Publications by authors named "Ware J"

Background: Fully automatic skull-stripping and tumor segmentation are crucial for monitoring pediatric brain tumors (PBT). Current methods, however, often lack generalizability, particularly for rare tumors in the sellar/suprasellar regions and when applied to real-world clinical data in limited data scenarios. To address these challenges, we propose AI-driven techniques for skull-stripping and tumor segmentation.

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Aims: Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).

Methods And Results: Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included.

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Article Synopsis
  • - Hypertrophic cardiomyopathy (HCM) was traditionally seen as caused by rare, high-risk single-gene changes, but new research indicates common low-risk variants (LowSVs) also play a significant role in the disease.
  • - In a study of over 6000 patients, 12 LowSVs were discovered, which are relatively common in the general population and more prevalent in HCM patients, suggesting they may influence disease severity and risk.
  • - While LowSVs alone are linked to a later onset of HCM and fewer complications, their presence alongside more severe genetic variants increases health risks significantly.
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  • * A large study involving nearly 10,000 DCM cases and close to a million controls identified 70 significant genetic locations linked to the disease, revealing the importance of heart muscle cells in its development.
  • * The research also indicates that factors like higher body weight and blood pressure may contribute to DCM, and genetic risk scores can help predict the condition across different populations.
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  • Dilated cardiomyopathy (DCM) is a major cause of heart failure, and this study analyzes genetic factors by examining 14,256 DCM cases and 36,203 participants from the UK Biobank for related traits.
  • Researchers discovered 80 genomic risk loci and pinpointed 62 potential effector genes tied to DCM, including some linked to rare variants.
  • The study uses advanced transcriptomics to explore how cellular functions contribute to DCM, showing that polygenic scores can help predict the disease in the general population and emphasize the importance of genetic testing and development of precise treatments.
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  • Cardiac trabeculae are muscular structures in the heart that have a crucial but not fully understood role in heart function and disease.
  • A study involving over 47,000 participants from the UK Biobank found links between trabecular shape and rare genetic variants in 56 genes related to heart muscle function and development.
  • The research also revealed 68 genetic regions associated with heart condition pathways, indicating that variations in trabeculation may influence the severity of heart diseases like hypertrophic and dilated cardiomyopathy.
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  • The study explores the use of advanced neural network-derived ECG features to predict cardiovascular disease and mortality, aiming to uncover subtle, important indicators that traditional methods might miss.
  • Using data from over 1.8 million patients and various international cohorts, researchers identified three distinct phenogroups, with one, phenogroup B, showing a significantly higher mortality risk—20% more than phenogroup A.
  • The findings suggest that neural network ECG features not only indicate future health risks like atrial fibrillation and ischemic heart disease but also highlight specific genetic loci that may contribute to these risks.
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Background: An improved understanding of the natural history in NYHA functional class I patients with obstructive hypertrophic cardiomyopathy (oHCM) is needed.

Objectives: Using a multicenter registry (SHaRe [Sarcomeric Human Cardiomyopathy Registry]), this study described the natural history in patients with oHCM who were classified as NYHA functional class I at the initial visit compared with patients classified as NYHA functional class II and reported baseline characteristics associated with incident clinical events.

Methods: Incident events assessed included a composite of NYHA functional class III to IV symptoms, left ventricular ejection fraction <50%, atrial fibrillation, stroke, ventricular arrhythmias, septal reduction therapy, ventricular assist device or transplantation, or death.

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Background: Hypereosinophilic syndromes (HES) are defined as hypereosinophilia with eosinophil-related clinical manifestations, some of which overlap in presentation with asthma, atopic dermatitis, eosinophilic esophagitis, and/or chronic rhinosinusitis with nasal polyps. Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count and rare eosinophil-related complications.

Objective: To determine whether eosinophil-related complications of dupilumab are increased in HES.

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Background: Neonatal Intensive Care Units utilize incubators to sustain core temperatures associated with transepidermal water loss. High relative humidity in incubators provides an environment for fungi to grow. In August 2022, mold was identified growing in 11 (85%) Neonatal Intensive Care Unit incubators.

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Background: Cardiomyopathies are clinically important conditions, with a strong genetic component. National genomic initiatives such as 100,000 Genome Project (100KGP) provide opportunity to study these rare conditions at scale beyond conventional research studies.

Methods: We present the clinical and molecular characteristics of the 100KGP cohort, comparing paediatric and adult probands with diverse cardiomyopathies.

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Article Synopsis
  • - The AI-ECG risk estimator (AIRE) platform was developed to improve predictions of future disease and mortality risks from electrocardiograms (ECGs), addressing limitations in existing models related to individual actionability and biological plausibility.
  • - AIRE utilizes deep learning and survival analysis on a massive dataset of over 1.16 million ECGs to predict patient-specific mortality risks and timelines, validated across diverse international cohorts.
  • - The platform demonstrated high accuracy for predicting various health risks, such as all-cause mortality and heart failure, and identified biological pathways linked to cardiac health, making it a promising tool for clinical use globally.
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Bacterial membrane vesicle (BMV) nanoparticles are secreted naturally by bacteria throughout their lifecycle and are a rich source of biomarkers from the parent bacteria, but they are currently underutilized for clinical diagnostic applications, such as pathogen identification, due to the time-consuming and low-yield nature of traditional recovery methods required for analysis. The recovery of BMVs is particularly difficult from complex biological fluids. Here, we demonstrate a recovery method that uses dielectrophoretic (DEP) forces generated on electrokinetic microfluidic chips to isolate and analyze BMVs from human plasma.

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Insect coloration has evolved in response to multiple pressures, and in Odonata (dragonflies and damselflies) a body of work supports a role of wing color in a variety of visual signals and potentially in thermoregulation. Previous efforts have focused primarily on melanistic coloration even though wings are often multicolored, and there has yet to be comprehensive comparative analyses of wing color across broad geographic regions and phylogenetic groups. Percher vs.

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Background: Aerobic exercise capacity is an independent predictor of mortality in dilated cardiomyopathy (DCM), but the central mechanisms contributing to exercise intolerance in DCM are unknown. The aim of this study was to characterize coronary microvascular function in DCM and determine if cardiovascular magnetic resonance (CMR) measures are associated with aerobic exercise capacity.

Methods: Prospective case-control comparison of adults with DCM and matched controls.

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Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD.

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Objective: The objective was to evaluate the safety and efficacy of ultra-rapid-acting insulin with the Boost and Ease-off features of the Cambridge hybrid closed-loop system.

Methods: A secondary analysis of Boost and Ease-off from two double-blind, randomized, crossover hybrid closed-loop studies comparing (1) Fiasp to insulin aspart (n = 25), and (2) Lyumjev to insulin lispro (n = 26) was carried out. Mean glucose on initialization of Boost and Ease-off, change in glucose 60 and 120 minutes after initialization, duration and frequency of use, mean glucose, and time in, above, and below target glucose range were calculated for periods of Boost use, Ease-off use, or neither.

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Objective: We aimed to evaluate the longer-term safety and efficacy of hybrid closed-loop (CL) therapy in very young children with type 1 diabetes (T1D).

Research Design And Methods: Following a 16-week multinational, randomized crossover trial comparing hybrid CL with sensor-augmented pump (SAP) therapy in 74 very young children aged 1-7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared with the primary-phase SAP period and primary-phase CL period.

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Background: A diagnosis of type 1 diabetes in a young person can create vulnerability for sleep. Historically it has been rare for young people to be offered a closed-loop system soon after diagnosis meaning that studies examining sleep under these circumstances in comparison with standard treatment have not been possible. In this study, we examine sleep in young people (and their parents) who were provided with hybrid closed-loop therapy at diagnosis of type 1 diabetes versus those who receive standard treatment over a 2-year period.

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Article Synopsis
  • Septal reduction therapy (SRT) significantly improves symptoms for patients with obstructive hypertrophic cardiomyopathy (HCM), but its long-term results and predictors of adverse outcomes still need more study.* -
  • An analysis of data from the SHARE registry revealed that among 1,832 patients who underwent SRT, the 30-day mortality rate was low at 0.4%, and after approximately 6.8 years, rates for HCM-related death, heart failure, and ventricular arrhythmias were relatively low.* -
  • Key findings included that older age at SRT increases risks for HCM death and heart failure outcomes, while female patients showed higher susceptibility to heart failure complications post-treatment.*
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Aims: In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after therapy withdrawal. This follow-up investigates the longer-term effects of therapy withdrawal.

Methods And Results: TRED-HF was a randomized trial investigating heart failure therapy withdrawal in patients with recovered DCM over 6 months.

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Deep learning models can predict uptake of emerging contaminants in plants with improved accuracy because they leverage advanced data-driven approaches to capture non-linear relationships that traditional models struggle to address. Traditional models suffer from low accuracy in predicting transpiration stream concentration factor (TSCF) and root concentration factor (RCF). This study applied deep neural networks (DNN), recurrent neural networks (RNN), and long short-term memory (LSTM) to enhance the accuracy of predictive models for TSCF and RCF.

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In the past decade, genetic testing for cardiac disease has become part of routine clinical care. A genetic diagnosis provides the possibility to clarify risk for relatives. For family planning, a genetic diagnosis provides reproductive options, including prenatal diagnosis and preimplantation genetic testing, that can prevent an affected parent from having a child with the genetic predisposition.

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Article Synopsis
  • Pathogenic variants in the desmoplakin (DSP) gene lead to a unique type of cardiomyopathy that doesn't fit neatly into existing categories like DCM, NDLVC, or ARVC, with limited past studies on potential predictors of severe outcomes.
  • Researchers analyzed 800 patients with DSP variants from a global network over an average of 3.7 years, finding that 17.4% experienced sustained ventricular arrhythmias (VAs) and 9.0% had heart failure (HF) hospitalizations.
  • Key risk factors for developing VAs included female sex, history of non-sustained and sustained VAs, and lower left ventricular ejection fraction, while T-wave inversion was linked to HF
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