The cases of four patients experiencing ventricular arrhythmia secondary to drug-induced hypokalaemia requiring treatment by a previously implanted cardioverter defibrillator (ICD) are reported here. ...In three cases, hypokalaemia developed within a short period of time after modification of diuretic regimen with loop and thiazide diuretics had been carried out or potassium-sparing drugs had been withdrawn. In one patient, hypokalaemia occurred after months of treatment with several potassium-sparing and non-potassium-sparing diuretics. The fact that the combination of thiazide and loop diuretics can be associated with pronounced hypokalaemia and life-threatening arrhythmias, which may be terminated by device treatment in patients with an ICD but may be fatal in patients with structural heart disease but without an ICD, is highlighted here. Prompt recognition and correction of hypokalaemia is mandatory if such patients present to the emergency department.
Wood ant species show differences in their social structure, especially in the level of polygyny (number of laying queens per nest) and polydomy (number of nest per colony), both within and between ...species. We demonstrate here for the first time that Formica lugubris displays two different social forms in close proximity in alpine unmanaged forests of the Swiss National Park. The genetic data (7 microsatellite loci) and field data indicate that one population is mostly monogynous to weakly polygynous (r = 0.438) and monodomous, the second one being polygynous (r = 0.113) and polydomous. Within this latter population new nests are founded by budding, leading to the observed high density of nests. These two different social structures, possibly being two expressions of a same continuum, could be explained by several ecological or environmental factors (e.g. habitat saturation, resource competition) and also historical effects.
Recessive dystrophic epidermolysis bullosa is characterized by a functional deficit of the type VII collagen protein due mutations in the COL7A1 gene. Gene augmentation therapies are challenging for ...this disorder due to the large size of the gene as well as the risk of insertional mutagenesis. Cellular therapies are associated with suboptimal therapeutic response due to graft rejection/graft versus host disease. To abrogate these risks we explored the possibility of using the engineered transcription activator like effector nucleases (TALENs) in a precision genome-editing approach for correction of a patient specific mutation. In totality, these data further establish TALENs as viable tools for broad human genome targeting in a patient specific manner for permanent in situ gene correction. Further, the ability to generate inducible pluripotent stem cells from gene corrected fibroblasts and the excellent safety profile of this reagent as determined by this first reported deep sequencing data set for TALENs provides proof-of-concept that will cooperatively facilitate human translational application.
Glutamate dehydrogenase catalyses the oxidative deamination of glutamate to 2-oxoglutarate with concomitant reduction of NAD(P)(+), and has been shown to be widely distributed in nature across ...species ranging from psychrophiles to hyperthermophiles. Extensive characterisation of this enzyme isolated from hyperthermophilic organisms has led to its adoption as a model system for analysing the determinants of thermal stability. The crystal structure of the extremely thermostable glutamate dehydrogenase from Thermococcus litoralis has been determined at 2.5 A resolution, and has been compared to that from the hyperthermophile Pyrococcus furiosus. The two enzymes are 87 % identical in sequence, yet differ 16-fold in their half-lives at 104 degrees C. This is the first reported comparative analysis of the structures of a multisubunit enzyme from two closely related yet distinct hyperthermophilies. The less stable T. litoralis enzyme has a decreased number of ion pair interactions; modified patterns of hydrogen bonding resulting from isosteric sequence changes; substitutions that decrease packing efficiency; and substitutions which give rise to subtle but distinct shifts in both main-chain and side-chain elements of the structure. This analysis provides a rational basis to test ideas on the factors that confer thermal stability in proteins through a combination of mutagenesis, calorimetry, and structural studies.
The ManUp Study is designed to investigate innovative approaches for delivery of physical activity and healthy nutrition messages to men aged 35-54 years living in Gladstone, Queensland, Australia; a ...region where over 50% of the population holds no formal educational qualifications, 40% are low income earners, and 48% work as...
Thyroid volume measurement by ultrasonography (US) is essential in numerous clinical diagnostic and therapeutic fields. While known to be limited, the accuracy and precision of two-dimensional (2D) ...US thyroid volume measurement have not been thoroughly characterized.
We sought to assess the intra- and interobserver variability, accuracy and precision of thyroid volume determination by conventional 2D US in healthy adults using reference volumes determined by three-dimensional (3D) US. Design,
In a prospective blinded trial, thyroid volumes of ten volunteers were determined repeatedly by nine experienced sonographers using conventional 2D US (ellipsoid model). The values obtained were statistically compared to the so-called true volumes determined by 3D US (multiplanar approximation), the so-called gold standard, to estimate systematic errors and relative deviations of individual observers.
The standard error of measurement (SEM) for one observer and successive measurements (intraobserver variability), was 14%, and for different observers and repeated measurements (interobserver variability), 17%. The minimum relative thyroid volume change significantly different at the 95% level was 39% for the same observer and 46% for different observers. Regarding accuracy, the mean value of the differences showed a significant thyroid volume overestimation (17%, p < 0.01) by 2D relative to 3D US.
2D US is appropriate for routine thyroid volumetry. Nevertheless, the so-called human factor (random error) should be kept in mind and correction is needed for methodical bias (systematic error). Further efforts are required to improve the accuracy and precision of 2D US thyroid volumetry by optimizing the underlying geometrical modeling or by the application of 3D US.
In this work, a set of low-temperature thick-film dielectrics consisting of two high-lead low-temperature glasses, stabilised by various amounts of alumina filler, is characterised on alumina and ...aluminium metal, as a function of firing temperature. Corresponding resistors based on the same glasses as the dielectrics, but with RuO
2 as a conductive phase, were studied on the dielectrics. The purpose of these materials is to enable deposition of thick-film electronics onto substrates such as glass and metals (steel, aluminium, brass, titanium), which cannot be exposed to the standard high-temperature 850
°C thick-film firing cycle. Satisfactory insulating properties were obtained, and the properties of the resulting resistors are promising, but managing thermal mismatch was found to be a major issue regarding the mechanical integrity.
We examine the generation of a magnetic field in a solar-like star and its effects on the internal distribution of the angular velocity. We suggest that the evolution of a rotating star with magnetic ...fields leads to an equilibrium value of the differential rotation. This equilibrium is determined by the magnetic coupling, which favours a constant rotation profile, and meridional circulation which tends to build differential rotation. The global equilibrium stage is close to solid body rotation between about 0.7 and 0.2 $R_{\odot}$, in good agreement with helioseismic measurements.
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