Impact on the NHS and health of the UK's trade and cooperation relationship with the EU, and beyond.

The UK's relationship with the European Union (EU) is now embodied in two principal legal instruments: the EU-UK Trade and Cooperation Agreement, which formally entered into force on 1 May 2021; and the Withdrawal Agreement, with its Protocol on Ireland/Northern Ireland, which continues to apply. Using a 'building blocks' framework for analysis of national health systems derived from the World Health Organisation, this article examines the likely impacts in the UK of this legal settlement on the National Health Service (NHS), health and social care. Specifically, we determine the extent to which the trade, cooperation and regulatory aspects of those legal measures support positive impacts for the NHS and social care. We show that, as there is clear support for positive health and care outcomes in only one of the 17 NHS 'building blocks', unless mitigating action is taken, the likely outcomes will be detrimental. However, as the legal settlement gives the UK a great deal of regulatory freedom, especially in Great Britain, we argue that it is crucial to track the effects of proposed new health and social care-related policy choices in the months and years ahead.

An analysis of subject areas and country participation for all health-related projects in the EU's FP5 and FP6 programmes.

BACKGROUND: Previous analyses concerning health components of European Union (EU)-funded research have shown low project participation levels of the 12 newest member states (EU-12). Additionally, there has been a lack of subject-area analysis. In the Health Research for Europe project, we screened all projects of the EU's Framework Programmes for research FP5 and FP6 (1998-2006) to identify health research projects and describe participation by country and subject area. METHODS: FP5 and FP6 project databases were acquired and screened by coders to identify health-related projects, which were then categorized according to the 47 divisions of the EU Health Portal (N = 2728 projects) plus an extra group of 'basic/biotech' projects (N = 1743). Country participation and coordination rates for projects were also analyzed. RESULTS: Approximately 20% of the 26 946 projects (value €29.2bn) were health-related (N = 4756. Value €6.04bn). Within the health categories, the largest expenditures were cancer (11.9%), 'other' (i.e. not mental health or cardiovascular) non-communicable diseases (9.5%) and food safety (9.4%). One hundred thirty-two countries participated in these projects. Of the 27 EU countries (and five partner countries), north-western and Nordic states acquired more projects per capita. The UK led coordination with > 20% of projects. EU-12 countries were generally under-represented for participation and coordination. CONCLUSIONS: Combining our findings with the associated literature, we comment on drivers determining distribution of participation and funds across countries and subject areas. Additionally, we discuss changes needed in the core EU projects database to provide greater transparency, data exploitation and return on investment in health research.

Europe's 'Horizon 2020' science funding programme: how is it shaping up?

Over the past 15 years, the European Union (EU) has spent around €80 billion on science research via Framework Programmes (FP5, FP6 and FP7). In 2014, a new programme, Horizon 2020, will likely invest another €70 billion over 6 years. Health research has been a major part: between 12% and 17% was spent on official FP5 and FP6 health research lines, although our work categorizing all EU science projects puts the health-related investment proportion nearer to 20%. Here, we compare our analyses and experiences with the European Commission's own impact assessments and plans that inform the Horizon 2020 programme. Much is moving in the right direction but some key gaps are overlooked. We discuss four areas: red tape, what to fund, harnessing informatics and neglect of Eastern Europe.

The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia.

Deficits in executive functions are key features of schizophrenia. Rodent behavioral paradigms used so far to find animal correlates of such deficits require extensive effort and time. The puzzle box is a problem-solving test in which mice are required to complete escape tasks of increasing difficulty within a limited amount of time. Previous data have indicated that it is a quick but highly reliable test of higher-order cognitive functioning. We evaluated the use of the puzzle box to explore executive functioning in five different mouse models of schizophrenia: mice with prefrontal cortex and hippocampus lesions, mice treated sub-chronically with the NMDA-receptor antagonist MK-801, mice constitutively lacking the GluA1 subunit of AMPA-receptors, and mice over-expressing dopamine D2 receptors in the striatum. All mice displayed altered executive functions in the puzzle box, although the nature and extent of the deficits varied between the different models. Deficits were strongest in hippocampus-lesioned and GluA1 knockout mice, while more subtle deficits but specific to problem solving were found in the medial prefrontal-lesioned mice, MK-801-treated mice, and in mice with striatal overexpression of D2 receptors. Data from this study demonstrate the utility of the puzzle box as an effective screening tool for executive functions in general and for schizophrenia mouse models in particular.

Difficulties of tracing health research funded by the European Union.

OBJECTIVE: European Union (EU) information from research projects, including key findings, should be available on the European Commission's Community Research and Development Information Service (CORDIS) database. We describe the results of the Health Research for Europe (HR4E) project which aimed to synthesize results of health research from the EU's Fifth and Sixth Framework Programmes (FP5 and FP6) of research. METHODS: Screening of titles and abstracts of all projects funded within FP5 and FP6 to identify health-related projects followed by allocation of such projects to one of the 47 themes of the European Union's Health Portal. Extraction of key findings relevant for policy and practice from data on the CORDIS database and, in a subset of 182 projects selected from five themes, attempted contact with project co-ordinators to obtain missing information. RESULTS: The information held on CORDIS was inadequate, with many fields not completed. Data were rarely updated after the project had been funded. Of the 182 attempts to contact co-ordinators, useful information was obtained in only 17% of cases, with many contact details missing or unverifiable. CONCLUSIONS: CORDIS does not meet its stated objectives of facilitating and disseminating EU research. There is a clear need to review the systems designed to manage the CORDIS platform.

The XVth World Congress of Psychiatric Genetics, October 7-11, 2007: Rapporteur summaries of oral presentations.

The World Congress of Psychiatric Genetics (WCPG) has become an annual event since the early 1990's sponsored by the International Society of Psychiatric Genetics (ISPG). Each year the latest published and unpublished findings are aired for discussion by representatives of the majority of research programs on this topic world-wide. The 2007 congress was held in New York City and attracted over 1000 researchers. The topics emphasized included results from whole genome association studies, the significance of copy number variation and the important contributions of epigenetic events to psychiatric disorders. There were over 20 oral sessions devoted to these and other topics of interest. Young investigator recipients of travel awards served as rapporteurs to summarize sessions and these summaries follow.

Neuronal neprilysin overexpression is associated with attenuation of Abeta-related spatial memory deficit.

Converging evidence links abnormally high brain concentrations of amyloid-beta peptides (Abeta) to the pathology of Alzheimer's disease (AD). Lowering brain Abeta levels, therefore, is a therapeutic strategy for the treatment of AD. Neuronal neprilysin upregulation led to increased degradation of Abeta, reduced the formation of Abeta-plaques and the associated cytopathology, but whether overexpression of neprilysin can improve cognition is unknown. We show that neuronal overexpression of neprilysin improved the Morris water maze memory performance in mice with memory deficits resulting from overexpression of the AD-causing mutated human amyloid precursor protein (APP). This improvement was associated with decreased brain levels of Abeta and with unchanged endoproteolytic processing of APP. These results provide the evidence that lowering of brain Abeta levels by increasing its degradation can improve cognitive functions in vivo, and suggest that increasing the activity of neprilysin in brain may be effective in preventing cognitive decline in AD.

Assessing reliability, heritability and general cognitive ability in a battery of cognitive tasks for laboratory mice.

This report includes the first sibling study of mouse behavior, and presents evidence for a heritable general cognitive ability (g) factor influencing cognitive batteries. Data from a population of male and female outbred mice (n = 84), and a replication study of male sibling pairs (n = 167) are reported. Arenas employed were the T-maze, the Morris water maze, the puzzle box, the Hebb-Williams maze, object exploration, a water plus-maze, and a second food-puzzle arena. The results show a factor structure consistent with the presence of g in mice. Employing one score per arena, this factor accounts for 41% of the variance in the first study (or 36% after sex regression) and 23% in the second, where this factor also showed sibling correlations of 0.17-0.21, which translates into an upper-limit heritability estimate of around 40%. Reliabilities of many tasks are low and consequently set an even lower ceiling for inter-arena or sibling correlations. Nevertheless, the factor structure is seen to remain fairly robust across permutations of the battery composition and the current findings fit well with other recent studies.

A comparison of wild-caught wood mice and bank voles in the Intellicage: assessing exploration, daily activity patterns and place learning paradigms.

Our previous work has revealed very high baseline neurogenesis in the dentate gyrus of wood mice as compared particularly to bank voles; a difference which may be related to learning capacity. This study explored whether the newly-developed Intellicage system could be used to compare these species in simple spatial learning paradigms. The Intellicage is essentially a group-housing cage that also allows continuous automatic recording of each individual's behaviour. Seven wild-caught bank voles (Clethrionomys glareolus) were compared with seven wild-caught long-tailed wood mice (Apodemus sylvaticus) in the Intellicage system over 9 days. During the first 90 min after entering the cage, the wood mice were substantially more exploratory than the bank voles (P = 0.003). Over subsequent days, both species showed nocturnal activity increases with voles being 3.7 times more active overall. In the spatial learning paradigms, there were significant species-by-time interactions with wood mice outperforming bank voles on both place learning (P = 0.027) and subsequent reversal (P = 0.006). Conclusions are firstly that the wood mice show superior learning abilities in this paradigm, and secondly that the Intellicage serves as a valuable cognitive testing arena for small wild rodents, or for circumstances where cognition must be compared independent of different responses to handling or novel environments.

X inactivation as a source of behavioural differences in monozygotic female twins.

Although members of monozygotic twin pairs are identical in genome sequence, they may differ in patterns of gene expression. One early and irreversible process affecting gene expression, which can create differences within pairs of female monozygotic twins, is X inactivation - one twin can express mainly paternally-received genes on the X chromosome while the other twin expresses mainly maternally-received genes. It follows that non-identical X chromosome expression may cause female monozygotic twins to correlate less strongly than male monozygotic twins on complex behavioural traits affected by X-linked loci. We tested this hypothesis using data from around 4000 same-sex twin pairs on 9 social, behavioural and cognitive measures at ages 2, 3 and 4. Consistent with our hypothesis, monozygotic males were generally more similar than monozygotic females. Three of four significant differences were in traits showing higher correlations in males than females, and these traits - prosocial behaviour, peer problems, and verbal ability - have all been proposed previously in the literature as being influenced by genes on the X chromosome. Interestingly, dizygotic twins showed the reverse pattern of correlations for similar variables, which is also consistent with the X inactivation hypothesis; taken together, then, our monozygotic and dizygotic results suggest the presence of quantitative trait loci on the X chromosome.