Background And Purpose: Magnetic resonance imaging - linear accelerator (MRI-linac) systems permit imaging of tumours to guide treatment. Dynamic contrast enhanced (DCE)-MRI allows investigation of tumour perfusion. We assessed the feasibility of performing DCE-MRI on a 1.
View Article and Find Full Text PDFBackground And Objectives: Despite effective secondary prevention, including oral anticoagulant (OAC) therapy, the risk of recurrent stroke (RS) in patients with atrial fibrillation (AF) remains substantial with an annualized risk of 3.2%-6.5% per year.
View Article and Find Full Text PDFThe Easter mantle plume has produced one of the longest hotspot tracks in the Pacific Ocean. While previous studies have focused on the eastern side extending across the Nazca Plate, we use Ar/Ar isotopic and geochemical data to investigate the less explored western side around the Easter Microplate. We propose a dynamic model in which a deeper (600 km-depth), less buoyant mantle exerts a westward force on the East Pacific Rise (EPR), while a more buoyant plume region drives Easter hotspot volcanism and a localised acceleration in seafloor spreading.
View Article and Find Full Text PDFAdverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions.
View Article and Find Full Text PDFOxygen-enhanced MRI (OE-MRI) has shown promise for quantifying and spatially mapping tumor hypoxia, either alone or in combination with perfusion imaging. Previous studies have validated the technique in mouse models and in patients with cancer. Here, we report the first evidence that OE-MRI can track change in tumor oxygenation induced by two drugs designed to modify hypoxia.
View Article and Find Full Text PDFFolate-dependent one-carbon (C1) metabolism encompasses distinct cytosolic and mitochondrial pathways connected by an interchange among serine, glycine, and formate. In both the cytosol and mitochondria, folates exist as polyglutamates, with polyglutamylation catalyzed by folylpolyglutamate synthetase (FPGS), including cytosolic and mitochondrial isoforms. Serine is metabolized by serine hydroxymethyltransferase (SHMT)2 in the mitochondria and generates glycine and C1 units for cellular biosynthesis in the cytosol.
View Article and Find Full Text PDFMany individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD.
View Article and Find Full Text PDFBackground: Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC.
View Article and Find Full Text PDFRespiratory syncytial virus (RSV) is the leading cause of hospitalisation for respiratory infection in young children. RSV disease severity is known to be age-dependent and highest in young infants, but other correlates of severity, particularly the presence of additional respiratory pathogens, are less well understood. In this study, nasopharyngeal swabs were collected from two cohorts of RSV-positive infants <12 months in Spain, the UK, and the Netherlands during 2017-20.
View Article and Find Full Text PDFPurpose: To demonstrate proof-of-concept of a T *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers.
Methods: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied.
Purpose: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI.
Methods: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery.
Acetate metabolism is an important metabolic pathway in many cancers and is controlled by acetyl-CoA synthetase 2 (ACSS2), an enzyme that catalyzes the conversion of acetate to acetyl-CoA. While the metabolic role of ACSS2 in cancer is well described, the consequences of blocking tumor acetate metabolism on the tumor microenvironment and antitumor immunity are unknown. We demonstrate that blocking ACSS2, switches cancer cells from acetate consumers to producers of acetate thereby freeing acetate for tumor-infiltrating lymphocytes to use as a fuel source.
View Article and Find Full Text PDFAdvances in genomic technologies have significantly improved the management of colorectal cancer (CRC). Several biomarkers have been identified in CRC that enable personalization in the use of biologic agents that have shown to enhance the clinical outcomes of patients. However, technologies used for their determination generate massive amounts of information that can be difficult for the clinician to interpret and use adequately.
View Article and Find Full Text PDFBackground: We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo.
Methods: We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dose-corrected adherence (indication-corrected adherence+≥50% of drug dose target).
Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014.
View Article and Find Full Text PDFObjective: This study aimed to determine whether lower extremity fracture fixation technique and timing (≤24 vs. >24 hours) impact neurologic outcomes in TBI patients.
Methods: A prospective observational study was conducted across 30 trauma centers.
Background: Weight bias exhibited by health care students may continue into their future practice, compromising the provision of care that people living with overweight or obesity receive. This highlights the need to comprehensively examine the extent to which weight bias is present among health care students and the factors that may be associated with students' weight bias.
Methods: In this cross-sectional study, Australian university students enrolled in health care courses were invited via social media advertisements, snowball and convenience sampling, and by making direct contact with universities to complete an online survey.
Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation.
View Article and Find Full Text PDFBackground: A team approach is one of the most effective ways to lower blood pressure (BP) in uncontrolled hypertension, but different models for organizing team-based care have not been compared directly.
Methods: A pragmatic, cluster-randomized trial compared 2 interventions in adult patients with moderately severe hypertension (BP≥150/95 mm Hg): (1) clinic-based care using best practices and face-to-face visits with physicians and medical assistants; and (2) telehealth care using best practices and adding home BP telemonitoring with home-based care coordinated by a clinical pharmacist or nurse practitioner. The primary outcome was change in systolic BP over 12 months.