Publications by authors named "Scott Clarke"
Cost-Effectiveness Analysis of Molecular Testing for Indeterminate Thyroid Nodules in Nova Scotia.
J Otolaryngol Head Neck Surg
October 2024
Background: The objective of the following retrospective review was to perform a cost-effectiveness analysis of the use of molecular testing of indeterminate thyroid nodules compared to current management practices in Nova Scotia, Canada.
Methods: All cases of cytologically indeterminate thyroid nodules from January 1st, 2014 to December 31st, 2018 were reviewed. All interventions related to an indeterminate thyroid nodule were recorded.
Article Synopsis
- Evaluating the progress of hepatitis C virus (HCV) elimination is crucial for Aboriginal and Torres Strait Islander peoples due to higher infection rates compared to non-Aboriginal peoples who inject drugs (PWID) in Australia.
- The ETHOS Engage study assessed HCV prevalence and self-reported treatment among 2,395 PWID, finding that 23% identified as Aboriginal, with HCV prevalence at 23% for Aboriginal and 21% for non-Aboriginal participants.
- To achieve HCV elimination goals, it's essential to ensure equal access to healthcare for Aboriginal PWID, addressing factors such as homelessness and drug use that hinder treatment.
Article Synopsis
- 14-3-3 proteins are essential for managing cellular responses to stress and DNA damage, influencing processes like metabolism, cell cycle, migration, and apoptosis by binding to specific proteins after they're modified by kinases.
- Despite identifying over 200 proteins that interact with 14-3-3 through proteomic studies, the specific kinases involved in these interactions are often unknown.
- Researchers developed a method to pinpoint these kinase-specific interactions, discovering that the protein PABPC1 is a target for kinases Chk1 and MK2, with a specific site (Ser-470) crucial for its binding to 14-3-3; loss of this binding leads to increased cell growth and reduced cell death following DNA damage
Tactical decision games (TDGs) have been used in healthcare and other safety-critical industries to develop non-technical skills training (NTS). TDGs have been shown to be a realistic, feasible, and useful way of teaching NTS such as decision making, task prioritisation, situational awareness, and team working. Our 12-tips for using TDG to teach NTS are based on our experience of integrating them into an undergraduate medical and nursing programme.
View Article and Find Full Text PDFActin filaments are central to numerous biological processes in all domains of life. Driven by the interplay with molecular motors, actin binding and actin modulating proteins, the actin cytoskeleton exhibits a variety of geometries. This includes structures with a curved geometry such as axon-stabilizing actin rings, actin cages around mitochondria and the cytokinetic actomyosin ring, which are generally assumed to be formed by short linear filaments held together by actin cross-linkers.
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- Physicians are increasingly exploring 3D printing technology for creating medical devices and customized models, as it offers a more cost-effective and quicker alternative to traditional methods.
- A study was conducted to identify and analyze commercially available, user-friendly 3D printers under $15,000, resulting in a decision-making tool for clinicians.
- The paper emphasizes the "3Ms of 3D printing" to assist surgeons in navigating the complexities of 3D printing and provides useful resources for selecting suitable printers to enhance personalized medical solutions.
Identifying patients at risk of futile resuscitation: palliative care indicators in out-of-hospital cardiac arrest.
BMJ Support Palliat Care
September 2022
Article Synopsis
- A study assessed patients with advanced life-limiting conditions who experienced out-of-hospital cardiac arrest (OHCA) to evaluate the risk of futile cardiopulmonary resuscitation (CPR) and the need for anticipatory care planning (ACP).
- In a review of 283 OHCA cases, it found that 12.4% had a high risk of futile CPR, while 71.4% were categorized as low risk, with a significant percentage of those at intermediate to high risk dying shortly after arriving at the emergency department.
- The study suggests that nearly 30% of these patients undergo unnecessary CPR despite having palliative care indicators, highlighting the importance of better emergency treatment planning to minimize inappropriate resuscitation
Article Synopsis
- Researchers are using un-natural amino acids (UNAA) to modify proteins, enhancing their study and engineering for specific functions.
- This is done by repurposing the amber codon (UAG) to incorporate UNAAs, utilizing a specially designed tRNA and a unique enzyme called amino-acyl tRNA synthetase (aaRS).
- The study demonstrates successful incorporation of several UNAAs into proteins like green fluorescent protein (GFP) and showcases their potential for investigating protein functions in zebrafish.
Actins are major eukaryotic cytoskeletal proteins, and they are involved in many important cell functions, including cell division, cell polarity, wound healing and muscle contraction. Despite obvious drawbacks, muscle actin, which is easily purified, is used extensively for biochemical studies of the non-muscle actin cytoskeleton. Here, we report a rapid and cost-effective method to purify heterologous actins expressed in the yeast Actin is expressed as a fusion with the actin-binding protein thymosin β4 and purified by means of an affinity tag introduced in the fusion.
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- High content imaging allows researchers to analyze multiple aspects of the cell cycle simultaneously, including DNA content and cell proliferation markers.
- 5'-Ethynyl-2'-deoxyuridine (EdU) is a more efficient method for detecting DNA synthesis in cells compared to the traditional BrdU method.
- The chapter outlines techniques for measuring S-phase progression with EdU and monitoring apoptosis through caspase 3 activation using a specific detection reagent.
Click Chemistry for Analysis of Cell Proliferation in Flow Cytometry.
Curr Protoc Cytom
October 2017
The measurement of cellular proliferation is fundamental to the assessment of cellular health, genotoxicity, and the evaluation of drug efficacy. Labeling, detection, and quantification of cells in the synthesis phase of cell cycle progression are not only important for characterizing basic biology, but also in defining cellular responses to drug treatments. Changes in DNA replication during S-phase can provide valuable insights into mechanisms of cell growth, cell cycle kinetics, and cytotoxicity.
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- 3D printing is being explored for creating customized radiotherapy boluses and applicators, allowing for precise treatment in oncology.
- The study discusses real patient cases, highlighting successful applications in treating various skin cancers like squamous cell carcinoma and basal cell carcinoma using printed boluses for photon and electron therapies.
- The results show that these 3D-printed structures provide an acceptable fit and treatment plan efficiency while sparing nearby organs, demonstrating the potential of 3D printing in enhancing radiotherapy outcomes.
Article Synopsis
- This study investigates the likelihood of individuals with systemic lupus erythematosus (SLE) also having other connective tissue diseases (CTDs) like Sjögren's syndrome and rheumatoid arthritis.
- A survey was administered to 500 SLE patients, revealing that 96% screened positive for at least one additional CTD, with 13% positive for two or more.
- The findings suggest that increased focus on potential additional CTDs in SLE patients could improve treatment approaches and highlight the usefulness of the CTD screening questionnaire (CSQ) in clinical settings, despite some limitations in the study. *
Article Synopsis
- - DNA damage triggers a signaling network that can stop the cell cycle and promote repair or cell death, with chromatin structure playing a key role in how this response works.
- - Researchers used a high-content multiplex RNA interference screen to study the impact of chromatin-modifying genes on the DNA damage response, focusing on how these genes react to ionizing radiation.
- - The study highlights an isoform of Brd4 as an inhibitor of DNA damage signaling; its absence relaxes chromatin, allowing for faster cell recovery and increased survival post-radiation, while its presence does the opposite, suggesting Brd4's crucial role in regulating chromatin and DNA damage responses.
The immune response to exogenous protein has been shown to reduce therapeutic efficacy in animal models of enzyme replacement therapy. A previously published study demonstrated an immunosuppressive regimen which successfully induced immune tolerance to α-L-iduronidase in canines with mucopolysaccharidosis I. The two key requirements for success were high-affinity receptor-mediated enzyme uptake, conferred by mannose 6-phosphate conjugation, and immunosuppression with low-dose antigen exposure.
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- Out-of-hospital cardiac arrest (OHCA) is a critical emergency, and the success of survival largely depends on effective prehospital resuscitation, which includes non-technical skills like leadership and communication.
- A pilot study called TOPCAT2 was conducted in Edinburgh to evaluate the implementation of a specialist second-tier paramedic response for OHCA, involving advanced training and simulation techniques.
- The study found that activating the second-tier paramedic did not delay overall ambulance response times and showed a promising increase in successful outcomes, with a return of spontaneous circulation rate of 22.5% for cases attended by the trained paramedics.
Article Synopsis
- * A single injection of estrogen increased heat production in visceral fat and skeletal muscle, while repeated injections maintained this elevated heat production without affecting food intake.
- * Continuous estrogen treatment reduced food intake but did not increase thermogenesis; mechanisms like AMP activation were observed, indicating that a pulsed estrogen exposure is key for stimulating heat production in female sheep.
Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling.
Am J Physiol Regul Integr Comp Physiol
November 2012
This study aimed to determine whether postprandial temperature excursions in skeletal muscle are consistent with thermogenesis or altered blood flow. Temperature probes were implanted into the vastus lateralis muscle of ovariectomized ewes, and blood flow was assessed using laser-Doppler flowmetry (tissue flow) and transit-time ultrasound flowmetry (femoral artery flow). The animals were program-fed between 1100 and 1600, and temperature and blood flow were measured during intravenous administration of either isoprenaline or phenylephrine and during feeding and meal anticipation.
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- Azides that can chelate copper facilitate faster "Click chemistry" reactions (CuAAC) compared to non-chelating azides under biocompatible conditions.
- This enhanced reaction speed enables effective site-specific protein labeling on live cell surfaces using low copper concentrations (10–40 µM), achieving better signal detection than previous methods.
- The approach also improves the detection sensitivity for alkyne-modified proteins and RNA, which can be labeled through metabolic feeding.
Article Synopsis
- Adiposity regulation differs between sexes, largely influenced by sex steroids, leading to unclear impacts of androgens like testosterone in males vs. females.!* -
- In a study with castrated male and female sheep, testosterone didn't affect food intake but altered temperature dynamics, showing higher muscle temperature in males and reduced heat production from testosterone treatment in them only.!* -
- Findings also revealed that testosterone led to lower glucose levels during feeding in males, suggesting possible brain center differentiation affects energy expenditure mechanisms between sexes.!*
Article Synopsis
- - Adult human mesenchymal stem cells (hMSC) are unique cells found mainly in bone marrow and fat that can turn into various tissue types like bone and cartilage.
- - The International Society for Cellular Therapy (ISCT) has set criteria to define hMSC, including their ability to adhere to surfaces and differentiate into specific cell types.
- - Flow cytometry is a key technique used for analyzing hMSC by measuring their immunophenotypic profile, growth potential, and DNA content, allowing researchers to make better decisions regarding cell expansion and harvesting.
Background: Hyperglycaemia is a common occurrence during cardiac surgery, however, there remains some uncertainty surrounding the role of tight glycaemic control (blood glucose <180 mg/dL) during and/or after surgery. The aim of this study was to systematically review the literature to determine the effects of tight versus normal glycaemic control, during and after cardiac surgery, on measures of morbidity and mortality.
Method: The literature was systematically reviewed, based on pre-determined search criteria, for clinical trials evaluating the effect of tight versus normal glycaemic control during and/or after cardiac surgery.
Article Synopsis
- Changes in DNA replication during S-phase provide key insights into cell growth, cycle timing, and how cells react to toxins.
- A popular method to track cell proliferation involves using thymidine analogs, where multiple analogs at different times help map cell cycle kinetics.
- This text introduces a dual-pulse method combining the thymidine analog EdU with BrdU, allowing precise detection of cell division without cross-reactivity between the two methods.
Article Synopsis
- The study explores the use of EdU (5-ethynyl-2'-deoxyuridine) as an alternative to BrdU (5-bromo-2'-deoxyuridine) for assessing cell proliferation in breast cancer cells.
- The researchers found that EdU allows for accurate continuous cell labeling and comparable results to BrdU, but long-term exposure to EdU can negatively impact cell viability, particularly in SK-BR-3 cells.
- While both SK-BR-3 and BT474 cells showed cell cycle arrests with EdU treatment, only SK-BR-3 experienced necrotic cell death, making it important to evaluate individual cell response to EdU when testing cell proliferation.