Publications by authors named "Linton A"

Background: The Joint Commission defines a sentinel event as "surgery or other invasive procedure performed at the wrong site, on the wrong patient, or that is the wrong (unintended) procedure for a patient regardless of the type of procedure or the magnitude of the outcome." At our institution, we observed a low but consistent rate of incorrect surgical line placement for pediatric patients with cancer.

Study Design: Following quality improvement methodology and using the resources available on a large academic medical campus we designed and implemented a new multi-factorial process to schedule and place surgical central lines for pediatric patients with cancer.

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Research has shown an inconsistent relationship between spatial abilities and learning outcomes from virtual anatomical tools. Instructors must understand this relationship to select appropriate resources for diverse learners. To identify appropriate tests for measuring spatial ability and evaluate the effectiveness of virtual anatomical resources, this study compared 96 students' visuospatial ability (measured using the Mental Rotation Task [MRT] and Landmark Position on a Map [LPM] tests) with learning outcomes from experimental anatomy sessions and undergraduate anatomical course examinations.

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By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis.

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Purpose: Although the mechanisms underlying glaucomatous neurodegeneration are not yet well understood, cellular and small animal models suggest that LC astrocytes undergo early morphologic and functional changes, indicating their role as early responders to glaucomatous stress. These models, however, lack the LC found in larger animals and humans, leaving the morphology of LC astrocytes and their role in glaucoma initiation underexplored. In this work, we aimed to characterize the morphology of LC astrocytes and determine differences and similarities with astrocytes in the mouse glial lamina (GL), the analogous structure in a prominent glaucoma model.

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Mechanical loosening is a leading cause of failure of total knee arthroplasties (TKAs) for which obesity may be a risk factor. With rising rates of obesity and increasing incidence of TKA, the identification of factors to mitigate this cause of failure is necessary. The purpose of this study is to determine if the use of a tibial stem extender (TSE) decreases the risk of mechanical loosening in patients with obesity undergoing TKA.

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Reduced hours of instruction are reported within the gross anatomy education literature. Anatomy instruction continues to be challenged with motivating and inspiring learners to value the contribution of gross anatomy knowledge to their career development alongside increased organizational demands for efficiency and effectiveness. To address these demands, this retrospective study sought to understand how the relative timing and amount of gross anatomy instruction were related to examination performance.

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Objectives: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3).

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Introduction: Consolidation durvalumab following platinum-based chemoradiotherapy (CRT) significantly improved overall survival for patients with unresectable stage III non-small cell lung cancer (NSCLC) in the PACIFIC trial. However, older patients were underrepresented in PACIFIC, and subsequent analyses suggested trends toward poorer survival and increased toxicity in patients aged ≥70 years old. We assessed the effectiveness and safety of consolidation durvalumab following CRT in older Australian patients with unresectable stage III NSCLC.

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Testicular tumors are relatively rare in children and those in prepubertal children tend to present with different histological types and behaviors than their postpubertal counterparts. The majority of these pre- and peripubertal testicular tumors tend to be benign and those that are malignant, tend to present at low stages, not generally requiring systemic treatment. Here we present a rare case of a peri-pubertal, mixed nonseminomatous germ cell tumor of the testes which was found to be widely metastatic at presentation, classifying as poor risk disease.

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Article Synopsis
  • Mesothelin (MSLN) is a special marker found in some cancer types, and scientists want to use it to develop new personalized cancer treatments.
  • In a study, researchers tested tissue samples from 75 patients with mesothelioma to see how MSLN was expressed and if it could help predict patient survival.
  • They found that many patients had MSLN in their tumors, and certain levels of MSLN were linked to better chances of living longer, suggesting it can help doctors choose better treatments.
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Introduction: Many patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine (lignocaine) has the potential to help manage neuropathic cancer-related pain when administered as an extended, continuous subcutaneous infusion.

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Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia along with Alzheimer's disease (AD) and, importantly, VCID often manifests as a comorbidity of AD(Vemuri and Knopman 2016; Schneider and Bennett 2010)(Vemuri and Knopman 2016; Schneider and Bennett 2010). Despite its common clinical manifestation, the mechanisms underlying VCID disease progression remains elusive. In this review, existing knowledge is used to propose a novel hypothesis linking well-established risk factors of VCID with the distinct neurodegenerative cascades of neuroinflammation and chronic hypoperfusion.

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Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics conditions and pathological conditions such as cancer. In comparison to biospecimens taken from tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options.

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We sought to examine incidence and predictors of eosinophilic myocardial hypersensitivity (EMH) in a cohort of patients in the home inotrope program of a quaternary cardiac transplant center. Patients on home inotropes with progression to heart transplantation or ventricular assist device (VAD) between January 2000 and May 2020 were included. EMH was diagnosed by the presence of an interstitial predominate eosinophilic infiltrate within the myocardium by experienced cardiac pathologists.

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Purpose Of Review: Spondylolysis remains one of the most common causes of lower back pain in the pediatric and adolescent populations and is particularly prevalent in young sporting individuals. Despite this, approaches to diagnostic imaging and both conservative and surgical treatment vary widely among surgeons. The current review investigates recent literature on the etiology, clinical presentation, diagnosis, and treatment of spondylolysis.

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Article Synopsis
  • The study aims to assess the effectiveness and safety of intermittent docetaxel chemotherapy guided by plasma levels of methylated glutathione S-transferase Pi-1 in men with metastatic castration-resistant prostate cancer (CRPC).
  • It involves a randomized phase-2 trial with 120 patients across six Australian centers, where participants will be pre-screened based on their methylated levels before and during treatment.
  • The primary outcome is radiographic progression-free survival, while secondary outcomes include patient safety, overall survival, and treatment costs, with results expected to provide insights on using the biomarker for treatment decisions.
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Anatomy faculty with cadaver-based laboratory courses were presented with a significant challenge in March 2020 to create equivalent learning experiences without cadaveric access. The undergraduate domestic animal anatomy course at the Colorado State University was halfway into a 16-week semester when COVID-19 lockdown orders and the transition to remote instruction began. The new course curriculum was critically evaluated using student surveys and course outcome data.

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The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT.

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Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM.

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Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis. The relationship between asbestos exposure and MPM incidence is well-established. The incidence rate of MPM in Australia and New Zealand is among the highest globally.

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Innovative reforms in medical education will require instructional tools to support these changes and to give students more flexibility in where and how they learn. At Colorado State University, the software program Virtual Canine Anatomy (VCA) was developed to assist student learning both inside and outside the anatomical laboratory. The program includes interactive anatomical photographs of dissected canine cadavers, dissection instructions with accompanying videos and diagrams, radiographs, and three-dimensional models.

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Background And Purpose: The μ-opioid receptor (μ receptor) is the primary target for opioid analgesics. The 7-transmembrane (TM) and 6TM μ receptor isoforms mediate inhibitory and excitatory cellular effects. Here, we developed compounds selective for 6TM- or 7TM-μ receptors to further our understanding of the pharmacodynamic properties of μ receptors.

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Background: The diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM.

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Background: 5-HT receptor (5-HT R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT Rs have limited their use. Since 5-HT Rs are expressed in the colonic epithelium and their stimulation accelerates colonic propulsion in vitro, we tested whether luminally acting 5-HT R agonists promote intestinal motility.

Methods: Non-absorbed 5-HT R agonists, based on prucalopride and naronapride, were assessed for potency at the 5-HT R in vitro, and for tissue and serum distribution in vivo in mice.

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Purpose: To identify the approximately 12% with inherited cancer predisposition, all men with metastatic prostate cancer (mPC) should be offered germline genetic testing. This guides treatment choices and impacts cancer prevention in the family. Limited genetic services globally present a barrier to testing.

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