A comparison of Ashtekar's and Friedrich's formalisms of spatial infinity

Penrose's idea of asymptotic flatness provides a framework for understanding the asymptotic structure of gravitational fields of isolated systems at null infinity. However, the studies of the asymptotic behaviour of fields near spatial infinity are more challenging due to the singular nature of spatial infinity in a regular point compactification for spacetimes with non-vanishing ADM mass. Two different frameworks that address this challenge are Friedrich's cylinder at spatial infinity and Ashtekar's definition of asymptotically Minkowskian spacetimes at spatial infinity that give rise to the three-dimensional asymptote at spatial infinity $\mathcal{H}$. Both frameworks address the singularity at spatial infinity although the link between the two approaches had not been investigated in the literature. This article aims to show the relation between Friedrich's cylinder and the asymptote as spatial infinity. To do so, we initially consider this relation for Minkowski spacetime. It can be shown that the solution to the conformal geodesic equations provides a conformal factor that links the cylinder and the asymptote. For general spacetimes satisfying Ashtekar's definition, the conformal factor cannot be determined explicitly. However, proof of the existence of this conformal factor is provided in this article. Additionally, the conditions satisfied by physical fields on the asymptote $\mathcal{H}$ are derived systematically using the conformal constraint equations. Finally, it is shown that a solution to the conformal geodesic equations on the asymptote can be extended to a small neighbourhood of spatial infinity by making use of the stability theorem for ordinary differential equations. This solution can be used to construct a conformal Gaussian system in a neighbourhood of $\mathcal{H}$

SEMDSA/ACE-SA Guideline for the Management of Hypothyroidism in Adults

Background: Hypothyroidism is a common clinical condition confronting all healthcare practitioners yet there remains uncertainty about the optimal medication and optimum treatment targets. In addition, many patients remain symptomatic despite using recommended medications and attaining recommended treatment targets.Methods: All endocrinologists in South Africa who consented to be part of the guideline process were assigned various aspects of the management of patients with thyroid disease. In each section the current literature was reviewed and the level of evidence was graded. This information was then presented at a guideline meeting. Where evidence was lacking a consensus among participants was adopted.Results: This guideline provides 11 recommendations for the management of primary hypothyroidism, secondary hypothyroidism and subclinical hypothyroidism in adults.Conclusions: This is the first South African guideline for the management of hypothyroidism in adults and represents a comprehensive review of the current literature in an attempt to provide evidence-based guidance for all healthcare practitioners regarding the many clinical aspects encountered when managing patients with hypothyroidism

Anatomy, morphology and evolution of the patella in squamate lizards and tuatara (Sphenodon punctatus)

The patella (kneecap) is the largest and best-known of the sesamoid bones, postulated to confer biomechanical advantages including increasing joint leverage and reinforcing the tendon against compression. It has evolved several times independently in amniotes, but despite apparently widespread occurrence in lizards, the patella remains poorly characterised in this group and is, as yet, completely undescribed in their nearest extant relative Sphenodon (Rhynchocephalia). Through radiography, osteological and fossil studies we examined patellar presence in diverse lizard and lepidosauromorph taxa, and using computed tomography, dissection and histology we investigated in greater depth the anatomy and morphology of the patella in 16 lizard species and 19 Sphenodon specimens. We have found the first unambiguous evidence of a mineralised patella in Sphenodon, which appears similar to the patella of lizards and shares several gross and microscopic anatomical features. Although there may be a common mature morphology, the squamate patella exhibits a great deal of variability in development (whether from a cartilage anlage or not, and in the number of mineralised centres) and composition (bone, mineralised cartilage or fibrotendinous tissue). Unlike in mammals and birds, the patella in certain lizards and Sphenodon appears to be a polymorphic trait. We have also explored the evolution of the patella through ancestral state reconstruction, finding that the patella is ancestral for lizards and possibly Lepidosauria as a whole. Clear evidence of the patella in rhynchocephalian or stem lepidosaurian fossil taxa would clarify the evolutionary origin(s) of the patella, but due to the small size of this bone and the opportunity for degradation or loss we could not definitively conclude presence or absence in the fossils examined. The pattern of evolution in lepidosaurs is unclear but our data suggest that the emergence of this sesamoid may be related to the evolution of secondary ossification centres and/or changes in knee joint conformation, where enhancement of extensor muscle leverage would be more beneficial.Sophie Regnault, Marc E. H. Jones, Andrew A. Pitsillides, John R. Hutchinso

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Conservative management of grade 1V renal injury with complete transection: a case report

The expectant management of high grade renal injuries in hemodynamically stable children has gained increasing acceptance amongst paediatric surgeons. However, patients with grade 1V injury with complete renal transection have been identified as a subgroup with a poor outcome that may benefit from early operative intervention

Role of optimization algorithms based fuzzy controller in achieving induction motor performance enhancement.

Three-phase induction motors (TIMs) are widely used for machines in industrial operations. As an accurate and robust controller, fuzzy logic controller (FLC) is crucial in designing TIMs control systems. The performance of FLC highly depends on the membership function (MF) variables, which are evaluated by heuristic approaches, leading to a high processing time. To address these issues, optimisation algorithms for TIMs have received increasing interest among researchers and industrialists. Here, we present an advanced and efficient quantum-inspired lightning search algorithm (QLSA) to avoid exhaustive conventional heuristic procedures when obtaining MFs. The accuracy of the QLSA based FLC (QLSAF) speed control is superior to other controllers in terms of transient response, damping capability and minimisation of statistical errors under diverse speeds and loads. The performance of the proposed QLSAF speed controller is validated through experiments. Test results under different conditions show consistent speed responses and stator currents with the simulation results

Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.

Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli

A validated stability-indicating HPLC method for determination of varenicline in its bulk and tablets

A simple, sensitive and accurate stability-indicating HPLC method has been developed and validated for determination of varenicline (VRC) in its bulk form and pharmaceutical tablets. Chromatographic separation was achieved on a Zorbax Eclipse XDB-C8 column (150 mm × 4.6 mm i.d., particle size 5 μm, maintained at ambient temperature) by a mobile phase consisted of acetonitrile and 50 mM potassium dihydrogen phosphate buffer (10:90, v/v) with apparent pH of 3.5 ± 0.1 and a flow rate of 1.0 ml/min. The detection wavelength was set at 235 nm. VRC was subjected to different accelerated stress conditions. The degradation products, when any, were well resolved from the pure drug with significantly different retention time values. The method was linear (r = 0.9998) at a concentration range of 2 - 14 μg/ml. The limit of detection and limit of quantitation were 0.38 and 1.11 μg/ml, respectively. The intra- and inter-assay precisions were satisfactory; the relative standard deviations did not exceed 2%. The accuracy of the method was proved; the mean recovery of VRC was 100.10 ± 1.08%. The proposed method has high throughput as the analysis involved short run-time (~ 6 min). The method met the ICH/FDA regulatory requirements. The proposed method was successfully applied for the determination of VRC in bulk and tablets with acceptable accuracy and precisions; the label claim percentages were 99.65 ± 0.32%. The results demonstrated that the method would have a great value when applied in quality control and stability studies for VRC