Comparison of adeno-associated virus pseudotype 1, 2, and 8 vectors administered by intramuscular injection in the treatment of murine phenylketonuria

Phenylketonuria (PKU) is caused by hepatic phenylalanine hydroxylase (PAH) deficiency and is associated with systemic accumulation of phenylalanine (Phe). Previously we demonstrated correction of murine PKU after intravenous injection of a recombinant type 2 adeno-associated viral vector pseudotyped with type 8 capsid (rAAV2/8), which successfully directed hepatic transduction and Pah gene expression. Here, we report that liver PAH activity and phenylalanine clearance were also restored in PAH-deficient mice after simple intramuscular injection of either AAV2 pseudotype 1 (rAAV2/1) or rAAV2/8 vectors. Serotype 2 AAV vector (rAAV2/2) was also investigated, but long-term phenylalanine clearance has been observed only for pseudotypes 1 and 8. Therapeutic correction was shown in both male and female mice, albeit more effectively in males, in which correction lasted for the entire period of the experiment (>1 year). Although phenylalanine levels began to rise in female mice at about 8-10 months after rAAV2/8 injection they remained only mildly hyperphenylalaninemic thereafter and subsequent supplementation with synthetic tetrahydrobiopterin resulted in a transient decrease in blood phenylalanine. Alternatively, subsequent administration of a second vector with a different AAV pseudotype to avoid immunity against the previously administrated vector was also successful for long-term treatment of female PKU mice. Overall, this relatively less invasive gene transfer approach completes our previous studies and allows comparison of complementary strategies in the development of efficient PKU gene therapy protocols

An operational analysis of Lake Surface Water Temperature

Operational analyses of Lake Surface Water Temperature (LSWT) have many potential uses including improvement of numerical weather prediction (NWP) models on regional scales. In November 2011, LSWT was included in the Met Office Operational Sea Surface Temperature and Ice Analysis (OSTIA) product, for 248 lakes globally. The OSTIA analysis procedure, which has been optimised for oceans, has also been used for the lakes in this first version of the product. Infra-red satellite observations of lakes and in situ measurements are assimilated. The satellite observations are based on retrievals optimised for Sea Surface Temperature (SST) which, although they may introduce inaccuracies into the LSWT data, are currently the only near-real-time information available. The LSWT analysis has a global root mean square difference of 1.31 K and a mean difference of 0.65 K (including a cool skin effect of 0.2 K) compared to independent data from the ESA ARC-Lake project for a 3-month period (June to August 2009). It is demonstrated that the OSTIA LSWT is an improvement over the use of climatology to capture the day-to-day variation in global lake surface temperatures

Georectifying drone image data over water surfaces without fixed ground control: Methodology, uncertainty assessment and application over an estuarine environment

Light-weight consumer-grade drones have the potential to provide geospatial image data to study a broad range of oceanic processes. However, rigorously tested methodologies to effectively and accurately geolocate and rectify these image data over mobile and dynamic water surfaces, where temporally fixed points of reference are unlikely to exist, are limited. We present a simple to use automated workflow for georectifying individual aerial images using position and orientation data from the drone’s on-board sensor (i.e. direct-georectification). The presented methodology includes correcting for camera lens distortion and viewing angle and exploits standard mathematics and camera data processing techniques. The method is used to georectify image datasets from test flights with different combinations of altitude and camera angle. Using a test site over land, directly-georectified images, as well as the same images georectified using standard photogrammetry software, are evaluated using a network of known ground control points. The novel methodology performs well with the camera at nadir (both 10 m and 25 m above ground level) and exhibits a mean spatial accuracy of ±1 m. The same accuracy is achieved when the camera angle is 30◦ at 10 m above ground level but decreases to ±2.9 m at 30◦ and 25 m. The accuracy changes because the uncertainties are a function of the altitude and angle of the camera versus the ground. Drone in-flight positioning errors can reduce the accuracy further to ±5 m with the camera at 30◦ and 25 m. An ensemble approach is used to map the uncertainties within the camera field-of-view to show how they change with viewing distance and drone position and orientation. The complete approach is demonstrated over an estuarine environment that includes the shoreline and open water, producing results consistent with the land-based field-tests of accuracy. Overall, the workflow presented here provides a low cost and agile solution for direct-georectification of drone-captured image data over water surfaces. This approach could be used for collecting and processing image data from drones or ship-mounted cameras to provide observations of ocean colour, sea-ice, ocean glitter, sea surface roughness, white-cap coverage, coastal water quality, and river plumes. The Python scripts for the complete image georectification workflow, including uncertainty map generation, are available from https://github.com/JamieLab/SArONG

Use of satellite observations for operational oceanography: recent achievements and future prospects

The paper gives an overview of the development of satellite oceanography over the past five years focusing on the most relevant issues for operational oceanography. Satellites provide key essential variables to constrain ocean models and/or serve downstream applications. New and improved satellite data sets have been developed and have directly improved the quality of operational products. The status of the satellite constellation for the last five years was, however, not optimal. Review of future missions shows clear progress and new research and development missions with a potentially large impact for operational oceanography should be demonstrated. Improvement of data assimilation techniques and developing synergetic use of high resolution satellite observations are important future priorities

The insecure airway: a comparison of knots and commercial devices for securing endotracheal tubes

BACKGROUND: Endotracheal Tubes (ETTs) are commonly secured using adhesive tape, cloth tape, or commercial devices. The objectives of the study were (1) To compare degrees of movement of ETTs secured with 6 different commercial devices and (2) To compare movement of ETTs secured with cloth tape tied with 3 different knots (hitches). METHODS: A 17 cm diameter PVC tube with 14 mm "mouth" hole in the side served as a mannequin. ETTs were subjected to repeated jerks, using a cable and pulley system. Measurements: (1) Total movement of ETTs relative to "mouth" (measure used for devices) (2) Slippage of ETT through securing knot (measure used for knots). RESULTS: Among commercial devices, the Dale(® )showed less movement than other devices, although some differences between devices did not reach significance. Among knots, Magnus and Clove Hitches produced less slippage than the Cow Hitch, but these differences did not reach statistical significance. CONCLUSION: Among devices tested, the Dale(® )was most secure. Within the scope offered by the small sample sizes, there were no statistically significant differences between the knots in this study

Phenylketonuria in Portugal: Genotype-Phenotype Correlations Using Molecular, Biochemical, and Haplotypic Analyses

The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease.info:eu-repo/semantics/publishedVersio

An ensemble of eddy-permitting global ocean reanalyses from the MyOcean project

A set of four eddy-permitting global ocean reanalyses produced in the framework of the MyOcean project have been compared over the altimetry period 1993–2011. The main differences among the reanalyses used here come from the data assimilation scheme implemented to control the ocean state by inserting reprocessed observations of sea surface temperature (SST), in situ temperature and salinity profiles, sea level anomaly and sea-ice concentration. A first objective of this work includes assessing the interannual variability and trends for a series of parameters, usually considered in the community as essential ocean variables: SST, sea surface salinity, temperature and salinity averaged over meaningful layers of the water column, sea level, transports across pre-defined sections, and sea ice parameters. The eddy-permitting nature of the global reanalyses allows also to estimate eddy kinetic energy. The results show that in general there is a good consistency between the different reanalyses. An intercomparison against experiments without data assimilation was done during the MyOcean project and we conclude that data assimilation is crucial for correctly simulating some quantities such as regional trends of sea level as well as the eddy kinetic energy. A second objective is to show that the ensemble mean of reanalyses can be evaluated as one single system regarding its reliability in reproducing the climate signals, where both variability and uncertainties are assessed through the ensemble spread and signal-to-noise ratio. The main advantage of having access to several reanalyses differing in the way data assimilation is performed is that it becomes possible to assess part of the total uncertainty. Given the fact that we use very similar ocean models and atmospheric forcing, we can conclude that the spread of the ensemble of reanalyses is mainly representative of our ability to gauge uncertainty in the assimilation methods. This uncertainty changes a lot from one ocean parameter to another, especially in global indices. However, despite several caveats in the design of the multi-system ensemble, the main conclusion from this study is that an eddy-permitting multi-system ensemble approach has become mature and our results provide a first step towards a systematic comparison of eddy-permitting global ocean reanalyses aimed at providing robust conclusions on the recent evolution of the oceanic state