Feasibility of the Engager™ aortic transcatheter valve system using a flexible over-the-wire design

OBJECTIVES The aim was to investigate the safety and feasibility of the redesigned Engager™ transcatheter aortic valve implantation (TAVI) system. METHODS Transapical aortic valve implantation with the Engager™ valve prosthesis was intended in 11 patients, and performed in 10. Endpoints were defined according to the valve academic research consortium recommendations for reporting outcomes of TAVI in clinical trials. RESULTS All 10 patients were implanted successfully. No devicerelated or delivery system complications like coronary obstruction or aortic dissection emerged. One patient (10%) died from non-device-related reasons at post-operative day 23 of multi-organ failure. The invasively measured peak-to-peak gradient after valve implantation was 7.1±3.5mmHg. In 90%, there was no or only trivial (≤grad I) aortic regurgitation due to paravalvular leakage. In 10% of the patients, aortic regurgitation grade I-II was observed. At 30-day follow up, the mean gradient was 15.6±4.9mmHg, and no more than a mild transvalvular and paravalvular aortic regurgitation was seen as assessed by transthoracic echocardiography. CONCLUSIONS Application of the Engager™ TAVI system is safe and feasible. Prosthesis deployment in an anatomically correct position was facilitated by the design of the valve prosthesis and was successful in all patients. No device or delivery-system-related complications emerged. Safety and feasibility endpoints were met. Good results concerning the aortic valve performance after implantation and at 30-day follow up were ascertained. These results encouraged the start of a European Pivotal trial including patients to dat

Future observational and modelling needs identified on the basis of the existing shelf data

NOWESP has compiled a vast quantity of existing data from the North-West European Shelf. Such a focused task is without precedence. It is now highly recommended that one, or a few national and international data centres or agencies should be chosen and properly supported by the EU, where all available observational data, including the NOWESP data, are collected, stored, regularly updated by the providers of the data, and made available to the researchers. International agreement must be reached on the quality control procedures and quality standards for data to be stored in these data bases. Proper arrangements should be made to preserve the economic value of the data for their "owners" without compromising use of the data by researchers or duplicating data collecting efforts. The continental shelf data needed are concentration fields of temperature, salinity, nutrients, suspended matter and chlorophyll, which can be called "climatological" fields. For this purpose at least one monthly survey on the whole European shelf is needed at least during five years, with a proper spatial resolution e.g. 1 degree by 1 degree, and at least in those areas where climatological data are now totally lacking. From the modelling point of view an alternative would be the availability of data from sufficiently representative fixed stations on the shelf, with weekly sampling for several years

A simulation-based phantom model for generating synthetic mitral valve image data-application to MRI acquisition planning

PURPOSE: Numerical phantom methods are widely used in the development of medical imaging methods. They enable quantitative evaluation and direct comparison with controlled and known ground truth information. Cardiac magnetic resonance has the potential for a comprehensive evaluation of the mitral valve (MV). The goal of this work is the development of a numerical simulation framework that supports the investigation of MRI imaging strategies for the mitral valve. METHODS: We present a pipeline for synthetic image generation based on the combination of individual anatomical 3D models with a position-based dynamics simulation of the mitral valve closure. The corresponding images are generated using modality-specific intensity models and spatiotemporal sampling concepts. We test the applicability in the context of MRI imaging strategies for the assessment of the mitral valve. Synthetic images are generated with different strategies regarding image orientation (SAX and rLAX) and spatial sampling density. RESULTS: The suitability of the imaging strategy is evaluated by comparing MV segmentations against ground truth annotations. The generated synthetic images were compared to ones acquired with similar parameters, and the result is promising. The quantitative analysis of annotation results suggests that the rLAX sampling strategy is preferable for MV assessment, reaching accuracy values that are comparable to or even outperform literature values. CONCLUSION: The proposed approach provides a valuable tool for the evaluation and optimization of cardiac valve image acquisition. Its application to the use case identifies the radial image sampling strategy as the most suitable for MV assessment through MRI

Thermohaline forcing and interannual variability of northwestern inflows into the northern North Sea

A long-established, 127 km-long hydrographic section in the northern North Sea at 59.28°N that runs from the eastern coast of Orkney (2.23°W) to the central North Sea (0°) crosses the path of the main inflows of Atlantic water. Data from 122 occupations between 1989 and 2015 are examined to determine the annual cycle and long-term trends of temperature, salinity and depth-varying geostrophic flow across the section. In an average year, the geostrophic flow referenced to the seafloor is at its narrowest (40 km) in winter, during which time it is driven by the strong horizontal salinity gradient; the horizontal temperature gradient is very weak. Velocity exceeds 4 cm s−1, but transport is at a minimum (0.11 Sv). In the deeper water in the east of the section, thermal stratification develops throughout summer and persists until October, whereas the west is tidally mixed all year. The bottom temperature gradient becomes the primary driver of the geostrophic flow, which is fastest (9 cm s−1) in September and broadest (100 km) in October. Maximum transport (0.36 Sv) occurs in October. Throughout the summer, the horizontal salinity gradient weakens, as does its contribution to the flow. However, it nevertheless acts to broaden the flow west of the location of the strongest horizontal temperature gradient. Section-mean de-seasoned temperature is found to be positively correlated to the Atlantic Multidecadal Oscillation and negatively correlated to the North Atlantic Oscillation. These results refine our understanding of the thermohaline forcing of Atlantic inflow into the northern North Sea, particularly in relation to the salinity distribution. Understanding the variability of this inflow is important for understanding the dynamics of the North Sea ecosystem

Interplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43.

Phosphorylation and lipidation provide posttranslational mechanisms that contribute to the distribution of cytosolic proteins in growing nerve cells. The growth-associated protein GAP43 is susceptible to both phosphorylation and S-palmitoylation and is enriched in the tips of extending neurites. However, how phosphorylation and lipidation interplay to mediate sorting of GAP43 is unclear. Using a combination of biochemical, genetic, and imaging approaches, we show that palmitoylation is required for membrane association and that phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane. Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts. Sorting to the neuritic tip required palmitoylation and active transport and was increased by phosphorylation-mediated plasma membrane interaction. Vesicle tracking revealed transient association of a fraction of GAP43 with exocytic vesicles and motion at a fast axonal transport rate. Simulations confirmed that a combination of diffusion, dynamic plasma membrane interaction and active transport of a small fraction of GAP43 suffices for efficient sorting to growth cones. Our data demonstrate a complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells. Palmitoylation tags GAP43 for global sorting by piggybacking on exocytic vesicles, whereas phosphorylation locally regulates protein mobility and plasma membrane targeting of palmitoylated GAP43

Captive-born collared peccary (Pecari tajacu, Tayassuidae) fails to discriminate between predator and non-predator models

Captive animals may lose the ability to recognize their natural predators, making conservation programs more susceptible to failure if such animals are released into the wild. Collared peccaries are American tayassuids that are vulnerable to local extinction in certain areas, and conservation programs are being conducted. Captive-born peccaries are intended for release into the wild in Minas Gerais state, southeastern Brazil. In this study, we tested the ability of two groups of captive-born collared peccaries to recognize their predators and if they were habituated to humans. Recognition tests were performed using models of predators (canids and felids) and non-predators animals, as well as control objects, such as a plastic chair; a human was also presented to the peccaries, and tested as a separate stimulus. Anti-predator defensive responses such as fleeing and threatening displayswere not observed in response to predator models. Predator detection behaviors both from visual and olfactory cues were displayed, although they were not specifically targeted at predator models. These results indicate that collared peccaries were unable to recognize model predators. Habituation effects, particularly on anti-predator behaviors, were observed both with a 1-h model presentation and across testing days. Behavioral responses to humans did not differ from those to other models. Thus, if these animals were to be released into the wild, they should undergo anti-predator training sessions to enhance their chances of survival

Propagation of Tau aggregates.

Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells. In mice, the intracerebral injection of Tau inclusions induced the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Short fibrils constituted the major species of seed-competent Tau. The existence of several human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist