A critique of the regulation of data science in healthcare research in the European Union

The EU offers a suitable milieu for the comparison and harmonisation of healthcare across different languages, cultures, and jurisdictions (albeit with a supranational legal framework), which could provide improvements in healthcare standards across the bloc. There are specific ethico-legal issues with the use of data in healthcare research that mandate a different approach from other forms of research. The use of healthcare data over a long period of time is similar to the use of tissue in biobanks. There is a low risk to subjects but it is impossible to gain specific informed consent given the future possibilities for research. Large amounts of data on a subject present a finite risk of re-identification. Consequently, there is a balancing act between this risk and retaining sufficient utility of the data. Anonymising methods need to take into account the circumstances of data sharing to enable an appropriate balance in all cases. There are ethical and policy advantages to exceeding the legal requirements and thereby securing the social licence for research. This process would require the examination and comparison of data protection laws across the trading bloc to produce an ethico-legal framework compatible with the requirements of all member states. Seven EU jurisdictions are given consideration in this critique

What are data? A categorization of the data sensitivity spectrum

The definition of data might at first glance seem prosaic, but formulating a definitive and useful definition is surprisingly difficult. This question is important because of the protection given to data in law and ethics. Healthcare data are universally considered sensitive (and confidential), so it might seem that the categorisation of less sensitive data is relatively unimportant for medical data research. This paper will explore the arguments that this is not necessarily the case and the relevance of recognizing this. The categorization of data and information requires re-evaluation in the age of Big Data in order to ensure that the appropriate protections are given to different types of data. The aggregation of large amounts of data requires an assessment of the harms and benefits that pertain to large datasets linked together, rather than simply assessing each datum or dataset in isolation. Big Data produce new data via inferences, and this must be recognized in ethical assessments. We propose a schema for a granular assessment of data categories. The use of schemata such as this will assist decision-making by providing research ethics committees and information governance bodies with guidance about the relative sensitivities of data. This will ensure that appropriate and proportionate safeguards are provided for data research subjects and reduce inconsistency in decision making

Biomechanics of the human lens and accommodative system: functional relevance to physiological states

The ability of the human lens to accommodate is mediated by the ciliary muscle and zonule; the manifest optical power changes depend on the shape and material properties of the lens. The latter are difficult to measure with accuracy and, given the dynamic aspects of accommodation and the ageing of cells and tissues, the biomechanics of the lens is neither fixed nor constant. A range of techniques have been developed to measure both ageing trends and spatial variations in the mechanical properties and these have yielded a diverse array of findings and respective conclusions. The majority of quasi-static measurements, where the observation time is in minutes or hours, indicate that the stiffness of the lens increases with age at a faster rate in the lens centre than in the periphery. Dynamic measurements show that lens material properties are dependent on the loading frequency. Recent in vivo analyses suggest that, along the optic axis, profiles of elastic moduli are very similar to profiles of refractive index. This review assesses the advantages and limitations of different measurement techniques and consequent variations in elastic moduli that have been found. Consideration is given to the role of computational modelling and the various modelling methods that have been applied. The changes in mechanical properties of the lens associated with ageing and pathology and future implications for implant design are discussed

Maximum human objectively measured pharmacologically stimulated accommodative amplitude

Purpose: To measure the maximum, objectively measured, accommodative amplitude, produced by pharmacologic stimulation. Methods: Thirty-seven healthy subjects were enrolled, with a mean age of 20.2±1.1 years, corrected visual acuity of 20/20, and mean spherical equivalent refraction (SER) =–0.83±1.60 diopters. For each subject, the right pupil was dilated with phenylephrine 10%. After 30 minutes, the pupil was measured, the left eye was patched, and the right eye was autorefracted. Pilocarpine 4% was then instilled in the right eye, followed by phenylephrine. At 45 minutes after the pilocarpine, autorefraction and pupil size were again measured. Results: Mean pupil size pre- and postpilocarpine was 8.0±0.8 mm and 4.4±1.9 mm, respectively. Pre- and postpilocarpine, the mean SER was –0.83±1.60 and –10.55±4.26 diopters, respectively. The mean pilocarpine-induced accommodative amplitude was 9.73±3.64 diopters. Five subjects had accommodative amplitudes ≥14.00 diopters. Accommodative amplitude was not significantly related to baseline SER (p-value =0.24), pre- or postpilocarpine pupil size (p-values =0.13 and 0.74), or change in pupil size (p-value =0.37). Iris color did not statistically significantly affect accommodative amplitude (p-value =0.83). Conclusion: Following topically applied pilocarpine, the induced objectively measured accommodation in the young eye is greater than or equal to the reported subjectively measured voluntary maximum accommodative amplitude

Ethylene glycol coated nanoceria protects against oxidative stress in human lens epithelium

Chronic diseases are rising in incidence and prevalence because of increases in life expectancy in many parts of the world coupled with advances in medicine which manage disease progression, rather than curing and alleviating the causes. Cataract is one such chronic condition. Identifying a therapeutic intervention that is successful in reversing or preventing cataracts may have applications for other chronic diseases of protein misfolding, such as diabetes and Alzheimer's disease as these have similar causation factors, notably oxidative stress and/or glycation. Cerium oxide nanoparticles (nanoceria) which have antioxidant, radioprotective and enzyme-mimetic properties have the potential to lead to an effective non-surgical treatment. However, nanoceria stability in physiological media is poor thus hindering their effective use in biomedical applications. Here we report a highly efficient one-pot synthesis of nanoceria (2–5 nm) coated with ethylene glycol, that is colloidally stable in physiological media and exhibits multiwavelength photoluminescence. The formulation, up to concentrations of 200 μg ml−1, was not toxic to human lens epithelial cells and had no adverse effect on the cellular morphology or proliferation rate. More significantly, these nanoceria showed protective effects against oxidative stress induced by hydrogen peroxide in lens epithelial cells. Electron microscopy studies show the internalization and cytoplasmic localization of the nanoceria was found to be largely in the perinuclear region

Imaging shear stress distribution and evaluating the stress concentration factor of the human eye.

Healthy eyes are vital for a better quality of human life. Historically, for man-made materials, scientists and engineers use stress concentration factors to characterise the effects of structural non-homogeneities on their mechanical strength. However, such information is scarce for the human eye. Here we present the shear stress distribution profiles of a healthy human cornea surface in vivo using photo-stress analysis tomography, which is a non-intrusive and non-X-ray based method. The corneal birefringent retardation measured here is comparable to that of previous studies. Using this, we derive eye stress concentration factors and the directional alignment of major principal stress on the surface of the cornea. Similar to thermometers being used for monitoring the general health in humans, this report provides a foundation to characterise the shear stress carrying capacity of the cornea, and a potential bench mark for validating theoretical modelling of stresses in the human eye in future

The importance of parameter choice in modelling dynamics of the eye lens

The lens provides refractive power to the eye and is capable of altering ocular focus in response to visual demand. This capacity diminishes with age. Current biomedical technologies, which seek to design an implant lens capable of replicating the function of the biological lens, are unable as yet to provide such an implant with the requisite optical quality or ability to change the focussing power of the eye. This is because the mechanism of altering focus, termed accommodation, is not fully understood and seemingly conflicting theories require experimental support which is difficult to obtain from the living eye. This investigation presents finite element models of the eye lens based on data from human lenses aged 16 and 35 years that consider the influence of various modelling parameters, including material properties, a wide range of angles of force application and capsular thickness. Results from axisymmetric models show that the anterior and posterior zonules may have a greater impact on shape change than the equatorial zonule and that choice of capsular thickness values can influence the results from modelled simulations