70 research outputs found
Pediatric cataract, myopic astigmatism, familial exudative vitreoretinopathy and primary open-angle glaucoma co-segregating in a family
Purpose: To describe an Australian pedigree of European descent with a variable autosomal dominant phenotype of: pediatric cortical cataract (CC), asymmetric myopia with astigmatism, familial exudative vitreoretinopathy (FEVR), and primary open-angle glaucoma (POAG).
Methods: Probands with CC, FEVR, and POAG were enrolled in three independent genetic eye studies in Tasmania. Genealogy confirmed these individuals were closely related and subsequent examination revealed 11 other family members with some or all of the associated disorders.
Results: Twelve individuals had CC thought to be of childhood onset, with one child demonstrating progressive lenticular opacification. One individual had severe retinal detachment while five others had dragged retinal vessels. Seven individuals had POAG. Seven individuals had myopia in at least one eye ≤-3 Diopters. DNA testing excluded mutations in myocilin, trabecular meshwork inducible glucocorticoid response (MYOC) and tetraspanin 12 (TSPAN12). Haplotype analysis excluded frizzled family receptor 4 (FZD4) and low density lipoprotein receptor-related protein 5 (LRP5), but only partly excluded EVR3. Multipoint linkage analysis revealed multiple chromosomal single-nucleotide polymorphisms (SNPs) of interest, but no statistically significant focal localization.
Conclusions: This unusual clustering of ophthalmic diseases suggests a possible single genetic cause for an apparently new cataract syndrome. This family’s clinical ocular features may reflect the interplay between retinal disease with lenticular changes and axial length in the development of myopia and glaucoma
Identifying genetic biomarkers predicting response to anti-vascular endothelial growth factor injections in diabetic macular edema
Intraocular anti-vascular endothelial growth factor (VEGF) therapies are the front-line treatment for diabetic macular edema (DME); however, treatment response varies widely. This study aimed to identify genetic determinants associated with anti-VEGF treatment response in DME. We performed a genome-wide association study on 220 Australian patients with DME treated with anti-VEGF therapy, genotyped on the Illumina Global Screening Array, and imputed to the Haplotype Reference Consortium panel. The primary outcome measures were changes in central macular thickness (CMT in microns) and best-corrected visual acuity (BCVA in ETDRS letters) after 12 months. Association between single nucleotide polymorphism (SNP) genotypes and DME outcomes were evaluated by linear regression, adjusting for the first three principal components, age, baseline CMT/BCVA, duration of diabetic retinopathy, and HbA1c. Two loci reached genome-wide significance (p −8) for association with increased CMT: a single SNP on chromosome 6 near CASC15 (rs78466540, p = 1.16 × 10−9) and a locus on chromosome 12 near RP11-116D17.1 (top SNP rs11614480, p = 2.69 × 10−8). Four loci were significantly associated with reduction in BCVA: two loci on chromosome 11, downstream of NTM (top SNP rs148980760, p = 5.30 × 10−9) and intronic in RP11-744N12.3 (top SNP rs57801753, p = 1.71 × 10−8); one near PGAM1P1 on chromosome 5 (rs187876551, p = 1.52 × 10−8); and one near TBC1D32 on chromosome 6 (rs118074968, p = 4.94 × 10−8). In silico investigations of each locus identified multiple expression quantitative trait loci and potentially relevant candidate genes warranting further analysis. Thus, we identified multiple genetic loci predicting treatment outcomes for anti-VEGF therapies in DME. This work may potentially lead to managing DME using personalized treatment approaches
An introduction to the Australian and New Zealand flux tower network - OzFlux
© Author(s) 2016. OzFlux is the regional Australian and New Zealand flux tower network that aims to provide a continental-scale national research facility to monitor and assess trends, and improve predictions, of Australia's terrestrial biosphere and climate. This paper describes the evolution, design, and current status of OzFlux as well as provides an overview of data processing. We analyse measurements from all sites within the Australian portion of the OzFlux network and two sites from New Zealand. The response of the Australian biomes to climate was largely consistent with global studies except that Australian systems had a lower ecosystem water-use efficiency. Australian semi-arid/arid ecosystems are important because of their huge extent (70 %) and they have evolved with common moisture limitations. We also found that Australian ecosystems had a similar radiation-use efficiency per unit leaf area compared to global values that indicates a convergence toward a similar biochemical efficiency. The two New Zealand sites represented extremes in productivity for a moist temperate climate zone, with the grazed dairy farm site having the highest GPP of any OzFlux site (2620 gC m-2 yr-1) and the natural raised peat bog site having a very low GPP (820 gC m-2 yr-1). The paper discusses the utility of the flux data and the synergies between flux, remote sensing, and modelling. Lastly, the paper looks ahead at the future direction of the network and concludes that there has been a substantial contribution by OzFlux, and considerable opportunities remain to further advance our understanding of ecosystem response to disturbances, including drought, fire, land-use and land-cover change, land management, and climate change, which are relevant both nationally and internationally. It is suggested that a synergistic approach is required to address all of the spatial, ecological, human, and cultural challenges of managing the delicately balanced ecosystems in Australasia
Not Quite Right: Representations of Eastern Europeans in ECJ Discourse
Although the increasing responsiveness of the Court of Justice of the European Union (the ‘ECJ’) jurisprudence to western Member States’ concerns regarding Central and Eastern European (‘CEE’) nationals’ mobility has garnered academic attention, ECJ discourse has not been scrutinised for how it approaches the CEE region or CEE movers. Applying postcolonial theory, this article seeks to fill this gap and to explore whether there are any indications that ECJ discourse is in line with the historical western-centric inferiorisation of the CEE region. A critical discourse analysis of a set of ECJ judgments and corresponding Advocate General opinions pertaining to CEE nationals illustrates not only how the ECJ adopts numerous discursive strategies to maintain its authority, but also how it tends to prioritise values of the western Member States, while overlooking interests of CEE movers. Its one-sided approach is further reinforced by referring to irrelevant facts and negative assumptions to create an image of CEE nationals as socially and economically inferior to westerners, as not belonging to the proper EU polity and as not quite deserving of EU law’s protections. By silencing CEE nationals’ voices, while disregarding the background of east/west socio-economic and political power differentials and precariousness experienced by many CEE workers in the west, such racialising discourse normalises ethnicity- and class-based stereotypes. These findings also help to contextualise both EU and western policies targeting CEE movers and evidence of their unequal outcomes in the west, and are in line with today’s nuanced expressions of racisms. By illustrating the ECJ’s role in addressing values pertinent to mobile CEE individuals, this study facilitates a fuller appreciation of the ECJ’s power in shaping and reflecting western-centric EU identity and policies. Engaging with such issues will not only allow us to better appreciate—and question—the ECJ’s legitimacy, but might also facilitate a better understanding of power dynamics within the EU. This study also makes significant theoretical and methodological contributions. It expands (and complicates) the application of postcolonial theory to contemporary intra-EU processes, while illustrating the usefulness of applying critical discourse analysis to exploring differentiation, exclusion, subordination and power within legal language
Increasing female participation in municipal elections via the use of local radio in conflict-affected settings: The case of the West Bank municipal elections 2017
The 2017 West Bank Municipal elections were framed by locally-based non-governmental organisations (NGOs) and the Palestinian Authorities – albeit to a lesser extent – in terms of the desirability of increasing female participation in them in two particular ways: participation as representatives and participation as voters. Both aspects of participation were supported by extensive radio campaigns conducted by locally-based NGOs. The effectiveness of these campaigns and the approaches used form the basis of this article. Using a mixed methods approach consisting of both quantitative and qualitative data, it concludes that radio has endemic socio-technical advantages for reaching women, particularly in conflict-affected areas, and that broadcasting content aimed at women by women is essential in terms of increasing their representation and voting
A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.
This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H
Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions
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