Publications by authors named "McLaren D"

The permissive "science first" approach has failed, but a nondeployment deal might yet enable responsible research.

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With the current therapeutic modalities available to endocrinologists, control of GH and IGF-I is now possible in almost all patients with acromegaly with multi-modality therapy. Despite biochemical control of GH and IGF-I, patients with acromegaly continue to experience impaired quality of life. Although there are likely multiple factors contributing to this dissatisfaction with current medical therapies, in particular the widely utilised injectable long-acting somatostatin receptor ligands (iSRL), is a contributor.

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Protein kinetics can be quantified by coupling stable isotope tracer methods with mass spectrometry readouts; however, inter-connected decision points in the experimental design affect the complexity of the workflow and impact data interpretations. For example, choosing between a single bolus (pulse-chase) or a continuous exposure protocol influences subsequent decisions regarding when to measure and how to model the temporal labeling of a target protein. Herein, we examine the merits of in vivo tracer protocols, we direct attention towards stable isotope tracer experiments that rely on administering a single bolus since these are generally more practical to use as compared to continuous administration protocols.

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Introduction: Microgrants for health promotion have the potential to engage communities in designing and implementing place-based interventions to improve health and social outcomes. However, the evidence base around microgrants for health promotion is limited. This study presents the evaluation of a health service-funded microgrant program for health promotion in rural Australia.

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Background: Insomnia is common after stroke and is associated with poorer recovery and greater risk of subsequent strokes. Yet, no insomnia measures have been validated in English-speaking individuals affected by stroke.

Aims: This prospective diagnostic validation study investigated the discriminatory validity and optimal diagnostic cut-off of the Sleep Condition Indicator when screening for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) insomnia disorder post-stroke.

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Background And Objective: Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule.

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Background And Purpose: The adoption of hypo-fractionated stereotactic body radiotherapy (SBRT) for treating prostate cancer has led to an increase in specialised techniques for monitoring prostate motion. The aim of this study was to comprehensively review a radiation therapist (RTT) led treatment process in which two such systems were utilised, and present initial findings on their use within a SBRT prostate clinical trial.

Materials And Methods: 18 patients were investigated, nine were fitted with the Micropos RayPilot (RP) system (Micropos Medical, Gothenburg, SE) and nine were fitted with the Micropos Raypilot Hypocath (HC) system.

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Protecting qubits from accidental measurements is essential for controlled quantum operations, especially during state-destroying measurements or resets on adjacent qubits, in protocols like quantum error correction. Current methods to preserve atomic qubits against such disturbances waste coherence time, extra qubits, and introduce additional errors. We demonstrate the feasibility of in-situ state-reset and state-measurement of trapped ions, achieving  >99.

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Interests in covalent drugs have grown in modern drug discovery as they could tackle challenging targets traditionally considered "undruggable". The identification of covalent binders to target proteins typically involves directly measuring protein covalent modifications using high-resolution mass spectrometry. With a continually expanding library of compounds, conventional mass spectrometry platforms such as LC-MS and SPE-MS have become limiting factors for high-throughput screening.

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Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle.

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  • The study investigates the effectiveness of the AKT inhibitor capivasertib when combined with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who did not respond well to prior treatments with abiraterone acetate and docetaxel.
  • Conducted as a double-blind, randomized phase 2 trial with 100 men, the primary focus was on the composite response rate, which showed no significant improvement with the combination treatment compared to placebo.
  • Analysis revealed that patients with PTEN loss had poorer overall survival regardless of treatment, with common side effects including diarrhea and fatigue, indicating that while the combination was tolerable, it did not enhance treatment outcomes.
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  • This study explored how brain degeneration correlates with the progression of amyotrophic lateral sclerosis (ALS) by analyzing brain scans of 149 ALS patients and 144 healthy controls.
  • Researchers used a texture analysis method on MRI scans to identify "autocorrelation," a biomarker indicating brain degeneration, focusing on different stages of the disease.
  • Results showed that brain changes varied significantly depending on the criteria used for patient classification, suggesting that standard clinical trial measures may not fully capture the extent of brain degeneration in ALS patients.
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Fast-paced pharmaceutical process developments (e.g., high-throughput experimentation, directed evolution, and machine learning) involve the introduction of fast, sensitive, and accurate analytical assays using limited sample volumes.

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Background: A proportion of patients with adrenal insufficiency (AI) require increases in their maintenance glucocorticoids following the Covid-19 vaccine as a result of vaccine-related symptoms or development of incipient or frank adrenal crisis. In a large cohort of AI patients, we aim to characterise symptoms, changes in glucocorticoid dosage, occurrence of adrenal crises and whether there are differences between the mRNA and adenovirus vector vaccines.

Patients And Methods: Patients with AI of any aetiology were invited to complete a short, structured questionnaire of their experience of the Covid-19 vaccination.

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  • - Macrophomina phaseolina is a fungal pathogen responsible for charcoal rot, affecting around 500 plant species globally, and it notably causes yield losses in soybean crops, particularly in eastern Canada and the USA, but has not been reported in western Canada.
  • - Manitoba, a significant soybean producer, has been conducting annual surveys for root diseases since 2012; however, charcoal rot’s presence was investigated following symptoms observed in soybeans from various fields there in August 2020.
  • - In a laboratory analysis of 600 roots from 40 fields, black streaking and other symptoms indicative of root rot were recorded, and pathogen isolation revealed black microsclerotia in cultures from three fields, leading to the identification of multiple fungal isolates.
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Issue Addressed: Community participation in planning, delivery, and evaluation of health promotion (HP) programs is a poorly explored topic. However, this approach has the potential to improve health outcomes and reduce health inequities, particularly for residents of rural and remote areas.

Methods: This case study describes the outputs of an academic-health service partnership in rural Victoria.

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Precision radiotherapy refers to the ability to deliver radiation doses with sub-millimetre accuracy. It does not however consider individual variation in tumour or normal tissue response, failing to maximise tumour control and minimise toxicity. Combining precise delivery with personalised dosing, through analysis of cell-free DNA, would redefine precision in radiotherapy.

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RIG-I (retinoic acid inducible gene-I) can sense subtle differences between endogenous and viral RNA in the cytoplasm, triggering an anti-viral immune response through induction of type I interferons (IFN) and other inflammatory mediators. Multiple crystal and cryo-EM structures of RIG-I suggested a mechanism in which the C-terminal domain (CTD) is responsible for the recognition of viral RNA with a 5'-triphoshate modification, while the CARD domains serve as a trigger for downstream signaling, leading to the induction of type I IFN. However, to date contradicting conclusions have been reached around the role of ATP in the mechanism of the CARD domains ejection from RIG-I's autoinhibited state.

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Multimodality cancer therapy has led to remarkable improvements in survival of childhood and young adult cancer, with survival rates exceeding 85%. Such remission rates come with their own adverse sequelea or 'late effects'. Although the cause of these late effects is multi-factorial, radiation-related adverse effects are one of the most prevalent.

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  • White mold, caused by the fungus (Lib.) de Bary, is a major challenge for dry bean production in Canada, with high disease levels observed over four growing seasons.
  • The study found that white mold incidence varies by bean market class, with pinto beans being the most affected at an average of 33% disease incidence.
  • Disease management strategies should prioritize fungicide use alongside plant genetics, irrigation practices, and other agronomic methods, as current predictive models based on weather and spore counts were not effective.
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  • The study aims to improve the understanding of non-functioning pituitary microadenomas (micro-NFPAs) and their natural progression to inform patient care.
  • Conducted across 23 endocrine departments in the UK, it analyzed clinical data from 459 patients over a median of 3.5 years, assessing tumor growth and hormonal changes.
  • Results indicate a low probability of tumor growth (7.8% at 3 years) and rare development of hypopituitarism, suggesting that follow-up MRIs every 3 years and less frequent hormonal checks are adequate for managing micro-NFPAs.
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  • Adding concurrent chemotherapy to radiotherapy enhances treatment outcomes for patients with muscle-invasive bladder cancer, with a meta-analysis indicating better disease control with a hypofractionated schedule.
  • The RAIDER clinical trial compared standard and adaptive radiotherapy in patients with unifocal bladder cancer, assessing acute toxicity based on therapy and fractionation schedules.
  • Results showed that individuals receiving concomitant therapy experienced significantly higher rates of acute grade 2+ gastrointestinal toxicity in the 20-fraction group, but not in the 32-fraction group, highlighting differences in toxicity based on treatment regimens.
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The discovery of peptide therapeutics represents a fast-growing segment of pharmaceutical research. During the early discovery process, a large number of peptide candidates needs to be rapidly screened for metabolic stability in relevant biological matrices. In most cases, peptide stability assays are quantified using LC-MS/MS, which may take hours to analyze 384 samples and generates liters of solvent waste.

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We tested for a forage allowance effect on the milk yield of early lactation dairy cow herds grazing swards sown with perennial ryegrass ( L.), white clover ( L.) and plantain ( L.

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  • The study developed machine learning models to predict rectal toxicities caused by radiation therapy for prostate cancer, focusing on three specific clinical outcomes.
  • Researchers analyzed data from 183 patients, using features derived from CT scans and radiation dosimetry, and applied multiple classifiers to assess the relationship between these features and the toxicities.
  • The findings demonstrated that combining radiomic and dosimetric features improved prediction accuracy, particularly for hemorrhage, indicating the potential of these methods in personalized treatment planning.
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