Cisplatin drug delivery using gold-coated iron oxide nanoparticles for enhanced tumour targeting with external magnetic fields

The platinum-based chemotherapeutic drug cisplatin is highly effective in the treatment of solid tumours, but its use is restricted by poor bioavailability, severe dose-limiting side effects and rapid development of drug resistance. In light of this we have tethered the active component of cisplatin to goldcoated iron oxide nanoparticles to improve its delivery to tumours and increase its efficacy. Iron oxide nanoparticles (FeNPs) were synthesised via a co-precipitation method before gold was reduced onto the surface (Au@FeNPs). Aquated cisplatin was used to attach {Pt(NH3)2} to the nanoparticles by a thiolated polyethylene glycol linker forming the desired product (Pt@Au@FeNP). The nanoparticles were characterised by dynamic light scattering, scanning transmission electron microscopy, UV–Vis spectrophotometry, inductively coupled plasma mass spectrometry and electron probe microanalysis. The nanoparticles increase in size as they are constructed, with the synthesised FeNPs having a diameter of 5– 50 nm, which increases to 20–80 nm for the Au@FeNPs, and to 60–120 nm for the Pt@Au@FeNPs. Nanoparticle drug loading was found to be 7.9 10 4 moles of platinum per gram of gold. The FeNPs appear to have little inherent cytotoxicity, whereas the Au@FeNPs are as active as cisplatin in the A2780 and A2780/cp70 cancer cell lines. More importantly the Pt@Au@FeNPs are up to 110-fold more cytotoxic than cisplatin. Finally, external magnets were used to demonstrate that the nanoparticles could be accumulated in specific regions and that cell growth inhibition was localised to those areas

A global fund for social protection : Lessons from the diverse experiences of global health, agriculture and climate funds

The recent social, ecological and economic crises have not only revealed the gaps in social protection systems across the world, but also drawn global attention to the ways in which international financial and development architectures have failed to support universal social protection systems and floors. Within this context, this Working Paper examines the idea of a global fund for social protection which has emerged as a potential solution to these structural failings. By drawing on the experiences of seven global funds across the health, climate, and agriculture sectors, the aim of this Working Paper is to identify key lessons that can guide the possible implementation of a prospective global fund for social protection. Through a careful analysis of the governance structures, norms and standards of these funds, the Working Paper makes recommendations to be taken into consideration if a global fund for social protection is to be developed and implemented

Regional differences in clonal Japanese knotweed revealed by chemometrics-linked attenuated total reflection Fourier-transform infrared spectroscopy

Abstract: Background: Japanese knotweed (R. japonica var japonica) is one of the world’s 100 worst invasive species, causing crop losses, damage to infrastructure, and erosion of ecosystem services. In the UK, this species is an all-female clone, which spreads by vegetative reproduction. Despite this genetic continuity, Japanese knotweed can colonise a wide variety of environmental habitats. However, little is known about the phenotypic plasticity responsible for the ability of Japanese knotweed to invade and thrive in such diverse habitats. We have used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, in which the spectral fingerprint generated allows subtle differences in composition to be clearly visualized, to examine regional differences in clonal Japanese knotweed. Results: We have shown distinct differences in the spectral fingerprint region (1800–900 cm− 1) of Japanese knotweed from three different regions in the UK that were sufficient to successfully identify plants from different geographical regions with high accuracy using support vector machine (SVM) chemometrics. Conclusions: These differences were not correlated with environmental variations between regions, raising the possibility that epigenetic modifications may contribute to the phenotypic plasticity responsible for the ability of R. japonica to invade and thrive in such diverse habitats

The MUARC-TAC enhanced crash investigation study: study update, analysis of crash types and contributing factors [Abstract]

This paper presents an update of the Monash University Accident Research Centre (MUARC) – Transport Accident Commission (TAC) Enhanced Crash Investigation Study (ECIS) as well as an exploration of the characteristics of injured drivers, crash types and factors implicated in crash occurrence. Three configurations are of particularly high frequency and severity, whilst crashes involving young and older drivers are different in nature and have different contributing factors. Fatigue, driver error, and pre-crash driver blackouts due to medical conditions were prominent contributing factors. Injury severity would be significantly lower in 32% of cases if either front or side airbags were fitted. The findings point to key risk factors that can be addressed in road safety strategies

The MUARC-TAC enhanced crash investigation study: a platform to understand the causes and consequences of serious injury crashes.

Background: In recognising the consequences of serious injury crashes, the Transport Accident Commission (TAC) commissioned Monash University Accident Research Centre (MUARC) to undertake the Enhanced Crash Investigation Study (ECIS). This paper describes the program components, seven key research questions and technical innovations used in the study. We describe the information collected and outline a ‘Safe Systems Failure Analysis’ used for each case. Project Method: Participants in ECIS include drivers aged 18 years and older seriously injured in crashes on public Victorian roads. Drivers are recruited whilst inpatients at a major trauma hospital and where possible interviews conducted. The ECIS team inspects their crashed vehicle and critically analyses the crash environment. Event Data Recorder (EDR, black-box) data is acquired from vehicles where possible and crash reconstructions are undertaken. Each case is submitted to an internal panel review with a sub-sample of cases presented to external panels throughout Victoria. This process leads to each case being submitted to a Safe Systems Failure Analysis where contributing factors and countermeasures are identified by a broad group of stakeholders. The ECIS control arm permits examination of the relationship between certain factors, such as speed and crash occurrence. Results and Discussion: In addition to describing the study, we provide an example of how the identification of crash factors, using a Safe Systems paradigm based on real-world serious injury crashes, can lead to the identification of targeted countermeasures, each with an identified policy action. Implications: This paper will demonstrate a method for creating a robust evidence base upon which government road safety policy can be built. By scaling up individual crash findings to the broader crash population, countermeasures and associated policy actions can be appropriately prioritised

What drivers do while speeding: examining the associations between speeding and driver distraction through the Enhanced Crash Investigation Study protocol [Abstract]

This paper represents an exploratory analysis to assess the feasibility of assessing the relationship between driver speed and engagement in potentially distracting behaviours. Control data from the ECIS project are examined. These data include both objective speed measurements recorded via laser camera positioned at ECIS case-vehicle crash locations as well as retrospective self-reported driving behaviours from drivers recorded at these sites. Exploratory analysis suggests that the activities reported by drivers with recorded speeds above the limit may differ from the activities reported by those recorded on or below the limit

European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years.

Diagnosing asthma in children represents an important clinical challenge. There is no single gold standard test to confirm the diagnosis. Consequently, both over-, and under-diagnosis of asthma are frequent in children.A Task Force (TF) supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine PICO (Population, Intervention, Comparator and Outcome) questions. The TF conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full text articles. All TF members approved the final decision for inclusion of research papers. The TF assessed the quality of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.The TF then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The TF formulated recommendations using the GRADE Evidence to Decision framework.Based on the critical appraisal of the evidence and the Evidence to Decision Framework the TF recommends spirometry, bronchodilator reversibility testing and FeNO as first line diagnostic tests in children under investigation for asthma. The TF recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy