Publications by authors named "Geoffrey Holmes"

Background: Gastroenterologists still raise concerns about adopting a non-biopsy strategy for diagnosing celiac disease (CeD) in adults.

Aim: To assess the performance of the concurrent detection of two autoantibodies targeting two independent antigens, tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP).

Methods: This prospective, multicenter, binational study collected consecutive patients with a high pre-test probability for CeD.

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Background: Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease.

Methods: In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy.

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No-biopsy diagnostic approach to coeliac disease.

Gastroenterol Hepatol Bed Bench

January 2023

This brief review outlines contributions that Michael Marsh and others made to understanding the structure and function of the upper small bowel mucosa and the formation of abnormalities that occur in coeliac disease (CD). He introduced his classification of lesions 30 years ago that has been widely adopted. The development and use of serological tests to screen for and diagnose CD in children and adults without the need for a small bowel biopsy in a considerable proportion is also recognised and will gain traction.

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SHapley Additive exPlanation (SHAP) values (Lundberg & Lee, 2017) provide a game theoretic interpretation of the predictions of machine learning models based on Shapley values (Shapley, 1953). While exact calculation of SHAP values is computationally intractable in general, a recursive polynomial-time algorithm called TreeShap (Lundberg et al., 2020) is available for decision tree models.

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Cross-domain few-shot learning has many practical applications. This paper attempts to shed light on suitable configurations of feature exactors and 'shallow' classifiers in this machine learning setting. We apply ResNet-based feature extractors pretrained on two versions of the ImageNet dataset to five target domains with different degrees of similarity to ImageNet, varying the feature extractor size, the network stage at which features are extracted, and the learning algorithm applied to the extracted features.

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Background: Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation.

Objectives: We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands.

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Article Synopsis
  • The study looked for ways to help older women with breast cancer make better treatment choices by testing two decision support tools.
  • The tools included an online risk predictor, a decision guide, and an information booklet to help with choices like surgery or chemotherapy.
  • Researchers found that many doctors and patients didn’t always use the online tools due to reasons like lack of internet access or patients already having made decisions.
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Background: Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL).

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Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective.

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Background: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy.

Methods: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years.

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In vivo direct drug targeting aims at delivering drug molecules loaded on microrobots to the diseased site using the shortest possible physiological routes, which potentially improves targeting efficiency and reduces systemic toxicity. It is thus essential to consider realistic in-body limitations for direct drug targeting applications. Here, we present a novel controller for microrobot maneuver by considering four key in vivo constraints: non-Euclidean structure of capillaries, irreversibility of blood flow, invisibility of microvasculature, and inaccuracy of microrobot tracking.

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Introduction: Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study.

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Objectives: The presence of dementia co-existing with a diagnosis of breast cancer may render management more challenging and have a substantial impact on oncological outcomes. The aim of this study was to examine the treatment and outcomes of older women with co-existing cognitive impairment and primary breast cancer.

Materials And Methods: A prospective, multicentre UK cohort study of women aged 70 years or over with primary operable breast cancer.

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Background: Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET.

Methods: Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer.

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In this paper, we present a novel controller for steering nanorobots in lattice-like vessel systems while avoiding potential obstacles such as the vessel walls without any prior knowledge of the obstacles' positions. The proposed control method consists of two sub-modules, namely a blind obstacle avoidance (BOA) and a model predictive control (MPC). In the case that a nanorobot might encounter an obstacle on its path, the BOA module is activated, which gives rise to a desirable heading angle to change the direction of the nanorobot's movement to bypass the obstacle.

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Recent progress in the development of new methods for cancer treatment has shown advantages of multiple therapies over mono-therapy. In particular, direct drug targeting (DDT) combined with mixed immunotherapy and chemotherapy has the potential to mitigate the undesired side-effects allied with conventional therapies, where nanorobots in DDT carry therapeutic agents through the blood vessel channel in order to localize and target diseased tissue with a safe drug interaction. This process can be modeled by a "touchable" (i.

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Objective: The performance of targeted immuno-chemotherapy of tumor is highly exposed to drug absorption in systemic circulation, which reduces its efficiency and increases side-effects. Direct drug targeting (DDT) combined with immuno-chemotherapy has the potential to mitigate the undesired systemic exposure, by using drug-loaded nanorobots to target cancer cells with the shortest possible physiological routes. This process can be modeled by the "touchable" (i.

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The development of highly performing serological tests to identify patients with coeliac disease (CD), allowed large scale screening studies to be carried out and the results transformed our understanding of the prevalence of the condition in the general population. The next logical step was to ask whether CD could be reliably diagnosed by these tests without the need for small intestinal biopsies. This was shown to be the case.

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Objective: With the advent of screening tests, it was hypothesised that milder cases of coeliac disease coming to diagnosis might have reduced risk of mortality. An earlier publication did not support this view. We have re-examined this issue employing a larger number of patients followed for a further 8 years.

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Objectives: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens.

Design: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015.

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Objective: To determine trends in diagnosis of coeliac disease (CD) in patients attending a single centre 1958-2014 and provide figures for prevalence and incidence in those born in Derby city over 4 decades. To explore a link between deprivation and prevalence and characteristics of CD in Asians.

Design: An unselected, consecutive series of 2410 adult patients with CD diagnosed in the catchment area of the Derby hospitals was identified.

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Objectives: Growing evidence supports the view that the diagnosis of coeliac disease (CD) can be made by serological tests alone, although this approach is still not widely accepted. We previously showed in retrospective and prospective studies that in adults an IgA-tissue transglutaminase antibody cut-off can be defined above which the positive predictive value for CD is 100%. Following a change in the analytical method for measuring the antibody, our objectives were to re-examine this finding in a larger series of adults to ascertain whether a diagnosis of CD can be reliably made in a proportion of patients without the need for small bowel biopsy and to re-evaluate the diagnostic guidelines used in our centre.

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