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Critical thinking is identified as a key educational outcome in higher education curricula; however, it is not trivial to support students in building this multifaceted skill. In this study, we evaluated a brief online learning intervention focusing on informal fallacy identification, a hallmark critical-thinking skill. The intervention used a bite-sized video learning approach, which has been shown to promote student engagement. Video-based learning was implemented within a precision teaching (PT) framework, which modulates the exposure of individual learners to the learning material to enable them to build ‘fluency’ in the targeted skills. In one of the learning conditions, PT was applied synergistically with domain-general problem-based training to support generalisation. The intervention consisted of two learning episodes and was administered to three groups (learning conditions) of 19 participants each: a PT fluency-based training group; a PT + group, where PT was combined with problem-based training; and a self-directed learning control group. All three groups showed comparable improvements in fallacy identification on taught (post-episode tests) and unseen materials (post-intervention assessment), with lower-scoring participants showing higher gains than high-scoring participants. The results of the knowledge retention tests a week later were also comparable between groups. Importantly, in the domain-general fallacy-identification assessment (post-intervention), the two PT groups showed higher improvements than the control group. These findings suggest that the integration of bite-sized video learning technologies with PT can improve students’ critical-thinking skills. Furthermore, PT, on its own or combined with problem-based training, can improve their skill to generalise learning to novel contexts. We discuss the educational implications of our findings.

In order to establish objective criteria for road traffic accident (RTA) hotspots, this paper examines the application of three different hotspot analysis methods to both identify and rank the RTA hotspots. The three methods selected are the network Kernel Density Estimation (KDE+) method, the Getis-Ord GI* method, and a recently proposed risk-based method that accounts for RTA frequency, severity and socioeconomic costs - STAA method. The study road, Jalan Tutong, is a major dual-carriageway connecting major residential and commercial areas from the west of Brunei-Muara district and beyond to the capital, Bandar Seri Begawan. The RTA data consists of cases reported to the police during a 5-year period from 2012 to 2016. The RTA data were digitised and prepared, before being imported into ESRI ArcGIS 10.2 software for analysis using each of these methods. The outcomes, particularly the location, extent and priority of the RTA hotspots, are subsequently compared to results from road safety audits, in order to determine the relative merits and drawbacks of each method. The findings from the comparative study would be useful to recommend the most suitable method to identify and rank the RTA hotspots for the study road.

ABSTRACT The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Self‐assembly of lipid‐based liquid crystalline (LLC) nanoparticles is a formulation art arising from the hydrophilic–lipophilic qualities and the geometric packing of amphiphilic lipid molecules in an aqueous environment. The diversity of commercialized amphiphilic lipids and an increased understanding of the physicochemical factors dictating their membrane curvature has enabled versatile architectural design and engineering of LLC nanoparticles. While these exotic nanostructured materials are hypothesized to form the next generation of smart therapeutics for a broad field of biomedical applications, biological knowledge particularly on the systemic biocompatibility or cytotoxicity of LLC materials remains unclear. Here, an overview on the interactions between LLCs of different internal nanostructures and biological components (including soluble plasma constituents, blood cells, and isolated tissue cell lines) is provided. Factors affecting cell–nanoparticle tolerability such as the type of lipids, type of steric stabilizers, nanoparticle surface charges, and internal nanostructures (or lipid phase behaviors) are elucidated. The mechanisms of cellular uptake and lipid transfer between neighboring membrane domains are also reviewed. A critical analysis of these studies sheds light on future strategies to transform LLC materials into a viable therapeutic entity ideal for internal applications. An overview of the relationships between nanostructure, composition, and biological behaviors of liquid crystalline lipid self‐assemblies is presented. A clear understanding of the biofate and bioeffect of these nanostructured materials is imperative for predicting a viable formulation design exploitable for internal therapeutic applications.

Both lamellar and non-lamellar configurations are naturally present in bio-membranes, and the synthetic lipid-based liquid crystalline nano-assemblies, mimicking these unique structures, (including liposomes, cubosomes and hexosomes) are applicable in the controlled delivery of bioactives. However, it remains uncertain whether these nanosystems retain their original phase identity upon contact with blood circulating cells. This study highlights a novel biological cell flow-through approach at the synchrotron-based small angle X-ray scattering facility (bio-SAXS) to unravel their real-time phase evolution when incubated with human monocytic cells (THP-1) in suspension. Phytantriol-based cubosomes were identified to undergo monocytic cell-induced phase transformation from cubic to hexagonal phase periodicity. On the contrary, hexosomes exhibited time-dependent growth of a swollen hexagonal phase (i.e., larger lattice parameters) without displaying alternative phase characteristics. Similarly, liposomes remained undetectable for any newly evolved phase identity. Consequently, this novel in situ bio-SAXS study concept is valuable in delivering new important insights into the bio-fates of various lipid-based nanosystems under simulated human systemic conditions.

To investigate the role of self-emulsifying lipids and porous silica particles in enhancing supersaturated drug loading and biopharmaceutical performance of nanostructured silica-lipid hybrid (SLH) systems. Two lovastatin (LOV)-SLHs were engineered from self-emulsifying lipid (Gelucire 44/14; Gattefossé, Lyon, France) and Aerosil 380 (SLH-A; Evonik Industries, Essen, Germany) or Syloid 244FP silica (SLH-S; Grace Davison Discovery Sciences, Rowville, Australia). The LOV-SLHs encapsulated LOV at 10% w/w, which is ≥3-fold higher than typical lipid formulations in the absence of porous silica. The LOV-SLHs retained self-emulsifying lipid-associated solubilization benefits and improved drug solubilization by twofold in simulated intestinal condition. SLH-S, with larger surface area (299 m /g), was superior to SLH-A (184 m /g) in optimizing oral bioavailability, suggesting a critical role of the silica geometry. Bioavailability of SLH-S was 2.8- and 1.3-fold higher than pure drug and drug suspension in Gelucire 44/14, respectively. In conclusion, SLHs profit from advantages associated with both self-emulsifying lipids and porous silica, and provide potentially improved therapy against coronary artery disease.

ABSTRACT Purpose To investigate the dose linearity of celecoxib (CEL) pharmacokinetics from various non-lipid and lipid-based formulations; to probe the mechanisms of CEL absorption from a nano-structured silica-lipid hybrid (SLH) microparticle dosage form. Methods Single-dose pharmacokinetic parameters of CEL were determined in fasted rats at dose levels of 5, 20 and 50 mg/kg in aqueous suspensions of pure CEL, Celebrex ® and CEL-SLH microparticles formulated using medium-chain lipids (Miglyol 812 or Capmul MCM) and Aerosil ® silica nanoparticles. An in vitro lipolysis model was used to characterise the dynamic solubilisation state of CEL under digesting conditions. Results CEL-SLH formulations and Celebrex ® consistently produced a 2-fold higher maximum plasma concentration ( C max ) and bioavailability ( AUC 0→∞ ) than pure CEL in a dose-linear manner within the dose range of 5–50 mg/kg CEL (R 2  > 0.8). Lipolysis drug phase partition data indicate a 2.5–7.5-fold higher CEL solubilising capacity resulting from the digestion of SLH microparticles as compared to the simulated fasted state endogenous micelles. Strong correlations were obtained between maximum CEL solubilisation levels during lipolysis and in vivo pharmacokinetic parameters (R 2  > 0.9). Conclusions Collectively, the results highlight the potential of the SLH microparticles in enhancing the bioavailability of CEL in a dose-linear manner as facilitated by supersaturated solubilisation of CEL in the intestinal milieu.

Background The objective of this meta-analysis was to assess the association of sarcopenia defined on computed tomography (CT) head and neck with survival in head and neck cancer patients. Methods Following a PROSPERO-registered protocol, two blinded reviewers extracted data and evaluated the quality of the included studies using the Quality In Prognostic Studies (QUIPS) tool, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. A meta-analysis was conducted using maximally adjusted hazard ratios (HRs) with the random-effects model. Heterogeneity was measured using the I 2 statistic and was investigated using meta-regression and subgroup analyses where appropriate. Results From 37 studies (11,181 participants), sarcopenia was associated with poorer overall survival (HR 2.11, 95% confidence interval [CI] 1.81–2.45; p  < 0.01), disease-free survival (HR 1.76, 95% CI 1.38–2.24; p  < 0.01), disease-specific survival (HR 2.65, 95% CI 1.80–3.90; p  < 0.01), progression-free survival (HR 2.24, 95% CI 1.21–4.13; p  < 0.01) and increased chemotherapy or radiotherapy toxicity (risk ratio 2.28, 95% CI 1.31–3.95; p  < 0.01). The observed association between sarcopenia and overall survival remained significant across different locations of cancer, treatment modality, tumor stages and geographical region, and did not differ between univariate and multivariate HRs. Statistically significant correlations were observed between the C3 and L3 cross-sectional area, skeletal muscle mass, and skeletal muscle index. Conclusions Among patients with head and neck cancers, CT-defined sarcopenia was consistently associated with poorer survival and greater toxicity.

Statistics literacy and critical thinking have become increasingly important for Higher Education (HE) and employability in the 21st century; however, teaching these topics or skills remains a major challenge. This PhD attempted to address this challenge through technology-enhanced video-based learning (VBL). Three iterations of 'bite-sized' VBL interventions focusing on statistics literacy or critical thinking were implemented. The bite-sized VBL approach was enhanced with progressive peer-assisted learning (PAL), a pedagogical approach where students learn from senior students who have recently completed the same course. The interventions also included Precision Teaching (PT), a behaviourally-grounded teaching approach that builds 'fluency' on learnt skills and benefits students learning in VBL settings. In the first iteration of the intervention (Study 1), an online VBL intervention for consolidating previously learned statistical skills was developed. The use of PAL varied across three 'presenter conditions': lecturer-led, peer-imitating-lecturer, or peer-led. Participants presented a high performance in post-episode assessments, irrespective of presenter conditions and reported remarkably positive views towards bite-sized VBL. The second iteration (Study 2) evaluated an integrated VBL and PT intervention for a broad range of statistics topics. A PT intervention group achieved consistently higher scores in all end-of-episode assessments than a self-directed learning control group. Both groups showed significant and comparable improvements in statistics attainment and reported more positive feelings towards statistics post-intervention. The final iteration (Study 3) extended the integrated VBL and PT approach to critical thinking skills, focusing on fallacy identification. Three groups of participants, a 'PT' group, a 'PT+' group, where PT was combined with problem-based training, and a 'self-directed learning' control group, completed two learning episodes. All groups showed significant and comparable improvements in fallacy identification on taught and unseen materials, while lower-scoring participants had higher gains than high-scoring participants. The results on delayed recall a week later were also comparable between groups. Crucially, the two PT groups showed bigger improvements than the control group in the domain-general fallacy-identification assessment post-intervention. The original contributions of this project to knowledge are threefold. First, PT is flexible enough to support learning quantitative and more complex skills in VBL. Second, video-based PAL strategies share similar benefits to lecturer-led learning whilst being more congruent with the learners' level of competence. Third, bite-sized VBL has a great potential to support university students in learning as a supplementary teaching aid.