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Reallocations of time between daily activities such as sleep, sedentary behavior and physical activity are differentially associated with markers of physical, mental and social health. An individual's most desirable allocation of time may differ depending on which outcomes they value most, with these outcomes potentially competing with each other for reallocations. We aimed to develop an interactive app that translates how self-selected time reallocations are associated with multiple health measures. We used data from the Australian Child Health CheckPoint study (n = 1685, 48% female, 11-12 y), with time spent in daily activities derived from a validated 24-h recall instrument, %body fat from bioelectric impedance, psychosocial health from the Pediatric Quality of Life Inventory and academic performance (writing) from national standardized tests. We created a user-interface to the compositional isotemporal substitution model with interactive sliders that can be manipulated to self-select time reallocations between activities. The time-use composition was significantly associated with body fat percentage (F = 2.66, P < .001), psychosocial health (F = 4.02, P < .001), and academic performance (F = 2.76, P < .001). Dragging the sliders on the app shows how self-selected time reallocations are associated with the health measures. For example, reallocating 60 minutes from screen time to physical activity was associated with -0.8 [95% CI -1.0 to -0.5] %body fat, +1.9 [1.4 to 2.5] psychosocial score and +4.5 [1.8 to 7.2] academic performance. Our app allows the health associations of time reallocations to be compared against each other. Interactive interfaces provide flexibility in selecting which time reallocations to investigate, and may transform how research findings are disseminated.

Heat flow measurements collected throughout the Auka and JaichMaa Ja'ag' hydrothermal vent fields in the central graben of the Southern Pescadero Basin, southern Gulf of California, indicate upflow of hydrothermal fluids associated with rifting dissipate heat in excess of 10 W/m2 around faults that have a few kilometers in length. Paradoxically, longer faults do not show signs of venting. Heat flow anomalies slowly decay to background values of ∼2 W/m2 at distances of ∼1 km from these faults following an inverse square-root distance law. We develop a near-fault model of heat transport in steady state for the Auka vent field based on the fundamental Green's function solution of the heat equation. The model includes the effects of circulation in fracture networks, and the lateral seepage of geothermal brines to surrounding hemipelagic sediments. We use an optimal fitting method to estimate the reservoir depth, permeability, and circulation rate. Independently derived constraints for the model, indicate the heat source is at a depth of ∼5.7 km; from the model, permeability and flow rates in the fracture system are ∼10−14 m2 and 10−6 m/s, respectively, and ∼10−16 m2 and 10−8 m/s in the basin aquitards, respectively. Model results point to the importance of fault scaling laws in controlling sediment-hosted vent fields and slow circulation throughout low permeability sediments in controlling the brine's chemistry. Although the fault model seems appropriate and straightforward for the Pescadero vents, it does seem to be the exception to the other known sediment-hosted vent fields in the Pacific.

Heat flow measurements collected throughout the Auka and JaichMaa Ja'ag' hydrothermal vent fields in the central graben of the Southern Pescadero Basin, southern Gulf of California, indicate upflow of hydrothermal fluids associated with rifting dissipate heat in excess of 10 W/m2 around faults that have a few kilometers in length. Paradoxically, longer faults do not show signs of venting. Heat flow anomalies slowly decay to background values of ∼2 W/m2 at distances of ∼1 km from these faults following an inverse square-root distance law. We develop a near-fault model of heat transport in steady state for the Auka vent field based on the fundamental Green's function solution of the heat equation. The model includes the effects of circulation in fracture networks, and the lateral seepage of geothermal brines to surrounding hemipelagic sediments. We use an optimal fitting method to estimate the reservoir depth, permeability, and circulation rate. Independently derived constraints for the model, indicate the heat source is at a depth of ∼5.7 km; from the model, permeability and flow rates in the fracture system are ∼10−14 m2 and 10−6 m/s, respectively, and ∼10−16 m2 and 10−8 m/s in the basin aquitards, respectively. Model results point to the importance of fault scaling laws in controlling sediment-hosted vent fields and slow circulation throughout low permeability sediments in controlling the brine's chemistry. Although the fault model seems appropriate and straightforward for the Pescadero vents, it does seem to be the exception to the other known sediment-hosted vent fields in the Pacific.

Heat flow measurements collected throughout the Auka and JaichMaa Ja'ag' hydrothermal vent fields in the central graben of the Southern Pescadero Basin, southern Gulf of California, indicate upflow of hydrothermal fluids associated with rifting dissipate heat in excess of 10 W/m2 around faults that have a few kilometers in length. Paradoxically, longer faults do not show signs of venting. Heat flow anomalies slowly decay to background values of ∼2 W/m2 at distances of ∼1 km from these faults following an inverse square-root distance law. We develop a near-fault model of heat transport in steady state for the Auka vent field based on the fundamental Green's function solution of the heat equation. The model includes the effects of circulation in fracture networks, and the lateral seepage of geothermal brines to surrounding hemipelagic sediments. We use an optimal fitting method to estimate the reservoir depth, permeability, and circulation rate. Independently derived constraints for the model, indicate the heat source is at a depth of ∼5.7 km; from the model, permeability and flow rates in the fracture system are ∼10−14 m2 and 10−6 m/s, respectively, and ∼10−16 m2 and 10−8 m/s in the basin aquitards, respectively. Model results point to the importance of fault scaling laws in controlling sediment-hosted vent fields and slow circulation throughout low permeability sediments in controlling the brine's chemistry. Although the fault model seems appropriate and straightforward for the Pescadero vents, it does seem to be the exception to the other known sediment-hosted vent fields in the Pacific.

Periodic revisions of the Global Heat Flow Database (GHFD) take place under the auspices of the International Heat Flow Commission (IHFC) of the International Association of Seismology and Physics of the Earth's Interior (IASPEI). A growing number of heat-flow values, advances in scientific methods, digitization, and improvements in database technologies all warrant a revision of the structure of the GHFD that was last amended in 1976. We present a new structure for the GHFD, which will provide a basis for a reassessment and revision of the existing global heat-flow data set. The database fields within the new structure are described in detail to ensure a common understanding of the respective database entries. The new structure of the database takes advantage of today's possibilities for data management. It supports FAIR and open data principles, including interoperability with external data services, and links to DOI and IGSN numbers and other data resources (e.g., world geological map, world stratigraphic system, and International Ocean Drilling Program data). Aligned with this publication, a restructured version of the existing database is published, which provides a starting point for the upcoming collaborative process of data screening, quality control and revision. In parallel, the IHFC will work on criteria for a new quality scheme that will allow future users of the database to evaluate the quality of the collated heat-flow data based on specific criteria.

Heat flow measurements collected throughout the Auka and JaichMaa Ja'ag' hydrothermal vent fields in the central graben of the Southern Pescadero Basin, southern Gulf of California, indicate upflow of hydrothermal fluids associated with rifting dissipate heat in excess of 10 W/m2 around faults that have a few kilometers in length. Paradoxically, longer faults do not show signs of venting. Heat flow anomalies slowly decay to background values of ∼2 W/m2 at distances of ∼1 km from these faults following an inverse square-root distance law. We develop a near-fault model of heat transport in steady state for the Auka vent field based on the fundamental Green's function solution of the heat equation. The model includes the effects of circulation in fracture networks, and the lateral seepage of geothermal brines to surrounding hemipelagic sediments. We use an optimal fitting method to estimate the reservoir depth, permeability, and circulation rate. Independently derived constraints for the model, indicate the heat source is at a depth of ∼5.7 km; from the model, permeability and flow rates in the fracture system are ∼10−14 m2 and 10−6 m/s, respectively, and ∼10−16 m2 and 10−8 m/s in the basin aquitards, respectively. Model results point to the importance of fault scaling laws in controlling sediment-hosted vent fields and slow circulation throughout low permeability sediments in controlling the brine's chemistry. Although the fault model seems appropriate and straightforward for the Pescadero vents, it does seem to be the exception to the other known sediment-hosted vent fields in the Pacific.

Herein, an isothermal padlock probe-based assay for the simple and portable detection of pathogens coupled with a glucose oxidase (GOx)-based electrochemical readout is reported. Infectious diseases remain a constant threat on a global scale, as in recurring pandemics. Rapid and portable diagnostics hold the promise to tackle the spreading of diseases and decentralising healthcare to point-of-care needs. Ebola, a hypervariable RNA virus causing fatalities of up to 90% for recent outbreaks in Africa, demands immediate attention for bedside diagnostics. The design of the demonstrated assay consists of a rolling circle amplification (RCA) technique, responsible for the generation of nucleic acid amplicons as RCA products (RCPs). The RCPs are generated on magnetic beads (MB) and subsequently, connected via streptavidin-biotin bonds to GOx. The enzymatic catalysis of glucose by the bound GOx allows for an indirect electrochemical measurement of the DNA target. The RCPs generated on the surface of the MB were confirmed by scanning electron microscopy, and among other experimental conditions such as the type of buffer, temperature, concentration of GOx, sampling and measurement time were evaluated for the optimum electrochemical detection. Accordingly, 125 μg mL−1 of GOx with 5 mM glucose using phosphate buffer saline (PBS), monitored for 1 min were selected as the ideal conditions. Finally, we assessed the analytical performance of the biosensing strategy by using clinical samples of Ebola virus from patients. Overall, this work provides a proof-of-concept bioassay for simple and portable molecular diagnostics of emerging pathogens using electrochemical detection, especially in resource-limited settings., QC 20200421

International Ocean Discovery Program (IODP) Expedition 385 drilled organic-rich sediments with sill intrusions on the flanking regions and in the northern axial graben in Guaymas Basin, a young marginal rift basin in the Gulf of California. Guaymas Basin is characterized by a widely distributed, intense heat flow and widespread off-axis magmatism expressed by a dense network of sill intrusions across the flanking regions, which is in contrast to classical mid-ocean ridge spreading centers. The numerous off-axis sills provide multiple transient heat sources that mobilize buried sedimentary carbon, in part as methane and other hydrocarbons, and drive hydrothermal circulation. The resulting thermal and geochemical gradients shape abundance, composition, and activity of the deep subsurface biosphere of the basin. Drill sites extend over the flanking regions of Guaymas Basin, covering a distance of ~81 km from the from the northwest to the southeast. Adjacent Sites U1545 and U1546 recovered the oldest and thickest sediment successions (to ~540 meters below seafloor [mbsf]; equivalent to the core depth below seafloor, Method A [CSF-A] scale), one with a thin sill (a few meters in thickness) near the drilled bottom (Site U1545), and one with a massive, deeply buried sill (~356–430 mbsf) that chemically and physically affects the surrounding sediments (Site U1546). Sites U1547 and U1548, located in the central part of the northern Guaymas Basin segment, were drilled to investigate a 600 m wide circular mound (bathymetric high) and its periphery. The dome-like structure is outlined by a ring of active vent sites called Ringvent. It is underlain by a remarkably thick sill at shallow depth (Site U1547). Hydrothermal gradients steepen at the Ringvent periphery (Holes U1548A–U1548C), which in turn shifts the zones of authigenic carbonate precipitation and of highest microbial cell abundance toward shallower depths. The Ringvent sill was drilled several times and yielded remarka

International Ocean Discovery Program (IODP) Expedition 385 drilled organic-rich sediments with sill intrusions on the flanking regions and in the northern axial graben in Guaymas Basin, a young marginal rift basin in the Gulf of California. Guaymas Basin is characterized by a widely distributed, intense heat flow and widespread off-axis magmatism expressed by a dense network of sill intrusions across the flanking regions, which is in contrast to classical mid-ocean ridge spreading centers. The numerous off-axis sills provide multiple transient heat sources that mobilize buried sedimentary carbon, in part as methane and other hydrocarbons, and drive hydrothermal circulation. The resulting thermal and geochemical gradients shape abundance, composition, and activity of the deep subsurface biosphere of the basin. Drill sites extend over the flanking regions of Guaymas Basin, covering a distance of ~81 km from the from the northwest to the southeast. Adjacent Sites U1545 and U1546 recovered the oldest and thickest sediment successions (to ~540 meters below seafloor [mbsf]; equivalent to the core depth below seafloor, Method A [CSF-A] scale), one with a thin sill (a few meters in thickness) near the drilled bottom (Site U1545), and one with a massive, deeply buried sill (~356–430 mbsf) that chemically and physically affects the surrounding sediments (Site U1546). Sites U1547 and U1548, located in the central part of the northern Guaymas Basin segment, were drilled to investigate a 600 m wide circular mound (bathymetric high) and its periphery. The dome-like structure is outlined by a ring of active vent sites called Ringvent. It is underlain by a remarkably thick sill at shallow depth (Site U1547). Hydrothermal gradients steepen at the Ringvent periphery (Holes U1548A–U1548C), which in turn shifts the zones of authigenic carbonate precipitation and of highest microbial cell abundance toward shallower depths. The Ringvent sill was drilled several times and yielded remarka

International Ocean Discovery Program (IODP) Expedition 385 drilled organic-rich sediments with sill intrusions on the flanking regions and in the northern axial graben in Guaymas Basin, a young marginal rift basin in the Gulf of California. Guaymas Basin is characterized by a widely distributed, intense heat flow and widespread off-axis magmatism expressed by a dense network of sill intrusions across the flanking regions, which is in contrast to classical mid-ocean ridge spreading centers. The numerous off-axis sills provide multiple transient heat sources that mobilize buried sedimentary carbon, in part as methane and other hydrocarbons, and drive hydrothermal circulation. The resulting thermal and geochemical gradients shape abundance, composition, and activity of the deep subsurface biosphere of the basin. Drill sites extend over the flanking regions of Guaymas Basin, covering a distance of ~81 km from the from the northwest to the southeast. Adjacent Sites U1545 and U1546 recovered the oldest and thickest sediment successions (to ~540 meters below seafloor [mbsf]; equivalent to the core depth below seafloor, Method A [CSF-A] scale), one with a thin sill (a few meters in thickness) near the drilled bottom (Site U1545), and one with a massive, deeply buried sill (~356–430 mbsf) that chemically and physically affects the surrounding sediments (Site U1546). Sites U1547 and U1548, located in the central part of the northern Guaymas Basin segment, were drilled to investigate a 600 m wide circular mound (bathymetric high) and its periphery. The dome-like structure is outlined by a ring of active vent sites called Ringvent. It is underlain by a remarkably thick sill at shallow depth (Site U1547). Hydrothermal gradients steepen at the Ringvent periphery (Holes U1548A–U1548C), which in turn shifts the zones of authigenic carbonate precipitation and of highest microbial cell abundance toward shallower depths. The Ringvent sill was drilled several times and yielded remarka

International Ocean Discovery Program (IODP) Expedition 385 drilled organic-rich sediments with sill intrusions on the flanking regions and in the northern axial graben in Guaymas Basin, a young marginal rift basin in the Gulf of California. Guaymas Basin is characterized by a widely distributed, intense heat flow and widespread off-axis magmatism expressed by a dense network of sill intrusions across the flanking regions, which is in contrast to classical mid-ocean ridge spreading centers. The numerous off-axis sills provide multiple transient heat sources that mobilize buried sedimentary carbon, in part as methane and other hydrocarbons, and drive hydrothermal circulation. The resulting thermal and geochemical gradients shape abundance, composition, and activity of the deep subsurface biosphere of the basin. Drill sites extend over the flanking regions of Guaymas Basin, covering a distance of ~81 km from the from the northwest to the southeast. Adjacent Sites U1545 and U1546 recovered the oldest and thickest sediment successions (to ~540 meters below seafloor [mbsf]; equivalent to the core depth below seafloor, Method A [CSF-A] scale), one with a thin sill (a few meters in thickness) near the drilled bottom (Site U1545), and one with a massive, deeply buried sill (~356–430 mbsf) that chemically and physically affects the surrounding sediments (Site U1546). Sites U1547 and U1548, located in the central part of the northern Guaymas Basin segment, were drilled to investigate a 600 m wide circular mound (bathymetric high) and its periphery. The dome-like structure is outlined by a ring of active vent sites called Ringvent. It is underlain by a remarkably thick sill at shallow depth (Site U1547). Hydrothermal gradients steepen at the Ringvent periphery (Holes U1548A–U1548C), which in turn shifts the zones of authigenic carbonate precipitation and of highest microbial cell abundance toward shallower depths. The Ringvent sill was drilled several times and yielded remarka

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Understanding the interaction between different combinatorial optimization problems is a challenging task of high relevance for numerous real-world applications including modern computer and memory architectures as well as high performance computing. Recently, the Traveling Thief Problem (TTP), as a combination of the classical traveling salesperson problem and the knapsack problem, has been introduced to study these interactions in a systematic way. We investigate the underlying non-linear Packing While Traveling Problem (PWTP) of the TTP where items have to be selected along a fixed route. We give an exact dynamic programming approach for this problem and a fully polynomial time approximation scheme (FPTAS) when maximizing the benefit that can be gained over the baseline travel cost. Our experimental investigations show that our new approaches outperform current state-of-the-art approaches on a wide range of benchmark instances.

Understanding the interaction between different combinatorial optimization problems is a challenging task of high relevance for numerous real-world applications including modern computer and memory architectures as well as high performance computing. Recently, the Traveling Thief Problem (TTP), as a combination of the classical traveling salesperson problem and the knapsack problem, has been introduced to study these interactions in a systematic way. We investigate the underlying non-linear Packing While Traveling Problem (PWTP) of the TTP where items have to be selected along a fixed route. We give an exact dynamic programming approach for this problem and a fully polynomial time approximation scheme (FPTAS) when maximizing the benefit that can be gained over the baseline travel cost. Our experimental investigations show that our new approaches outperform current state-of-the-art approaches on a wide range of benchmark instances.

Hydrothermal vent fields located in the gap between known sites in Guaymas Basin and 21°N on the East Pacific Rise were discovered on the Alarcón Rise and in southern Pescadero Basin. The Alarcón Rise spreading segment was mapped at 1-m resolution by an autonomous underwater vehicle. Individual chimneys were identified using the bathymetric data. Vent fields were interpreted as active from temperature anomalies in water column data and observed and sampled during remotely operated vehicle dives. The Ja Sít, Pericú, and Meyibó active fields are near the eruptive fissure of an extensive young lava flow. Vent fluids up to 360 °C from Meyibó have compositions similar to northern East Pacific Rise vents. The Tzab-ek field is 850 m west of the volcanic axis, and active chimneys rise up to 33 m above a broad sulfide mound. The inactive field is 10 km north-northeast along the rift axis, and most sulfide chimneys are enriched in Zn and associated elements that are transported at lower temperature compared to the more Cu-rich active fields. In southern Pescadero Basin, the Auka field is on the margin of a sediment-filled graben at 3,670-m depth. Discharging fluids are clear, contain hydrocarbons, and have neutral pH, elevated salinity, and temperatures up to 291 °C. They have deposited massive mounds of calcite with minor sulfide. The fluids are compositionally similar to those in Guaymas Basin, produced by high-temperature basalt-seawater interaction followed by reaction with sediment. The paucity of sulfide minerals suggests subsurface deposition of metals.

TLRs, including TLR4, have been shown to play a crucial role in cardiovascular inflammatory-based diseases. The main goal of this study was to determine the potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling. HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.7 macrophages and Angiotensin II-infused apolipoprotein E-deficient mice were in vitro and in vivo models, respectively. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 on TLR4 functional activity in response to bacterial LPS (in vitro) and endogenous ligands of sterile inflammation (in vitro and in vivo). Following activation of TLR4, in vitro and in vivo data revealed that FP7 inhibited p38 MAPK and p65 NF-kB phosphorylation associated with down-regulation of a number of TLR4-dependent pro-inflammatory proteins. In addition to inhibition of LPS-induced TLR4 signalling, FP7 negatively regulated TLR4 activation in response to ligands of sterile inflammation (hydroperoxide-rich oxidised LDL, in vitro and Angiotensin II infusion, in vivo). These results demonstrate the ability of FP7 to negatively regulate in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling both in humans and mice, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of vascular inflammatory diseases.

Hydrothermal vent fields located in the gap between known sites in Guaymas Basin and 21°N on the East Pacific Rise were discovered on the Alarcón Rise and in southern Pescadero Basin. The Alarcón Rise spreading segment was mapped at 1-m resolution by an autonomous underwater vehicle. Individual chimneys were identified using the bathymetric data. Vent fields were interpreted as active from temperature anomalies in water column data and observed and sampled during remotely operated vehicle dives. The Ja Sít, Pericú, and Meyibó active fields are near the eruptive fissure of an extensive young lava flow. Vent fluids up to 360 °C from Meyibó have compositions similar to northern East Pacific Rise vents. The Tzab-ek field is 850 m west of the volcanic axis, and active chimneys rise up to 33 m above a broad sulfide mound. The inactive field is 10 km north-northeast along the rift axis, and most sulfide chimneys are enriched in Zn and associated elements that are transported at lower temperature compared to the more Cu-rich active fields. In southern Pescadero Basin, the Auka field is on the margin of a sediment-filled graben at 3,670-m depth. Discharging fluids are clear, contain hydrocarbons, and have neutral pH, elevated salinity, and temperatures up to 291 °C. They have deposited massive mounds of calcite with minor sulfide. The fluids are compositionally similar to those in Guaymas Basin, produced by high-temperature basalt-seawater interaction followed by reaction with sediment. The paucity of sulfide minerals suggests subsurface deposition of metals.

TLRs, including TLR4, have been shown to play a crucial role in cardiovascular inflammatory-based diseases. The main goal of this study was to determine the potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling. HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.7 macrophages and Angiotensin II-infused apolipoprotein E-deficient mice were in vitro and in vivo models, respectively. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 on TLR4 functional activity in response to bacterial LPS (in vitro) and endogenous ligands of sterile inflammation (in vitro and in vivo). Following activation of TLR4, in vitro and in vivo data revealed that FP7 inhibited p38 MAPK and p65 NF-kB phosphorylation associated with down-regulation of a number of TLR4-dependent pro-inflammatory proteins. In addition to inhibition of LPS-induced TLR4 signalling, FP7 negatively regulated TLR4 activation in response to ligands of sterile inflammation (hydroperoxide-rich oxidised LDL, in vitro and Angiotensin II infusion, in vivo). These results demonstrate the ability of FP7 to negatively regulate in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling both in humans and mice, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of vascular inflammatory diseases.

N/A

Aims/hypothesis: We sought to evaluate the impact of diabetes mellitus on long-term outcome in patients with unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy. Methods: We carried out a prospective cohort study in 270 diabetic and 1163 non-diabetic patients with unstable angina and non-ST-segment elevation myocardial infarction. All patients underwent coronary angiography and, if appropriate, subsequent revascularisation within 24 hours of admission. The primary endpoint was all-cause mortality during follow-up for up to 60 months. Results: Diabetic patients had less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction. Percutaneous coronary intervention was performed in 53% of diabetic patients and 56% of non-diabetic patients. Coronary artery bypass grafting was done in 21% of diabetic patients and 12% of non-diabetic patients. In-hospital mortality (4.1% vs 1.3%; hazard ratio 3.47; 95% CI: 1.57 to 7.64; p=0.002) and long-term mortality (9.7% vs 4.9%; hazard ratio 2.11; 95% CI: 1.33 to 3.36; p=0.002) were significantly higher in diabetic patients. After adjustment for differences in baseline characteristics, diabetes mellitus was no longer an independent predictor of long-term mortality (hazard ratio 1.43; 95% CI: 0.74 to 2.78; p=0.292). Conclusions/interpretation: Diabetic patients treated with a very early invasive strategy for unstable angina and non-ST-segment elevation myocardial infarction have a higher in-hospital and long-term mortality that is largely explained by their less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957)

The 2014 guidelines are mainly concerned with the decision-making process regarding the revascularization policy for patients with coronary artery disease. The need for emergency or urgent revascularization in patients with ST segment elevationmyocardial infarction or non-ST segment elevation acute coronary syndromes is again highlighted in the current guidelines. The decision-making process is, however, more demanding for patients with stable coronary artery disease due to the variety of treatment options that are available. Indeed, patient-related factors may profoundly impact the decisionmaking process as long as existing evidence provides no clear survival advantages for one of the treatment options. An essential component of the multidisciplinary approach is the heart team, which is mainly made up of non-invasive cardiologists, cardiac surgeons and interventional cardiologists. Although the decision-making process should provide the best revascularization option for each patient, it should also support an efficient clinical workflow. For this reason, the interdisciplinary heart team is encouraged to formulate institutional protocols to guide revascularization strategies for common case scenarios. The institutional protocols are not only based on existing evidence as reflected in the current guidelines on myocardial revascularization but also on the specific experience and strengths of local departments of interventional cardiology and cardiac surgery.

Einleitung: Aktuelle Studien zeigen unzureichende Vitamin D3 Serumspiegel von Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereichs (HNSCC) und weisen auf einen Zusammenhang zu einer schlechteren Prognose hin. In dieser Studie haben wir sowohl die Prävalenz eines Vitamin D3 Mangels als auch die zytotoxische Aktivität der Natürlichen Killerzellen (ADCC) von HNSCC-Patienten vor und nach Vitamin D3 Substitution untersucht.Methoden: Es wurden Blutproben von 107 HNSCC-Patienten und 98 gesunden Probanden gesammelt und ihr 25-OH-Vitamin D Serumspiegel bestimmt. Für eine Auswahl beider Gruppen wurde zusätzlich die ADCC gegenüber FaDu-Zellen ermittelt. Dies erfolgte mit Hilfe eines Lactatdehydrogenase-Tests, jeweils mit oder ohne Zugabe von Cetuximab. Dieselben Probanden erhielten für 12 Wochen 2.000 IE Vitamin D3 pro Tag. Anschließend wurden Blutproben entnommen, um den Vitamin D3 Serumspiegel und die ADCC zu bestimmen.Ergebnisse: Die untersuchten HNSCC-Patienten wiesen im Vergleich zu den gesunden Probanden einen hoch signifikanten Vitamin D3 Mangel auf (p<0,0001). Ein Trend hin zu höheren Vitamin D3 Serumspiegeln in HPV-positiven Fällen war zu beobachten. Patienten mit Lymphknotenmetastasen (N+) zeigten signifikant niedrigere Vitamin D3 Serumspiegel, als Patienten ohne (N0; p=0,037). Eine Vitamin D3 Substitution führte zu einer signifikanten Zunahme der ADCC bei allen gesunden und der Hälfte der HNSCC-Probanden.Schlussfolgerungen: Der Vitamin D3 Serumspiegel von HNSCC-Patienten sollte aufmerksam beobachtet werden, da wir in dieser Studie einen deutlichen Mangel nachweisen konnten. Dieser Mangel scheint zusätzlich mit einer höheren Rate lymphogener Metastasierung und einer verminderten, NK-Zell vermittelten Zytotoxizität assoziiert zu sein.Der Erstautor gibt keinen Interessenkonflikt an.

The 2014 guidelines are mainly concerned with the decision-making process regarding the revascularization policy for patients with coronary artery disease. The need for emergency or urgent revascularization in patients with ST segment elevationmyocardial infarction or non-ST segment elevation acute coronary syndromes is again highlighted in the current guidelines. The decision-making process is, however, more demanding for patients with stable coronary artery disease due to the variety of treatment options that are available. Indeed, patient-related factors may profoundly impact the decisionmaking process as long as existing evidence provides no clear survival advantages for one of the treatment options. An essential component of the multidisciplinary approach is the heart team, which is mainly made up of non-invasive cardiologists, cardiac surgeons and interventional cardiologists. Although the decision-making process should provide the best revascularization option for each patient, it should also support an efficient clinical workflow. For this reason, the interdisciplinary heart team is encouraged to formulate institutional protocols to guide revascularization strategies for common case scenarios. The institutional protocols are not only based on existing evidence as reflected in the current guidelines on myocardial revascularization but also on the specific experience and strengths of local departments of interventional cardiology and cardiac surgery.

An der Entstehung von Restenose nach Herzkatheterbehandlung sind Interleukin 1 beta (IL-1 beta), Interleukin 6 (IL-6) und PDGF entscheidend beteiligt. Diese sind als Marker einer entzündlichen Interaktion zwischen koinkubierten MNC und HUVEC bekannt. Ziel war es, den Anstieg dieser Entzündungsmarker bei Koinkubation von HUVEC und MNC zu erfassen, und die Hemmung dieser entzündlichen Interaktion mittels der körpereigenen Zytokine IL-4, IL-10 und IL-13 zu analysieren. Durch Zugabe von IL-4 kann die Freisetzung von IL-6 und PDGF gehemmt werden. IL-10 hemmt die Freisetzung von IL-1 beta; und IL-6, IL-13 die PDGF Freisetzung. Es ist folglich möglich durch die Zytokine IL-4, IL-10 und IL-13 eine Entzündungsreaktion zu hemmen. Weitere Versuche sollen folgen um, die Wirkung dieser Zytokine auf die Restenoseentwicklung zu untersuchen., Interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and PDGF are highly participating on the origin of coronary in-stent restenosis after angioplasty. These interleukins are known to be markers, released by the inflammatory interaction in the coincubation of MNC and HUVEC. Measurement of these inflammatory markers, produced by coincubated HUVEC and MNC was done. Aim of the study was to examine the suppression of this interleukin-release after human cytokines IL-4, IL-10 and IL-13 have been added to the coincubation. With the addition of IL-4 to a coincubation of MNC and HUVEC the release of IL-6 and PDGF can be reduced. Adding IL-10 the release of IL-1 beta and IL-6 can also be reduced. Adding IL-13 a reduced release of PDGF was found. Concluding the results, IL-4, IL-10 and IL-13 suppress an inflammatory reaction when MNC and HUVEC get coincubated. Further trials should be done to analyse the effect of these cytokines on in-stent restenosis.

Im Rahmen dieser Dissertation wurde der Effekt des GPIIb/IIIa-Rezeptor-Blockers Abciximab auf die linksventrikuläre Funktion bei Patienten untersucht, denen nach einem akuten Myokardinfarkt und erfolgreicher Rekanalisation innerhalb von 48 Stunden nach dem Auftreten von Schmerzsymptomatik koronare Stents implantiert wurden. Die insgesamt 200 Patienten randomisierten wir in zwei Gruppen (Abciximab plus niedrig dosiertes Heparin oder Standardheparindosis ohne Abciximab). Sowohl unmittelbar nach dem Eingriff, als auch 14 Tage und sechs Monate danach bestimmte ich mit Hilfe der Centerline-Methode die regionale Wandbewegung in der Infarkt-Region und die globale Auswurffraktion. Sowohl die lokale als auch die globale linksventrikuläre Funktion waren nach 14 Tagen in der Abciximab-Gruppe signifikant besser. Nach 6 Monaten war die Änderung des Wandbewegungsindizes in dieser Gruppe immer noch signifikant höher., In this thesis the effect of GPIIb/IIIa-receptor blocker abciximab on the left ventricular function in acute myocardial infarction was investigated. Coronary stents were implanted in patients within 48 hours after appearance of infarction symptoms. 200 patients have been randomly allocated in two groups of therapy (standard-heparin and Abciximab plus low heparin dose). Immediately after intervention as well as 2 weeks and 6 months later the regional wall motion and the global ejection fraction have been measured with centreline method. The local as well as the global left ventricular function were after 2 weeks better in the abciximab group. After 6 months the improvement of wall motion index was in this group still higher.

Diese prospektive, randomisierte Studie prüfte den Einfluß dreier Fibrinogenrezeptorblocker, Abciximab, Tirofiban und Eptifibatide, auf Thrombozyten bei Patienten, die eine koronare Stentimplantation erhielten. Neben der Aggregation wurden Veränderungen am Fibrinogenrezeptor, Degranulation der Thrombozyten und Zellinteraktionen zwischen Plättchen und Monozyten gemessen. Die wichtigsten Ergebnisse dieser Studie sind, daß zwei Stunden nach Therapiebeginn zwischen den drei Substanzen in den klinisch empfohlenen Dosierungen keine signifikanten Unterschiede in Bezug auf ihre Wirkung auf die Thrombozytenfunktion ex vivo vorliegen., This prospective, randomized study compared the platelet effects of three glycoprotein IIb/IIIa antagonists, abciximab, tirofiban and eptifibatide, in patients untergoing coronary stent placement. We investigated the platelet aggregation, the expression of the glycoprotein IIb/IIIa receptor, the thrombocyte degranulation and interactions between monocytes and platelets. The major results of this study are that there were no significant differences in the antiplatelet effects ex vivo after 2 hours between the three drugs at currently recommended doses.

An der Entstehung von Restenose nach Herzkatheterbehandlung sind Interleukin 1 beta (IL-1 beta), Interleukin 6 (IL-6) und PDGF entscheidend beteiligt. Diese sind als Marker einer entzündlichen Interaktion zwischen koinkubierten MNC und HUVEC bekannt. Ziel war es, den Anstieg dieser Entzündungsmarker bei Koinkubation von HUVEC und MNC zu erfassen, und die Hemmung dieser entzündlichen Interaktion mittels der körpereigenen Zytokine IL-4, IL-10 und IL-13 zu analysieren. Durch Zugabe von IL-4 kann die Freisetzung von IL-6 und PDGF gehemmt werden. IL-10 hemmt die Freisetzung von IL-1 beta; und IL-6, IL-13 die PDGF Freisetzung. Es ist folglich möglich durch die Zytokine IL-4, IL-10 und IL-13 eine Entzündungsreaktion zu hemmen. Weitere Versuche sollen folgen um, die Wirkung dieser Zytokine auf die Restenoseentwicklung zu untersuchen., Interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and PDGF are highly participating on the origin of coronary in-stent restenosis after angioplasty. These interleukins are known to be markers, released by the inflammatory interaction in the coincubation of MNC and HUVEC. Measurement of these inflammatory markers, produced by coincubated HUVEC and MNC was done. Aim of the study was to examine the suppression of this interleukin-release after human cytokines IL-4, IL-10 and IL-13 have been added to the coincubation. With the addition of IL-4 to a coincubation of MNC and HUVEC the release of IL-6 and PDGF can be reduced. Adding IL-10 the release of IL-1 beta and IL-6 can also be reduced. Adding IL-13 a reduced release of PDGF was found. Concluding the results, IL-4, IL-10 and IL-13 suppress an inflammatory reaction when MNC and HUVEC get coincubated. Further trials should be done to analyse the effect of these cytokines on in-stent restenosis.

Objectives: The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such as atherosclerosis and aneurysm. The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development. Methods: Human umbilical vein endothelial cells (HUVEC) and Angiotensin II-induced experimental AAA development were our in vitro and in vivo models respectively. Western blotting, antibody array and ELISA approaches were used to explore the effect of IAXO-102 on TLR4 functional activity on two levels: modulation of TLR4-induced mitogen activated protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4 dependent proinflammatory proteins. Results: Following activation of TLR4, in vitro/in vivo data revealed that IAXO-102 inhibited MAPK and p65 NF-kB phosphorylation associated with down regulation of the expression of TLR4 and TLR4 dependent proinflammatory proteins. Furthermore, IAXO-102 decreased Angiotensin II-induced aortic expansion, rupture and incidence of AAA. Conclusions: These results demonstrate the ability of IAXO-102 to negatively regulate TLR4 signalling and to inhibit experimental AAA development, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of AAA.