Why the UK must trigger Article 50 immediately

Sebastian KoehlerDespite the UK’s referendum on 23 June, David Cameron has so far not decided to trigger Article 50 of the Lisbon Treaty, which outlines how a country can voluntarily leave the EU. Sebastian Koehler argues that this process should not be delayed any further given the uncertainty which is damaging the UK economy. He writes that while Britain remains an EU member state, the country is now effectively marginalised from EU decision-making and has little to gain from taking longer than need be to negotiate its exit

Is 24/7 remote patient management in heart failure necessary? Results of the telemedical emergency service used in the TIM‐HF and in the TIM‐HF2 trials

Aims: Telemedical emergency services for heart failure (HF) patients are usually provided during business hours. However, many emergencies occur outside of business hours. This study evaluates if a 24/7 telemedical emergency service is needed for the remote management of high-risk HF patients. Methods: and results The study included 1119 patients merged from the TIM-HF and TIM-HF2 trials [age 69 +/- 11, 73% male, left ventricular ejection fraction 37% +/- 13, 557 New York Heart Association (NYHA) II/562 NYHA III]. Patients received a 24/7 physician-guided emergency service provided by the telemedical centre (TMC) in addition to remote management within business hours. During emergency calls, patient status, symptoms, electronic patient record, and instant telemonitoring data were evaluated by the TMC physician. Following diagnosis, patients were referred for hospital admission or instructed to stay at home. Apart from the TMC, patients could place a call to the public emergency service at any time. Seven hundred sixty-eight emergency calls were placed over 1383 patient years (0.56 calls/patient year). Five hundred twenty-six calls (69%) occurred outside business hours. There were 146 (19%) emergency calls for worsening HF, 297 (39%) other cardiovascular, and 325 (42%) non-cardiac causes, with a similar pattern inside and outside business hours. Of the 1119 patients, 417 (37%) placed at least one emergency call. Patients with NYHA Class III, higher N-terminal prohormone of brain natriuretic peptide (>1.400 pg/mL) levels, ischaemic aetiology of HF, implanted defibrillator, and impaired renal function had a higher probability of placing emergency calls. During study follow-up, patients who made an emergency call had a higher all-cause mortality (22% vs. 11%, P = 0.007 in TIM-HF; 16% vs. 4%, P < 0.001 in TIM-HF2) and more unplanned hospitalizations (324 vs. 162, P < 0.001 in TIM-HF; 545 vs. 180, P < 0.001 in TIM-HF2). Of the total 1,211 unplanned hospital admissions, 492 (41%) were initiated by a patient emergency call. Three hundred seventy-nine calls (49%) were placed to the TMC, whereas 389 calls (51%) were made to the public emergency service. Three hundred twenty-six (84%) of the calls to the public emergency service resulted in acute hospitalizations. The TMC initiated 202 (53%) hospital admissions; 177 (47%) patients were advised to stay at home. All patients that remained at home were alive during a prespecified safety period of 7 days post-call. Diagnoses made by the TMC physician were confirmed in 83% of cases by the hospital. Conclusion: A telemedical emergency service for high-risk HF patients is safe and should operate 24/7 to reduce unplanned hospitalizations. Emergency calls could be considered as a marker for higher morbidity and mortality

Este é um Caminho ou um Atalho? desemprego e turnout no comportamento eleitoral dos portugueses no sentido da Europa (1987-2014)

Quando no dia 19 de Julho de 1987 se realizaram as primeiras eleições para o Parlamento Europeu em território nacional, nada poderia prever que depois de quase trinta anos o sentimento português em relação à União Europeia (UE) seria tão distinto do de então. Alvo de intervenção externa desde 2011, Portugal encontra-se, ainda, a lutar contra os efeitos que a crise do subprime gerou, resultado da crise das dívidas soberanas europeias. A percentagem na taxa de desemprego atual prova bem a devastação económica que o país teve que lidar nos últimos anos. Curiosamente, e apesar de parecer intuitivamente contraditório, a participação nas urnas, em especial nas eleições para o Parlamento Europeu de 2014, não registraram valores de turnout tão baixos como expectável. Portugal é quase sempre apresentado, em estudos comparativos, como tendo uma baixa participação política. Todavia, neste momento de crise e de desencantamento com a UE tal não se manifesta pelo aumento da abstenção. Porque é que isto acontece? Esta dúvida leva-nos a alguns pontos recentemente desenvolvidos a partir da literatura sobre turnout. Estes aspectos indicam o caminho no sentido dos efeitos provenientes da relação entre variáveis até agora não debatidas. Nessa linha de pensamento questionamos como é que o desemprego afeta o turnout? Mais especiicamente, como é que isto ocorre ao nível regional? E nessa senda, como é que o efeito decorrente da relação entre desemprego e turnout é condicionado pela intervenção da troika nos assuntos do Estado português

[I] Localised, ephemeral grounding of the Fimbul Ice Shelf, East Antarctica, as revealed from tidally modulated cryoseismicity

The Tenth Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 4 Dec. / 3F Seminar room, National Institute of Polar Researc

Possible Consequences for TGF-β1 Signaling

Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet. Examining the interaction of all components of the TGF-β1:receptor complex with sHA by surface plasmon resonance, we could show that highly sulfated HA (sHA3) blocks binding of TGF-β1 to its TGF-β receptor-I (TβR-I) and -II (TβR-II). However, sequential addition of sHA3 to the TβR-II/TGF-β1 complex led to a significantly stronger recruitment of TβR-I compared to a complex lacking sHA3, indicating that the order of binding events is very important. Molecular modeling suggested a possible molecular mechanism in which sHA3 could potentially favor the association of TβR-I when added sequentially. For the first time bioactivity of TGF-β1 in conjunction with sHA was investigated at the receptor level. TβR-I and, furthermore, Smad2 phosphorylation were decreased in the presence of sHA3 indicating the formation of an inactive signaling complex. The results contribute to an improved understanding of the interference of sHA3 with TGF-β1:receptor complex formation and will help to further improve the design of functional biomaterials that interfere with TGF-β1-driven skin fibrosis

Earthworm diversity and ecosystem services in agriculture – Choosing appropriate taxon indicators and measurements

Agriculture and biodiversity are strongly linked. Whilst agriculture is a main driver impacting biodiversity, farmers could benefit from ecosystem services linked to biodiversity. Hence, indicators of functional biodiversity are needed. However, finding correct indicator values is not trivial. Earthworms were sampled on nine German farms with a combined method. In total 3205 earthworms from 10 species were collected. Six measurements applicable as taxon indicators were calculated for the data.Keywords: soil diversity, interpolation, extrapolation, biodiversity indices, biodiversity estimator

The influence of disease categories on gene candidate predictions from model organism phenotypes

Background The molecular etiology is still to be identified for about half of the currently described Mendelian diseases in humans, thereby hindering efforts to find treatments or preventive measures. Advances, such as new sequencing technologies, have led to increasing amounts of data becoming available with which to address the problem of identifying disease genes. Therefore, automated methods are needed that reliably predict disease gene candidates based on available data. We have recently developed Exomiser as a tool for identifying causative variants from exome analysis results by filtering and prioritising using a number of criteria including the phenotype similarity between the disease and mouse mutants involving the gene candidates. Initial investigations revealed a variation in performance for different medical categories of disease, due in part to a varying contribution of the phenotype scoring component. Results In this study, we further analyse the performance of our cross-species phenotype matching algorithm, and examine in more detail the reasons why disease gene filtering based on phenotype data works better for certain disease categories than others. We found that in addition to misleading phenotype alignments between species, some disease categories are still more amenable to automated predictions than others, and that this often ties in with community perceptions on how well the organism works as model. Conclusions In conclusion, our automated disease gene candidate predictions are highly dependent on the organism used for the predictions and the disease category being studied. Future work on computational disease gene prediction using phenotype data would benefit from methods that take into account the disease category and the source of model organism data

Exposure to Household Air Pollution from Biomass Cookstoves and Blood Pressure Among Women in Rural Honduras: A Cross‐Sectional Study

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed cross‐sectional associations of 24‐hour mean concentrations of personal and kitchen fine particulate matter (PM2.5), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleaner‐burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24‐hour PM2.5 concentrations of 126 μg/m3 (77) and 360 μg/m3 (374), while Justa stove users’ exposures were 66 μg/m3 (38) and 137 μg/m3(194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7‐4.3) per unit increase in natural log‐transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3‐8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0‐2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups