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"Evans, Holly"
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My brother Charlie
A girl tells what it is like living with her twin brother who has autism and sometimes finds it hard to communicate with words, but who, in most ways, is just like any other boy. Includes authors' note about autism.
Book
Attachment as a mechanism influencing end-of-life communication: An analogue investigation
Talking about dying when faced with end-of-life may be important for achieving optimal outcomes for young people and their families. Given the lack of research on young people’s communication around end-of-life and death, this analogue study examined the role of attachment theory in conversations about dying. Experiment 1 assessed attachment security of 80 healthy young adults and randomised them to receive either an induction that raised awareness of one’s attachment figures or a neutral induction, and then primed them with an imagined scenario where they were diagnosed with an incurable illness. Participants then completed a self-report measure of their willingness to discuss end-of-life topics with family, friends, or a psychologist. The experimental attachment induction did not increase willingness to talk about end-of-life concepts. Experiment 2 extended this design and asked participants to describe these conversations and assessed the content of their imagined end-of-life conversations. Experiment 2 replicated the finding that enhancing individuals’ awareness of key attachment figures did not increase participants’ willingness to engage in end-of-life conversations. However, heightened attachment awareness led participants to talk more about their relationship with the person they were hypothetically talking with. Across both experiments, avoidant attachment tendencies reduced the likelihood that participants receiving the attachment prime would want to engage in end-of-life conversation. Overall, it seems there are important differences between individuals on willingness to talk about death, and this may be influenced by one’s attachment style. These results raise implications for the importance of attachment in the therapeutic relationship for healthcare professionals working with young people with life-limiting illnesses, such as cancer. Further research may shed light on how an individually tailored approach, taking into account attachment security, achieves the best outcomes for individuals who require end-of-life conversations.
Journal Article
Advances in Cryopreservation of Bull Sperm
Cryopreservation of semen and artificial insemination have an important, positive impact on cattle production, and product quality. Through the use of cryopreserved semen and artificial insemination, sperm from the best breeding bulls can be used to inseminate thousands of cows around the world. Although cryopreservation of bull sperm has advanced beyond that of other species, there are still major gaps in the knowledge and technology bases. Post-thaw viability of sperm is still low and differs significantly among the breeding bulls. These weaknesses are important because they are preventing advances both in fundamental science of mammalian gametes and reproductive biotechnology. Various extenders have been developed and supplemented with chemicals to reduce cryodamage or oxidative stress with varying levels of success. More detailed insights on sperm morphology and function have been uncovered through application of advanced tools in modern molecular and cell biology. This article provides a concise review of progress in the cryopreservation of bull sperm, advances in extender development, and frontiers using diverse techniques of the study of sperm viability. This scientific resource is important in animal biotechnology because with the advances in discovery of sperm fertility markers, there is an urgent need to improve post-thaw viability and fertility of sperm through enhanced cryopreservation for precision agriculture to produce food animals to ensure food security on the global scale.
Journal Article
The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase
Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis, independent of RANK ligand, which disrupts normal bone homeostasis leading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications.
Journal Article
Examining the Priorities, Needs and Preferences of Men with Metastatic Prostate Cancer in Designing a Personalised eHealth Exercise Intervention
BackgroundFew individuals with metastatic prostate cancer have access to prostate cancer-specific exercise support, despite demonstrated benefits. eHealth tools, such as websites, may be viable options for increasing access. To be effective and acceptable, future eHealth websites need to consider end-users’ perspectives, capacity and needs. We aim to provide insight into these factors by exploring daily priorities, activities and health literacy of individuals with metastatic prostate cancer and their perspectives towards exercise and exercise-based web-based eHealth interventions.MethodsSemi-structured interviews explored participant’s experiences and understanding of their disease, exercise levels, advice received from health care providers, as well as acceptability of and suggested content for an eHealth tool. A thematic analysis was undertaken.ResultsInterviews were conducted with eighteen Australians (55–83 years; M = 71.5, SD = 8.9) living with metastatic prostate cancer. Needing to perform daily responsibilities was a key priority. Participants had limited understanding of the benefits of prostate cancer-specific exercise, and less than half discussed exercise with their health team. Fourteen men felt they could report metastases location, but only four could provide detailed information, which has clinical implications for exercise prescription. A potential web-based intervention was considered acceptable by seventeen men for reasons such as affordability, accessibility and convenience. User-friendly design and practitioner support were important.ConclusionsResults identified key aspects useful for person-centred design of exercise programs. Participants were positive towards the proposed web-based tool and expressed the need for individualised, user-friendly and reliable information with support from a professional embedded. Lastly, not all participants could accurately report metastasis locations.
Journal Article
NOD/SCID-GAMMA Mice Are an Ideal Strain to Assess the Efficacy of Therapeutic Agents Used in the Treatment of Myeloma Bone Disease
Animal models of multiple myeloma vary in terms of consistency of onset, degree of tumour burden and degree of myeloma bone disease. Here we describe five pre-clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the effects of therapeutic agents on myeloma bone disease. Groups of 7-8 week old female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or patient-derived myeloma cells. At the first signs of morbidity in each tumour group all animals were sacrificed. Tumour load was measured by histological analysis, and bone disease was assessed by micro-CT and standard histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed high tumour bone marrow infiltration of the long bones with low variability, resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient-derived myeloma cells showed lower tumour bone marrow infiltration and less bone disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice resulted in an aggressive, short-term model of myeloma with mice exhibiting signs of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time of tumour cell injection or once tumour was established prevented JJN3-induced bone disease but did not reduce tumour burden, whereas, carfilzomib treatment given once tumour was established significantly reduced tumour burden. Injection of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less aggressive longer-term models of myeloma with mice exhibiting signs of morbidity 8 weeks later. Treating U266-induced disease with zoledronic acid prevented the formation of osteolytic lesions and trabecular bone loss as well as reducing tumour burden whereas, carfilzomib treatment only reduced tumour burden. In summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide robust models to study anti-myeloma therapies, particularly those targeting myeloma bone disease.
Journal Article
ARQ-197, a small-molecule inhibitor of c-Met, reduces tumour burden and prevents myeloma-induced bone disease in vivo
The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit. We hypothesized that ARQ-197 (Tivantinib), a small molecule c-Met inhibitor, would reduce myeloma cell growth and prevent myeloma-associated bone disease in a murine model. In vitro we assessed the effects of ARQ-197 on myeloma cell proliferation, cytotoxicity and c-Met protein expression in human myeloma cell lines. In vivo we injected NOD/SCID-γ mice with PBS (non-tumour bearing) or JJN3 cells and treated them with either ARQ-197 or vehicle. In vitro exposure of JJN3, U266 or NCI-H929 cells to ARQ-197 resulted in a significant inhibition of cell proliferation and an induction of cell death by necrosis, probably caused by significantly reduced levels of phosphorylated c-Met. In vivo ARQ-197 treatment of JJN3 tumour-bearing mice resulted in a significant reduction in tumour burden, tumour cell proliferation, bone lesion number, trabecular bone loss and prevented significant decreases in the bone formation rate on the cortico-endosteal bone surface compared to the vehicle group. However, no significant differences on bone parameters were observed in non-tumour mice treated with ARQ-197 compared to vehicle, implying that in tumour-bearing mice the effects of ARQ-197 on bone cells was indirect. In summary, these res ults suggest that ARQ-197 could be a promising therapeutic in myeloma patients, leading to both a reduction in tumour burden and an inhibition of myeloma-induced bone disease.
Journal Article
Evaluating a web-based computer-tailored physical activity intervention for those living with and beyond lung cancer (ExerciseGuide UK): protocol for a single group feasibility and acceptability study
Background
Lung cancer is the leading cause of cancer-related death globally. Physical activity and exercise provide unequivocal benefits to those living with and beyond lung cancer. However, few of those living with and beyond cancer meet the national physical activity guidelines. Various barriers exist for this population’s engagement in physical activity and exercise, such as the lack of knowledge and lack of tailored information, little access to exercise specialists, fatigue, and mobility challenges. Digitally delivered programmes have the potential to address several of these barriers, with techniques like “computer-tailoring” available to enable the delivery of tailored content at a time and place that is convenient. However, evaluation of such programmes is needed prior to implementation. This protocol describes a single group study that will examine the feasibility and acceptability of an online tool (ExerciseGuide UK) that provides those living with and beyond lung cancer web-based computer-tailored physical activity prescription and modules underpinned by behaviour change theories.
Methods
Thirty-five individuals diagnosed with lung cancer, or cancer affecting the lung (e.g. pleural mesothelioma), will be recruited into a single-intervention arm. The platform will provide tailored resources and a personalised physical activity programme using IF-THEN algorithms. Exercise prescription will be tailored on factors such as self-reported specific pain location, exercise history, and current physical fitness. In addition, modules grounded in behaviour change will supplement the physical activity programme and will focus on topics such as exercise benefits, safety, goal setting, and tracking. The primary outcome will be assessed using pre-established criteria on feasibility and mixed-methods approach for acceptability.
Secondary outcomes will explore changes in the physical activity, quality of life, anxiety, and depression.
Discussion
This manuscript describes the protocol for a study examining the feasibility and acceptability of a web-based computer-tailored physical activity intervention for those living with and beyond lung cancer. The publication of this protocol aims to increase the transparency of the methods, report pre-determined criteria, and aid replication of the study and associated materials. If feasible and acceptable, this intervention will inform future studies of digital-based interventions.
Trail registration
ClinicalTrails.gov
, NCT05121259. Registered on November 16, 2021.
Journal Article
Lipidomic markers of sperm cryotolerance in cattle
The objective of the current study was to determine the fatty acid composition of sperm from Holstein bulls with different freezability (Good and Poor;
n
= 12). Fatty acids were extracted from frozen sperm in 1:2 (v/v) chloroform–methanol solvent, fractionated into neutral and polar fractions, and composition determined by gas chromatography–mass spectrometry. Thirty-four fatty acids were quantified and their concentrations and percentages within each lipid fraction were calculated. Overall, saturated fatty acids (SFA) were predominant, accounting for 71 to 80% of fatty acids in neutral and polar lipid factions. There were marked differences in fatty acid composition between the lipid fractions (
P
< 0.001). The branched chain fatty acid (BCFA) concentration (15 to 18 µg) was almost twice as much as polyunsaturated fatty acids (PUFA) concentration found in the polar lipid fraction (8 to 9 µg;
P
< 0.001). Sperm with different freezability phenotypes only had a few differences in 22:0, 18:1 cis 9, and 14:0 13-methyl fatty acids (
P
≤ 0.011). These results are significant because they reveal key understandings of fatty acid composition of sperm membrane and lay a foundation for the manipulation of membrane integrity, fluidity, and stability to advance the assisted reproductive technologies.
Journal Article
Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial
Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3–18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159–2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer.
Journal Article