Publications by authors named "Sharp A"

Background: Induction of labour (IOL) is a common obstetric intervention in the UK, affecting up to 33% of deliveries. IOL aims to achieve a vaginal delivery prior to spontaneous onset of labour to prevent harm from ongoing pregnancy complications and is known to prevent stillbirths and reduce neonatal intensive care unit admissions. However, IOL doesn't come without risk and overall, 20% of mothers having an induction will still require a caesarean section birth and in primiparous mothers this rate is even higher.

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Atrial fibrillation (AF) is the most prevalent clinical arrhythmia, posing significant mortality and morbidity challenges. Outcomes of current catheter ablation treatment strategies are suboptimal, highlighting the need for innovative approaches. A major obstacle lies in the inability to comprehensively assess both structural and functional remodelling in AF.

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Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.

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As a transcription factor, GLI1 plays an important role in cell cycle regulation, DNA replication, and DNA damage responses. The aberrant activation of GLI1 has been associated with cancers such as glioma, osteosarcoma, and rhabdomyosarcoma. The binding of GLI1 to a specific DNA sequence was achieved by five tandem zinc finger motifs (Zif motifs) on the N-terminal part of the molecule.

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Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection against diet-induced obesity. In this study, we used temporal metabolomics on HeLa cells to show that MTCH2 deletion results in a high ATP demand, an oxidized cellular environment, and elevated utilization of lipids, amino acids, and carbohydrates, accompanied by a decrease in several metabolites.

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Purpose: To compare stone clearance and complications between a 'wide' (9 × 50 mm) and 'narrow' shockwave focus (6 × 28 mm) when undertaking shockwave lithotripsy (SWL) in patients with renal or ureteric stones.

Methods: Data from patients undergoing SWL using the dual focus Storz Modulith SLX-F2 lithotripter at a single centre were prospectively collected between February 2018 and September 2020. Patients were matched by stone size, location, and number of treatments.

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Background: A CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia in two Chinese families. Expanded repeats ranged from 45 to 100 units, with CAA sequence interruptions in the 5' region and an uninterrupted CAG tract in the 3' tail.

Objective: Here, we assess the population distribution of the THAP11 repeat, and its contribution to neurological diseases.

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Objectives: The goal of this project was to investigate the impact of musical experience, hearing loss, and age on music perception in older adults. The authors hypothesized that older adults with a varying degree of musical experience would perform better at music perception tasks than their counterparts without musical experience while controlling for age and hearing loss.

Design: This study used a descriptive correlational cross-sectional design.

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Most genetic association studies focus on binary variants. To identify the effects of multi-allelic variation of tandem repeats (TRs) on human traits, we perform direct TR genotyping and phenome-wide association studies in 168,554 individuals from the UK Biobank, identifying 47 TRs showing fine-mapped associations with 73 traits. We replicate 23 of 31 (74%) of these associations in the All of Us cohort.

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Article Synopsis
  • - PARP inhibitors show promise in treating castration-resistant prostate cancer (CRPC) with homologous recombination repair (HRR) defects, but the reasons behind resistance are not completely understood.
  • - A study from the TOPARP-B trial found that 79% of BRCA2/PALB2-mutated tumors exhibited reversion mutations at the end of treatment, with many related to POLQ-mediated DNA repair mechanisms.
  • - In cases of BRCA2 homozygous deletions, rare subclones lacking the BRCA2 deletion are selected for after PARP inhibitor treatment, indicating the necessity for restored HRR function in developing resistance.
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It has been proposed that low power, high frequency ultrasound can augment the ability of thrombolytic agents to dissolve clot in patients with venous thromboembolism. We created a bench model to examine what role and mechanism ultrasound may have in this process. Fibrin polymerisation was analysed through modified light-scattering experiments with the inclusion of catheter-mediated ultrasound application.

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Background: Catheter-based radiofrequency renal denervation (RF RDN) has recently been approved as an adjunctive treatment for hypertensive patients without adequate blood pressure control. This study assessed the cost-effectiveness of RF RDN in the United States based on contemporary clinical evidence.

Methods: A decision-analytic Markov model projected costs, quality-adjusted life years (QALY), and clinical events for an active cohort treated with RF RDN and a control cohort treated with standard-of-care (defined as 1, 2, or 3 antihypertensive medications).

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Introduction: Despite international commitment to achieving the end of HIV as a public health threat, progress is off-track and existing gaps have been exacerbated by COVID-19's collision with existing pandemics. Born out of models of political accountability and historical healthcare advocacy led by people living with HIV, community-led monitoring (CLM) of health service delivery holds potential as a social accountability model to increase the accessibility and quality of health systems. However, the effectiveness of the CLM model in strengthening accountability and improving service delivery relies on its alignment with evidence-based principles for social accountability mechanisms.

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Objective: Opioid overdose is a public health epidemic adversely impacting individuals and communities. To combat this, California passed a law mandating that prescribers offer a naloxone prescription in certain circumstances. Our objective was to evaluate associations with California's naloxone prescription mandate and emergency department (ED) overdose visits/hospitalizations, opioid and naloxone prescribing, and 30-day mortality.

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Introduction: The novel Confirm Rx™ implantable cardiac monitor (ICM) with SharpSense™ technology incorporates a new P-wave discriminator designed to improve AF detection. This study aimed to evaluate the diagnostic performance of the Confirm Rx™ ICM in detecting AF episodes of varying durations.

Methods: We conducted a multicenter retrospective analysis of consecutive patients implanted with a Confirm Rx™ ICM (v1.

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Although anticoagulation remains the cornerstone treatment for patients with acute pulmonary embolism (PE), catheter-directed therapy (CDT) has generated great interest as an adjunctive option for those presenting with hemodynamic decompensation or high risk for deterioration and in whom systemic thrombolysis has failed or is contraindicated. However, randomized controlled data supporting the efficacy and safety of CDT in addition to antithrombotic therapy in patients with high-risk and intermediate- to high-risk PE compared with anticoagulation and systemic thrombolysis alone are lacking. This paucity of high-quality data hampers guideline recommendations regarding the optimal therapeutic approach in such patients with PE.

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There is a growing interest in using the tactile modality as a compensation or sensory augmentation tool in various fields. The Multichannel Vibrotactile Glove was designed to meet the needs of these diverse disciplines and overcome the limitations of current sound-to-touch technologies. Using 12 independent haptic exciters on each finger's back and on the palm, the device can convey acoustic information to cutaneous vibrotactile receptors with precise control of the location, frequency, timing, and intensity.

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Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease.

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Article Synopsis
  • Repeat expansion disorders (REDs) are mostly neurological diseases affecting about 1 in 3,000 people worldwide, but true prevalence may be underestimated due to varied symptoms and geographic factors.
  • Analysis of genetic data from over 82,000 individuals indicates that the actual frequency of REDs is about 1 in 283, suggesting many cases go undiagnosed.
  • Most REDs are found across diverse populations, countering the idea that some are limited to specific ethnic groups, which has important implications for health care and genetic counseling.
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