A large pericardial effusion and bilateral pleural effusions as the initial manifestations of Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is a condition characterized by recurrent febrile poly-serositis. Typical presentations of the disease include episodes of fever, abdominal pain and joint pains. Chest pain is a less common presentation. We report a case of FMF which presented with a large pericardial effusion and bilateral pleural effusions in a lady who had no positive family history and negative genetic testing.peer-reviewe

Fungal genomics challenges the dogma of name-based biosecurity

Microorganisms have inadvertently been spread via the global movement and trade of their substrates, such as animals, plants, and soil. This intercontinental exchange in the current era of globalisation has given rise to significant increases in the distribution of known pests and pathogens. Importantly, it has also resulted in many novel, emerging, infectious diseases. Biosecurity and quarantine, which aim to prevent the establishment of foreign or harmful organisms in a non-native area, are under significant pressure due to the massive increases in travel and trade. Traditionally, quarantine regulations have been implemented based on pathogens that already cause significant disease problems on congener hosts in other parts of the world (e.g., Q-bank, available at http://www.q-bank.eu). Well-known pathogens are described, named, and studied to determine their disease cycle, epidemiology, and impact. Their importance is assessed based on their risk of infection, establishment, and economic or environmental consequences. This then shapes phytosanitary practices.The Tree Protection Co-operative Programme (TPCP), THRIP initiative of the Department of Trade and Industry, Department of Science and Technology (DST)/ National Research Foundation (NRF), and Centre of Excellence in Tree Health Biotechnology (CTHB).http://www.plospathogens.orgam2016Forestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant PathologyPlant Scienc

2018: Art & Mobilities Network Inaugural Symposium Instant Journal (Peter Scott Gallery)

"Mobilities has been gaining momentum through networks, conferences, books, special issues, exhibitions and in the practices of artists, writers and curators. In recognition of this activity we are forming an Art & Mobilities network through which to consolidate, celebrate and develop this work.Inspired by the recent foregrounding of Mobility and the Humanities (Pearce & Merriman, 2018) and drawing on last November's successful Mobile Utopia Exhibition amongst others, the Centre for Mobilities Research (CEMORE) at Lancaster University are pleased to hold a UK Art & Mobilities Network Inaugural Symposium 2018 on the 3rd of July 2018. The aim of the symposium is to bring together people in the UK who are active in the field of mobilities and art in order to discuss the distinctive contribution that art makes to mobilities research and vice versa. We would be delighted if you can join us for this one-day event to help shape the network, particularly in the context of a fast-changing world, not just socio-politically but in terms of the place of art in the academy and vice versa. There are nearly 30 key international artists and researchers gathered on this day both locally and via Skype. We invite all participants in the symposium to bring with them an artwork, artefact, written statement or quote that can be displayed as a ‘pop up’ exhibition. These artefacts will be used during the day to focus discussion around different facets of mobilities and art." (Jen Southern, Kai Syng Tan, Emma Rose, Linda O'Keeffe Editors

Distinct molecular signatures of clinical clusters in people with type 2 diabetes:an IMI-RHAPSODY study

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous diseas

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes