The Wesley-St Andrew's Research Institute

Abstract Immune-checkpoint inhibitors (ICIs) are the primary treatment for advanced cutaneous squamous cell carcinoma (cSCC). Tumour microenvironment differences between immunocompetent and immunocompromised patients may underpin the development of effective biomarkers. Across 4 cSCC patients, we profiled 190 consecutively gridded, pathology assigned, regions of interest, using the GeoMx Discovery Protein Atlas (1116 protein markers). Expression profiles underscored by metabolic and immunological activity, including type I interferon signalling, differentiate patient immune competency.

Abstract While there have been therapeutic advancements in treatments for non-small cell lung cancer (NSCLC), we have a limited understanding of how the tumour composition and spatial heterogeneity influences clinical outcomes. Here, we performed a multiomic analysis of 61 NSCLC patients treated with adjuvant chemotherapy and curative resection, integrating spatial transcriptomics, spatial proteomics, and deep learning to profile the tumour microenvironment (TME). We identified spatial-metabolic alterations associated with disease recurrence in and between cells in the TME, involving glutamine import, glycolytic, and lipid oxidation pathways. Based on protein expression, we found spatially distinct regions linked to tumour recurrence, implicating specific roles for tumour associated macrophages, metabolic pathways, and major histocompatibility complex (MHC) proteins. Moreover, transcriptomic analysis revealed histology-specific gene expression changes and metabolic and inflammation pathway associations with tumour recurrence. This comprehensive multiomic analysis highlights the complex immunological and metabolic dynamics characteristic of disease recurrence in adjuvant chemotherapy treated NSCLC.

Abstract Introduction Australia has a geographically tiered health system which is reinforced by a long-term pattern of urban-centric policymaking. As a result, people living in rural and remote areas have poor health outcomes, a high rate of preventable hospitalisations, and premature death. Virtual healthcare has been proposed as a strategy for improving geographical health equity, but many clinicians and health service leaders consider telehealth and virtual healthcare to be substandard compared with traditional face-to-face delivery. It is important to ensure that new services for people in rural and remote areas are designed and delivered to the same standard as traditional health services in metropolitan areas. Methods This was a qualitative thematic study with a focus on identification of hidden meaning representing unconscious bias. Interviews were conducted with clinicians and health service leaders (February-July 2023, Queensland, Australia) to inform the design and delivery of a new private virtual hospital. Three rounds of analysis were conducted by three coders using reflexive practices. Results 26 participants: 5 health service leaders, 3 clinicians, and 18 who were both a leader and clinician. Three themes were identified: 1) traditional face-to-face healthcare is better than telehealth; 2) virtual healthcare offers an opportunity for rural and remote residents with limited access to face-to-face healthcare; 3) telehealth is better than nothing. Theme three focused on participants’ acceptance of substandard healthcare when the alternative is no healthcare at all. Discussion Taken together, the three themes indicate a tacit acceptance of a lower standard of healthcare for people living in rural and remote areas. This reflects a known urban-centric bias of healthcare policy makers. If a lower standard is considered acceptable because it is ‘better than nothing’ this may negatively influence the design/ delivery of virtual healthcare services in rural and remote areas. This urban-centric bias must be addressed to ensure equitable access to appropriate health services and health outcome equivalency.

Abstract The placement of an endotracheal tube for children with acute or critical illness is a low frequency and high-risk procedure, associated with high rates of first attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) uses high oxygen flow rates (approximately 2L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time has not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases frequency of first attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper we describe the detailed statistical analysis plan as an update the previously published protocol.

Lutetium-177-PSMA (LuPSMA) is a targeted systemic radioligand treatment for metastatic castration-resistant prostate cancer (mCRPC). LuPSMA is considered as an experimental treatment not yet used in routine practice. Here, we report our experience following the introduction of LuPSMA therapy at our institution. Referred mCRPC patients were assessed for treatment suitability including Gallium-68-PSMA PET/CT and blood tests. Suitable patients underwent up to four cycles of LuPSMA treatment. Response to treatment was assessed by changes in serum prostate-specific antigen (PSA) levels. Toxicity was assessed by recording of adverse events. In an 18month period, 50 patients underwent 132 cycles of LuPSMA therapy. Patients underwent a median of three cycles each (range: 1-4) and the mean administered amount of activity per cycle was 5.9 GBq (range: 3.5-8.2 GBq). PSA decline could be calculated for 49 patients, with a best PSA decline of≥50% observed in 22 patients (44.9%). Adverse events were reported across 45 of 132 LuPSMA cycles. Most adverse events were grade I (42/45) and the remaining three events were grade II. Initial experience at our site supports the use of LuPSMA as an emerging safe and effective treatment for mCRPC. Since introducing LuPSMA therapy at our institution, 44.9% of patients have experienced a decline in PSA level≥50% with low or minimal toxicity. This is an important finding as these patients had previously exhausted all available treatment options. Overall, we have found patients and their primary care doctors have eagerly accepted LuPSMA as another line of defence against mCRPC.

This paper presents the positioning, navigation and awareness (PNA) system developed for the Underwater Robotic Mining System of the !VAMOS! project [1]. It describes the main components of the !VAMOS! system, the PNA sensors in each of those components, the global architecture of the PNA system, and its main subsystems: Position and Navigation, Realtime Mine Modeling, 3D Virtual reality HMI and Real-time grade system. General results and lessons learn during the first mining field trial in Lee Moor, Devon, UK during the months of September and October 2017 are presented.

Workplace smoking cessation programs can effectively assist employees to quit smoking. However, little is known about employees' attitudes towards engagement in workplace smoking cessation programs. This study aimed to address the limited understanding of the interaction between employee characteristics and their health beliefs toward engaging in a workplace smoking cessation program. Self-report data was collected from 897 employees of a mining company operating in two remote towns in Australia. The majority of participants were male (73%), the mean age was 36.9 years (SD = 11.5). Chi square tests of independence were used to analyze relationships between employee characteristics and smoking cessation engagement attitudes. Engagement attitudes included: A desire to cease smoking; desire for assistance with the smoking cessation process; and intention to participate in a workplace smoking intervention. The findings from this study indicated that attitudes towards engagement in smoking cessation programs varied for mining employees according to gender, age, perceived severity, perceived self-efficacy, and stage of readiness to change. These findings provide insights that health promotion practitioners may apply to inform the design and marketing of effective workplace smoking cessation programs for similar employees.