A new class of stem cells in South Africa: iPS cells

Created from adult rather than embryonic cells, induced pluripotent stem (iPS) cells represent a breakthrough in stem cell science, and their pioneers have been recognised with the 2012 Nobel Prize in Medicine. These cells offer new hope in the treatment of pathogenetic diseases, but there is still a way to go on the road to effective therapeutic applications

The use of intravenous iron in pregnancy: for whom and when? A survey of Australian and New Zealand obstetricians

Background: Iron deficiency anaemia in pregnancy (IDAP) affects 11–18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP. Methods: An online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing. Results: Of 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed. Conclusions: Almost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.Sarah Smith-Wade, Giselle Kidson-Gerber, Antonia Shand, Luke Grzeskowiak and Amanda Henr

Associations between stratospheric variability and tropospheric blocking

There is widely believed to be a link between stratospheric flow variability and stationary, persistent “blocking” weather systems, but the precise nature of this link has proved elusive. Using data from the ERA-40 Reanalysis and an atmospheric general circulation model (GCM) with a well-resolved stratosphere (HadGAM), it is shown that there are in fact several different highly significant associations, with blocking in different regions being related to different patterns of stratospheric variability. This is true in both hemispheres and in both data sets. The associations in HadGAM are shown to be very similar to those in ERA-40, although the model has a tendency to underestimate both European blocking and the wave number 2 stratospheric variability to which this is related. Although the focus is on stratospheric variability in general, several of the blocking links are seen to occur in association with the major stratospheric sudden warmings. In general, the direction of influence appears to be upward, as blocking anomalies are shown to modify the planetary stationary waves, leading to an upward propagation of wave activity into the stratosphere. However, significant correlations are also apparent with the zonal mean flow in the stratosphere leading the occurrence of blocking at high latitudes. Finally, the underestimation of blocking is an enduring problem in GCMs, and an example has recently been given in which improving the resolution of the stratosphere improved the representation of blocking. Here, however, another example is given, in which increasing the stratospheric resolution unfortunately does not lead to an improvement in blocking

Isothermal Elastohydrodynamic Lubrication Analysis of Heavily Loaded Hypoid Gear Pairs

A numerical model able to predict the pressure distribution and the film thickness in heavily loaded elliptical EHL contacts is developed and presented in this study. The operating conditions, such as the contact load and the velocities of the mating surfaces, are representative of the corresponding conditions present in automotive differential hypoid gear pair units. The EHL solver presented is able to predict the minimum and central film thickness of the lubricating oil as well as the pressure distribution assuming isothermal and Newtonian conditions. Results are presented for a full quasi-static meshing cycle. A comparison between the numerically calculated values of the central and the minimum film thickness is performed against the corresponding values produced using the Chittenden-Dowson formula. A very good agreement is observed between the values of the central film thickness. However, it is shown that the minimum film thickness values using the Chittenden-Dowson formula can deviate up to 40% compared with the corresponding values which are calculated numerically

Film Thickness Investigation in Heavily Loaded Hypoid Gear Pair Elastohydrodynamic Conjunctions

Introduction: Hypoid gear pairs are some of the most highly loaded components of the differential unit in modern automobiles. Prediction of wear rate and generated friction require determination of lubricant film thickness. However, only very few investigations have addressed the issue of thin elastohydrodynamic films in hypoid gear pairs. The main reason for dearth of analysis in this regard has been the need for accurate determination of transient contact geometry and kinematics of interacting surfaces throughout a typical meshing cycle. Furthermore, combined gear dynamics and lubrication analysis of any pairs of simultaneous meshing teeth pairs is required. Simon [1] was among the first to deal with these issues. He used Tooth Contact Analysis (TCA) in order to calculate the instantaneous contact geometry and load for any teeth pair during their meshing cycle. However, in his study, the load carried by the hypoid pair was quite low, making the application of the results limited and not entirely suitable for real life operating conditions of typical hypoid gear pairs of vehicular differentials, which is of interest in the current paper. Xu and Kahraman [2] performed numerical prediction of power losses and consequently the film thickness for highly loaded hypoid gear pairs. However, in their study only the one-dimensional Reynolds equation was employed. Consequently, the effect of lubricant side leakage in the passage through the contact was ignored. A more recent study by Mohammadpour et al. [3] employed realistic gear geometry data (through the use of TCA) for calculation of film thickness time history through mesh. The two-dimensional Reynolds equation, accounting for the side leakage of the lubricant, was solved numerically. It was shown that the side leakage component of the entraining velocity can significantly influence the film thickness. With regard to hypoid gear dynamics, several studies should be mentioned. Wang and Lim [4] studied the dynamic response of hypoid gear pairs under the influence of time varying meshing stiffness. Yang and Lim [5] created a model able to predict the dynamic response of a hypoid gear pair by taking into account the lateral translations of their shafts due to the compliance of the supporting bearings. Karagiannis et al. [6-7] studied the dynamics of automotive differential hypoid gear pairs by taking into account the velocity dependent resistive torque at the gear caused by aerodynamic drag and tyre-road rolling resistance. The study integrated the gear dynamics with the generated viscous and boundary conjunctional friction

Spinocerebellar ataxia type 7 in South Africa: Epidemiology, pathogenesis and therapy

Disorders of the nervous system represent a significant proportion of the global burden of non-communicable diseases, due to the trend towards ageing populations. The Department (now Division) of Human Genetics at the University of Cape Town (UCT) has been involved in pioneering research into these diseases since the appointment of Prof. Peter Beighton as Head of Department in 1972. Beighton’s emphasis on understanding the genetic basis of disease laid the groundwork for investigations into several monogenic neurodegenerative conditions, including Huntington’s disease and the polyglutamine spinocerebellar ataxias (SCAs). In particular, SCA7, which occurs at an unusually high frequency in the South African (SA) population, was identified as a target for further research and therapeutic development. Beginning with early epidemiological surveys, the SCA7 project progressed to molecular genetics-based investigations, leading to the identification of a founder effect in the SA SCA7 patient population in the mid-2000s. Capitalising on the founder haplotype shared by many SCA7 patients, UCT researchers went on to develop the first population-specific gene-silencing approach for the disease. More recently, efforts have shifted to the development of a more accurate model to decipher the precise mechanisms of neurodegeneration, using induced pluripotent stem cells derived from SA SCA7 patients. In many ways, the SA SCA7 journey reflects the legacy and vision of Prof. Peter Beighton, and his efforts to establish world-class, collaborative research into diseases affecting the African continent.

Towards a fair comparison of statistical and dynamical downscaling in the framework of the EURO-CORDEX initiative

Both statistical and dynamical downscaling methods are well established techniques to bridge the gap between the coarse information produced by global circulation models and the regional-to-local scales required by the climate change Impacts, Adaptation, and Vulnerability (IAV) communities. A number of studies have analyzed the relative merits of each technique by inter-comparing their performance in reproducing the observed climate, as given by a number of climatic indices (e.g. mean values, percentiles, spells). However, in this paper we stress that fair comparisons should be based on indices that are not affected by the calibration towards the observed climate used for some of the methods. We focus on precipitation (over continental Spain) and consider the output of eight Regional Climate Models (RCMs) from the EURO-CORDEX initiative at 0.44? resolution and five Statistical Downscaling Methods (SDMs) ?analog resampling, weather typing and generalized linear models? trained using the Spain044 observational gridded dataset on exactly the same RCM grid. The performance of these models is inter-compared in terms of several standard indices ?mean precipitation, 90th percentile on wet days, maximum precipitation amount and maximum number of consecutive dry days? taking into account the parameters involved in the SDM training phase. It is shown, that not only the directly affected indices should be carefully analyzed, but also those indirectly influenced (e.g. percentile-based indices for precipitation) which are more difficult to identify. We also analyze how simple transformations (e.g. linear scaling) could be applied to the outputs of the uncalibrated methods in order to put SDMs and RCMs on equal footing, and thus perform a fairer comparison.We acknowledge the World Climate Research Programme’s Working Group on Regional Climate, and theWorking Group on CoupledModelling, former coordinating body of CORDEX and responsible panel for CMIP5. We also thank the climate modeling groups (listed in Table 1 of this paper) for producing and making available their model output. We also acknowledge the Earth System Grid Federation infrastructure and AEMET and University of Cantabria for the Spain02 dataset (available at http: //www.meteo.unican.es/en/datasets/spain02). All the statistical downscaling experiments have been computed using theMeteoLab software (http://www.meteo.unican.es/software/meteolab), which is an open-source Matlab toolbox for statistical downscaling. This work has been partially supported by CORWES (CGL2010-22158-C02) and EXTREMBLES (CGL2010-21869) projects funded by the Spanish R&D programme. AC thanks the Spanish Ministry of Economy and Competitiveness for the funding provided within the FPI programme (BES-2011-047612 and EEBB-I-13-06354), JMG acknowledges the support from the SPECS project (FP7-ENV-2012-308378) and JF is grateful to the EUPORIAS project (FP7-ENV-2012-308291). We also thank three anonymous referees for their useful comments that helped to improve the original manuscript

Foxf2: A Novel Locus for Anterior Segment Dysgenesis Adjacent to the Foxc1 Gene

Anterior segment dysgenesis (ASD) is characterised by an abnormal migration of neural crest cells or an aberrant differentiation of the mesenchymal cells during the formation of the eye's anterior segment. These abnormalities result in multiple tissue defects affecting the iris, cornea and drainage structures of the iridocorneal angle including the ciliary body, trabecular meshwork and Schlemm's canal. In some cases, abnormal ASD development leads to glaucoma, which is usually associated with increased intraocular pressure. Haploinsufficiency through mutation or chromosomal deletion of the human FOXC1 transcription factor gene or duplications of the 6p25 region is associated with a spectrum of ocular abnormalities including ASD. However, mapping data and phenotype analysis of human deletions suggests that an additional locus for this condition may be present in the same chromosomal region as FOXC1. DHPLC screening of ENU mutagenised mouse archival tissue revealed five novel mouse Foxf2 mutations. Re-derivation of one of these (the Foxf2W174R mouse lineage) resulted in heterozygote mice that exhibited thinning of the iris stroma, hyperplasia of the trabecular meshwork, small or absent Schlemm's canal and a reduction in the iridocorneal angle. Homozygous E18.5 mice showed absence of ciliary body projections, demonstrating a critical role for Foxf2 in the developing eye. These data provide evidence that the Foxf2 gene, separated from Foxc1 by less than 70 kb of genomic sequence (250 kb in human DNA), may explain human abnormalities in some cases of ASD where FOXC1 has been excluded genetically

Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007

Simon Hay and colleagues derive contemporary estimates of the global clinical burden of Plasmodium falciparum malaria (the deadliest form of malaria) using cartography-based techniques