Gurney

The identification of somatic RB1 variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) derived from aqueous humour (AH) can be used to identify somatic RB1 pathogenic variation. Here we report RB1 pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH...

BACKGROUND: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score...

Hormonal treatments (HT) for prostate cancer (e.g., androgen deprivation therapy) yield clinical and survival benefits, yet adverse cognitive changes may be a side effect. Since psychosocial factors are largely modifiable, interventions targeting these factors may help mitigate these adverse cognitive effects. This systematic review aimed to identify a range of psychosocial factors associated with cognitive function in individuals with prostate cancer undergoing HT and to determine whether these factors mitigate or exacerbate this effect...

OBJECTIVES: To evaluate the implementation of mifepristone and misoprostol for medical management of early pregnancy loss (EPL) in emergency departments (EDs) by comparing efficacy, complication, and follow-up rates for patients treated in EDs to those in the Complex Family Planning (CFP) outpatient office. STUDY DESIGN: In COVID-19's first wave, we expanded medication management of EPL to our EDs. This retrospective study evaluated 72 patients receiving mifepristone and misoprostol for EPL from 4/1/2020-3/31/2021, comparing treatment success, safety outcomes, and follow-up rates by location...

Aim: Currently, there exist no curative treatments for neurodegenerative disorders. Recently, there has been a resurgence of interest in the use of medicinal cannabis to improve neurological conditions. Methods: A 12-month, open label, dose-finding, safety and efficacy study was conducted including 48 subjects with a variety of neurodegenerative disorders. Results: In our participants, we observed a reduction in pain, improved sleep, enhanced well-being and less agitation. Conclusion: Our findings suggest that medicinal cannabis might be useful in patients with neurodegenerative disorders in controlling pain, enhancing sleep, reducing difficult behaviors, controlling unusual and complex symptoms when other treatments have failed - this offers medicinal cannabis a role in palliation...

BACKGROUND: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent...

Career shifts are a naturally occurring part of the trauma and acute care surgeon's profession. These transitions may occur at various timepoints throughout a surgeon's career and each has their own specific challenges. Finding a good fit for your first job is critical for ensuring success as an early career surgeon. Equally, understanding how to navigate promotions or a change in job location mid-career can be fraught with uncertainty. As one progresses in their career, knowing when to take on a leadership position is oftentimes difficult as it may mean a change in priorities...

Polycyclic aromatic compounds (PACs) - a large group of organic chemicals naturally present in petroleum deposits (i.e., petrogenic) or released into the environment by incomplete combustion of organic materials (i.e., pyrogenic) - represent a potential risk to the health of aquatic ecosystems. In high latitude freshwater ecosystems, concentrations of PACs may be increasing, yet there are limited studies in such systems to assess change and to understand threats. Using 10 years of contemporary data from passive samplers deployed across five regions (n = 43 sites) in the Mackenzie River Basin, we (i) describe baseline levels of PACs, (ii) assess spatiotemporal patterns, and (ii) evaluate the extent to which environmental factors (fire, snowmelt, and proximity to oil infrastructure) influence concentrations in this system...

INTRODUCTION: New Zealand has a population of only 5.5 million meaning that for many surgical procedures the country qualifies as a "low-volume center." However, the health system is well developed and required to provide complex surgical procedures that benchmark internationally against comparable countries. This investigation was undertaken to review regional variation and volumes of complex resection and palliative upper gastrointestinal (UGI) surgical procedures within New Zealand...

People frequently face decisions that require making inferences about withheld information. The advent of large language models coupled with conversational technology, e.g., Alexa, Siri, Cortana, and the Google Assistant, is changing the mode in which people make these inferences. We demonstrate that conversational modes of information provision, relative to traditional digital media, result in more critical responses to withheld information, including: (1) a reduction in evaluations of a product or service for which information is withheld and (2) an increased likelihood of recalling that information was withheld...

Pectoralis major (PM) rupture is a rare injury, commonly misdiagnosed, that affects mostly young male athletes aged 20-40 years. This type of injury is typically associated with weight lifting, especially bench pressing. In an occupational medicine setting, it is extremely rare and not much reported in the literature. We present the case of a 30-year-old trauma technician male who presented with right shoulder and chest pain following a popping sensation while pushing in full momentum a patient on a gurney accidentally set on break mode...

Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified CCUS patients by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS...

Oncolytic viruses (OV) are part of a burgeoning field of investigational oncolytic therapy (OT), in which lytic viruses dissolve advanced tumors productively and specifically. One such OT is a Coxsackievirus A21 (CVA21) based OV that is currently under clinical evaluation. A tissue culture infectious dose (TCID50) assay was used for CVA21 potency release and stability testing in early clinical development. The titer measured in this method was an extrapolated value from cytopathic effect (CPE) observed during the serial dilution but doesn't represent direct viral killing of cells...

Recent interest in the biology and function of peritoneal tissue resident macrophages (pMΦ) has led to a better understanding of their cellular origin, programming and renewal. The programming of pMΦ is dependent on microenvironmental cues and tissue specific transcription factors, including GATA6. However, the contribution of microRNAs remains poorly defined. We conducted a detailed analysis of the impact of GATA6-deficiency on microRNA expression in mouse pMΦ. Our data suggest that for many of the pMΦ, microRNA composition may be established during tissue specialization, and that the effect of GATA6 knockout is largely unable to be rescued in the adult by exogenous GATA6...

BACKGROUND: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC. METHODS: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430)...

The vertebrate basal ganglia play an important role in action selection-the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement...

OBJECTIVES: The objective of this study is to investigate the influence of diabetes on breast cancer-specific survival among women with breast cancer in Aotearoa/New Zealand. METHODS: This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rēhita Mate Ūtaetae-Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan-Meier method...

BACKGROUND: Intravoxel incoherent motion (IVIM)-corrected diffusion tensor imaging (DTI) potentially enhances return-to-play (RTP) prediction after hamstring injuries. However, the long scan times hamper clinical implementation. We assessed accelerated IVIM-corrected DTI approaches in acute hamstring injuries and explore the sensitivity of the perfusion fraction (f) to acute muscle damage. METHODS: Athletes with acute hamstring injury received DTI scans of both thighs < 7 days after injury and at RTP...

People-centred care is foundational to healthcare excellence. One urban Canadian long-term care residence recently participated in an initiative titled "Improving the Care Conference Experience" to engage residents and families in annual care conferences. The Institute for Healthcare Improvement introduced "care bundles" to group evidence-based practices within standard processes. For this initiative, one health region's Experience in Care team co-developed, implemented and evaluated an "experience bundle" for inclusive care conferences with key stakeholders including residents, family members, direct care providers and leadership...

Chlorella supplementation is reported to improve V˙O2max following extended supplementation periods (~3 weeks). However, there is little research on its impact over submaximal exercise intensities and following shorter supplementation regimens. This study aimed to investigate the efficacy of 6 g/day 2-day chlorella supplementation on exercise performance in healthy young adults. Twenty young healthy adults (Males = 16, Females = 4) (Age 22 ± 6 years, V˙O2max 42.7 ± 9.6 mL/(kg·min)) were recruited for this double-blinded, randomised cross-over study...