Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia - an observational study.

Understanding potential provocations of haemorrhage is important in a range of clinical settings, and particularly for people with abnormal vasculature. Patients with hereditary haemorrhagic telangiectasia (HHT) can report haemorrhage from nasal telangiectasia in real time, and suggested dietary factors may precipitate nosebleeds. To examine further, nosebleed severity, dietary supplement use, and blood indices were evaluated in an unselected group of 50 HHT patients recruited from a specialist UK service. Using the validated Epistaxis Severity Score, nosebleed severity ranged from 0 to 9.1 out of 10 (median 3.9). Using a Food Frequency Questionnaire, 24/50 (48%) participants reported use of dietary supplements in the previous year. A third (18/50; 36%) had used self prescribed, non-iron containing dietary supplements, ingesting between 1 and 3 different supplements each day. Eight (16%) used fish oils. Despite having more severe epistaxis (p = 0.012), the 12 iron supplement users had higher serum iron concentrations, and were able to maintain their red blood cell indices. In contrast, there was no evident benefit for the participants using non iron supplements. Furthermore, platelet counts and serum fibrinogen tended to be lower in fish oil/supplement users, and one fish oil user demonstrated reduced in vitro platelet aggregation. In conclusion, in this small study, a third of HHT patients used non-iron dietary supplements, and one in six ingested fish oils, unaware of their known anti-platelet activity. The scale of use, and potential of these "natural health supplements" to exacerbate nosebleeds has not been appreciated previously in HHT

Historical-institutionalist perspectives on the development of the EU budget system

The EU budget has only recently started to feature in theories of European integration. Studies typically adopt a historical-institutionalist framework, exploring notions such as path dependency. They have, however, generally been rather aggregated, or coarse-grained, in their approach. The EU budget has thus been treated as a single entity rather than a series of inter-linked institutions. This paper seeks to address these lacunae by adopting a fine-grained approach. This enables us to emphasize the connections that exist between EU budgetary institutions, in both time and space. We show that the initial set of budgetary institutions was unable, over time, to achieve consistently their treaty-based objectives. In response, rather than reform these institutions at potentially high political cost, additional institutions were layered on top of the extant structures. We thus demonstrate how some EU budgetary institutions have remained unchanged, whilst others have been added or changed over time

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

“A few sparks of inspiration”?: Analysing the outcomes of European Union cultural policy coordination

This article examines the outcomes of cultural policy coordination in the European Union using a case study of one policy priority in the 2011–2014 Work Plan for Culture. The Open Method of Coordination brings Member States together to exchange and cooperate on key policy priorities. Drawing on interviews with key actors as well as participant observation material, the article demonstrates the limited influence of the culture OMC on domestic policy, showing that domestic usage tends to be on the scale of individuals and organisations rather than Member State-wide. The article finishes by contextualising the outcomes, highlighting the constraints and challenges of intergovernmental coordination in fields where the EU holds a supporting competence

Divergence via Europeanisation: rethinking the origins of the Portuguese debt crisis

A founding myth of the euro was that profound economic convergence could be achieved across the core and periphery of Europe. Scholarship from within Comparative Political Economy (CPE) has compellingly pointed to this myth of convergence as the fundamental mistake of the euro project (Regan, “Imbalance of Capitalisms”). Economic and Monetary Union was applied across a range of incompatible varieties of capitalism with little appreciation for how difficult it would be for peripheral economies to overcome long-standing institutional stickiness. Yet, while institutional stickiness tells us much about the causes of declining competitiveness, it tells us much less about the origins of brand new patterns of debt-led growth. This article modifies this CPE account by drawing attention to the much overlooked case of Portugal. In contrast to CPE’s emphasis on institutional stickiness, this paper explores the ways in which negotiation of European integration has been generative of institutional transformation leading to debt-led growth in Portugal. By combining Europeanisation with CPE, this article shows that, far from an inability to do so, in the case of Portugal, it has been the attempt to ‘follow the rules’ of European Integration that explains its damaging patterns of debt-led growth

Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture

Mg2+ plays a vital role in platelet function, but despite implications for life-threatening conditions such as stroke or myocardial infarction, the mechanisms controlling [Mg2+](i) in megakaryocytes (MKs) and platelets are largely unknown. Transient receptor potential melastatin-like 7 channel (TRPM7) is a ubiquitous, constitutively active cation channel with a cytosolic alpha-kinase domain that is critical for embryonic development and cell survival. Here we report that impaired channel function of TRPM7 in MKs causes macrothrombocytopenia in mice (Trpm7(fl/fl-Pf4Cre)) and likely in several members of a human pedigree that, in addition, suffer from atrial fibrillation. The defect in platelet biogenesis is mainly caused by cytoskeletal alterations resulting in impaired proplatelet formation by Trpm7(fl/fl-Pf4Cre) MKs, which is rescued by Mg2+ supplementation or chemical inhibition of non-muscle myosin IIA heavy chain activity. Collectively, our findings reveal that TRPM7 dysfunction may cause macrothrombocytopenia in humans and mice

A Visit to Jakarta’s Bayt al-Qur’an

Nearly one hundred years ago the Dutch scholar C. Snouck Hurgronje, writing in the Netherlands Indies, published his article 'Islam and phonography' in which he described a contemporary interest in recordings of suras of the Qur'an made available for the phonograph. At the time, this innovation caused both interest and debate among Muslim scholars as to whether the use of this medium was Islamic, although it soon became accepted. The phonograph was later succeeded by the audiocassette. Now there are many interactive products available for the computer-literate Muslim- from various indexed and hyper-linked Qur'ans accessible through the internet, to CD-ROM packages designed for users who wish to learn to recite the Qur'an at home. Perhaps the most astounding aspect of the CD-ROM is its capacity to join the visual and aural experiences of the Qur'an. Yet, like its bakelite predecessor, the CDROM has evoked a modern debate over the application of such technology and the Islamic qualifications of its creators

Work and wellbeing: maximising the wellbeing of tomorrow’s workforce

Understanding wellbeing at work is key to implementing policies that optimise outcomes for employees and employers. People spend roughly a third of their waking hours at work, making it one of the most important domains of life to consider when seeking to improve wellbeing. Employee wellbeing has also been shown to shape organisational goals, including performance and retention. In this chapter, we focus on wellbeing from a subjective perspective - how employees evaluate their work and how they feel while doing it - and discuss its key drivers and consequences. We also summarise existing interventions aimed at improving wellbeing at work, noting that most take place at the organisational rather than the public policy level. We conclude by identifying areas for further research on measuring and improving wellbeing at work, as well as the key areas of focus for policymakers and organisational leaders who care about promoting employee wellbeing