Publications by authors named "Ruddle R"

Article Synopsis
  • Diffuse hemispheric gliomas, specifically H3G34R/V-mutant, are aggressive brain tumors with no current targeted therapies and come from neural precursor cells.
  • Researchers found that these tumors display developmental patterns similar to healthy brain interneurons and identified key genes that these tumor cells depend on, especially CDK6.
  • Targeting CDK6 with inhibitors showed promising results in reducing tumor growth and improving survival in experimental models, with one patient showing a significant response to treatment.
View Article and Find Full Text PDF

Introduction: Structured medication reviews (SMRs), introduced in the United Kingdom (UK) in 2020, aim to enhance shared decision-making in medication optimisation, particularly for patients with multimorbidity and polypharmacy. Despite its potential, there is limited empirical evidence on the implementation of SMRs, and the challenges faced in the process. This study is part of a larger DynAIRx (Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity) project which aims to introduce Artificial Intelligence (AI) to SMRs and develop machine learning models and visualisation tools for patients with multimorbidity.

View Article and Find Full Text PDF

Inflammation is a hallmark of cancer. In patients with cancer, peripheral blood myeloid expansion, indicated by a high neutrophil-to-lymphocyte ratio, associates with shorter survival and treatment resistance across malignancies and therapeutic modalities. Whether myeloid inflammation drives progression of prostate cancer in humans remain unclear.

View Article and Find Full Text PDF

The use of good-quality data to inform decision making is entirely dependent on robust processes to ensure it is fit for purpose. Such processes vary between organisations, and between those tasked with designing and following them. In this article we report on a survey of 53 data analysts from many industry sectors, 24 of whom also participated in in-depth interviews, about computational and visual methods for characterizing data and investigating data quality.

View Article and Find Full Text PDF

Background: Structured Medication Reviews (SMRs) are intended to help deliver the NHS Long Term Plan for medicines optimisation in people living with multiple long-term conditions and polypharmacy. It is challenging to gather the information needed for these reviews due to poor integration of health records across providers and there is little guidance on how to identify those patients most urgently requiring review.

Objective: To extract information from scattered clinical records on how health and medications change over time, apply interpretable artificial intelligence (AI) approaches to predict risks of poor outcomes and overlay this information on care records to inform SMRs.

View Article and Find Full Text PDF

Objectives: Missing data is the most common data quality issue in electronic health records (EHRs). Missing data checks implemented in common analytical software are typically limited to counting the number of missing values in individual fields, but researchers and organisations also need to understand multifield missing data patterns to better inform advanced missing data strategies for which counts or numerical summaries are poorly suited. This study shows how set-based visualisation enables multifield missing data patterns to be discovered and investigated.

View Article and Find Full Text PDF
Article Synopsis
  • CT900 is a new small molecule drug that inhibits thymidylate synthase and targets tumors overexpressing the α-folate receptor (α-FR).
  • In a clinical trial, doses between 1-12 mg/m2 were tested on patients with high-grade serous ovarian cancer, focusing on a dose of 12 mg/m2 given every two weeks.
  • The trial showed manageable side effects and a 21.9% overall response rate, with better outcomes in patients who had higher α-FR expression, indicating that CT900 has potential for further study.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigates how acute changes in protein signaling can help predict the sensitivity of non-small cell lung cancer (NSCLC) cells to targeted anticancer drugs, both individually and in combination.
  • Researchers examined the effects of seven different drugs on 52 phosphoproteins in 35 NSCLC cell lines and developed machine-learning models that successfully forecasted drug responses better than traditional mutation-based predictions.
  • The findings support the use of fast, protein-based analyses of cancer cells from patient samples to enhance treatment choices and potentially improve cancer therapy outcomes.
View Article and Find Full Text PDF

Aims: Digital pathology offers the potential for significant benefits in diagnostic pathology, but currently the efficiency of slide viewing is a barrier to adoption. We hypothesised that presenting digital slides for simultaneous viewing of multiple sections of tissue for comparison, as in those with immunohistochemical panels, would allow pathologists to review cases more quickly.

Methods: Novel software was developed to view synchronised parallel tissue sections on a digital pathology workstation.

View Article and Find Full Text PDF

Background: Dashboards can support data-driven quality improvements in health care. They visualize data in ways intended to ease cognitive load and support data comprehension, but how they are best integrated into working practices needs further investigation.

Objective: This paper reports the findings of a realist evaluation of a web-based quality dashboard (QualDash) developed to support the use of national audit data in quality improvement.

View Article and Find Full Text PDF

Somatic mutations in are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for -mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 ( = 150 nmol/L) and reduce DIPG cell viability but has limited ability to cross the blood-brain barrier.

View Article and Find Full Text PDF

Background: Secondary use of data via integrated health information technology is fundamental to many healthcare policies and processes worldwide. However, repurposing data can be problematic and little research has been undertaken into the everyday practicalities of inter-system data sharing that helps explain why this is so, especially within (as opposed to between) organisations. In response, this article reports one of the most detailed empirical examinations undertaken to date of the work involved in repurposing healthcare data for National Clinical Audits.

View Article and Find Full Text PDF

Event sequences are central to the analysis of data in domains that range from biology and health, to logfile analysis and people's everyday behavior. Many visualization tools have been created for such data, but people are error-prone when asked to judge the similarity of event sequences with basic presentation methods. This article describes an experiment that investigates whether local and global alignment techniques improve people's performance when judging sequence similarity.

View Article and Find Full Text PDF

Adapting dashboard design to different contexts of use is an open question in visualisation research. Dashboard designers often seek to strike a balance between dashboard adaptability and ease-of-use, and in hospitals challenges arise from the vast diversity of key metrics, data models and users involved at different organizational levels. In this design study, we present QualDash, a dashboard generation engine that allows for the dynamic configuration and deployment of visualisation dashboards for healthcare quality improvement (QI).

View Article and Find Full Text PDF
Article Synopsis
  • - The study explored the effectiveness and safety of using a combination of CDK4/6 inhibitor (palbociclib) and PI3K inhibitor (taselisib), along with the hormone therapy (fulvestrant), in treating advanced ER-positive HER2-negative breast cancer with specific genetic mutations.
  • - Results showed that the triplet therapy led to a 37.5% response rate in the targeted patient group, while both doublet and triplet therapies were well tolerated and provided durable disease control.
  • - High levels of cyclin E1 and changes in circulating tumor DNA (ctDNA) were linked to shorter progression-free survival, indicating that monitoring these factors could help refine treatment strategies for breast cancer patients.
View Article and Find Full Text PDF

Purpose: AT13148 is an oral AGC kinase inhibitor, which potently inhibits ROCK and AKT kinases. In preclinical models, AT13148 has been shown to have antimetastatic and antiproliferative activity.

Patients And Methods: The trial followed a rolling six design during dose escalation.

View Article and Find Full Text PDF
Article Synopsis
  • Preclinical studies suggest that combining PARP inhibitors (like olaparib) with PI3K/AKT pathway inhibitors (like capivasertib) is effective for treating certain tumors.
  • An investigator-led phase I trial tested this combination on 64 patients with advanced solid tumors, using an intrapatient dose-escalation approach to determine safety and efficacy.
  • Results showed that 44.6% of patients experienced clinical benefits, and the combination was well tolerated, indicating potential for further development in future clinical trials.
View Article and Find Full Text PDF

Healthcare organizations worldwide use quality dashboards to provide feedback to clinical teams and managers, in order to monitor care quality and stimulate quality improvement. However, there is limited evidence regarding the impact of quality dashboards and audit and feedback research focuses on feedback to individual clinicians, rather than to clinical and managerial teams. Consequently, we know little about what features a quality dashboard needs in order to provide benefit.

View Article and Find Full Text PDF

Introduction: To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal transduction inhibitors identified in preclinical models have previously been confirmed in early clinical studies.

View Article and Find Full Text PDF
Article Synopsis
  • About 50% of patients with metastatic castration-resistant prostate cancer (mCRPC) have issues with the PI3K/AKT/mTOR pathway due to lost PTEN, and combining treatments that target the androgen receptor and AKT could help them.
  • In a study, mCRPC patients who didn’t respond to previous treatments received different doses of capivasertib along with enzalutamide to evaluate safety and effectiveness.
  • The recommended dose of capivasertib was found to be 400 mg twice daily, with manageable side effects and some patients showing significant positive responses, particularly those with specific genetic characteristics.
View Article and Find Full Text PDF

Introduction: National audits are used to monitor care quality and safety and are anticipated to reduce unexplained variations in quality by stimulating quality improvement (QI). However, variation within and between providers in the extent of engagement with national audits means that the potential for national audit data to inform QI is not being realised. This study will undertake a feasibility evaluation of QualDash, a quality dashboard designed to support clinical teams and managers to explore data from two national audits, the Myocardial Ischaemia National Audit Project (MINAP) and the Paediatric Intensive Care Audit Network (PICANet).

View Article and Find Full Text PDF

Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in , encoding the serine/threonine kinase ALK2. Despite being an amenable drug target, little has been done to-date to systematically evaluate the role of in DIPG, nor to screen currently available inhibitors in patient-derived tumour models. Here we show the dependence of DIPG cells on the mutant receptor, and the preclinical efficacy of two distinct chemotypes of ALK2 inhibitor in vitro and in vivo.

View Article and Find Full Text PDF

The corresponding author of this article has informed us of concerns about the immunoblots in Fig. 2 which were carried out in the collaborating laboratory of Professor Ann Jackman.

View Article and Find Full Text PDF

Background: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients.

Patients And Methods: In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days).

View Article and Find Full Text PDF