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The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P, Fuchs endothelial corneal dystrophy (FECD) is one of the most common reasons for corneal transplantation, and is known to cluster in families. Here, the authors discover new genetic loci associated with FECD with sex-specific effects and implications for disease mechanism.

Background: Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD-affected and unaffected Descemet's membrane. Methods: Label-free quantitative proteomics using nanoscale ultra-performance liquid chromatography-mass spectrometry (nUPLC-MSE ) was employed on affected and unaffected Descemet's membrane extracts, and interesting findings were further investigated using quantitative reverse transcription-polymerase chain reaction and immunohistochemical techniques. Results: Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down-regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD-affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis. Conclusions: This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.

High rates of psychotropic medications are prescribed in aged care homes despite their limited effectiveness and associated adverse effects. We aim to evaluate the changes in prescription patterns for elderly residents with dementia in the ‘Harmony in the Bush Dementia Study’. Harmony in the Bush is a person-centered model of dementia care in nursing homes, based on the principles of Progressively Lowered Stress Threshold and person-centered music intervention. Our larger study (12 weeks period) was a quasi-experimental design conducted in five rural nursing homes in Australia. Medication charts (n = 31) were collected retrospectively from three rural aged care facilities. Medication data for each resident was collected from a three-month medication charts, pre-intervention, and post-intervention. Fifty-three staff participated in 31 semi-structured interviews and 8 focus groups at post-intervention, and at 1-month and 3-months follow up. The median age of the participants was 83 years, and 68% of them were female. Polypharmacy was measured in 87% (n = 27) of the participants. Hypertension, hyperlipidemia, diabetes, and the Alzheimer’s disease were the major comorbidities identified in residents. None of the residents received more than the maximum dose of psychotropic medications recommended by the guidelines. There was a reduction of 22.4% (77.4% vs 55%) in the use of at least any psychotropic medications, 19.6% (39% vs, 19.4%) reduction in antipsychotics and benzodiazepines (39% vs 19.4%), and 6.5% (42% vs 35.5%) reduction in antidepressants prescription medicines, when comparing residents’ medication charts data covering 3-months pre- and post-intervention, however, these changes were not statistically significant. Additionally, there was a decreasing trend in the use of inappropriate medications. Psychotropic medications were prescribed in up to 43% and anti-dementia medications in 44% of participants for more than 6 months. Three themes extracted from qualitative data include decrease behavioral and psychiatric symptoms of dementia due to medication weaning or dose tapering, other strategies to reduce medication use, and environmental or noise control. Our findings indicate that the Harmony in the Bush model as a non-pharmacological approach reduces the prescription of psychotropic medications in rural nursing homes as supported by findings from both quantitative and qualitative data. ANZCTR, ACTRN12618000263291 . Registered on 20th February 2018.

Quality of dementia care improves with a personalized approach to aged care, and knowledge of the disease process and unique care needs of residents with dementia. A personalized model of care can have a significant impact on the overall organizational culture in aged care homes. However, the dimensions of personalized aged care relating to dementia often remain under-managed. We aim to explore the factors that shape the dimensions of personalized dementia care in rural nursing homes using qualitative data of a mixed-method 'Harmony in the Bush' dementia study. The study participants included clinical managers, registered nurses, enrolled nurses and care workers from five rural aged care homes in Queensland and South Australia. One hundred and four staff participated in 65 semi-structured interviews and 20 focus groups at three phases: post-intervention, one-month follow-up and three-months follow-up. A multidimensional model of nursing home care quality developed by Rantz et al. (1998) was used in data coding and analysis of the factors. Three key themes including seven dimensions emerged from the findings: resident and family [resident and family centeredness, and assessment and care planning]; staff [staff education and training, staff-resident interaction and work-life balance]; and organization [leadership and organizational culture, and physical environment and safety]. A lack of consideration of family members views by management and staff, together with poorly integrated, holistic care plan, limited resources and absence of ongoing education for staff, resulted in an ineffective implementation of personalized dementia care. Understanding the dimensions and associated factors may assist in interpreting the multidimensional aspects of personalized approach in dementia care. Staff training on person-centered approach, assessment and plan, and building relationships among and between staff and residents are essential to improve the quality of care residents receive.

Fuchs' endothelial corneal dystrophy (FECD) is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs) and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC), in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR) assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats) in TCF4 and advanced FECD (P = 2.58 × 10-22; OR = 15.66 (95% CI: 7.79-31.49)). Genotypic analysis showed that 51% of cases (97) compared to 5% of controls (9) were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population.

The structure of amphibian communities in South Sudan (East Africa) has never been studied so far. In this paper, the community composition and the diversity patterns of amphibians in nine study sites and in four different habitat types in Jubek area of South Sudan, are analyzed. In addition, the effects of habitat types on the abundance patterns of each species are also explored by Generalized Linear Models. Both pitfall traps with drift fences and Active Search Visual encounter survey were used for the sampling of the amphibians. A total of 551 individuals from 14 species, and belonging to 9 different families, were recorded during the present study, with two ranid and one Ptychadenidae species dominating the sample (i.e., Phrynobatrachus natalensis , Hoplobatrachus occipitalis , Ptychadena nilotica ). The arthroleptid Leptopelis bocagii was reported for the first time in South Sudan. Despite an identical field effort among habitats, there was a statistically uneven number of individuals by habitat, with significantly higher-than-expected individuals found in wetlands/swamps and in farmlands. Farmlands had higher values for Shannon – Wiener and Evenness was much higher in stream and in farmlands than in any other habitats. Our study revealed a relatively low diversity of amphibian species across sites and habitats. For instance, whereas in our study we found a range of 2 – 13 species per locality and 4 – 11 species per habitat type, whereas there were up to 24 – 29 species per site in Uganda.

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Copyright: © 2010 Abhary et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Asymmetric dimethylarginine (ADMA), present in human serum, is an endogenous inhibitor of nitric oxide synthase and contributes to vascular disease. Dimethylarginine dimethylaminohydrolase (DDAH) is an ADMA degrading enzyme that has two isoforms: DDAHI and DDAHII. We sought to determine whether serum ADMA levels in type 2 diabetes are influenced by common polymorphisms in the DDAH1 and DDAH2 genes.

OBJECTIVE Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and l-arginine directly influence nitric oxide production. Our objective was to test whether serum ADMA, SDMA, or l-arginine levels correlate with diabetic retinopathy subtype or severity. RESEARCH DESIGN AND METHODS A total of 162 subjects with type 1 diabetes and 343 with type 2 diabetes, of whom 329 subjects had no diabetic retinopathy, 27 had nonproliferative diabetic retinopathy (NPDR), 101 had proliferative diabetic retinopathy (PDR), and 107 had clinically significant macular edema (CSME), were recruited. Blinding diabetic retinopathy was defined as severe NPDR, PDR, or CSME. Serum ADMA, SDMA, and l-arginine concentrations were determined by mass spectroscopy. RESULTS In multivariate analysis, blinding diabetic retinopathy, PDR, and nephropathy were associated with significantly increased serum levels of ADMA (P < 0.001), SDMA (P < 0.001), and l-arginine (P = 0.001). Elevated ADMA (P < 0.001) and SDMA (P < 0.001) were also significantly associated with CSME. CONCLUSIONS Severe forms of diabetic retinopathy are associated with elevated serum ADMA, SDMA, and l-arginine. Further investigation is required to determine whether these findings are of clinical relevance.

Performance and reliability are two major design concerns of flash-memory storage systems, especially for low-cost products. Although various excellent flash- memory management schemes are proposed, there is little work done on how to evaluate the designs or implementations of flash-memory storage systems. Many of the existing evaluation workloads for flash-memory storage systems still rely on those based on hard disks. This work aims at the needs of behavior analysis of flash-memory storage systems and their evaluations. In particular, a set of evaluation metrics and their corresponding access patterns are proposed. The behaviors of flash memory are also analyzed in terms of performance and reliability issues.

The turbulent flow which results when a circular jet issues into a crosswind is a noise source which is encountered during take-off and landing of certain types of V/STOL aircraft. The acoustic intensity of the noise from this flow is calculated by extending the freejet model of Ribner 1'2 to those crosswind jets for which the ratio of jet velocity to crosswind velocity is between 6 and 10. The extended model accounts for the non-circular cross section, the shortened potential core region, and the flow characteristics in the initial mixing region of the crosswind jet. The result of this analysis is an expression for the directivity function of the acoustic intensity from a crosswind jet of a V/STOL aircraft in flight. The maximum acoustic intensity is calculated to be in a direction which is slightly forward of the sidelines direction.

Two 14C-labelled leukotriene receptor antagonists were prepared from two aryl bromides and potassium [14C]cyanide. Potassium cyanide was converted to copper(I) [14C]cyanide and was subsequently used to displace the bromine atom from two aryl bromides, 2-dodecylbromobenzene and 2-(8-phenyloctyl)bromobenzene. The resulting nitriles were reduced to aldehydes with diisobutylaluminum hydride and the aldehydes were reacted with 3-mercaptopropionic acid to give 5-(2-dodecylphenyl)-4,6-dithianonanedioic acid (14C-SK&F 102081) and 5-[2-(8-phenyloctyl)phenyl]-4,6-dithianonanedioic acid (14C-SK&F 102922), respectively. These products were snythesized in about 30% overall yield with radiochemical purity of greater than 95%. Their structures were assigned based on the analytical data of the corresponding nonradiolabelled compounds obtained from the nonradioactive preparations.

Purpose To investigate the association between genetic variation at the matrix metalloproteinase-9 (MMP9) locus and primary angle closure glaucoma (PACG) in an Australian Caucasian population. Methods A total of 107 Australian patients with PACG and 288 age and sex-matched controls were included in the current study. Tag single nucleotide polymorphisms (SNPs) were selected and genotyped to cover the majority of common variation within MMP9. Allele, genotype and haplotype association analyses were conducted using PLINK. Results Two SNPs from MMP9, rs3918249 and rs17576 were significantly associated under the allelic model with p values of 0.006 for both SNPs. In addition, haplotype analysis revealed a protective haplotype TACGG to be significantly more frequent in controls (69%) than in PACG cases (59%), with p=0.006. Conclusions This study demonstrates an association between MMP9 SNPs rs3918249 and rs17576 and PACG in the Australian population, suggesting MMP9 may be involved in the pathogenesis of this blinding disease. Further replication will be helpful in confirming this finding before future clinical translation.