Regional inequalities in self-reported conditions and non-communicable diseases in European countries: Findings from the European Social Survey (2014) special module on the social determinants of health

Background: Within the European Union (EU), substantial efforts are being made to achieve economic and social cohesion, and the reduction of health inequalities between EU regions is integral to this process. This paper is the first to examine how self-reported conditions and non-communicable diseases (NCDs) vary spatially between and within countries. Methods: Using 2014 European Social Survey (ESS) data from 20 countries, this paper examines how regional inequalities in self-reported conditions and NCDs vary for men and women in 174 regions (levels 1 and 2 Nomenclature of Statistical Territorial Units, ‘NUTS’). We document absolute and relative inequalities across Europe in the prevalence of eight conditions: general health, overweight/obesity, mental health, heart or circulation problems, high blood pressure, back, neck, muscular or joint pain, diabetes and cancer. Results: There is considerable inequality in self-reported conditions and NCDs between the regions of Europe, with rates highest in the regions of continental Europe, some Scandinavian regions and parts of the UK and lowest around regions bordering the Alps, in Ireland and France. However, for mental health and cancer, rates are highest in regions of Eastern European and lowest in some Nordic regions, Ireland and isolated regions in continental Europe. There are also widespread and consistent absolute and relative regional inequalities in all conditions within countries. These are largest in France, Germany and the UK, and smallest in Denmark, Sweden and Norway. There were higher inequalities amongst women. Conclusion: Using newly available harmonized morbidity data from across Europe, this paper shows that there are considerable regional inequalities within and between European countries in the distribution of self-reported conditions and NCDs

The Development Of A Modern Foraminiferal Data Set For Sea-Level Reconstructions, Wakatobi Marine National Park, Southeast Sulawesi, Indonesia

We collected modern foraminiferal samples to characterize the foraminiferal environments and investigate the role that temporal and spatial variability may play in controlling the nature and significance of foraminiferal assemblages of the mangroves of Kaledupa, Wakatobi Marine National Park, Southeast Sulawesi, Indonesia. The study of foraminiferal live and dead assemblages indicates that dead assemblages are least prone to vary in time and space, and furthermore, they accurately represent the subsurface assemblages that are the focus of paleoenvironmental reconstructions. Further analyses of the dead assemblages indicate a vertical zonation of foraminifera within the intertidal zone. Zone D-Ia is dominated by agglutinated foraminifera Arenoparrella mexicana, Miliammina fusca, M. obliqua and Trochammina inflata. Zone D-Ib has mixed agglutinated/calcareous assemblages with species such as T. inflata and Ammonia tepida. Zone D-II is dominated by numerous calcareous species including A. tepida, Discorbinella bertheloti, Elphidium advenum and Quinqueloculina spp. Zone D-Ia is found to be the most accurate sea-level indicator and its assemblages are omnipresent world-wide. Zones D-Ib and D-II are subject to both spatial and temporal variations which must be included in any sea-level reconstructions

Regional employment and individual worklessness during the Great Recession and the health of the working-age population: cross-national analysis of 16 European countries

Studies from single countries suggest that local labour market conditions, including rates of employment, tend to be associated with the health of the populations residing in those areas, even after adjustment for individual characteristics including employment status. The aim of this study is to strengthen the cross-national evidence base on the influence of regional employment levels and individual worklessness on health during the period of the Great Recession. We investigate whether higher regional employment levels are associated with better health over and above individual level employment. Individual level data (N = 23,078 aged 15–64 years) were taken from 16 countries (Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Netherlands, Norway, Poland, Portugal, Spain, Sweden and United Kingdom) participating in the 2014 European Social Survey. Regional employment rates were extracted from Eurostat, corresponding with the start (2008) and end (2013) of the Great Recession. Health outcomes included self-reported heart or circulation problems, high blood pressure, diabetes, self-rated health, depression, obesity and allergies (as a falsification test). We calculated multilevel Poisson regression models, which included individuals nested within regions, controlling for potential confounding variables and country fixed effects. After adjustment for individual level socio-demographic factors, higher average regional employment rates (from 2008 to 2013) were associated with better health outcomes. Individual level worklessness was associated with worsened health outcomes, most strongly with poor self-rated health. In models including both individual worklessness and the average regional employment rate, regional employment remained associated with heart and circulation problems, depression and obesity. There was evidence of an interaction between individual worklessness and regional employment for poor self-rated health and depression. The findings suggest that across 16 European countries, for some key outcomes, higher levels of employment in the regional labour market may be beneficial for the health of the local population

Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons

Feature-selective firing allows networks to produce representations of the external and internal environments. Despite its importance, the mechanisms generating neuronal feature selectivity are incompletely understood. In many cortical microcircuits the integration of two functionally distinct inputs occurs nonlinearly through generation of active dendritic signals that drive burst firing and robust plasticity. To examine the role of this processing in feature selectivity, we recorded CA1 pyramidal neuron membrane potential and local field potential in mice running on a linear treadmill. We found that dendritic plateau potentials were produced by an interaction between properly timed input from entorhinal cortex and hippocampal CA3. These conjunctive signals positively modulated the firing of previously established place fields and rapidly induced new place field formation to produce feature selectivity in CA1 that is a function of both entorhinal cortex and CA3 input. Such selectivity could allow mixed network level representations that support context-dependent spatial maps.Howard Hughes Medical InstituteRikagaku Kenkyūjo (Japan

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data

Abstracts from the NIHR INVOLVE Conference 2017

n/

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe