New molecular mediators in tumor angiogenesis

Angiogenesis is essential for tumor growth and progression. It has been demonstrated that tumor growth beyond a size 1 to 2 mm3 requires the induction of new vessels. Angiogenesis is regulated by several endogenous stimulators and inhibitors of endothelial cell migration, proliferation and tube formation. Under physiological conditions these mediators of endothelial cell growth are in balance and vessel growth is limited. In fact, within the angiogenic balance endothelial cell turnover is sufficient to maintain a functional vascular wall but does not allow vessel growth. Tumor growth an progression has successfully been correlated to the serum concentration of angiogenic mediators. Furthermore, the vascular density of tumor tissues could be correlated to the clinical course of the disease in several tumor entities. Within the last years several new mediators of endothelial cell growth have been isolated e.g. angiopoietin 1, angiopoietin 2, midkine, pleiotropin, leptin and maspin. In this review we discuss the mechanisms leading to tumor angiogenesis and describe some of the newer mediators of endothelial cell stimulation and inhibition

Re-Composing YouTube: Vernacular Musical Aesthetics in the Digital Age

YouTube features a wide array of multimodal musical figurations, including fan-made music videos, musical aestheticisations of pre-circulating content, and musical self-performances. Jonas Wolf explores open-ended forms of musical creative relay on YouTube, delving into formal, imitative, affective, and (non-)institutional aspects of networked media remix and (self-)aestheticisation. Beyond creating value for non-musical fields of discourse, this study is directed at filling a gap in a largely ocularcentric domain of study. It provides a concise theory of vernacular composition within our time's total digital archive that accounts for socio-aesthetic phenomena and their relation to systems of knowledge, control, and discourse

Regulated Expansion of Electricity Transmission Networks: The Effects of Fluctuating Demand and Wind Generation

We study the performance of different regulatory approaches for the expansion of electricity transmission networks in the light of realistic demand patterns and fluctuating wind power. In particular, we are interested in the relative performance of a combined merchant-regulatory mechanism compared to a cost-based and a merchant-like approach. In contrast to earlier research, we explicitly include both an hourly time resolution and fluctuating wind power, which allows representing demand in a very realistic way. This substantially increases the real-world applicability of results compared to previous analyses, which were based on simplifying assumptions. We show that a combined merchant-regulatory regulation, which draws on a cap over the two-part tariff of the Transco, leads to welfare outcomes far superior to the modeled alternatives. This result proves to be robust over a range of different cases and sensitivity analyses. We also find that the intertemporal rebalancing of the two-part tariff carried out by the Transco so as to expand the network is such that the fixed tariff part turns out to be relatively large compared to extension costs.Electricity, Regulation, Transmission Expansion, Wind Power

Testing Regulatory Regimes for Power Transmission Expansion with Fluctuating Demand and Wind Generation

Adequate extension of electricity transmission networks is required for integrating fluctuating renewable energy sources, such as wind power, into electricity systems. We study the performance of different regulatory approaches for network expansion in the context of realistic demand patterns and fluctuating wind power. In particular, we are interested in the relative performance of a combined merchant-regulatory price-cap mechanism compared to a cost-based and a non-regulated approach. We include both an hourly time resolution and fluctuating wind power. This substantially increases the real-world applicability of results compared to previous analyses. We show that a combined merchant-regulatory regulation, which draws upon a cap over the two-part tariff of the transmission company, leads to welfare outcomes superior to the other modeled alternatives. This result proves to be robust over a range of different cases, including such with large amounts of fluctuating wind power. We also evaluate the outcomes of our detailed model using the extension plans resulting from a simplified model based on average levels of load and wind power. We show that this distorts the relative performance of the different regulatory approaches.The final publication is available at Springer via http://dx.doi.org/10.1007/s11149-014-9260-

Myokarditis und Sport – Untersuchung der Zusammenhänge anhand einer prospektiven klinischen Studie

Objectives: Myocarditis, defined as an inflammatory and necrotizing, non-ischaemic disease of the cardiac musculature, is considered as one of the most common causes of sudden cardiac death. Elite athletes seem to have an increased risk for (viral) infection and subsequent myocarditis due to increased exposure to pathogens or impaired immune systems. On the other hand, long periods of sedentary behaviour or sports restrictions after myocarditis may lead to a negative impact on cardiovascular health in later life. The European Society of Cardiology (ESC) provides recommendations regarding the return to sports after myocarditis, which we wanted to evaluate prospectively for their safety, feasibility, and outcome. Thereby, the influence of physical activity on the progression of myocarditis should be investigated in particular. Design and Methods: Every myocarditis patient with the capability to perform Cardio-Pulmonary Exercise Testing (CPET) who received treatment in our department was included in the study. Diagnostic criteria involved elevated cardiac biomarkers or an abnormal electrocardiogram (ST-elevation or T-wave inversion). Depending on the clinical severity of the disease, all received further examinations according to the ESC guidelines. These included transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (cMRI), as well as CPET at least once immediately prior to resumption of exercise. Observations and Results: 14 patients (twelve males and two females, average age of 15,6 years) with diagnosed myocarditis participated. None of the patients had a relapse of myocarditis or suffered fatal complications. Prior to the diagnosis, five patients (36%) participated in competitive sports on a regular basis. There was no difference in the clinical outcome between the competitive sports cohort and their sedentary counterparts. During the course of disease, the investigated parameters (Electrocardiogram, TTE, cMRI, CPET) of all patients had shown improvement at large. Proceeding physical activity during an ongoing symptomatic infection at the onset of myocarditis was associated with worse initial clinical findings (significantly more late gadolinium enhancement and impaired wall movement at initial cMRI, significantly higher NT-pro BNP and VE/VCO2 at initial CPET). However, the latter did not implicate a worse clinical outcome. Conclusions: In this study, the clinical implementation of the ESC recommendations regarding the return to sports after myocarditis was shown to be safe and without complications. At the end of the observation period, the overall cardiopulmonary fitness seemed not to be impaired through the imposed sports restrictions. The cohort showed consistent resumption of their habitual sporting activities one year after the onset of the myocarditis. An active lifestyle as well as competitive sports could not be identified as negative prognostic factors. Proceeding physical activity during an ongoing symptomatic infection at the onset of myocarditis seemed to impair the initial clinical stadium of the disease. Therefore, physical activity should not be performed during symptomatic (respiratory) infections in the presence of generalized symptoms (fever, fatigue) or symptoms below the upper respiratory tract or with elevated inflammation parameters. Physical activity can be resumed safely two to three days after the disappearing of the latter symptoms.Hintergrund und Ziele: Die Myokarditis, eine inflammatorische und nekrotisierende Erkrankung der Herzmuskulatur, ist eine der häufigsten Ursachen des plötzlichen Herztodes. Durch immunsuppressive Prozesse nach intensiver sportlicher Aktivität scheinen Leistungssportler:innen ein erhöhtes Risiko für (virale) Infekte und dadurch möglicherweise auch für die Ausbildung einer Myokarditis zu haben. Im Kontrast dazu kann ein inaktiver Lebensstil und ein primär im Sitzen verbrachter Tagesablauf negative Auswirkungen auf die kardiovaskuläre Gesundheit zur Folge haben. Sportverbote im Rahmen der Nachsorge einer Myokarditis könnten diesen Effekt zusätzlich verstärken. Die europäische Fachgesellschaft für Kardiologen (ESC) hat 2019 Empfehlungen zur Rückkehr zum Sport nach einer Myokarditis veröffentlicht. In der folgenden Studie sollten diese anhand eines prospektiven Studienkollektivs hinsichtlich ihrer Sicherheit, Durchführbarkeit sowie dem klinischen Endergebnis beurteilt und besonders der Einfluss von Sport auf die Progression der Erkrankung beobachtet werden. Methoden (Patient:innen, Material und Untersuchungsmethoden): Alle Patient:innen mit diagnostizierter Myokarditis, die in unserer Klinik vorstellig wurden und zur Spiroergometrie fähig waren, wurden in die Studie eingeschlossen. Als primäre Diagnosekriterien galten erhöhte kardiale Biomarker im Serum oder relevante Veränderungen (ST-Strecken Hebung oder T-Wellen Inversion) im Elektrokardiogramm (EKG). Alle Patient:innen erhielten entsprechend der ESC Empfehlungen weiterführende Untersuchungen in Abhängigkeit vom klinischen Schweregrad der Erkrankung. Diese Untersuchungen beinhalteten die Durchführung einer Echokardiografie und kardiovaskulären Magnetresonanztomografie (cMRT), sowie eine mindestens einmalige Teilnahme an einer Spiroergometrie vor der Wiederaufnahme der sportlichen Aktivität. Ergebnisse und Beobachtungen: 14 Patient:innen (zwölf männlich, zwei weiblich, Durchschnittsalter von 15,6 (± 3,6) Jahren) wurden in die Studie eingeschlossen. Es kam während dem gesamten Beobachtungszeitraum zu keinem Todesfall oder Krankheitsrezidiv. Fünf (36%) der Patient:innen nahmen im Vorfeld der Erkrankung regelmäßig an Wettkampfsport teil. Es zeigte sich kein Unterschied hinsichtlich des klinischen Outcomes zwischen der Subgruppe der Wettkampfsportler:innen und ihrem Gegenpart. Die klinischen Parameter (EKG, Echokardiografie, cMRT, Spiroergometrie) der Gesamtkohorte verbesserten sich im Krankheitsverlauf zunehmend. Die Ausübung von sportlicher Aktivität während einer symptomatischen Infektion zu Beginn der Myokarditis hatte die Ausbildung eines initial schwereren Krankheitsbildes zur Folge (signifikant häufiger Late-Gadolinium-Enhancements und Wandbewegungsstörungen in der initialen cMRT, signifikant erhöhtes NT-pro BNP und VE/VCO2 in der initialen Spiroergometrie). Das klinische Outcome wurde dadurch jedoch nicht beeinträchtigt. (Praktische) Schlussfolgerungen und Diskussion: In der vorliegenden Studie konnten die Empfehlungen der ESC zur Wiederaufnahme der sportlichen Aktivität nach einer Myokarditis sicher und komplikationsfrei in die klinische Praxis implementiert werden. Unter dem anhand der ESC Empfehlungen verordneten Sportverbot wurde die kardiovaskuläre Fitness im Beobachtungszeitraum nicht signifikant schlechter. Es konnte verglichen mit dem Zeitraum vor der Erkrankung keine Veränderung des Sportverhaltens ein Jahr nach Diagnosestellung der Myokarditis festgestellt werden. Ein aktiver Lebensstil und die Ausübung von Wettkampfsport waren kein negativ prognostischer Faktor für einen schwereren Krankheitsverlauf. Im Gegensatz dazu schien Sport während einer symptomatischen Infektion zu Beginn der Myokarditis das initiale klinische Stadium der Myokarditis zu beeinträchtigen. Demnach sollte während einer symptomatischen (respiratorischen) Infektion bei erhöhten Entzündungswerten oder dem Auftreten von generalisierten Symptomen (Fieber, Abgeschlagenheit) sowie Symptomen unterhalb der Halsregion keinerlei sportliche Aktivität ausgeübt werden. Sportliche Aktivitäten können jedoch zwei bis drei Tage nach dem Abklingen der oben genannten Symptome sicher wieder aufgenommen werden

Fases pré-analítica, analítica e pós-analítica no monitoramento laboratorial da anticoagulação com antagonistas da vitamina K

A trombose é uma doença caracterizada por eventos de hipercoagulabilidade. A terapêutica anticoagulante oral com antagonistas da vitamina K (AVKs) é amplamente indicada para prevenção e/ou controle de distúrbios da coagulação. O manuseio de administração dos AVKs é difícil devido à complexidade da definição da dose. Em geral, o monitoramento de indivíduos submetidos à terapêutica com AVK é realizado pela determinação do tempo de protrombina, em que se avalia o grau de anticoagulação através do coeficiente internacional normatizado. Invariavelmente, o fluxo do processamento laboratorial, que compreende as fases pré-analítica, analítica e pós-analítica, é importante para a fidedignidade dos resultados, repercutindo na conduta médica de forma determinante. O objetivo deste estudo foi a realização de uma revisão da literatura científica descritiva utilizando bases de dados eletrônicos para busca de materiais científicos, como Google Scholar, MEDLINE, LILACS, PubMed, SciELO e Science Direct. Abordamos alguns aspectos relacionados ao fluxo analítico da monitoração laboratorial em um laboratório de análises clínicas. Em conclusão, é necessária uma apropriada condução das fases analíticas para que seja possível o sucesso terapêutico com uso dos AVKs. Palavras-chave: Tempo de protrombina; coeficiente internacional normatizado; fases analítica

Power System Transformation toward Renewables: Investment Scenarios for Germany

We analyze distinctive investment scenarios for the integration of fluctuating renewables in the German power system. Using a combined model for dispatch, transmission, and investment, three different investment options are considered, including gas-fired power plants, pumped hydro storage, and transmission lines. We find that geographically optimized power plant investments dominate in the reference scenarios for 2024 and 2034. In scenarios with decreasedrenewable curtailment, storage and transmission requirements significantly increase. In an alternative scenario with larger investments into storage, system costs are only slightly higher compared to the reference; thus, considering potential system values of flexible pumped hydro storage facilities that are not included in the optimization, a moderate expansion of storage capacities appears to be a no-regret strategy from a system perspective. Additional transmission and storage investments may not only foster renewable integration, but also increase the utilization of emission-intensive plants. A comparison of results for 2024 and 2034 indicates that this is only a temporary effect. In the long run, infrastructure investments gain importance in the context of an ongoing energy transition from coal to renewables. Because of long lead times, planning and administrative procedures for large-scale projects should start early