Systematic review and meta-analysis are a gift to the modern researcher, delivering a crystallised understanding of the existing research data in any given space. This can include whether candidate drugs are likely to work or not and which are better than others, whether our models of disease have predictive value and how this might be improved and also how these all interact with disease pathophysiology.Grappling with the literature needed for such analyses is becoming increasingly difficult as the number of publications grows. However, narrowing the focus of a review to reduce workload runs the risk of diminishing the generalisability of conclusions drawn from such increasingly specific analyses.Moreover, at the same time as we gain greater insight into our topic, we also discover more about the flaws that undermine much scientific research. Systematic review and meta-analysis have also shown that the quality of much preclinical research is inadequate. Systematic review has helped reveal the extent of selection bias, performance bias, detection bias, attrition bias and low statistical power, raising questions about the validity of many preclinical research studies. This is perhaps the greatest virtue of systematic review and meta-analysis, the knowledge generated ultimately helps shed light on the limitations of existing research practice, and in doing so, helps bring reform and rigour to research across the sciences.In this commentary, we explore the lessons that we have identified through the lens of preclinical systematic review and meta-analysis.
The translation of nanoparticles to useful applications is often hindered by the reliability of synthetic methodologies to reproducibly generate larger particles of uniform size (diameter > 20 nm). The inability to precisely control nanoparticle crystallinity, size, and shape has significant implications on observed properties and therefore applications. A series of iron oxide particles have been synthesised and the impact of size as they agglomerate in aqueous media undergoing flow through a capillary tube has been studied. Reaction conditions for the production of large (side length > 40 nm) cubic magnetite (Fe3O4) have been optimised to produce particles with different diameters up to 150 nm. We have focussed on reproducibility in synthesis rather than dispersity of the size distribution. A simple oxidative cleavage of the as-synthesised particles surfactant coating transforms the hydrophobic oleic acid coated Fe3O4 to a hydrophilic system based on azelaic acid. The hydrophilic coating can be further functionalised, in this case we have used a simple biocompatible polyethylene glycol (PEG) coating. The ability of particles to either chain, flow, and fully/or partially aggregate in aqueous media has been tested in a simple in-house system made from commercial components. Fe3O4 nanoparticles (60–85 nm) with a simple PEG coating were found to freely flow at a 2 mm distance from a magnet over 3 min at a rate of 1 mL min−1. Larger particles with side lengths of ~150 nm, or those without a PEG coating were not able to fully block the tube. Simple calculations have been performed to support these observations of magnetic agglomeration.
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