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There have been impressive advances in the physical and mathematical modelling of complex physiological systems in the last few decades, with the potential to revolutionise personalised healthcare with patient-specific evidence-based diagnosis, risk assessment and treatment decision support using digital twins. However, practical progress and genuine clinical impact hinge on successful model calibration, parameter estimation and uncertainty quantification, which calls for novel innovative adaptions and methodological extensions of contemporary state-of-the-art inference techniques from Statistics and Machine Learning. In the present study, we focus on two computational fluid-dynamics (CFD) models of the blood systemic and pulmonary circulation. We discuss state-of-the-art emulation techniques based on deep learning and Gaussian processes, which are coupled with established inference techniques based on greedy optimisation, simulated annealing, Markov Chain Monte Carlo, History Matching and rejection sampling for computationally fast inference of unknown parameters of the CFD models from blood flow and pressure data. The inference task was set as a competitive challenge which the participants had to conduct within a limited time frame representative of clinical requirements. The performance of the methods was assessed independently and objectively by the challenge organisers, based on a ground truth that was unknown to the method developers. Our results indicate that for the systemic challenge, in which an idealised case of noise-free data was considered, the relative deviation from the ground-truth in parameter space ranges from 10−5% (highest-performing method) to 3% (lowest-performing method). For the pulmonary challenge, for which noisy data was generated, the performance ranges from 0.9% to 7% deviation for the parameter posterior mean, and from 35% to 570% deviation for the parameter posterior variance.

Ernest Moles,1– 4 David W Chang,1– 3 Friederike M Mansfeld,1– 3 Alastair Duly,1,2 Kathleen Kimpton,1 Amy Logan,1– 4 Christopher B Howard,5 Kristofer J Thurecht,5,6 Maria Kavallaris1– 4 1Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, 2052, Australia; 2UNSW Australian Centre for Nanomedicine, Faculty of Engineering, UNSW, Sydney, NSW, 2052, Australia; 3School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, NSW, 2052, Australia; 4UNSW RNA Institute, Faculty of Science, UNSW, Sydney, NSW, 2052, Australia; 5Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, QLD, 4072, Australia; 6Centre for Advanced Imaging, ARC Training Centre for Innovation in Biomedical Imaging Technologies, University of Queensland, St Lucia, QLD, 4072, AustraliaCorrespondence: Ernest Moles; Maria Kavallaris, Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, 2052, Australia, Email emoles@ccia.org.au; m.kavallaris@ccia.unsw.edu.auIntroduction: Despite improvements in chemotherapy and molecularly targeted therapies, the life expectancy of patients with advanced non-small cell lung cancer (NSCLC) remains less than 1 year. There is thus a major global need to advance new treatment strategies that are more effective for NSCLC. Drug delivery using liposomal particles has shown success at improving the biodistribution and bioavailability of chemotherapy. Nevertheless, liposomal drugs lack selectivity for the cancer cells and have a limited ability to penetrate the tumor site, which severely limits their therapeutic potential. Epidermal growth factor receptor (EGFR) is overexpressed in NSCLC tumors in about 80% of patients, thus representing a promising NSCLC-specific target for redirecting liposome-embedded chemotherapy to the tumor site.Methods: Herein, we investigated the targeting of PEGylated liposomal doxorubicin (Caelyx), a powerful off-the-shelf antitumoral liposomal drug, to EGFR as a therapeutic strategy to improve the specific delivery and intratumoral accumulation of chemotherapy in NSCLC. EGFR-targeting of Caelyx was enabled through its complexing with a polyethylene glycol (PEG)/EGFR bispecific antibody fragment. Tumor targeting and therapeutic potency of our treatment approach were investigated in vitro using a panel of NSCLC cell lines and 3D tumoroid models, and in vivo in a cell line-derived tumor xenograft model.Results: Combining Caelyx with our bispecific antibody generated uniform EGFR-targeted particles with improved binding and cytotoxic efficacy toward NSCLC cells. Effects were exclusive to cancer cells expressing EGFR, and increments in efficacy positively correlated with EGFR density on the cancer cell surface. The approach demonstrated increased penetration within 3D spheroids and was effective at targeting and suppressing the growth of NSCLC tumors in vivo while reducing drug delivery to the heart.Conclusion: EGFR targeting represents a successful approach to enhance the selectivity and therapeutic potency of liposomal chemotherapy toward NSCLC. Keywords: targeted drug delivery, bispecific antibodies, PEGylated liposomal doxorubicin, EGFR targeting, non-small cell lung cancer

Objective We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks’ gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance.Design and setting Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE).Participants All live births ≥34 weeks’ gestation between September 2020 and August 2021.Outcome measures EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age. We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures.Results Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals.Conclusion There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life.

Facilitators of research utilisation are important in the implementation of evidence-based practice. Numerous facilitators for nursing practice have been identified, but knowledge of the impact of demographic characteristics on these enablers of research utilisation is limited. The study’s aim was to determine nurses’ perceptions of the facilitators of research utilisation and assess differences in the facilitator of research utilisation score based on nurses’ demographic characteristics. A total of 2650 registered nurses from five hospitals in Riyadh, Saudi Arabia, were recruited for participation. A facilitator scale and self-designed demographic survey were used for data collection. The number of completed questionnaires was 1824 (69%). The results showed that many of the participants were female, aged between 20 to 40 years, and were expatriates mainly from the Philippines. Most respondents were clinical nurses with 6 to 10 years of experience. Many of the nurses had a bachelor’s degree and a qualification from the Asian region. The mean total facilitator score was 26.1, with strong facilitators of research, including advanced education, providing colleague support, more clinically focused research and employing nurses with research skills. Recommendations for the facilitation of research utilisation include a strengthening of the research curriculum in nursing education programs as well as through continuing professional education.

Little is known about the prevalence of cyberbullying among university students and less about whether they utilise anti-bullying policies. However, failure to report cyberbullying incidents to authorities would lessen the efficacy of these policies. This study investigated the prevalence of cyberbullying among university students and their reporting intentions for cyberbullying incidents. Two hundred and eighty-two students completed a survey on their intentions to report cyberbullying. Results found cyberbullying exists among university students and they would report to authorities if the policy outlined specific information. Students who had been cyber victimised were more likely to report than those students who had not been cyberbullied. Implications for universities are discussed.

This paper details an investigation into the synthesis and temperature stability testing of silver-nanofluids, aimed at producing three silver-based nanofluids with distinctive morphologies and absorption characteristics suitable for enhanced efficiency volumetric solar-thermal collectors, which could be combined with a suitable thermal storage system to provide low-carbon heating and hot-water. When combined the three silver-based nanofluids were designed to give spectrally broadband absorption of the incident solar radiation in the 300–1300 nm range. The starting point was a previously developed synthesis producing triangular silver-nanoparticles with a strong absorbance in the 850–950 nm range (Nanofluid 1). The effect of changing various reagents in the synthesis was then investigated. Increasing the silver nitrate concentration and changing the silver to reducing agent ratio produced Nanofluid 2 (strong absorbance in 650–750 nm range), containing smaller more rounded triangular nanoparticles. For Nanofluid 3, a two-step synthesis had to be adopted, with a seed nanofluid made initially by lowering the concentration of reducing agent (sodium borohydride) and oxidizing agent (hydrogen peroxide). Additional silver nitrate and reducing agent were added, giving a more concentrated nanofluid, containing small silver nanodiscs, with a 450 nm absorption maximum. These three nanofluids were combined together to give a broadband absorber and for the first time, the stability to a temperature of 70 °C measured using UV–vis–IR spectroscopy. Results indicate that although a broadband absorber based on silver can be designed it is not suitable for use without an appropriate stabilization strategy, due to a lack of spectral stability with temperature.