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PURPOSE To codesign, develop, and evaluate a smartphone app that includes patient-reported measures of symptoms and real-time advice in children's cancer. METHODS The Oncology Hub is a comprehensive approach to symptom management that includes a suite of codesigned tools and resources including clinical algorithms to determine the level of concern, symptom management advice, and resources for families of children with cancer. The evaluation involved Think Aloud interviews with parent and adolescent patients to complete tasks in the app as well as a User Experience questionnaire (score range, 0-120) and qualitative feedback. The accuracy of algorithms was determined by repeated testing of inputs and outputs over 4 weeks. RESULTS Design and wireframes were iteratively refined through consultation with parents and adolescents confirming the final design. Beta testing evaluation was then completed by 25 participants including two adolescents. Across all participants, 84% of tasks were easy to navigate, and the Oncology Hub demonstrated high usability, usefulness, and acceptability with participants' scores ranging between 90 and 120 (mean = 112.2, standard deviation = 9.43). Qualitative feedback was positive. Testing of algorithms identified inconsistencies in understanding between clinical research and coding teams; refinements were made until the expected response notifications were returned with 100% accuracy. CONCLUSION Technology offers new ways to think about how clinicians and families communicate and share information to harness the best of community and hospital services. Understanding how information is exchanged using health apps, and how this affects clinical workflow is critical to successful implementation, and optimizing symptom assessment and management in children with cancer.

Background Symptoms and associated distress in children diagnosed and treated for cancer are uniformly common, yet structured and systematic symptom monitoring is not yet commonplace. With increasing pressures on the healthcare workforce, improved systematic approaches to symptom management are required. Methods Medical, nursing and allied health oncology clinicians developed algorithms using consensus techniques to ascertain thresholds of concern for each symptom for the Symptom Screening in Pediatrics (SPPedi) tool, a Patient Reported Outcome Measure (PROM). Algorithm vetting and refinement were achieved through iterative interviews and consultation with clinicians. Self-management evidence-based recommendations for each symptom were developed. The algorithms were incorporated into an existing smartphone application (MyQCH), as part of the Oncology Hub, and an iterative evaluation is planned to test the feasibility, acceptability, safety, usefulness, and other domains including a hybrid effectiveness trial (ACTRN12621001084875). Discussion Digital solutions provide alternative options for communication, information, and education and opportunities to harness the best of community and hospital services. The Oncology Hub and RESPONSE system is a comprehensive approach to symptom management that includes a suite of tools and resources including a smartphone app that collects PROMs and delivers symptom management advice, as well as written resources for both the families of children with cancer and clinicians. Conclusions Using technology offers new ways to think about how clinicians and families communicate and share information. Understanding how information is exchanged using technology, and how this impacts clinical workflow is critical to successful implementation, and to ultimately optimise symptom assessment management in children with cancer.

Aim: Central venous access devices (CVADs) are vital medical devices to support the treatment of paediatric cancer; however, device occlusion is common, which disrupts treatment. This study aimed to improve the identification and management of CVAD occlusions in children with cancer, as well as to identify the demographic, clinical and device characteristics associated with increased risk for CVAD occlusion. Methods: A pre–post-implementation study was conducted at a metropolitan paediatric oncology facility in Australia, using the Theoretical Domains Framework. Patients with a CVAD for anti-cancer therapy were prospectively followed for occlusive events pre- and post- the implementation of clinical resources to support the identification and management of CVAD occlusive events. CVAD occlusion and management data were collected and compared pre- and post-implementation. Risk factors for CVAD occlusion were described by mixed-effects Poisson regression and incident rate ratios (IRR). Results: A total of 133 CVADs were inserted into 131 patients for a total of 6784 catheter days. The incidence of CVAD-related occlusion pre-implementation was 59.7 (95% confidence interval (CI) 51.4–69.0, per 1000 catheter days); compared to 31.6 (95% CI 26.4–37.6); P < 0.01) post-implementation of clinical resources. In multivariate models, other than post-implementation phases (IRR 0.51 (95% CI 0.32–0.81)), only neutropaenia significantly increased the risk of CVAD occlusion (IRR 2.14 (95% CI 1.15–3.97)). Conclusion: CVAD occlusions in paediatric oncology are common. The development and implementation of CVAD occlusion resources to guide the identification and management of occlusive episodes led to a significant decrease in occlusive events.

Central venous access devices (CVADs) are integral to cancer care provision. Despite the high prevalence of CVAD complications in children with cancer, preventative strategies are understudied.The aim of this study was to assess study feasibility, occlusive events, thrombolytic use, adverse events, and direct costs of catheter lock solutions.A single-center, parallel-group, pilot randomized controlled trial was undertaken at a tertiary-referral pediatric hospital in Australia. Children 18 years or younger with an oncological or malignant hematological condition and a CVAD were eligible. Participants were 1:1 randomized to (1) normal or (2) heparinized (10-100 U/mL; CVAD-type dependent) saline lock solutions.Of 217 children assessed for eligibility, 61 were recruited and randomized to normal (n = 30; 3850 CVAD days) or heparinized (n = 31; 4036 CVAD days) saline. Eligibility (52%) and recruitment (54%) feasibility targets were not met. Protocol adherence was high (95% assessments), with no attrition. Parent/clinician satisfaction of interventions was high (median, 10/10 clinicians/parents). Complete CVAD occlusion occurred in heparin only (n = 2, 6.7% CVADs; incidence rate [IR], 0.49/1000 CVAD days [0.06-1.78]). Central venous access device partial occlusion was detected in 23.3% of CVADs in heparin (n = 7; IR, 2.73/1000 CVAD days [1.36-4.87]) and 13.8% of CVADs in normal saline (n = 4; IR, 2.59/1000 CVAD days [1.24-4.77]). Thrombolytic agents were used in 16.7% heparin (5 CVADs) and 3.5% normal saline (1 CVAD). Adverse events did not differ between groups.Multisite randomized controlled trials examining CVAD locks are safe, but strategies and resources to increase recruitment and eligibility are required.Both routine CVAD lock solutions seem safe but may not prevent all forms of CVAD-associated harm.

PTH-23 Table 1Numbers of endoscopy requests triaged into each category across planned and routine waiting listsOutcome after consultant triage of endoscopy request Planned Routine No longer required 79 78 No change to request 202 159 Upgrade request to urgent 14 9 Change request to alternative planned interval 31 17 Total 326 263 157 (27%) of endoscopy requests were categorised as not required. Reasons for this included updated or incorrect adherence to surveillance guidelines (26%), clinical judgement deeming it no longer necessary (62%), or a change in the patient’s clinical status or unclear indication (12%).Conclusions1. 27% of endoscopy waiting list procedures were judged unnecessary.• Consultant led triage of endoscopy waiting lists resulted in an estimated cost saving of £67,993 (a 25% cost reduction) and a reduction in endoscopy work load.• Potential savings nationally from endoscopy waiting list triage are considerable.• Triage theoretically increased training opportunities by reducing workload.Greater awareness of current guidelines could reduce the number of endoscopies scheduled.

Habitat characteristics and microhabitat of organisms pose a number of choices to foraging species, for example where and how to search for prey, which prey to select and what foraging technique to employ. Predators can enhance the profitability of foraging by adapting their strategies flexibly in relation to prey characteristics and environmental factors. To investigate the influence of rocky shore characteristics viz., condition of rock, position of limpet on the rock, stage of tide, and limpet opening technique of oystercatcher on the profitability of limpet foraging, a total of 193 attacks on limpets (Patella spp.) by Eurasian oystercatchers (Haematopus ostralegus) were made on Lundy Island, UK, using focal animal sampling. Multiple regression revealed that profitability was influenced by the condition of the rock and the limpet opening technique employed by oystercatchers. The profitability of the limpet opening technique appears to be associated with the condition of the rock. Oystercatchers forage by adapting their foraging strategy in accordance with the nature of the rocks i.e. wetness on which they are foraging.

RuralCovidLife is part of Generation Scotland’s CovidLife project, investigating the impact of the COVID-19 pandemic and mitigation measures on people in Scotland. The RuralCovidLife project focuses on Scotland’s rural communities, and how they have been impacted by the pandemic. During survey development, Generation Scotland consulted with people living or working in rural communities, and collaborated with a patient and public involvement and engagement (PPIE) group composed of rural community leaders. Through this consultation work, the RuralCovidLife survey was developed to assess the issues most pertinent to people in rural communities, such as mental health, employment, transport, connectivity, and local communities. Between 14th October and 30th November 2020, 3,365 participants from rural areas in Scotland took part in the survey. Participant ages ranged from 16 to 96 (mean = 58.4, standard deviation [SD] = 13.3), and the majority of the participants were female (70.5%). Over half (51.3%) had taken part in the original CovidLife survey. RuralCovidLife includes a subsample (n = 523) of participants from the Generation Scotland cohort. Pre-pandemic data on health and lifestyle, as well as biological samples, are available for these participants. These participants’ data can also be linked to past and future healthcare records, allowing analysis of retrospective and prospective health outcomes. Like Generation Scotland, RuralCovidLife is designed as a resource for researchers. RuralCovidLife data, as well as the linked Generation Scotland data, is available for use by external researchers following approval from the Generation Scotland Access Committee. RuralCovidLife can be used to investigate mental health, well-being, and behaviour in participants living in rural areas during the COVID-19 pandemic, as well as comparisons with non-rural samples. Moreover, the sub-sample with full Generation Scotland data and linkage can be used to investigate the long-term health consequences of the COVID-19 pandemic in rural communities.

OBJECTIVE To evaluate the effectiveness of a clinical pathway in achieving antibiotic administration in less than 60 minutes for children with cancer, presenting with fever and neutropenia. Secondary objectives were to determine association between time to antibiotics (TTA) and other variables including fever duration, location of care and intravenous access types. METHODS Following introduction of the clinical pathway, we collected prospective data about management of all cases that did and did not use the pathway across multiple sites over 16 months. A follow-up audit was conducted after 12 months. RESULTS We evaluated a total of 453 presentations. Use of the clinical pathway was significantly associated with achieving TTA in less than 60 minutes (RR 0.69, 95% CI 0.56-0.85, p =

BackgroundHealthcare simulations generate moments of ‘cultural compression’ through which we transmit core values about our professional identities and the families we care for. The engagement of healthcare consumers in this process is useful to evaluate the values we transmit and ensure authenticity in the narratives we share.MethodsA simulation package on febrile neutropenia and port access was written by healthcare staff in consultation with the parent of a child with leukaemia. Healthcare consumer review was focused on the representation of the simulated parent within the simulation scripts. The child and his mother assisted in the development of supportive video resources on family perspectives on port access and demonstration of the procedure.ResultsThe involvement of healthcare consumers in the development of the scenario had positive impact on the design and the supportive resources, both of which created opportunities for patient advocacy and reinforced the centrality of healthcare consumers within the healthcare team.ConclusionsHealthcare consumer collaboration in scenario design was achievable and impactful without significant increased cost. We hope to promote the benefits of healthcare consumer consultation in simulation design to improve the pursuit of educational and cultural learning objectives.

Background: Guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) around the world vary greatly. Most institutions recommend the use of heparin to prevent occlusion; there is debate, however, regarding the need for heparin and evidence to suggest normal saline (0.9% sodium chloride) may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased cost. This is an update of the review published in 2015. Objectives: To assess the clinical effects (benefits and harms) of intermittent flushing of normal saline versus heparin to prevent occlusion in long-term central venous catheters in infants and children. Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases; World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 9 April 2019. We also undertook reference checking, citation searching and contact with study authors to identify additional studies. Selection criteria: We included randomised controlled trials (RCTs) that compared the efficacy of intermittent flushing with normal saline versus heparin to prevent occlusion of long-term CVCs in infants and children aged up to 18 years of age. We excluded temporary CVCs and peripherally inserted central catheters (PICC). Data collection and analysis: Two review authors independently assessed trial inclusion criteria, trial quality and extracted data. We assessed study quality with the Cochrane 'Risk of bias' tool. For dichotomous outcomes, we calculated the rate ratio (RR) and corresponding 95% confidence interval (CI). We pooled data using a random-effects model; and we used GRADE to assess the overall certainty of the evidence supporting the outcomes assessed in this review. Main results: We identified one new study for this update, bringing the total number of included studies to four (255 participants). The four trials directly compared the use of normal saline and heparin; the studies all used different protocols for the intervention and control arms, however, and all used different concentrations of heparin. Different frequencies of flushes were also reported between studies. In addition, not all studies reported on all outcomes. The certainty of the evidence ranged from moderate to very low because there was no blinding; heterogeneity and inconsistency between studies was high; and the CIs were wide. CVC occlusion was assessed in all four trials. We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated RR for CVC occlusion per 1000 catheter days between the normal saline and heparin groups was 0.75 (95% CI 0.10 to 5.51; 2 studies, 229 participants; very low certainty evidence). The estimated RR for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37; 2 studies, 231 participants; low-certainty evidence). The duration of catheter placement was reported to be similar for the two study arms in one study (203 participants; moderate-certainty evidence), and not reported in the remaining studies. Authors' conclusions: The review found that there was not enough evidence to determine the effects of intermittent flushing with normal saline versus heparin to prevent occlusion in long-term central venous catheters in infants and children. It remains unclear whether heparin is necessary to prevent occlusion, CVC-associated blood stream infection or effects duration of catheter placement. Lack of agreement between institutions around the world regarding the appropriate care and maintenance of these devices remains.

Penelope J Slater,1 Rachel M Edwards,2 Ashraf A Badat1 1Oncology Services Group, Queensland Children’s Hospital, Brisbane, QLD, Australia; 2Nursing Learning and Workforce Development, Queensland Children’s Hospital, Brisbane, QLD, Australia Purpose: Challenges experienced by staff in the Oncology Services Group at Queensland Children’s Hospital led to issues with staff retention, well-being, and stress on team culture. Therefore, a customized program was developed through a needs analysis to improve the well-being and resilience of oncology staff, enabling them to cope with stressors and critical incidents inherent in their everyday work and to flourish. The program included education, on-site counselors, mindfulness sessions, debriefing, well-being resources, and improved engagement, support, and communication.Methods: Evaluation of the program in the first year examined program participation, staff feedback following education workshops and mindfulness sessions, staff retention rates, and the results of an annual organizational staff survey and a program outcome survey.Results: Approximately 76% of staff attended the Introduction to Well-being workshop, and 98% of responses to survey questions were positive. Staff also provided positive feedback on the other well-being workshops and sessions embedded within existing education programs. Employee Assistance Program counseling sessions had an 81% uptake, with a wide variety of presenting issues, 62% related to work. All participants in mindfulness sessions agreed that it was a valuable tool to improve clinical practice, 94% said it had an immediate positive impact on their well-being, and 70% agreed that they were applying mindfulness principles outside the sessions. Staff retention and turnover improved. Staff reported a positive effect on awareness of self-care, addressing risks to resilience, seeking support from trusted colleagues, coping with critical incidents, and the ability to interact positively with patients and families.Conclusion: The evaluation showed a positive impact on staff well-being. Although there was a wide variety of successful interventions reported in the literature, sustainability needs to be considered. Feedback on this program found that staff appreciated being listened to, valued, and supported through the strategies, and the ongoing program will continue to monitor staff needs and be responsive in building their resilience and well-being. Keywords: staff well-being, resilience, burnout, vicarious trauma, self-care&nbsp

Background: Laboratory test in transport is a critical component of patient care, and capillary blood is a preferred sample type particularly in children. This study evaluated the performance of capillary blood testing on the epoc Point of Care Blood Analysis System (Alere Inc). Methods: Ten fresh venous blood samples was tested on the epoc system under the capillary mode. Correlation with GEM 4000 (Instrumentation Laboratory) was examined for Na+, K+, Cl-, Ca2+, glucose, lactate, hematocrit, hemoglobin, pO2, pCO2, and pH, and correlation with serum tested on Vitros 5600 (Ortho Clinical Diagnostics) was examined for creatinine. Eight paired capillary and venous blood was tested on epoc and ABL800 (Radiometer) for the correlation of Na+, K+, Cl-, Ca2+, glucose, lactate, hematocrit, hemoglobin, pCO2, and pH. Capillary blood from 23 apparently healthy volunteers was tested on the epoc system to assess the concordance to reference ranges used locally. Results: Deming regression correlation coefficients for all the comparisons were above 0.65 except for ionized Ca2+. Accordance of greater than 85% to the local reference ranges were found in all assays with the exception of pO2 and Cl-. Conclusion: Data from this study indicates that capillary blood tests on the epoc system provide comparable results to reference method for these assays, Na+, K+, glucose, lactate, hematocrit, hemoglobin, pCO2, and pH. Further validation in critically ill patients is needed to implement the epoc system in patient transport. Impact of the study: This study demonstrated that capillary blood tests on the epoc Point of Care Blood Analysis System give comparable results to other chemistry analyzers for major blood gas and critical tests. The results are informative to institutions where pre-hospital and inter-hospital laboratory testing on capillary blood is a critical component of patient point of care testing. Keywords: Epoc, Capillary, Transport, Blood gas, Point of care

Background: Generation Scotland (GS) is a population and family-based study of genetic and environmental health determinants. Recruitment to the Scottish Family Health Study component of GS took place between 2006-2011. Participants were aged 18 or over and consented to genetic studies, linkage to health records and recontact. Several recontact exercises have been successfully conducted aimed at a) recruitment to embedded or partner studies and b) the collection of additional data. As the cohort matures in age, we were interested in surveying attitudes to potential new approaches to data collection and recruitment. Methods: A ten-question online survey was sent to those participants who provided an email address. Results: We report a high level of positive responses to encouraging relatives to participate, to remote data and sample collection and for research access to stored newborn dried blood spots. Conclusions: The majority of current and prospective GS participants are likely to respond positively to future requests for remote data and sample collection.

Purpose: Fever and associated neutropenia presentations are frequent occurrences for children with cancer. Prompt treatment is required to prevent adverse outcomes; however, delays are common. In Australia's vast landscape, presentations occur in both tertiary metropolitan sites and smaller regional sites. Management and experiences differ between sites. Our primary aim was to identify the barriers to optimal management of febrile neutropenia in children with cancer from patient/parent and clinician perspectives. Methods: A mixed methods approach was used where quantitative data was supplemented by qualitative data. Data were prospectively collected from parents (n=81) and clinicians (n=42) about all children who presented with fever across multiple diverse hospital locations. A subset of parents (n=9) and clinicians (n=19) completed semi-structured interviews. Results: Delays in assessment and treatment were reported by 31% of parents and up to 36% of clinicians. Four distinct time points where delays occurred were identified: 1) pre-presentation; 2) initial assessment; 3) blood collection and establishing intravenous access, and 4) preparation and administration of antibiotics. Although reasons for delay were diverse, they were primarily related to clinician's knowledge and awareness of fever management, and intravenous access device factors. Interventions were formulated to target these barriers and streamline processes. Conclusion: We identified multifactorial reasons for delays at different time points in care. Regional centres and families have unique needs which require considerations and tailored interventions. Ongoing education, monitoring compliance with initiation of practice changes and identifying and overcoming barriers as they arise are strategies for improving management of the febrile child with cancer.

Penelope J Slater,1 Rachel M Edwards2 1Oncology Services Group, Queensland Children’s Hospital, South Brisbane, QLD, Australia; 2Nursing Learning and Workforce Development, Queensland Children’s Hospital, South Brisbane, QLD, Australia Purpose: Around 170 multidisciplinary staff of the Oncology Services Group at Queensland Children’s Hospital, Brisbane, care for children with oncology, hematology, and palliative care needs from throughout Queensland and northern New South Wales. A series of challenges impacted staff resilience and retention, and strategies were needed to improve staff well-being and enable them to flourish despite the inherent work stressors.Methods: A needs analysis was conducted using themes from Discovery Interviews with 51 staff, surveys related to “The Work Stressors Scale – Pediatric Oncology” and “The Work Rewards Scale – Pediatric Oncology” completed by 59 staff, and an organizational staff survey responded to by 51 staff.Results: The needs analysis informed the development of a customized Oncology Staff Well-being Program with a range of strategies aligned to a PERMA framework for flourishing (positive emotion, engagement, relationships, meaning, and accomplishment). Positive emotion areas included education on topics such as well-being, resilience, responding to escalating behaviors, grief and loss, and self-care. Staff attended the available mindfulness sessions, debriefing and counselors on site, developed self-care plans, and followed a well-being Facebook Group. Engagement was supported through exploring character strengths, improving communication, supporting innovation, and addressing frustrations and safety concerns. Relationships within the team were addressed through team building and social events. Meaning of the work was emphasized through sharing family updates and end of treatment celebrations. Accomplishments of staff were acknowledged in newsletters and meetings.Conclusion: The needs analysis drove a multifaceted approach to staff well-being with the development of strategies which aligned to a framework that would empower staff to flourish at work. Implementation and evaluation are ongoing and will be reported in a subsequent paper. Keywords: staff well-being, resilience, burnout, vicarious trauma, self-care&nbsp

Osteocytes integrate the responses of bone to mechanical and hormonal stimuli by poorly understood mechanisms. We report here that mice with conditional deletion of the parathyroid hormone (PTH) receptor 1 (Pth1r) in dentin matrix protein 1 (DMP1)-8kb-expressing cells (cKO) exhibit a modest decrease in bone resorption leading to a mild increase in cancellous bone without changes in cortical bone. However, bone resorption in response to endogenous chronic elevation of PTH in growing or adult cKO mice induced by a low calcium diet remained intact, because the increased bone remodeling and bone loss was indistinguishable from that exhibited by control littermates. In contrast, the bone gain and increased bone formation in cancellous and cortical bone induced by daily injections of PTH and the periosteal bone apposition induced by axial ulna loading were markedly reduced in cKO mice compared to controls. Remarkably, however, wild-type (WT) control littermates and transgenic mice overexpressing SOST injected daily with PTH exhibit similar activation of Wnt/β-catenin signaling, increased bone formation, and cancellous and cortical bone gain. Taken together, these findings demonstrate that Pth1r in DMP1-8kb-expressing cells is required to maintain basal levels of bone resorption but is dispensable for the catabolic action of chronic PTH elevation; and it is essential for the anabolic actions of daily PTH injections and mechanical loading. However, downregulation of Sost/sclerostin, previously shown to be required for bone anabolism induced by mechanical loading, is not required for PTH-induced bone gain, showing that other mechanisms downstream of the Pth1r in DMP1-8kb-expressing cells are responsible for the hormonal effect. © 2016 American Society for Bone and Mineral Research.

Objectives Point of care testing (POCT) contributes to diagnosis and monitoring with fast testing time and easily performed assays. We evaluated the Abaxis Piccolo Xpress point of care chemistry analyzer using the Liver Panel Plus discs for our pediatric patient population at Texas Children's Hospital. Design and methods Analytical performance was evaluated for precision and linearity using quality control materials and commercially available verification samples. Comparison studies were performed between Piccolo Xpress analyzer and Vitros 5600 analyzer using patient samples. Interference studies were carried out using nine different patient pool sera. Lipemia interference was removed using LipoClear for severely lipemic sample pools. Results Precision of all tests was excellent (CVs, Highlights • Liver Panel Plus analytes were evaluated on Piccolo Xpress chemistry analyzer. • All analytes except bilirubin, amylase, and GGT showed acceptable performance for precision and interference in our pediatric population.

FGFR3 is a clinically validated driver for muscle invasive bladder cancer (MIBC). 15-20% of MIBC patients express FGFR3 mutations, including point mutations in the extracellular domain (S249C, R248C, G370C, Y373C) and kinase domain (K650E) as well as in-frame fusions with dimerization domains (e.g., coiled-coil domain of TACC3). Generating an antibody-based therapeutic that potently inhibits multiple FGFR3 oncogenic mutants, with different activation mechanisms, remains as a challenge. Therefore, regular IgG-like and alternative format (AF) bispecific antibodies were explored to examine whether enhanced FGFR3 degradation can serve as a “pan-inhibition” solution for tackling multiple FGFR3 genetic aberrations. APLP2 has been identified as a cell surface receptor that undergoes rapid internalization and degradation. Cell surface CD63 plays a more complex role in intracellular trafficking by itself or with its associated surface protein, including both endocytosis and surface retention. Bispecific antibodies co-targeting APLP2 and HER2 have been shown to enhance HER2 internalization and lysosomal trafficking (Bay AP et al 2019). IgG-like and AF bispecific antibodies targeting FGFR3xAPLP2 or FGFR3xCD63 with varied valency and geometry were engineered, produced and characterized. AF bispecific antibodies showed significant enhancement (compared to parental antibody) of in vitro growth inhibition in bladder cancer cell lines expressing FGFR3 S249C mutation while maintaining potent inhibitory activity in cells expressing FGFR3-TACC3 mutant. Both FGFR3 and APLP2/CD63 binding sites contribute to enhanced bispecific antibody potency. Interestingly, different activities were observed in antibody-induced receptor degradation indicating that APLP2 and CD63 regulate FGFR3 trafficking via distinct mechanisms. FGFR3xAPLP2 AF bispecifics enhanced receptor degradation compared to parental FGFR3 antibody, while FGFR3xCD63 AF bispecifics increased growth inhibition without receptor degradation. Our proof-of-concept case study suggests that AF bispecific antibodies can be used as a single novel modality to offer more potent inhibition against diverse mechanisms of oncogenic receptor activation. Citation Format: Yan Yang, Arif Wibowo, Suhasini Avvaru, Zaoli Jiang, Antonio Luz, Ashique Rafique, Prasad Sarangapani, Ryan McKay, Michael Amatulli, Meghana Vootlakrishna, Rachel Edwards, Terra Potocky, Aynur Hermann, Christopher Daly, Gavin Thurston, John Chia-Yang Lin, Yang Shen. Alternative format bispecific antibodies targeting multiple oncogenic FGFR3 mutations in bladder cancer through different mechanisms [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 526.

Opioid use disorder (OUD) is reaching epidemic proportions worldwide, and is notoriously difficult to treat. Compassion focused therapy (CFT) has emerged as therapeutic tool for treating individuals exhibiting high levels of self-criticism and low self-esteem, both of which are common in OUD. Until now, however, there had been no research investigating this therapy in patients with OUD. Before running a premature clinical trial, it is important to fully assess the feasibility and acceptability of this treatment in this group of individuals. We aimed to assess the feasibility of CFT treatment in individuals with OUD in a short group intervention, which was co-created by the research team, service users and a local drugs service. The intervention involved three 2-hour sessions held over 3 weeks, where participants engaged in compassion-orientated psychoeducation and self-compassionate exercises. Individuals were randomly assigned to either the CFT group (n = 15), the active control (relaxation) group (n = 12) or the waitlist control group (n = 11). Of 103 individuals approached, 45% attended a baseline visit suggesting the treatment was acceptable to this group. A relatively low attrition rate across the 3 groups was found for CFT (21.1%), with no difference in drop-out between the groups. Qualitative analysis of interviews with participants identified a desire for more sessions. Compassion focused therapy was thus feasible and well-tolerated in those with OUD, and a further trial to evaluate any clinical differences may be warranted.

Background Gastroschisis is an abdominal wall defect through which the bowel herniates into the amniotic cavity. Surgical correction of gastroschisis is performed during infancy. Gynecologic concerns have not been described in this population as either an associated anomaly or complication of surgical repair. Case A 15-year-old nulliparous female patient presented with abdominal pain with a history of gastroschisis requiring 4 surgeries in infancy. Computed tomography scan showed an ovary located in the right upper quadrant, which was concerning for torsion. She was taken for a laparotomy with right oophorectomy after conservative management had failed. Summary and Conclusion Long-term gynecologic outcomes of patients with gastroschisis are not well documented. Because gastroschisis patients are known to have abdominal pain later in life, this case shows that the differential diagnosis should include etiologies beyond the gastrointestinal tract.

Young people with cancer have distinct clinical and psychosocial needs during and after cancer treatment. However, as adolescent and young adult (AYA) cancer is rare, and only recently recognized as specialty, health professionals may not have the skills, competence, and confidence to meet the needs of the young patient with cancer. The aim of this study was to identify the learning needs of health professionals providing cancer care to adolescents and young adults before and following the introduction of a state-wide AYA cancer education program.A survey of educational needs of health professionals was undertaken in 2013 at the commencement of the Queensland Youth Cancer Service. The survey was used to develop the education program of the service. The education program was delivered across the state in a variety of formats, covering a range of topics throughout 2013-2016. The second survey was completed in 2017. Results were compared to identify if educational needs or the self-rated confidence of health professionals in regard to AYA cancer care had changed over time.One hundred twenty-two participants completed the first survey and 73 completed the second. The most prominent educational needs in 2013 were palliative care and biomedical topics such as understanding AYA growth and development as well as specific AYA cancers and treatment. The second survey identified that palliative care education remained important; however, there was a shift toward health professionals request for more psychosocial and practical education on topics including fertility, sexuality, and managing late effects.To provide high-quality healthcare to AYAs with cancer, health professionals require ongoing opportunities for education and training.

Firearm policy in the United States has long been a serious policy issue. Much of the previous research on crime and firearms focused on the effects of states’ passage of concealed handgun licensing (CHL) legislation. Today, given the proliferation of CHL legislation and growing strength of the “pro-gun” movement, the primary policy focus has changed. State legislators now face issues concerning whether and how to increase access to CHLs. Because of this transformation, this research moves away from the research tradition focused on the effect of a legislative change allowing CHLs. Instead, we consider two issues more policy relevant in the current era: What are the dynamics behind CHL licensing? Do increases in concealed handgun licensing affect crime rates? Using county-level data, we found that the density of gun dealers and other contextual variables, rather than changing crime rates, had a significant effect on increases of the rates at which CHLs were issued. We also found no significant effect of CHL increases on changes in crime rates. This research suggests that the rate at which CHLs are issued and crime rates are independent of one another—crime does not drive CHLs; CHLs do not drive crime.

Introduction Central venous access devices (CVADs) provide essential and reliable vascular access, but infection is a common and serious complication with paediatric patients. CVAD bundles have been demonstrated to effectively reduce central line-associated bloodstream infections (CLABSI), but primarily during CVAD insertion. Another emerging strategy to encourage best practice is the use of a dedicated CVAD trolley for maintenance. Methods A quality-improvement initiative was undertaken to improve CVAD maintenance and to evaluate the effectiveness of the chosen interventions at the Royal Children's Hospital, Brisbane. Nursing staff from four wards within the hospital elected to participate and the wards were allocated to receive either Intervention A (CVAD maintenance bundle only) or Intervention B (CVAD maintenance bundle and dedicated CVAD trolley). Effectiveness of the interventions was evaluated by: (i) rate of CLABSI per 1000 catheter-days; and (ii) audits of clinician compliance with evidence-based CVAD maintenance strategies. Results During the initiative, the hospital-wide CLABSI rate decreased from 9.07 to 1.05 episodes per 1000 catheter-days ( P = 0.01). The rate of CLABSI in Intervention A wards reduced from 7.6 to 2.2 episodes per 1000 catheter-days ( P (P 0.001). Hospital-wide audits of clinician compliance increased from 11.9% to 3 5% (P = 0.001) in the Intervention A wards and to 83% (P 0.001) in the Intervention B wards. Conclusion Implementation of CVAD maintenance bundles and a dedicated CVAD trolley successfully reduced CLABSI and improved audited compliance to evidence-based practices within our tertiary paediatric hospital.

© 2017 Mouritsen, Edwards-Stuart, Ahn and Ahnert. The study of food consumption, in the broadest sense, intersects with a wide range of academic disciplines. The perception of food involves molecular biology, chemistry, soft-matter physics, neuroscience, psychology, physiology, and even machine learning. Our choices and preparation of food are of interest to anthropologists, social scientists, historians, philosophers, and linguists. The advent of information technology has enabled the accumulation and analysis of large amounts of food-related data, from the interactions of biomolecules and the chemical properties of aroma compounds to online recipes and food-related social media postings. In this perspective article, we outline several areas in which the availability and analysis of data can inform us about general principles that may underlie the perception of food and the diversity of culinary practice. One of these areas is the study of umami taste through a combination of chemical analysis and quantitative sensory evaluation for a wide range of fermented products. Another is the mapping of global culinary diversity by mining online recipes and the analysis of culinary habits recorded by individuals on social media. A third area is the study of the properties of flavor compounds and the application of these insights in the context of high-end gastronomy. These examples illustrate that large-scale data analysis is already transforming our understanding of food perception and consumption, and that it is likely to fundamentally influence our food choices and habits in the future.

Routine point-of-care (POC) glucose monitoring in the pediatric setting has become increasingly important, both for assessing hypoglycemia as well as hyperglycemia. A reliable and precise system is required to monitor pediatric patients.The aim of this study was to evaluate the Nova Biomedical StatStrip POC glucometer against the Roche ACCU-CHEK Inform in lieu of our currently used LifeScanSureStepFlexx POC glucose analyzer.Intra-assay and inter-assay precision, linearity, correlation and interference studies were performed as per the NCCLS criteria. An analysis of 37 pediatric samples across the linearity ranges of all the meters was used to assess concordance between the systems.The Nova StatStrip glucometer demonstrated an excellent coefficient of variation (5%) for glucose across the entire analytical measurement range. The Nova StatStrip also had good concordance with the central laboratory (Bland-Altman plots r(2)=0.01), while Roche Inform had poorer correlation (Bland-Altman plots r(2)=0.46). We also evaluated the effect of hematocrit (20-60%) and maltose (100-500mg/dL) on the Nova StatStrip analyzer and demonstrated that there is little to no interference by either.The Nova StatStrip system gave the best performance with acceptable imprecision, good correlation, and minimal to no interference from hematocrit levels or maltose. The Nova StatStrip is a satisfactory replacement for our POC glucometer system and, additionally, provides results in less time (just 6 s) utilizing a lower amount of blood with the advantage of being immediately interfaced to our laboratory information systems.

The science of cooking is being taught at a small handful of culinary schools across the globe, and there seems to be a general consensus that scientific understanding can be a valuable tool for an aspiring chef. There is however very little information available on how these scientific topics are being disseminated to chefs. In this communication, we will introduce and discuss two chef teaching environments where scientific topics are or have been taught: The Culinary Science Laboratory at Westminster Kingsway College in London and the Gastrolab at the University of Southern Denmark in Odense. Our conclusion is that the science of cooking is an important topic valuable for the education of the next generation of chefs, but there are challenges associated with teaching this academic subject in a vocational setting, and we feel that further research should be done to look into the methodology of teaching science in the kitchen, and that there is a need to develop a standardized syllabus for the delivery of this subject.