Development, validation and implementation of biomarker testing in cardiovascular medicine state-of-the-art: Proceedings of the European Society of Cardiology - Cardiovascular Round Table.

Many biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance characteristics or fail to meet regulatory standards for approval. Despite their potential, new technologies have added to the complexities of successful translation into clinical practice. Biomarker discovery and implementation requires a standardised approach that includes: identification of a clinical need; identification of a valid surrogate biomarker; stepwise assay refinement, demonstration of superiority over current standard-of-care; development and understanding of a clinical pathway; and demonstration of real-world performance. Successful biomarkers should improve efficacy or safety of treatment, while being practical at a realistic cost. Everyone involved in cardiovascular healthcare, including researchers, clinicians, and industry partners, are important stakeholders in facilitating the development and implementation of biomarkers. This paper provides suggestions for a development pathway for new biomarkers, discusses regulatory issues and challenges, and suggestions for accelerating the pathway to improve patient outcomes. Real life examples of successful biomarkers-high sensitivity cardiac troponin (hs-cTn), T2* cardiovascular magnetic resonance (CMR) imaging, and echocardiography-are used to illustrate the value of a standardised development pathway in the translation of concepts into routine clinical practice

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory

Longitudinal Visuomotor Development in a Malaria Endemic Area: Cerebral Malaria and Beyond

Paediatric cerebral malaria is the most serious complication of Plasmodium falciparum infection. While the majority recover, long-term cognitive impairment has been highlighted as a significant and neglected problem. Persistent or serious deficits in processes such as attention or behavioural inhibition should be manifest in changes to performance on oculomotor tasks. Therefore we investigated the impact of cerebral malaria on the development of reflexive pro-saccades and antisaccades. In a longitudinal study, 47 children previously admitted with retinopathy-confirmed cerebral malaria (mean age at admission 54 months), were compared with 37 local healthy controls (mean ages at first study visit 117 and 110 months respectively). In each of three or four test sessions, over a period of up to 32 months, participants completed 100 prosaccade tasks and 100 antisaccade tasks. Eye movements were recorded using infrared reflectance oculography; prosaccade, correct antisaccade and error prosaccade latency, and antisaccade directional error rate were calculated. Hierarchical linear modelling was used to investigate the effect of age and the influence of cerebral malaria on these parameters. Data were also collected from an independent, older group (mean age 183 months) of 37 local healthy participants in a separate cross-sectional study. Longitudinal data exhibited the expected decrease in latency with age for all saccade types, and a decrease in the antisaccade directional error rate. Hierarchical linear modelling confirmed that age had a statistically significant effect on all parameters (p< = 0.001). However, there were no statistically significant differences between the cerebral malaria and control groups. Combining groups, comparison with the literature demonstrated that antisaccade directional error rate for the Malawi sample was significantly higher than expected, while latencies for all saccade types were indistinguishable from published. The high directional error rate was also confirmed in the older, healthy Malawian participants from the cross sectional study. Our observation of similar oculomotor performance in cerebral malaria and control groups at long follow-up periods suggests that cerebral malaria survivors are not at a generally increased risk of persistent cognitive deficits. Our data raise questions about the prevailing hypothesis that cerebral malaria has gross impacts on the development of processes such as attention and behavioural inhibition. More importantly, our novel finding of a clear difference in antisaccade performance between all of the Malawi participants and published data suggests that the Malawian paediatric population as a whole faces serious challenges to cognitive development beyond cerebral malaria

Focus in Dutch reading: An eye-tracking experiment with heritage speakers of Turkish

Contains fulltext : 175221.pdf (publisher's version ) (Open Access)This study examines whether heritage speakers of Turkish in the Netherlands interpret focus in written Dutch sentences differently from L1 speakers of Dutch (controls). Where most previous studies examined effects from the dominant L2 on the heritage language, we investigated whether there are effects from the weaker heritage language on the dominant L2. Dutch and Turkish differ in focus marking. Dutch primarily uses prosody to encode focus, whereas Turkish uses prosody and syntax, with a preverbal area for focused information and a postverbal area for background information. In written sentences no explicit prosody is available, which possibly enhances the role of syntactic cues in interpreting focus. An eye-tracking experiment suggests that, unlike the controls, the bilinguals associate the preverbal area with focus and the postverbal area with background information. These findings are in line with transfer from the weaker L1 to the dominant L2 at the syntax-discourse interface.17 p

High-frequency trading : A trading technique that requires development of the regulation and supervision

Högfrekvenshandel är en växande handelsteknik på de finansiella marknaderna i både Sverige och USA. Genom införandet av EU-direktivet MiFID II i svensk rätt, kommer denna handelsteknik att regleras för första gången i Sverige. Även i USA finns ett regleringsförslag som väntar på att införas. Högfrekvenshandel är något nytt, teknologiskt och kontroversiellt på den finansiella marknaden och dess fördelar och nackdelar debatteras flitigt. I denna uppsats utreds vad högfrekvenshandel egentligen är, hur sådan handel kommer att definieras i lagtext, vilka för- och nackdelar som finns, samt vad de nya regleringarna kommer att innebära. En av de frågor som besvaras i uppsatsen är huruvida ett förbud mot högfrekvenshandel bör införas på den svenska marknaden. Svaret på den frågan är nekande. Om ett förbud mot högfrekvenshandel skulle införas, skulle det innebära ett steg tillbaka i såväl den tekniska som den ekonomiska utvecklingen. Den nya svenska regleringen angående högfrekvenshandel är ett viktigt steg för att lagstiftningen ska följa den tekniska utvecklingen. Regleringen kommer dock inte att medföra några nya regler för aktörerna på den finansiella marknaden, utan medför endast att de regler angående högfrekvenshandel som redan finns genom börsernas självreglering blir svensk lag. I denna uppsats presenteras både den svenska och den amerikanska finansiella marknaden, anledningen till detta är att skapa en djupare förståelse för den svenska regleringen och utvecklingen på den svenska finansiella marknaden. Den andra frågan som besvaras i uppsatsen har ett komparativt ändamål och tar sikte på vilka skillnader som finns mellan den svenska och den amerikanska marknaden vad gäller högfrekvens- och algoritmhandel. Den andra frågan besvaras löpande i uppsatsen genom jämförelse mellan de aktuella marknaderna. Enligt min åsikt är det inte många skillnader angående högfrekvenshandel på de två olika marknaderna. Till exempel är de risker med högfrekvenshandel som framställs för den svenska marknaden i stor utsträckning samma risker som framställs för den amerikanska marknaden. Jag kan även konstatera att högfrekvenshandel möjliggjordes på liknande sätt på både den svenska och den amerikanska marknaden, nämligen genom regelförändringar som främjade teknologisk utveckling på de finansiella marknaderna