pleural effusion in acute pulmonary embolism: characteristics and relevance

Author

Nuria Rodríguez-Núñez, Francisco Gude, Lucía Ferreiro, Elisa Landín-Rey, María Carreiras-Cuiña, Borja Otero, María Cruz Carbajales, Honorio J Martínez-Martínez, Carla Díaz-Louzao, Roi Soto-Feijoo, Juan Suárez Antelo, Maria E Toubes, and Luis Valdés-Cuadrado

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Introduction The characteristics and clinical relevance of pleural effusion (PLEF) in acute pulmonary embolism (APE) are not fully understood.Methods A single-centre, retrospective study was performed of patients admitted with APE classified according to the subsequent development or not of PLEF. A model was built to predict PLEF and its impact on 30-day all-cause mortality was investigated.Results A total of 1602 patients with APE were included (median age, 74 (61, 82) years; 674 men (42.1%); 382 (23.8%) with PLEF). PLEF was associated with a higher number of comorbidities (p=0.015); more peripheral APE (0.001); a higher frequency of pulmonary infarctions (p

Published
2024
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28. Surface Lin28A expression consistent with cellular stress parallels indicators of senescence

Author

Broughton, Kathleen, Esquer, Carolina, Echeagaray, Oscar, Firouzi, Fareheh, Shain, Grant, Ebeid, David, Monsanto, Megan, Yaareb, Dena, Golgolab, Leila, Gude, Natalie, and Sussman, Mark A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Cardiovascular, 1.1 Normal biological development and functioning, Animals, Mice, Cellular Senescence, Antioxidants, Aging, Oxidative Stress, Myocardium, Lin28A, Oxidative stress, Ploidy, Senescence, Surface marker, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

AimsDeclining cellular functional capacity resulting from stress or ageing is a primary contributor to impairment of myocardial performance. Molecular pathway regulation of biological processes in cardiac interstitial cells (CICs) is pivotal in stress and ageing responses. Altered localization of the RNA-binding protein Lin28A has been reported in response to environmental stress, but the role of Lin28A in response to stress in CICs has not been explored. Surface Lin28A redistribution is indicative of stress response in CIC associated with ageing and senescence.Methods and resultsLocalization of Lin28A was assessed by multiple experimental analyses and treatment conditions and correlated to oxidative stress, senescence, and ploidy in adult murine CICs. Surface Lin28A expression is present on 5% of fresh CICs and maintained through Passage 2, increasing to 21% in hyperoxic conditions but lowered to 14% in physiologic normoxia. Surface Lin28A is coincident with elevated senescence marker p16 and beta-galactosidase (β-gal) expression in CICs expanded in hyperoxia, and also increases with polyploidization and binucleation of CICs regardless of oxygen culture. Transcriptional profiling of CICs using single-cell RNA-Seq reveals up-regulation of pathways associated with oxidative stress in CICs exhibiting surface Lin28A. Induction of surface Lin28A by oxidative stress is blunted by treatment of cells with the antioxidant Trolox in a dose-dependent manner, with 300 μM Trolox exposure maintaining characteristics of freshly isolated CICs possessing low expression of surface Lin28A and β-gal with predominantly diploid content.ConclusionSurface Lin28A is a marker of environmental oxidative stress in CICs and antioxidant treatment antagonizes this phenotype. The biological significance of Lin28 surface expression and consequences for myocardial responses may provide important insights regarding mitigation of cardiac stress and ageing.

Published
2023

29. Conditional diffusion-based microstructure reconstruction

Author

Düreth, Christian, Seibert, Paul, Rücker, Dennis, Handford, Stephanie, Kästner, Markus, and Gude, Maik

Subjects
Condensed Matter - Materials Science
Abstract

Microstructure reconstruction, a major component of inverse computational materials engineering, is currently advancing at an unprecedented rate. While various training-based and training-free approaches are developed, the majority of contributions are based on generative adversarial networks. In contrast, diffusion models constitute a more stable alternative, which have recently become the new state of the art and currently attract much attention. The present work investigates the applicability of diffusion models to the reconstruction of real-world microstructure data. For this purpose, a highly diverse and morphologically complex data set is created by combining and processing databases from the literature, where the reconstruction of realistic micrographs for a given material class demonstrates the ability of the model to capture these features. Furthermore, a fiber composite data set is used to validate the applicability of diffusion models to small data set sizes that can realistically be created by a single lab. The quality and diversity of the reconstructed microstructures is quantified by means of descriptor-based error metrics as well as the Fr\'echet inception distance (FID) score. Although not present in the training data set, the generated samples are visually indistinguishable from real data to the untrained eye and various error metrics are computed. This demonstrates the utility of diffusion models in microstructure reconstruction and provides a basis for further extensions such as 2D-to-3D reconstruction or application to multiscale modeling and structure-property linkages.

Published
2022

35. Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation

Author

Faraz H. Khan, Debbie Zhao, Jong-Won Ha, Sherif F. Nagueh, Jens-Uwe Voigt, Allan L. Klein, Einar Gude, Kaspar Broch, Nicholas Chan, Gina M. Quill, Robert N. Doughty, Alistair Young, Ji-Won Seo, Eusebio García-Izquierdo, Vanessa Moñivas-Palomero, Susana Mingo-Santos, Tom Kai Ming Wang, Stephanie Bezy, Nobuyuki Ohte, Helge Skulstad, Carmen C. Beladan, Bogdan A. Popescu, Shohei Kikuchi, Vasileios Panis, Erwan Donal, Espen W. Remme, Martyn P. Nash, and Otto A. Smiseth

Subjects
Atrial fibrillation, Diastolic function, Echocardiography, Left atrium, Left ventricle, Filling pressure, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. Results In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e’), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF

Published
2024
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36. Efficacy and safety of eliapixant in endometriosis-associated pelvic pain: the randomized, placebo-controlled phase 2b SCHUMANN study

Author

Susanne Parke, Kerstin Gude, Katrin Roth, and Fabrizio Messina

Subjects
Endometriosis-associated pelvic pain, Eliapixant, P2X3 receptor antagonist, Phase 2b clinical trial, Gynecology and obstetrics, RG1-991, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP). Methods SCHUMANN was a randomized, placebo- and active comparator-controlled, double-blind to placebo and open-label to comparator, parallel-group, multicenter, dose-finding phase 2b study. The participants were women with surgically diagnosed endometriosis who fulfilled defined EAPP criteria. Participants were randomized 1:1:1:1 to twice daily (BID) 25 mg, 75 mg, or 150 mg oral eliapixant or a placebo for 12 weeks. An exploratory once-daily elagolix 150 mg treatment group was also included. The primary endpoint was the absolute change in mean worst EAPP from baseline to the end of intervention (EOI). Results Overall, 215 participants were randomized for treatment (44 to eliapixant 25 mg, 44 to eliapixant 75 mg, 43 to eliapixant 150 mg, 43 to a placebo, and 41 to elagolix 150 mg). For safety reasons, the study was terminated early; both treatment and enrollment stopped immediately, producing less than 50% of the planned number of completers. The study found no significant differences in EAPP reduction from baseline between groups and no significant dose-response model. The elagolix 150 mg group showed better pain reduction than any of the other groups. No new safety signals were observed, relative to the previously known safety profile of eliapixant, which was generally well tolerated. However, one case of moderate and probably drug-induced liver injury in a participant receiving eliapixant 150 mg BID supported the association between eliapixant and a potential increase in liver function values, defined before the start of the phase 2 program. Conclusions This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive. Clinical trial registration ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.

Published
2024
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37. Need for operational simplicity and timely disbursal of benefits—a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India

Author

Malu Mohan, Jeromie W. V. Thangaraj, Sumit Pandey, G. Sri Lakshmi Priya, Sivavallinathan Arunachalam, Rahul Sharma, Hemant Deepak Shewade, B. Aishwarya, K. Afeeq, Afsana Khatoon, B. Gokulvijay, Gude Sireesha, Kavita Chandra, S. Nandhakumar, Prince Samuel, C. Nanditha Viswanathan, Devika Shanmugasundaram, Raghuram Rao, Manoj V. Murhekar, and Kathiresan Jeyashree

Subjects
National Tuberculosis Elimination Programme, Nutritional status, Direct benefit transfer, Ni-kshay Poshan Yojana, Implementation, Cash transfer scheme, Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. Methods We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. Results Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. Conclusion The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.

Published
2024
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38. Specialty Medical Settings

Author

Vieux, Ulrick, Benotakeia, Andrew Shaw, Gude, Jayasudha, Fishkin, Ilona, Small, Gary, Maragakis, Alexandros, editor, and Janikian, Mari, editor

Published
2024
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45. Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Author

Jannik Boos, Caspar I. van der Made, Gayatri Ramakrishnan, Eamon Coughlan, Rosanna Asselta, Britt-Sabina Löscher, Luca V.C. Valenti, Rafael de Cid, Luis Bujanda, Antonio Julià, Erola Pairo-Castineira, J. Kenneth Baillie, Sandra May, Berina Zametica, Julia Heggemann, Agustín Albillos, Jesus M. Banales, Jordi Barretina, Natalia Blay, Paolo Bonfanti, Maria Buti, Javier Fernandez, Sara Marsal, Daniele Prati, Luisa Ronzoni, Nicoletta Sacchi, Joachim L. Schultze, Olaf Riess, Andre Franke, Konrad Rawlik, David Ellinghaus, Alexander Hoischen, Axel Schmidt, Kerstin U. Ludwig, Valeria Rimoldi, Elvezia M. Paraboschi, Alessandra Bandera, Flora Peyvandi, Giacomo Grasselli, Francesco Blasi, Francesco Malvestiti, Serena Pelusi, Cristiana Bianco, Lorenzo Miano, Angela Lombardi, Pietro Invernizzi, Alessio Gerussi, Giuseppe Citerio, Andrea Biondi, Maria Grazia Valsecchi, Marina Elena Cazzaniga, Giuseppe Foti, Ilaria Beretta, Mariella D'Angiò, Laura Rachele Bettini, Xavier Farré, Susana Iraola-Guzmán, Manolis Kogevinas, Gemma Castaño-Vinyals, Koldo Garcia-Etxebarria, Beatriz Nafria, Mauro D'Amato, Adriana Palom, Colin Begg, Sara Clohisey, Charles Hinds, Peter Horby, Julian Knight, Lowell Ling, David Maslove, Danny McAuley, Johnny Millar, Hugh Montgomery, Alistair Nichol, Peter J.M. Openshaw, Alexandre C. Pereira, Chris P. Ponting, Kathy Rowan, Malcolm G. Semple, Manu Shankar-Hari, Charlotte Summers, Timothy Walsh, Latha Aravindan, Ruth Armstrong, Heather Biggs, Ceilia Boz, Adam Brown, Richard Clark, Audrey Coutts, Judy Coyle, Louise Cullum, Sukamal Das, Nicky Day, Lorna Donnelly, Esther Duncan, Angie Fawkes, Paul Fineran, Max Head Fourman, Anita Furlong, James Furniss, Bernadette Gallagher, Tammy Gilchrist, Ailsa Golightly, Fiona Griffiths, Katarzyna Hafezi, Debbie Hamilton, Ross Hendry, Andy Law, Dawn Law, Rachel Law, Sarah Law, Rebecca Lidstone-Scott, Louise Macgillivray, Alan Maclean, Hanning Mal, Sarah McCafferty, Ellie Mcmaster, Jen Meikle, Shona C. Moore, Kirstie Morrice, Lee Murphy, Sheena Murphy, Mybaya Hellen, Wilna Oosthuyzen, Chenqing Zheng, Jiantao Chen, Nick Parkinson, Trevor Paterson, Katherine Schon, Andrew Stenhouse, Mihaela Das, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Lance Turtle, Tony Wackett, Mairi Ward, Jane Weaver, Nicola Wrobel, Marie Zechner, Gill Arbane, Aneta Bociek, Sara Campos, Neus Grau, Tim Owen Jones, Rosario Lim, Martina Marotti, Marlies Ostermann, Christopher Whitton, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, Peter May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, Suzanne Wood, Anne Zak, Olivier Zongo, Stephen Bonner, Keith Hugill, Jessica Jones, Steven Liggett, Evie Headlam, Nageswar Bandla, Minnie Gellamucho, Michelle Davies, Christopher Thompson, Marwa Abdelrazik, Dhanalakshmi Bakthavatsalam, Munzir Elhassan, Arunkumar Ganesan, Anne Haldeos, Jeronimo Moreno-Cuesta, Dharam Purohit, Rachel Vincent, Kugan Xavier, Kumar Rohit, Frater Alasdair, Malik Saleem, Carter David, Jenkins Samuel, Zoe Lamond, Wall Alanna, Jaime Fernandez-Roman, David O. Hamilton, Emily Johnson, Brian Johnston, Maria Lopez Martinez, Suleman Mulla, David Shaw, Alicia A.C. Waite, Victoria Waugh, Ingeborg D. Welters, Karen Williams, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O'Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Antcliffe, Dorota Banach, Stephen Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Archana Bashyal, Neil Davidson, Paula Hutton, Stuart McKechnie, Jean Wilson, David Baptista, Rebecca Crowe, Rita Fernandes, Rosaleen Herdman-Grant, Anna Joseph, Denise O'Connor, Meryem Allen, Adam Loveridge, India McKenley, Eriko Morino, Andres Naranjo, Richard Simms, Kathryn Sollesta, Andrew Swain, Harish Venkatesh, Jacyntha Khera, Jonathan Fox, Gillian Andrew, Lucy Barclay, Marie Callaghan, Rachael Campbell, Sarah Clark, Dave Hope, Lucy Marshall, Corrienne McCulloch, Kate Briton, Jo Singleton, Sohphie Birch, Lutece Brimfield, Zoe Daly, David Pogson, Steve Rose, Ceri Battle, Elaine Brinkworth, Rachel Harford, Carl Murphy, Luke Newey, Tabitha Rees, Marie Williams, Sophie Arnold, Petra Polgarova, Katerina Stroud, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Lina Grauslyte, Musarat Hussain, Mandeep Phull, Tatiana Pogreban, Lace Rosaroso, Erika Salciute, George Franke, Joanna Wong, Aparna George, Laura Ortiz-Ruiz de Gordoa, Emily Peasgood, Claire Phillips, Michelle Bates, Jo Dasgin, Jaspret Gill, Annette Nilsson, James Scriven, Carlos Castro Delgado, Deborah Dawson, Lijun Ding, Georgia Durrant, Obiageri Ezeobu, Sarah Farnell-Ward, Abiola Harrison, Rebecca Kanu, Susannah Leaver, Elena Maccacari, Soumendu Manna, Romina Pepermans Saluzzio, Joana Queiroz, Tinashe Samakomva, Christine Sicat, Joana Texeira, Edna Fernandes Da Gloria, Ana Lisboa, John Rawlins, Jisha Mathew, Ashley Kinch, William James Hurt, Nirav Shah, Victoria Clark, Maria Thanasi, Nikki Yun, Kamal Patel, Sara Bennett, Emma Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed Zaki, Azmerelda Abraheem, Peter Bamford, Kathryn Cawley, Charlie Dunmore, Maria Faulkner, Rumanah Girach, Helen Jeffrey, Rhianna Jones, Emily London, Imrun Nagra, Farah Nasir, Hannah Sainsbury, Clare Smedley, Tahera Patel, Matthew Smith, Srikanth Chukkambotla, Aayesha Kazi, Janice Hartley, Joseph Dykes, Muhammad Hijazi, Sarah Keith, Meherunnisa Khan, Janet Ryan-Smith, Philippa Springle, Jacqueline Thomas, Nick Truman, Samuel Saad, Dabheoc Coleman, Christopher Fine, Roseanna Matt, Bethan Gay, Jack Dalziel, Syamlan Ali, Drew Goodchild, Rhiannan Harling, Ravi Bhatterjee, Wendy Goddard, Chloe Davison, Stephen Duberly, Jeanette Hargreaves, Rachel Bolton, Miriam Davey, David Golden, Rebecca Seaman, Shiney Cherian, Sean Cutler, Anne Emma Heron, Anna Roynon-Reed, Tamas Szakmany, Gemma Williams, Owen Richards, Yusuf Cheema, Hollie Brooke, Sarah Buckley, Jose Cebrian Suarez, Ruth Charlesworth, Karen Hansson, John Norris, Alice Poole, Alastair Rose, Rajdeep Sandhu, Brendan Sloan, Elizabeth Smithson, Muthu Thirumaran, Veronica Wagstaff, Alexandra Metcalfe, Mark Brunton, Jess Caterson, Holly Coles, Matthew Frise, Sabi Gurung Rai, Nicola Jacques, Liza Keating, Emma Tilney, Shauna Bartley, Parminder Bhuie, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Bryan Yates, Jessica Reynolds, Helen Campbell, Maria Thompsom, Steve Dodds, Stacey Duffy, Sandra Greer, Karen Shuker, Ascanio Tridente, Reena Khade, Ashok Sundar, George Tsinaslanidis, Isobel Birkinshaw, Joseph Carter, Kate Howard, Joanne Ingham, Rosie Joy, Harriet Pearson, Samantha Roche, Zoe Scott, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, Maria Croft, Ian White, Victoria Frost, Maia Aquino, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Lim, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Christine Almaden-Boyle, Pauline Austin, Louise Cabrelli, Stephen Cole, Matt Casey, Susan Chapman, Clare Whyte, Yolanda Baird, Aaron Butler, Indra Chadbourn, Linda Folkes, Heather Fox, Amy Gardner, Raquel Gomez, Gillian Hobden, Luke Hodgson, Kirsten King, Michael Margarson, Tim Martindale, Emma Meadows, Dana Raynard, Yvette Thirlwall, David Helm, Jordi Margalef, Kristine Criste, Rebecca Cusack, Kim Golder, Hannah Golding, Oliver Jones, Samantha Leggett, Michelle Male, Martyna Marani, Kirsty Prager, Toran Williams, Belinda Roberts, Karen Salmon, Peter Anderson, Katie Archer, Karen Austin, Caroline Davis, Alison Durie, Olivia Kelsall, Jessica Thrush, Charlie Vigurs, Laura Wild, Hannah-Louise Wood, Helen Tranter, Alison Harrison, Nicholas Cowley, Michael McAlindon, Andrew Burtenshaw, Stephen Digby, Emma Low, Aled Morgan, Naiara Cother, Tobias Rankin, Sarah Clayton, Alex McCurdy, Cecilia Ahmed, Balvinder Baines, Sarah Clamp, Julie Colley, Risna Haq, Anne Hayes, Jonathan Hulme, Samia Hussain, Sibet Joseph, Rita Kumar, Zahira Maqsood, Manjit Purewal, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Jason Cupitt, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Bethan Deacon, Ceri Lynch, Carla Pothecary, Lisa Roche, Gwenllian Sera Howe, Jayaprakash Singh, Keri Turner, Hannah Ellis, Natalie Stroud, Jodie Hunt, Joy Dearden, Emma Dobson, Andy Drummond, Michelle Mulcahy, Sheila Munt, Grainne O'Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Susanne Cathcart, Katharine Duffy, Alex Puxty, Kathryn Puxty, Lynne Turner, Jane Ireland, Gary Semple, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Amanda Cowton, Andrea Kay, Melanie Kent, Kathryn Potts, Ami Wilkinson, Suzanne Campbell, Ellen Brown, Julie Melville, Jay Naisbitt, Rosane Joseph, Maria Lazo, Olivia Walton, Alan Neal, Peter Alexander, Schvearn Allen, Joanne Bradley-Potts, Craig Brantwood, Jasmine Egan, Timothy Felton, Grace Padden, Luke Ward, Stuart Moss, Susannah Glasgow, Lynn Abel, Michael Brett, Brian Digby, Lisa Gemmell, James Hornsby, Patrick MacGoey, Pauline O'Neil, Richard Price, Natalie Rodden, Kevin Rooney, Radha Sundaram, Nicola Thomson, Bridget Hopkins, Laura Thrasyvoulou, Heather Willis, Martyn Clark, Martina Coulding, Edward Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Rehman, Heather Savill, Victoria Turner, Charlotte Downes, Kathleen Holding, Katie Riches, Mary Hilton, Mel Hayman, Deepak Subramanian, Priya Daniel, Oluronke Adanini, Nikhil Bhatia, Maines Msiska, Rebecca Collins, Ian Clement, Bijal Patel, A. Gulati, Carole Hays, K. Webster, Anne Hudson, Andrea Webster, Elaine Stephenson, Louise McCormack, Victoria Slater, Rachel Nixon, Helen Hanson, Maggie Fearby, Sinead Kelly, Victoria Bridgett, Philip Robinson, Julie Camsooksai, Charlotte Humphrey, Sarah Jenkins, Henrik Reschreiter, Beverley Wadams, Yasmin Death, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Gillian Bell, Katy English, Amro Katary, Louise Wilcox, Michelle Bruce, Karen Connolly, Tracy Duncan, Helen T-Michael, Gabriella Lindergard, Samuel Hey, Claire Fox, Jordan Alfonso, Laura Jayne Durrans, Jacinta Guerin, Bethan Blackledge, Jade Harris, Martin Hruska, Ayaa Eltayeb, Thomas Lamb, Tracey Hodgkiss, Lisa Cooper, Joanne Rothwell, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Liana Lankester, Nikitas Nikitas, Colin Wells, Bethan Stowe, Kayleigh Spencer, Craig Brandwood, Lara Smith, Katie Birchall, Laurel Kolakaluri, Deborah Baines, Anila Sukumaran, Elena Apetri, Cathrine Basikolo, Laura Catlow, Bethan Charles, Paul Dark, Reece Doonan, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Tracey Cosier, Gemma Millen, Neil Richardson, Natasha Schumacher, Heather Weston, James Rand, Nicola Baxter, Steven Henderson, Sophie Kennedy-Hay, Christopher McParland, Laura Rooney, Malcolm Sim, Gordan McCreath, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James Morgan, Kirsten Sellick, Deborah Warren, Brian Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael Bentley, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Jocelyn Keshet-Price, Georgina Randell, Katie Stammers, Maria Bokhari, Vanessa Linnett, Rachael Lucas, Wendy McCormick, Jenny Ritzema, Amanda Sanderson, Helen Wild, Anthony Rostron, Alistair Roy, Lindsey Woods, Sarah Cornell, Fiona Wakinshaw, Kimberley Rogerson, Jordan Jarmain, Robert Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Caroline Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Georgia Bercades, David Brealey, Ingrid Hass, Niall MacCallum, Gladys Martir, Eamon Raith, Anna Reyes, Deborah Smyth, Letizia Zitter, Sarah Benyon, Suzie Marriott, Linda Park, Samantha Keenan, Elizabeth Gordon, Helen Quinn, Kizzy Baines, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, Krithivasan Praman, Alain Vuylsteke, Julie Zamikula, Bally Purewal, Vanessa Rivers, Stephanie Bell, Hayley Blakemore, Borislava Borislavova, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Kati Hayes, Matt Thomas, Ruth Worner, Kerry Smith, Deanna Stephens, Louise Mew, Esther Mwaura, Richard Stewart, Felicity Williams, Lynn Wren, Sara-Beth Sutherland, Emily Bevan, Jane Martin, Dawn Trodd, Geoff Watson, Caroline Wrey Brown, Amy Collins, Waqas Khaliq, Estefania Treus Gude, Olugbenga Akinkugbe, Alasdair Bamford, Emily Beech, Holly Belfield, Michael Bell, Charlene Davies, Gareth A.L. Jones, Tara McHugh, Hamza Meghari, Lauran O'Neill, Mark J. Peters, Samiran Ray, Ana Luisa Tomas, Iona Burn, Geraldine Hambrook, Katarina Manso, Ruth Penn, Pradeep Shanmugasundaram, Julie Tebbutt, Danielle Thornton, Jade Cole, Rhys Davies, Donna Duffin, Helen Hill, Ben Player, Emma Thomas, Angharad Williams, Denise Griffin, Nycola Muchenje, Mcdonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Reni Jacob, Cathy Jones, Craig Denmade, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Patricia Doble, Joanne Hutter, Corinne Pawley, Charmaine Shovelton, Marius Vaida, Deborah Butcher, Susie O'Sullivan, Nicola Butterworth-Cowin, Norfaizan Ahmad, Joann Barker, Kris Bauchmuller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Gary H. Mills, Ajay Raithatha, Matthew Wiles, Jayne Willson, Helen Newell, Alison Lye, Lorenza Nwafor, Claire Jarman, Sarah Rowland-Jones, David Foote, Joby Cole, Roger Thompson, James Watson, Lisa Hesseldon, Irene Macharia, Luke Chetam, Jacqui Smith, Amber Ford, Samantha Anderson, Kathryn Birchall, Kay Housley, Sara Walker, Leanne Milner, Helena Hanratty, Helen Trower, Patrick Phillips, Simon Oxspring, Ben Donne, Catherine Jardine, Dewi Williams, Alasdair Hay, Rebecca Flanagan, Gareth Hughes, Scott Latham, Emma McKenna, Jennifer Anderson, Robert Hull, Kat Rhead, Carina Cruz, Natalie Pattison, Rob Charnock, Denise McFarland, Denise Cosgrove, Ashar Ahmed, Anna Morris, Srinivas Jakkula, Asifa Ali, Megan Brady, Sam Dale, Annalisa Dance, Lisa Gledhill, Jill Greig, Kathryn Hanson, Kelly Holdroyd, Marie Home, Diane Kelly, Ross Kitson, Lear Matapure, Deborah Melia, Samantha Mellor, Tonicha Nortcliffe, Jez Pinnell, Matthew Robinson, Lisa Shaw, Ryan Shaw, Lesley Thomis, Alison Wilson, Tracy Wood, Lee-Ann Bayo, Ekta Merwaha, Tahira Ishaq, Sarah Hanley, Meg Hibbert, Dariusz Tetla, Chrsitopher Woodford, Latha Durga, Gareth Kennard-Holden, Debbie Branney, Jordan Frankham, Sally Pitts, Nigel White, Shondipon Laha, Mark Verlander, Alexandra Williams, Abdelhakim Altabaibeh, Ana Alvaro, Kayleigh Gilbert, Louise Ma, Loreta Mostoles, Chetan Parmar, Kathryn Simpson, Champa Jetha, Lauren Booker, Anezka Pratley, Colene Adams, Anita Agasou, Tracie Arden, Amy Bowes, Pauline Boyle, Mandy Beekes, Heather Button, Nigel Capps, Mandy Carnahan, Anne Carter, Danielle Childs, Denise Donaldson, Kelly Hard, Fran Hurford, Yasmin Hussain, Ayesha Javaid, James Jones, Sanal Jose, Michael Leigh, Terry Martin, Helen Millward, Nichola Motherwell, Rachel Rikunenko, Jo Stickley, Julie Summers, Louise Ting, Helen Tivenan, Louise Tonks, Rebecca Wilcox, Maureen Holland, Natalie Keenan, Marc Lyons, Helen Wassall, Chris Marsh, Mervin Mahenthran, Emma Carter, Thomas Kong, Helen Blackman, Ben Creagh-Brown, Sinead Donlon, Natalia Michalak-Glinska, Sheila Mtuwa, Veronika Pristopan, Armorel Salberg, Eleanor Smith, Sarah Stone, Charles Piercy, Jerik Verula, Dorota Burda, Rugia Montaser, Lesley Harden, Irving Mayangao, Cheryl Marriott, Paul Bradley, Celia Harris, Susan Anderson, Eleanor Andrews, Janine Birch, Emma Collins, Kate Hammerton, Ryan O'Leary, Michele Clark, Sarah Purvis, Russell Barber, Claire Hewitt, Annette Hilldrith, Karen Jackson-Lawrence, Sarah Shepardson, Maryanne Wills, Susan Butler, Silvia Tavares, Amy Cunningham, Julia Hindale, Sarwat Arif, Sarah Bean, Karen Burt, Michael Spivey, Carrie Demetriou, Charlotte Eckbad, Sarah Hierons, Lucy Howie, Sarah Mitchard, Lidia Ramos, Alfredo Serrano-Ruiz, Katie White, Fiona Kelly, Daniele Cristiano, Natalie Dormand, Zohreh Farzad, Mahitha Gummadi, Kamal Liyanage, Brijesh Patel, Sara Salmi, Geraldine Sloane, Vicky Thwaites, Mathew Varghese, Anelise C. Zborowski, John Allan, Tim Geary, Gordon Houston, Alistair Meikle, Peter O'Brien, Miranda Forsey, Agilan Kaliappan, Anne Nicholson, Joanne Riches, Mark Vertue, Elizabeth Allan, Kate Darlington, Ffyon Davies, Jack Easton, Sumit Kumar, Richard Lean, Daniel Menzies, Richard Pugh, Xinyi Qiu, Llinos Davies, Hannah Williams, Jeremy Scanlon, Gwyneth Davies, Callum Mackay, Joannne Lewis, Stephanie Rees, Metod Oblak, Monica Popescu, Mini Thankachen, Andrew Higham, Kerry Simpson, Jayne Craig, Rosie Baruah, Sheila Morris, Susie Ferguson, Amy Shepherd, Luke Stephen Prockter Moore, Marcela Paola Vizcaychipi, Laura Gomes de Almeida Martins, Jaime Carungcong, Inthakab Ali Mohamed Ali, Karen Beaumont, Mark Blunt, Zoe Coton, Hollie Curgenven, Mohamed Elsaadany, Kay Fernandes, Sameena Mohamed Ally, Harini Rangarajan, Varun Sarathy, Sivarupan Selvanayagam, Dave Vedage, Matthew White, Mandy Gill, Paul Paul, Valli Ratnam, Sarah Shelton, Inez Wynter, Siobhain Carmody, Valerie Joan Page, Claire Marie Beith, Karen Black, Suzanne Clements, Alan Morrison, Dominic Strachan, Margaret Taylor, Michelle Clarkson, Stuart D'Sylva, Kathryn Norman, Fiona Auld, Joanne Donnachie, Ian Edmond, Lynn Prentice, Nikole Runciman, Dario Salutous, Lesley Symon, Anne Todd, Patricia Turner, Abigail Short, Laura Sweeney, Euan Murdoch, Dhaneesha Senaratne, Michaela Hill, Thogulava Kannan, Wild Laura, Rikki Crawley, Abigail Crew, Mishell Cunningham, Allison Daniels, Laura Harrison, Susan Hope, Ken Inweregbu, Sian Jones, Nicola Lancaster, Jamie Matthews, Alice Nicholson, Gemma Wray, Helen Langton, Rachel Prout, Malcolm Watters, Catherine Novis, Anthony Barron, Ciara Collins, Sundeep Kaul, Heather Passmore, Claire Prendergast, Anna Reed, Paula Rogers, Rajvinder Shokkar, Meriel Woodruff, Hayley Middleton, Oliver Polgar, Claire Nolan, Kanta Mahay, Dawn Collier, Anil Hormis, Victoria Maynard, Cheryl Graham, Rachel Walker, Ellen Knights, Alicia Price, Alice Thomas, Chris Thorpe, Teresa Behan, Caroline Burnett, Jonathan Hatton, Elaine Heeney, Atideb Mitra, Maria Newton, Rachel Pollard, Rachael Stead, Vishal Amin, Elena Anastasescu, Vikram Anumakonda, Komala Karthik, Rizwana Kausar, Karen Reid, Jacqueline Smith, Janet Imeson-Wood, Denise Skinner, Jane Gaylard, Dee Mullan, Julie Newman, Alison Brown, Vikki Crickmore, Gabor Debreceni, Joy Wilkins, Liz Nicol, Rosie Reece-Anthony, Mark Birt, Alison Ghosh, Emma Williams, Louise Allen, Eva Beranova, Nikki Crisp, Joanne Deery, Tracy Hazelton, Alicia Knight, Carly Price, Sorrell Tilbey, Salah Turki, Sharon Turney, Joshua Cooper, Cheryl Finch, Sarah Liderth, Alison Quinn, Natalia Waddington, Tina Coventry, Susan Fowler, Michael MacMahon, Amanda McGregor, Anne Cowley, Judith Highgate, Jane Gregory, Susan O'Connell, Tim Smith, Luigi Barberis, Shameer Gopal, Nichola Harris, Victoria Lake, Stella Metherell, Elizabeth Radford, Amelia Daniel, Joanne Finn, Rajnish Saha, Nikki White, Phil Donnison, Fiona Trim, Beena Eapen, Jenny Birch, Laura Bough, Josie Goodsell, Rebecca Tutton, Patricia Williams, Sarah Williams, Barbara Winter-Goodwin, Ailstair Nichol, Kathy Brickell, Michelle Smyth, Lorna Murphy, Samantha Coetzee, Alistair Gales, Igor Otahal, Meena Raj, Craig Sell, Paula Hilltout, Jayne Evitts, Amanda Tyler, Joanne Waldron, Kate Beesley, Sarah Board, Agnieszka Kubisz-Pudelko, Alison Lewis, Jess Perry, Lucy Pippard, Di Wood, Clare Buckley, Peter Barry, Neil Flint, Patel Rekha, Dawn Hales, Lara Bunni, Claire Jennings, Monica Latif, Rebecca Marshall, Gayathri Subramanian, Peter J. McGuigan, Christopher Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Watkins Claire, Liam Botfield, Joanna Butler, Catherine Dexter, Jo Fletcher, Atul Garg, Aditya Kuravi, Poonam Ranga, Emma Virgilio, Zakaula Belagodu, Bridget Fuller, Anca Gherman, Olumide Olufuwa, Remi Paramsothy, Carmel Stuart, Naomi Oakley, Charlotte Kamundi, David Tyl, Katy Collins, Pedro Silva, June Taylor, Laura King, Charlotte Coates, Maria Crowley, Phillipa Wakefield, Jane Beadle, Laura Johnson, Janet Sargeant, Madeleine Anderson, Ailbhe Brady, Rebekah Chan, Jeff Little, Shane McIvor, Helena Prady, Helen Whittle, Bijoy Mathew, Ben Attwood, Penny Parsons, Geraldine Ward, Pamela Bremmer, West Joe, Baird Tracy, Ruddy Jim, Ellie Davies, Sonia Sathe, Catherine Dennis, Alastair McGregor, Victoria Parris, Sinduya Srikaran, Anisha Sukha, Noreen Clarke, Jonathan Whiteside, Mairi Mascarenhas, Avril Donaldson, Joanna Matheson, Fiona Barrett, Marianne O'Hara, Laura Okeefe, Clare Bradley, Christine Eastgate-Jackson, Helder Filipe, Daniel Martin, Amitaa Maharajh, Sara Mingo Garcia, Glykeria Pakou, Mark De Neef, Kathy Dent, Elizabeth Horsley, Muhmmad Nauman Akhtar, Sandra Pearson, Dorota Potoczna, Sue Spencer, Melanie Clapham, Rosemary Harper, Una Poultney, Polly Rice, Rachel Mutch, Lisa Armstrong, Hayley Bates, Emma Dooks, Fiona Farquhar, Brigid Hairsine, Chantal McParland, Sophie Packham, Rehana Bi, Barney Scholefield, Lydia Ashton, Linsha George, Sophie Twiss, David Wright, Manish Chablani, Amy Kirkby, Kimberley Netherton, Kim Davies, Linda O'Brien, Zohra Omar, Emma Perkins, Tracy Lewis, Isobel Sutherland, Karen Burns, Dr Ben Chandler, Kerry Elliott, Janine Mallinson, Alison Turnbull, Prisca Gondo, Bernard Hadebe, Abdul Kayani, Bridgett Masunda, Taya Anderson, Dan Hawcutt, Laura O'Malley, Laura Rad, Naomi Rogers, Paula Saunderson, Kathryn Sian Allison, Deborah Afolabi, Jennifer Whitbread, Dawn Jones, Rachael Dore, Matthew Halkes, Pauline Mercer, Lorraine Thornton, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Ritoo Kapoor, David Loader, Karen Castle, Sally Humphreys, Ruth Tampsett, Katherine Mackintosh, Amanda Ayers, Wendy Harrison, Julie North, Suzanne Allibone, Roman Genetu, Vidya Kasipandian, Amit Patel, Ainhi Mac, Anthony Murphy, Parisa Mahjoob, Roonak Nazari, Lucy Worsley, Andrew Fagan, Thomas Bemand, Ethel Black, Arnold Dela Rosa, Ryan Howle, Shaman Jhanji, Ravishankar Rao Baikady, Kate Colette Tatham, Benjamin Thomas, Dina Bell, Rosalind Boyle, Katie Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Abigail Taylor, Rachel Anne Hughes, Helen Thomas, Alun Rees, Michaela Duskova, Janet Phipps, Suzanne Brooks, Michelle Edwards, Sheena Quaid, Ekaterina Watson, Adam Brayne, Emma Fisher, Jane Hunt, Peter Jackson, Duncan Kaye, Nicholas Love, Juliet Parkin, Victoria Tuckey, Lynne Van Koutrik, Sasha Carter, Benedict Andrew, Louise Findlay, Katie Adams, Jen Service, Alison Williams, Claire Cheyne, Anne Saunderson, Sam Moultrie, Miranda Odam, Kathryn Hall, Isheunesu Mapfunde, Charlotte Willis, Alex Lyon, Chunda Sri-Chandana, Joslan Scherewode, Lorraine Stephenson, Sarah Marsh, John Hardy, Henry Houlden, Eleanor Moncur, Ambreen Tariq, Arianna Tucci, Maria Hobrok, Ronda Loosley, Heather McGuinness, Helen Tench, Rebecca Wolf-Roberts, Val Irvine, Benjamin Shelley, Claire Gorman, Abhinav Gupta, Elizabeth Timlick, Rebecca Brady, Barry Milligan, Arianna Bellini, Jade Bryant, Anton Mayer, Amy Pickard, Nicholas Roe, Jason Sowter, Alex Howlett, Katy Fidler, Emma Tagliavini, and Kevin Donnelly

Subjects
SARS-CoV-2, host genetics, toll-like receptor 7, targeted sequencing, rare variants, variant collapsing analysis, Genetics, QH426-470
Abstract

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Published
2024
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46. Breast Cancer Diagnosis Using Virtualization and Extreme Learning Algorithm Based on Deep Feed Forward Networks

Author

G Siva Shankar, Edeh Michael Onyema, Balasubramanian Prabhu Kavin, Venkataramaiah Gude, and BVV Siva Prasad

Subjects
Biology (General), QH301-705.5
Abstract

One of the leading causes of death for women worldwide is breast cancer. Early detection and prompt treatment can reduce the risk of breast cancer-related death. Cloud computing and machine learning are crucial for disease diagnosis today, but they are especially important for those who live in distant places with poor access to healthcare. While machine learning-based diagnosis tools act as primary readers and aid radiologists in correctly diagnosing diseases, cloud-based technology can also assist remote diagnostics and telemedicine services. The promise of techniques based on Artificial Neural Networks (ANN) for sickness diagnosis has attracted the attention of several re-searchers. The 4 methods for the proposed research include preprocessing, feature extraction, and classification. A Smart Window Vestige Deletion (SWVD) technique is initially suggested for preprocessing. It consists of Savitzky-Golay (S-G) smoothing, updated 2-stage filtering, and adaptive time window division. This technique separates each channel into multiple time periods by adaptively pre-analyzing its specificity. On each window, an altered 2-stage filtering process is then used to retrieve some tumor information. After applying S-G smoothing and integrating the broken time sequences, the process is complete. In order to deliver effective feature extraction, the Deep Residual based Multiclass for architecture (DRMFA) is used. In histological photos, identify characteristics at the cellular and tissue levels in both tiny and large size patches. Finally, a fresh customized strategy that combines a better crow forage-ELM. Deep learning and the Extreme Learning Machine (ELM) are concepts that have been developed (ACF-ELM). When it comes to diagnosing ailments, the cloud-based ELM performs similarly to certain cutting-edge technology. The cloud-based ELM approach beats alternative solutions, according to the DDSM and INbreast dataset results. Significant experimental results show that the accuracy for data inputs is 0.9845, the precision is 0.96, the recall is 0.94, and the F1 score is 0.95.

Published
2024
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47. Two-way Dispatched function in Sonic hedgehog shedding and transfer to high-density lipoproteins

Author

Kristina Ehring, Sophia Friederike Ehlers, Jurij Froese, Fabian Gude, Janna Puschmann, and Kay Grobe

Subjects
Signaling, hedgehog, proteolysis, Dispatched, high-density lipoprotein, cholesterol, Medicine, Science, Biology (General), QH301-705.5
Abstract

The Sonic hedgehog (Shh) signaling pathway controls embryonic development and tissue homeostasis after birth. This requires regulated solubilization of dual-lipidated, firmly plasma membrane-associated Shh precursors from producing cells. Although it is firmly established that the resistance-nodulation-division transporter Dispatched (Disp) drives this process, it is less clear how lipidated Shh solubilization from the plasma membrane is achieved. We have previously shown that Disp promotes proteolytic solubilization of Shh from its lipidated terminal peptide anchors. This process, termed shedding, converts tightly membrane-associated hydrophobic Shh precursors into delipidated soluble proteins. We show here that Disp-mediated Shh shedding is modulated by a serum factor that we identify as high-density lipoprotein (HDL). In addition to serving as a soluble sink for free membrane cholesterol, HDLs also accept the cholesterol-modified Shh peptide from Disp. The cholesteroylated Shh peptide is necessary and sufficient for Disp-mediated transfer because artificially cholesteroylated mCherry associates with HDL in a Disp-dependent manner, whereas an N-palmitoylated Shh variant lacking C-cholesterol does not. Disp-mediated Shh transfer to HDL is completed by proteolytic processing of the palmitoylated N-terminal membrane anchor. In contrast to dual-processed soluble Shh with moderate bioactivity, HDL-associated N-processed Shh is highly bioactive. We propose that the purpose of generating different soluble forms of Shh from the dual-lipidated precursor is to tune cellular responses in a tissue-type and time-specific manner.

Published
2024
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48. Hypothesis testing for matched pairs with missing data by maximum mean discrepancy: An application to continuous glucose monitoring

Author

Matabuena, Marcos, Félix, Paulo, Ditzhaus, Marc, Vidal, Juan, and Gude, Francisco

Subjects
Statistics - Methodology, Statistics - Machine Learning
Abstract

A frequent problem in statistical science is how to properly handle missing data in matched paired observations. There is a large body of literature coping with the univariate case. Yet, the ongoing technological progress in measuring biological systems raises the need for addressing more complex data, e.g., graphs, strings and probability distributions, among others. In order to fill this gap, this paper proposes new estimators of the maximum mean discrepancy (MMD) to handle complex matched pairs with missing data. These estimators can detect differences in data distributions under different missingness mechanisms. The validity of this approach is proven and further studied in an extensive simulation study, and results of statistical consistency are provided. Data from continuous glucose monitoring in a longitudinal population-based diabetes study are used to illustrate the application of this approach. By employing the new distributional representations together with cluster analysis, new clinical criteria on how glucose changes vary at the distributional level over five years can be explored.

Published
2022

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