Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore.

The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat.

Psychosocial assessment of adolescents and young adults in paediatric hospital settings: patient and staff perspectives on implementation of the e-HEEADSSS.

BACKGROUND: The main causes of morbidity and mortality for adolescents and young adults are preventable and stem from psychosocial and behavioural concerns. Psychosocial assessments can help clinicians to identify and respond holistically to risks and strengths that may impact upon a young person's physical and mental health. Despite broad support at a policy level, the implementation of routine psychosocial screening for young people remains varied in Australian health settings. The current study focused on the pilot implementation of a digital patient-completed psychosocial assessment (the e-HEEADSSS) at the Sydney Children's Hospital Network. The aim of this research was to evaluate patient and staff barriers and facilitators to local implementation. METHODS: The research used a qualitative descriptive research design. Semi-structured interviews were conducted online with 8 young patients and 8 staff members who had completed or actioned an e-HEEADSSS assessment within the prior 5 weeks. Qualitative coding of interview transcripts was carried out in NVivo 12. The Consolidated Framework for Implementation Research guided the interview framework and qualitative analyses. RESULTS: Results demonstrated strong support for the e-HEEADSSS from patients and staff. Key reported facilitators included strong design and functionality, reduced time requirements, greater convenience, improved disclosure, adaptability across settings, greater perceived privacy, improved fidelity, and reduced stigma for young people. The key barriers were related to concerns over available resources, the sustainability and continuity of staff training, perceived availability of clinical pathways for follow-up and referrals, and risks related to off-site completions. Clinicians need to adequately explain the e-HEEADSSS assessment to patients, educate them about it, and make sure that they receive timely feedback on the results. Greater reassurance and education regarding the rigour of confidentiality and data handling procedures is required for patients and staff. CONCLUSIONS: Our findings indicate that continued work is required to support the integration and sustainability of digital psychosocial assessments for young people at the Sydney Children's Hospital Network. The e-HEEADSSS shows promise as an implementable intervention to achieve this goal. Further research is required to determine the scalability of this intervention across the broader health system.

Implementation science in adolescent healthcare research: an integrative review.

BACKGROUND: Multiple theories, models and frameworks have been developed to assist implementation of evidence-based practice. However, to date there has been no review of implementation literature specific to adolescent healthcare. This integrative review therefore aimed to determine what implementation science theories, models and frameworks have been applied, what elements of these frameworks have been identified as influential in promoting the implementation and sustainability of service intervention, and to what extent, in what capacity and at what time points has the contribution of adolescent consumer perspectives on evidence implementation been considered.  METHODS: An integrative design was used and reported based on a modified form of the PRISMA (2020) checklist. Seven databases were searched for English language primary research which included any implementation science theory, model or framework developed for/with adolescents or applied in relation to adolescent healthcare services within the past 10 years. Content and thematic analysis were applied with the Consolidated Framework for Implementation Research (CFIR) used to frame analysis of the barriers and facilitators to effective implementation of evidence-informed interventions within youth health settings. RESULTS: From 8717 citations, 13 papers reporting 12 studies were retained. Nine different implementation science theories, frameworks or approaches were applied; six of 12 studies used the CFIR, solely or with other models. All CFIR domains were represented as facilitators and barriers for implementation in included studies. However, there was little or no inclusion of adolescents in the development or review of these initiatives. Only three mentioned youth input, occurring in the pre-implementation or implementation stages. CONCLUSIONS: The few studies found for this review highlight the internationally under-developed nature of this topic. Flagging the importance of the unique characteristics of this particular age group, and of the interventions and strategies to target it, the minimal input of adolescent consumers is cause for concern. Further research is clearly needed and must ensure that youth consumers are engaged from the start and consistently throughout; that their voice is prioritised and not tokenistic; that their contribution is taken seriously. Only then will age-appropriate evidence implementation enable innovations in youth health services to achieve the evidence-based outcomes they offer. TRIAL REGISTRATION: PROSPERO 2020 CRD42020201142 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=201142.

Building evidence into youth health policy: a case study of the Access 3 knowledge translation forum.

BACKGROUND: Effective integration of evidence and youth perspectives into policy is crucial for supporting the future health and well-being of young people. The aim of this project was to translate evidence from the Access 3 project to support development of a new state policy on youth health and well-being within New South Wales (NSW), Australia. Ensuring the active contribution of young people within policy development was a key objective of the knowledge translation (KT) process. METHODS: The KT activity consisted of a 1-day facilitated forum with 64 purposively sampled stakeholders. Participants included eight young people, 14 policy-makers, 15 academics, 22 clinicians or managers from NSW health services, four general practitioners and one mental health service worker. Research to be translated came from the synthesized findings of the NSW Access 3 project. The design of the forum included stakeholder presentations and group workshops, guided by the 2003 Lavis et al. KT framework that was improved by the Grimshaw et al. KT framework in 2012. Members of the Access 3 research team took on the role of knowledge brokers throughout the KT process. Participant satisfaction with the workshop was evaluated using a brief self-report survey. Policy uptake was determined through examination of the subsequent NSW Youth Health Framework 2017-2024. RESULTS: A total of 25 policy recommendations were established through the workshop, and these were grouped into six themes that broadly aligned with the synthesized findings from the Access 3 project. The six policy themes were (1) technology solutions, (2) integrated care and investment to build capacity, (3) adolescent health checks, (4) workforce, (5) youth participation and (6) youth health indicators. Forum members were asked to vote on the importance of individual recommendations. These policy recommendations were subsequently presented to the NSW Ministry of Health, with some evidence of policy uptake identified. The majority of participants rated the forum positively. CONCLUSIONS: The utilization of KT theories and active youth engagement led to the successful translation of research evidence and youth perspectives into NSW youth health policy. Future research should examine the implementation of policy arising from these KT efforts.

Inhibition of farnesyl pyrophosphate (FPP) and/or geranylgeranyl pyrophosphate (GGPP) biosynthesis and its implication in the treatment of cancers.

Dysregulation of isoprenoid biosynthesis is implicated in numerous biochemical disorders that play a role in the onset and/or progression of age-related diseases, such as hypercholesterolemia, osteoporosis, various cancers, and neurodegeneration. The mevalonate metabolic pathway is responsible for the biosynthesis of the two key isoprenoid metabolites, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational prenylation of various proteins, including the small GTP-binding proteins (GTPases), with either FPP or GGPP is vital for proper localization and activation of these proteins. Prenylated GTPases play a critical role in cell signaling, proliferation, cellular plasticity, oncogenesis, and cancer metastasis. Pre-clinical and clinical studies strongly suggest that inhibition of protein prenylation can be an effective treatment for non-skeletal cancers. In this review, we summarize the most recent drug discovery efforts focusing on blocking protein farnesylation and/or geranylgeranylation and the biochemical and structural data available in guiding the current on-going studies in drug discovery. Furthermore, we provide a summary on the biochemical association between disruption of protein prenylation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR) signaling, and cancer.

Frequent whole blood donors: understanding this population and predictors of lapse.

BACKGROUND: Frequent blood donors are an important resource as they contribute many donations over their lifetime. The aim of this research was to develop a demographic profile of Australian frequent whole blood donors and to determine predictors of lapse within this group. STUDY DESIGN AND METHODS: Routinely collected data were used to profile individuals who had donated whole blood frequently (three or more times) between December 2010 and November 2011. Two segments were identified: 1) existing donors who had donated before December 2010 and 2) new donors who had not donated before December 2010. Donation records were followed to the end of December 2013 to examine retention. RESULTS: A total of 90,867 donated frequently between December 2010 and November 2011. The group was composed of slightly more men (51.4%), was typically of middle socioeconomic status, and many were employed in skilled trades such as a builder or a plumber (21.3%). Existing donors (n = 81,762) were significantly older, more likely to be male, and more likely to have a D- blood type compared to the smaller group of new donors (n = 9105). For both segments, being older and male and having a D- blood type increased the likelihood of return in the follow-up period. Deferrals and adverse events had negative impacts on retention for both groups. CONCLUSIONS: This study highlights specific factors that blood collection agencies may focus on to support continued donation among frequent donors.

A Covalent Cysteine-Targeting Kinase Inhibitor of Ire1 Permits Allosteric Control of Endoribonuclease Activity.

The unfolded protein response (UPR) initiated by the transmembrane kinase/ribonuclease Ire1 has been implicated in a variety of diseases. Ire1, with its unique position in the UPR, is an ideal target for the development of therapies; however, the identification of specific kinase inhibitors is challenging. Recently, the development of covalent inhibitors has gained great momentum because of the irreversible deactivation of the target. We identified and determined the mechanism of action of the Ire1-inhibitory compound UPRM8. MS analysis revealed that UPRM8 inhibition occurs by covalent adduct formation at a conserved cysteine at the regulatory DFG+2 position in the Ire1 kinase activation loop. Mutational analysis of the target cysteine residue identified both UPRM8-resistant and catalytically inactive Ire1 mutants. We describe a novel covalent inhibition mechanism of UPRM8, which can serve as a lead for the rational design and optimization of inhibitors of human Ire1.

The Blood Donor Anxiety Scale: a six-item state anxiety measure based on the Spielberger State-Trait Anxiety Inventory.

BACKGROUND: Research demonstrates that anxiety elevates the risk of blood donors experiencing adverse events, which in turn deters the performance of repeat blood donations. Identifying donors suffering from heightened state anxiety is important to assess the impact of evidence-based interventions. This study analyzed the appropriateness of a shortened version of the state subscale of the State-Trait Anxiety Inventory (STAI) in a blood donation context. STUDY DESIGN AND METHODS: STAI-State questionnaire data were collected from two separate samples of Australian blood donors (n = 919 and n = 824 after cleaning). Responses to demographic, donation history, and adverse reaction questions were also obtained. Identification of items and analysis was performed systematically to assess and compare internal reliability and content, construct, convergent, and criterion validity of three potential short-form state anxiety scales. RESULTS: Of the three short-form scales tested, STAI-State six-item scale demonstrated the best metric properties with the least number of items across both sample groups. Cronbach's alpha was acceptable (α = 0.844 and α = 0.820), correlated positively with the original measure (r = 0.927 and r = 0.931) and criterion-related variables, and maintained the two-dimension factorial structure of the original measure. CONCLUSION: The six-item short version of the STAI-State subscale presented the most reliable and valid scale for use with blood donors. A validated donor anxiety tool provides a standardized assessment and record of donor anxiety to gauge the effectiveness of ongoing efforts to enhance the donation experience.

Improving first-time donor attendance rates through the use of enhanced donor preparation materials.

BACKGROUND: Many nondonors are positive about blood donation and this motivates booking an appointment to donate. However, as their appointment approaches barriers to donating-such as anxiety-may become salient and deter attendance. Building on research of France and colleagues demonstrating the positive effect of enhanced preparation materials on donor recruitment, this study sought to determine whether these materials could effectively boost first donation appointment attendance. STUDY DESIGN AND METHODS: A field study comprising a 3 (brochure: none, e-mail, hard copy) × 2 (national call center [NCC] contact: none, call) between-subjects design was conducted with 3646 nondonors who had scheduled their first appointment. Participants in the brochure conditions received either a hard copy or an e-mailed link to electronic materials modeled on the donor preparation research of France and colleagues. Participants in the NCC call condition also received a call scripted in line with these preparation materials. The key outcome was new donor attendance rate. RESULTS: Although first-appointment attendance rates were high in the control (no additional contact) condition at 85.07% of those not canceling in advance, dual exposure to the preparation materials through a NCC call and an electronic brochure boosted attendance. The relative risk of attending in the NCC call and electronic brochure condition was 1.0836 (95% confidence interval, 1.0352-1.1343; p = 0.0006), with attendance 8.36% higher than in the control. This gain in attendance came at a relative increase in recruitment costs of 2%. CONCLUSION: The use of tailored communication to address new donors' concerns and prepare them for donating bolsters attendance rates.

Lost in translation: Knowledge, attitudes and practices in donors experiencing a vasovagal reaction.

BACKGROUND: Vasovagal symptoms have implications for donor safety and retention. This study explored knowledge, attitudes and practices in donors experiencing a vasovagal reaction. MATERIALS AND METHODS: Semi-structured interviews were conducted with donors (n = 30) who experienced a donation-related vasovagal reaction. RESULTS: Donors were unaware of applied muscle tension or fluid loading techniques despite availability of information. Some donors engaged in excessive pre-donation hydration. Procedural knowledge was limited for first-time plasma donors. DISCUSSION: Future interventions should focus on adherence to pre-donation fluid loading and muscle tensing exercises during key donation time-points. Education for new plasma donors also appears important.

Sustained benefits of autologous serum eye drops on self-reported ocular symptoms and vision-related quality of life in Australian patients with dry eye and corneal epithelial defects.

BACKGROUND: This research examined the effect of autologous serum eye drops (ASED) on ocular symptoms, visual-related functioning and quality of life for patients failing other therapies. METHODS: Patients (N = 77) were asked to complete a survey prior to ASED use, and 2 and 12 months post-treatment. RESULTS: Significant improvements in symptom frequency and severity were documented for dryness, ocular pain and grittiness at 2 and 12 months. Patients felt more in control and required less help from others at 12 months. CONCLUSIONS: ASED produce sustained benefits to dry eye symptoms, improve feelings of control and reduce requirements for assistance from others.

Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors.

BACKGROUND: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. STUDY DESIGN AND METHODS: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. RESULTS: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. CONCLUSION: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.

Development and implementation of Australian State, territory, and national policy on the health and wellbeing of adolescents and young adults: An exploration of policy actor perspectives using the Consolidated Framework for Implementation Research.

OBJECTIVES: Government policies that support the health and wellbeing of young people (aged 10 to 25) can have important individual and societal impacts. The aim of this study was to explore policy actor perspectives on the development and implementation of Australian government policies focussed on the health and wellbeing of young people. METHODS: We utilised a qualitative research design consisting of semi-structured interviews with policy actors with experience working with Australian youth health policies. Our interview guide and analyses were informed by the Consolidated Framework for Implementation Research (CFIR). We interviewed 19 participants from various national, state, and territory bodies. RESULTS: Several specific barriers and facilitators to policy development and implementation were identified using the Consolidated Framework for Implementation Research. Key policy development barriers were limited available resources (e.g. staffing and funding) and low relative priority within health and political systems. Key policy implementation barriers were limited available resources, limited policy compatibility with health services, cosmopolitanism issues related to interagency collaboration, and a lack of policy evaluation. Meaningful engagement of young people could also be improved. CONCLUSIONS: Although Australian youth health policies are perceived as evidence-based and comprehensively developed, the ability to promote implementation remains stalled. IMPLICATIONS FOR PUBLIC HEALTH: The development of policy implementation plans, monitoring and evaluation mechanisms, funding and resources, and a strong commitment to removing barriers to working across multiple departments and systems is required to improve outcomes for young people.

Discovery and Evaluation of C6-Substituted Pyrazolopyrimidine-Based Bisphosphonate Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase and Evaluation of Their Antitumor Efficacy in Multiple Myeloma, Pancreatic Ductal Adenocarcinoma, and Colorectal Cancer.

Novel C6-substituted pyrazolo[3,4-d]pyrimidine- and C2-substituted purine-based bisphosphonate (C6-PyraP-BP and C2-Pur-BP, respectively) inhibitors of the human geranylgeranyl pyrophosphate synthase (hGGPPS) were designed and evaluated for their ability to block the proliferation of multiple myeloma (MM), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) cells. Pyrazolo[3,4-d]pyrimidine analogs were identified that induce selective intracellular target engagement leading to apoptosis and downregulate the prenylation of Rap-1A in MM, PDAC, and CRC cells. The C6-PyraP-BP inhibitor RB-07-16 was found to exhibit antitumor efficacy in xenograft mouse models of MM and PDAC, significantly reducing tumor growth without substantially increasing liver enzymes or causing significant histopathologic damage, usually associated with hepatotoxicity. RB-07-16 is a metabolically stable compound in cross-species liver microsomes, does not inhibit key CYP 450 enzymes, and exhibits good systemic circulation in rat. Collectively, the current studies provide encouraging support for further optimization of the pyrazolo[3,4-d]pyrimidine-based GGPPS inhibitors as potential human therapeutics for various cancers.

Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs.

Cannabidiol (CBD) containing dog food and treats are widely commercially available, mirroring the growing popularity of CBD as a supplement for humans. Despite this, experimental evidence of the safety and efficacy of long-term oral exposure in dogs is lacking. The purpose of this study was to address the gap in knowledge around the longer-term suitability and tolerance of a broad-spectrum CBD (THC-free) distillate in clinically healthy dogs. The study was a randomized, placebo-controlled, and blinded study where one group of twenty dogs received daily CBD capsules at a dose of 4 mg/kg of body weight (BW) for a period of 6 months. The control group of twenty dogs received placebo capsules. A comprehensive suite of physiological health measures was performed throughout the study at baseline, and after 2, 4, 10, 18, and 26 weeks of exposure, followed by 4 weeks of washout. CBD concentrations were measured at the same cadence in plasma, feces and urine. Health measures included biochemistry, hematology, urinalysis, in addition to fortnightly veterinary examinations, twice daily well-being observations, and a daily quality-of-life survey. Biochemistry and hematology showed no clinically significant alterations apart from a transient elevation in alkaline phosphatase (ALP) in just over half of the dogs receiving CBD. This elevation was observed in the absence of concurrent elevations of other liver parameters, and without any adverse effects on health and wellbeing. Furthermore, bone alkaline phosphatase (BALP) was simultaneously elevated with a significant, strong (r > 0.9) positive correlation between the two measures, suggesting that the elevation of total ALP was at least partly due to the bone-derived isoform. This study provides evidence that a once-daily oral dose of 4 mg CBD/kg BW is well tolerated in clinically healthy dogs for a duration of 6-months.

Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion.

As the most favoured animal companion of humans, dogs occupy a unique place in society. Understanding the senses of the dog can bring benefits to both the dogs themselves and their owners. In the case of bitter taste, research may provide useful information on sensitivity to, and acceptance of, diets containing bitter tasting materials. It may also help to protect dogs from the accidental ingestion of toxic substances, as in some instances bitter tasting additives are used as deterrents to ingestion. In this study we examined the receptive range of dog bitter taste receptors (Tas2rs). We found that orthologous dog and human receptors do not always share the same receptive ranges using in vitro assays. One bitter chemical often used as a deterrent, denatonium benzoate, is only moderately active against dTas2r4, and is almost completely inactive against other dog Tas2rs, including dTas2r10, a highly sensitive receptor in humans. We substituted amino acids to create chimeric dog-human versions of the Tas2r10 receptor and found the ECL2 region partly determined denatonium sensitivity. We further confirmed the reduced sensitivity of dogs to this compound in vivo. A concentration of 100µM (44.7ppm) denatonium benzoate was effective as a deterrent to dog ingestion in a two-bottle choice test indicating higher concentrations may increase efficacy for dogs. These data can inform the choice and concentration of bitter deterrents added to toxic substances to help reduce the occurrence of accidental dog poisonings.

Synthesis and Evaluation of Structurally Diverse C-2-Substituted Thienopyrimidine-Based Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase.

Novel analogues of C-2-substituted thienopyrimidine-based bisphosphonates (C2-ThP-BPs) are described that are potent inhibitors of the human geranylgeranyl pyrophosphate synthase (hGGPPS). Members of this class of compounds induce target-selective apoptosis of multiple myeloma (MM) cells and exhibit antimyeloma activity in vivo. A key structural element of these inhibitors is a linker moiety that connects their (((2-phenylthieno[2,3-d]pyrimidin-4-yl)amino)methylene)bisphosphonic acid core to various side chains. The structural diversity of this linker moiety, as well as the side chains attached to it, was investigated and found to significantly impact the toxicity of these compounds in MM cells. The most potent inhibitor identified was evaluated in mouse and rat for liver toxicity and systemic exposure, respectively, providing further optimism for the potential value of such compounds as human therapeutics.

CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies.

Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada's publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin's lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.

Australian federal, state and territory policy on the health and wellbeing of young people: A scoping review.

BACKGROUND: The health and wellbeing of young people are critical for the future of society but the extent to which they are addressed by overarching Australian Federal, State and Territory health policy is difficult to determine. Analysing high-level youth health policy will help establish how Australian governments are articulating and prioritising issues and may guide local and international health agendas. METHODS: This scoping review aimed to determine the extent, range and nature of Australian high-level government policy focused on the general health and wellbeing of the general population of young people. Policies published by Australian Federal, State, or Territory government departments between 2008 and 2019 were thematically analysed employing Braun and Clark's six-step recursive framework. FINDINGS: Twelve policy documents met inclusion criteria. Three meta-themes emerged, comprising policy development, youth health challenges, and policy goals. Policy goals fell into three ubiquitous and overarching categories focused on supporting public health, promoting equity, and improving the health system for young people. CONCLUSIONS: A number of youth-specific health policies have been developed by Australian governments in recent years. Whilst goals and strategies are clearly articulated, more can be done to ensure a youth voice in policy development. The policy goals of supporting public health, promoting equity and improving the health system deserve consideration from other countries developing youth health policies.