Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

Fluxes of organic contaminants from the river catchment into, through and out of the Humber Estuary, UK

This paper summarises the work done on the distribution and reactivity of organic contaminants (simazine, atrazine, lindane, fluoranthene, pyrene, PCB 77, PCB 118) in the Humber Estuary and associated major rivers, as part of the LOIS programme. The preliminary flux calculations show that the most important contributors of selected organic contaminants were the rivers Trent (45% of simazine, 20% of atrazine), Aire (30% of simazine and 33% of atrazine), Don (36 and 37% of fluoranthene and pyrene) and Ouse (18% of fluoranthene and pyrene). For lindane and PCBs, the Aire and Ouse were the key sources. The water flow in all the rivers shows strong seasonal variations, as do the contaminant concentrations. As a result, the mean daily fluxes of these contaminants displayed a strong seasonality. Annual mean concentrations of simazine and atrazine decreased by more than 50% over the period 1994-1995 in most of the rivers, probably as a result of their restricted use in the UK. Mass balance calculations show that the Humber is a sink for atrazine, lindane, PCB 77 and PCB 118, although the degree of removal is generally much lower for atrazine and lindane than for PCB 77 and PCB 118. Mass balance results also show that the Humber can either be a source of fluoranthene and pyrene (in the suspended particulate phase), or a sink (in the dissolved phase), although overall the Humber acts as sink. The budget exercise represents an attempt to quantify the input and output of selected organic contaminants from catchment to ocean. However, due to limited data and assumptions involved in calculations, the estimates should be considered as an order of magnitude approximation. Further improvement both in resolution and accuracy is required.

Establishing the validity of English GP Patient Survey items evaluating out-of-hours care

Background A 2014 national audit used the English General Practice Patient Survey (GPPS) to compare service users’ experience of out-of-hours general practitioner (GP) services, yet there is no published evidence on the validity of these GPPS items. Objectives Establish the construct and concurrent validity of GPPS items evaluating service users’ experience of GP out-of-hours care. Methods Cross-sectional postal survey of service users (n=1396) of six English out-of-hours providers. Participants reported on four GPPS items evaluating out-of-hours care (three items modified following cognitive interviews with service users), and 14 evaluative items from the Out-of-hours Patient Questionnaire (OPQ). Construct validity was assessed through correlations between any reliable (Cochran's α>0.7) scales, as suggested by a principal component analysis of the modified GPPS items, with the ‘entry access’ (four items) and ‘consultation satisfaction’ (10 items) OPQ subscales. Concurrent validity was determined by investigating whether each modified GPPS item was associated with thematically related items from the OPQ using linear regressions. Results The modified GPPS item-set formed a single scale (α=0.77), which summarised the two-component structure of the OPQ moderately well; explaining 39.7% of variation in the ‘entry access’ scores (r=0.63) and 44.0% of variation in the ‘consultation satisfaction’ scores (r=0.66), demonstrating acceptable construct validity. Concurrent validity was verified as each modified GPPS item was highly associated with a distinct set of related items from the OPQ. Conclusions Minor modifications are required for the English GPPS items evaluating out-of-hours care to improve comprehension by service users. A modified question set was demonstrated to comprise a valid measure of service users’ overall satisfaction with out-of-hours care received. This demonstrates the potential for the use of as few as four items in benchmarking providers and assisting services in identifying, implementing and assessing quality improvement initiatives.

Solid-liquid interfacial free energy out of equilibrium

The properties of the interface between solid and melt are key to solidification and melting, as the interfacial free energy introduces a kinetic barrier to phase transitions. This makes solidification happen below the melting temperature, in out-of-equilibrium conditions at which the interfacial free energy is ill defined. Here we draw a connection between the atomistic description of a diffuse solid-liquid interface and its thermodynamic characterization. This framework resolves the ambiguities in defining the solid-liquid interfacial free energy above and below the melting temperature. In addition, we introduce a simulation protocol that allows solid-liquid interfaces to be reversibly created and destroyed at conditions relevant for experiments. We directly evaluate the value of the interfacial free energy away from the melting point for a simple but realistic atomic potential, and find a more complex temperature dependence than the constant positive slope that has been generally assumed based on phenomenological considerations and that has been used to interpret experiments. This methodology could be easily extended to the study of other phase transitions, from condensation to precipitation. Our analysis can help reconcile the textbook picture of classical nucleation theory with the growing body of atomistic studies and mesoscale models of solidification.

Moving Out of Conflict: Negotiating Social Identity in Response to Segregation in Northern Ireland

This paper examines the impact of territoriality on young people’s everyday experiences in Northern Ireland’s segregated communities. It shows how urban encounters are reproduced through negotiating differences and the ways in which living in divided communities escalates moods of social inequality and spatial imbalances. The empirical study undertaken in the city of Derry shows how individuals and community groups position and identify themselves under the impact of social segregation. Building on Gordon Allport’s (1954) theories of contact, I explain how people in Derry have established their own sense of belonging, of who they are, based on their group memberships which eventually became an important source of pride and selfesteem. They also presented their own intertextual references as a cause of routine survival and belonging, allowing them to be more constructive about their future. Under deeply rooted segregation in Northern Ireland, the young generations are sought to provide lasting change to foster peace and integration between the two communities.

Why Putin has pulled Russia out of Syria

By formally quitting during a ceasefire he himself masterminded – and on the back of significant military gains – Putin can leave with his head held high. Having proven his critics wrong and demonstrated the capability of Russia’s military (and its new weapons – a splendid advert to any buyers of Russian arms), Putin can now concentrate on the diplomatic aspect of the peace process, something at which Moscow usually excels.

‘Harmonising the precaution out of the precautionary principle? The need for maintaining flexibility and an interpretative role’

The precautionary principle has the potential to act as a valuable tool in food law. It operates in areas of scientific uncertainty, calling for protective measures where there are potential threats to human health (or the environment). However, the manner of the principle’s incorporation and implementation within legislation are key to its effectiveness and general legitimacy. Specific considerations include the role and nature of risk assessments, assessors, sources of evidence, divergent opinions, risk communication, other legitimate factors and the weighting of interests. However, more fundamentally, the crystallisation of approaches and removal of all flexibility would undermine the principle’s central tenets. Firstly, principles crucially play a guiding and interpretative role. Secondly, reflexive modernisation and continuing scientific uncertainty call for the precautionary principle’s continued application – precautionary measures do not end the precautionary principle’s relevance. This can be partially achieved through the legislation so as to facilitate later precautionary measures, e.g. through temporary authorisations, derogations and safeguard clauses. However, crucially, it requires that the legislation also be interpreted in light of the precautionary principle. This paper investigates the logic behind the Court of Justice of the EU’s judgments and the circumstances that enable or deter the Court in taking, or permitting, stronger precautionary approaches. Although apparently inconsistent, a number of contextual factors including the legislative provisions and actors involved influence the judgments substantially. The analysis provides insight into improving the principle’s incorporation to facilitate its continued application and maintenance of flexibility, whilst bearing in mind the general desirability of objectivity and legal certainty.