Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination

Blood-brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal-appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls. Using single and double immunofluorescence and confocal microscopy, the TJ-associated protein zonula occludens-1 (ZO-1) was examined across lesion types and tissue categories, and in relation to fibrinogen leakage. Confocal image data sets were analysed for 2198 MS and 1062 control vessels. Significant differences in the incidence of TJ abnormalities were detected between the different lesion types in MS and between MS and control white matter. These were frequent in oil-red O (ORO)+ active plaques, affecting 42% of vessel segments, but less frequent in ORO- inactive plaques (23%), NAWM (13%), and normal (3.7%) and neurological controls (8%). A similar pattern was found irrespective of the vessel size, supporting a causal role for diffusible inflammatory mediators. In both NAWM and inactive lesions, dual labelling showed that vessels with the most TJ abnormality also showed most fibrinogen leakage. This was even more pronounced in active lesions, where 41% of vessels in the highest grade for TJ alteration showed severe leakage. It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage. TJ abnormality and BBB leakage in inactive lesions suggests either failure of TJ repair or a continuing pathological process. In NAWM, it suggests either pre-lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease-modifying therapy

Keeping a sense of proportion but losing all perspective: a critique of Gorard's notion of the 'Politician's Error'

In 1999 Stephen Gorard published an article in this journal in which he provided a trenchant critique of what he termed the `politician's error' in analysing differences in educational attainment. The main consequence of this error, he argued, has been the production of misleading findings in relation to trends in educational performance over time that have, in turn, led to misguided and potentially damaging policy interventions. By using gender differences in educational attainment as a case study, this article begins by showing how Gorard's notion of the politician's error has been largely embraced and adopted uncritically by those within the field. However, the article goes on to demonstrate how Gorard's own preferred way of analysing such differences – by calculating and comparing proportionate changes in performance between groups – is also inherently problematic and can lead to the production of equally misleading findings. The article will argue that there is a need to develop a more reliable and valid way of measuring trends in educational performance over time and will show that one of the simplest ways of doing this is to make use of existing, and widely accepted, measures of effect size.

Linnaeus was right all along: Ulva and Enteromorpha are not distinct genera.

Ulva, one of the first Linnaean genera, was later circumscribed to consist of green seaweeds with distromatic blades, and Enteromorpha Link was established for tubular forms. Although several lines of evidence suggest that these generic constructs are artificial, Ulva and Enteromorpha have been maintained as separate genera. Our aims were to determine phylogenetic relationships among taxa currently attributed to Ulva, Enteromorpha, Umbraulva Bae et I.K. Lee and the monotypic genus Chloropelta C.E. Tanner, and to make any nomenclatural changes justified by our findings. Analyses of nuclear ribosomal internal transcribed spacer DNA (ITS nrDNA) (29 ingroup taxa including the type species of Ulva and Enteromorpha), the chloroplast-encoded rbcL gene (for a subset of taxa) and a combined data set were carried out. All trees had a strongly supported clade consisting of all Ulva, Enteromorpha and Chloropelta species, but Ulva and Enteromorpha were not monophyletic. The recent removal of Umbraulva olivascens (P.J.L. Dangeard) Bae et I.K. Lee from Ulva is supported, although the relationship of the segregate genus Umbraulva to Ulvaria requires further investigation. These results, combined with earlier molecular and culture data, provide strong evidence that Ulva, Enteromorpha and Chloropelta are not distinct evolutionary entities and should not be recognized as separate genera. A comparison of traits for surveyed species revealed few synapomorphies. Because Ulva is the oldest name, Enteromorpha and Chloropelta are here reduced to synonymy with Ulva, and new combinations are made where necessary.