Atomic coherent-state representation of the spectrum of scattered light from a cooperative system and numerical results

The problem of light scattering from an atomic system under cooperative conditions is analyzed. The atomic correlation function is constructed using the atomic coherent-state representation in a form that is ideally suited for numerical computations. Explicit results are reported for a system of five atoms and the question of the existence of additional side bands is analyzed

Brittle Cornea Syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial Keratoconus.

Purpose: Brittle cornea syndrome 1 (BCS1) is a rare recessive condition characterised by extreme thinning of the cornea and sclera, caused by mutations in ZNF469. Keratoconus is a relatively common disease characterised by progressive thinning and ectasia of the cornea. The aetiology of keratoconus is complex and not yet understood, but rare ZNF469 variants have recently been associated with disease. We investigated the phenotype of BCS1 carriers with known pathogenic ZNF469 mutations, and recruited families in which aggregation of keratoconus was observed to establish if rare variants in ZNF469 segregated with disease. Methods: Patients and family members were recruited and underwent comprehensive anterior segment examination including corneal topography. Blood samples were donated and genomic DNA was extracted. The coding sequence and splice sites of ZNF469 were PCR amplified and Sanger sequenced. Results: Four carriers of three BCS1-associated ZNF469 loss-of-function mutations (p.[ Glu1392Ter], p.[Gln1930Argfs*6], p.[Gln1930fs*133]) were examined and none had keratoconus. One carrier had partially penetrant features of BCS1, including joint hypermobility. ZNF469 sequencing in 11 keratoconus families identified 9 rare (MAF≤0.025) variants predicted to be potentially damaging. However, in each instance the rare variant(s) identified, including two previously reported as potentially keratoconus-associated, did not segregate with the disease. Conclusions: The presence of heterozygous loss-of-function alleles in the ZNF469 gene did not cause keratoconus in the individuals examined. None of the rare non-synonymous ZNF469 variants identified in the familial cohort conferred a high risk of keratoconus, therefore, genetic variants contributing to disease pathogenesis in these 11 families remain to be identified

Stemming the tide: progress towards resolving the causes of decline and implementing management responses for the disappearing mammal fauna of northern Australia

Introduction: Recent studies at sites in northern Australia have reported severe and rapid decline of several native mammal species, notwithstanding an environmental context (small human population size, limited habitat loss, substantial reservation extent) that should provide relative conservation security. All of the more speciose taxonomic groups of mammals in northern Australia have some species for which their conservation status has been assessed as threatened, with 53 % of dasyurid, 47 % of macropod and potoroid, 33 % of bandicoot and bilby, 33 % of possum, 30 % of rodent, and 24 % of bat species being assessed as extinct, threatened or near threatened. However, the geographical extent and timing of declines, and their causes, remain poorly resolved, limiting the application of remedial management actions.\ud \ud Material and methods: Focusing on the tropical savannas of northern Australia, this paper reviews disparate recent and ongoing studies that provide information on population trends across a broader geographic scope than the previously reported sites, and examines the conservation status and trends for mammal groups (bats, macropods) not well sampled in previous monitoring studies. It describes some diverse approaches of studies seeking to document conservation status and trends, and of the factors that may be contributing to observed patterns of decline.\ud \ud Results and Discussion: Current trends and potential causal factors for declines. The studies reported demonstrate that the extent and timing of impacts and threats have been variable across the region, although there is a general gradational pattern of earlier and more severe decline from inland lower rainfall areas to higher rainfall coastal regions. Some small isolated areas appear to have retained their mammal species, as have many islands which remain critical refuges. There is now some compelling evidence that predation by feral cats is implicated in the observed decline, with those impacts likely to be exacerbated by prevailing fire regimes (frequent, extensive and intense fire), by reduction in ground vegetation cover due to livestock and, in some areas, by 'control' of dingoes. However the impacts of dingoes may be complex, and are not yet well resolved in this area. The relative impacts of these individual factors vary spatially (with most severe impacts in higher rainfall and more rugged areas) and between different mammal species, with some species responding idiosyncratically: the most notable example is the rapid decline of the northern quoll (Dasyurus hallucatus) due to poisoning by the introduced cane toad (Rhinella marina), which continues to spread extensively across northern Australia. The impact of disease, if any, remains unresolved.\ud \ud Conservation Management Responses. Recovery of the native mammal fauna may be impossible in some areas. However, there are now examples of rapid recovery following threat management. Priority conservation actions include: enhanced biosecurity for important islands, establishment of a network of feral predator exclosures, intensive fire management (aimed at increasing the extent of longer-unburnt habitat and in delivering fine scale patch burning), reduction in feral stock in conservation reserves, and acquisition for conservation purposes of some pastoral lands in areas that are significant for mammal conservation

Ectopic GRHL2 Expression Due to Non-coding Mutations Promotes Cell State Transition and Causes Posterior Polymorphous Corneal Dystrophy 4

In a large family of Czech origin, we mapped a locus for an autosomal-dominant corneal endothelial dystrophy, posterior polymorphous corneal dystrophy 4 (PPCD4), to 8q22.3-q24.12. Whole-genome sequencing identified a unique variant (c.20+544G>T) in this locus, within an intronic regulatory region of GRHL2. Targeted sequencing identified the same variant in three additional previously unsolved PPCD-affected families, including a de novo occurrence that suggests this is a recurrent mutation. Two further unique variants were identified in intron 1 of GRHL2 (c.20+257delT and c.20+133delA) in unrelated PPCD-affected families. GRHL2 is a transcription factor that suppresses epithelial-to-mesenchymal transition (EMT) and is a direct transcriptional repressor of ZEB1. ZEB1 mutations leading to haploinsufficiency cause PPCD3. We previously identified promoter mutations in OVOL2, a gene not normally expressed in the corneal endothelium, as the cause of PPCD1. OVOL2 drives mesenchymal-to-epithelial transition (MET) by directly inhibiting EMT-inducing transcription factors, such as ZEB1. Here, we demonstrate that the GRHL2 regulatory variants identified in PPCD4-affected individuals induce increased transcriptional activity in vitro. Furthermore, although GRHL2 is not expressed in corneal endothelial cells in control tissue, we detected GRHL2 in the corneal "endothelium" in PPCD4 tissue. These cells were also positive for epithelial markers E-Cadherin and Cytokeratin 7, indicating they have transitioned to an epithelial-like cell type. We suggest that mutations inducing MET within the corneal endothelium are a convergent pathogenic mechanism leading to dysfunction of the endothelial barrier and disease

A New Method to Predict the Epidemiology of Fungal Keratitis by Monitoring the Sales Distribution of Antifungal Eye Drops in Brazil

Purpose: Fungi are a major cause of keratitis, although few medications are licensed for their treatment. The aim of this study is to observe the variation in commercialisation of antifungal eye drops, and to predict the seasonal distribution of fungal keratitis in Brazil. Methods: Data from a retrospective study of antifungal eye drops sales from the only pharmaceutical ophthalmologic laboratory, authorized to dispense them in Brazil (Opthalmos) were gathered. These data were correlated with geographic and seasonal distribution of fungal keratitis in Brazil between July 2002 and June 2008. Results: A total of 26,087 antifungal eye drop units were sold, with a mean of 2.3 per patient. There was significant variation in antifungal sales during the year (p < 0.01). A linear regression model displayed a significant association between reduced relative humidity and antifungal drug sales (R-2 = 0.17, p < 0.01). Conclusions: Antifungal eye drops sales suggest that there is a seasonal distribution of fungal keratitis. A possible interpretation is that the third quarter of the year (a period when the climate is drier), when agricultural activity is more intense in Brazil, suggests a correlation with a higher incidence of fungal keratitis. A similar model could be applied to other diseases, that are managed with unique, or few, and monitorable medications to predict epidemiological aspects.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Cientifico e Tecnologico [302005/2009-9]Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao PauloFundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paul

Deconstructing compassionate conservation

Compassionate conservation focuses on 4 tenets: first, do no harm; individuals matter; inclusivity of individual animals; and peaceful coexistence between humans and animals. Recently, compassionate conservation has been promoted as an alternative to conventional conservation philosophy. We believe examples presented by compassionate conservationists are deliberately or arbitrarily chosen to focus on mammals; inherently not compassionate; and offer ineffective conservation solutions. Compassionate conservation arbitrarily focuses on charismatic species, notably large predators and megaherbivores. The philosophy is not compassionate when it leaves invasive predators in the environment to cause harm to vastly more individuals of native species or uses the fear of harm by apex predators to terrorize mesopredators. Hindering the control of exotic species (megafauna, predators) in situ will not improve the conservation condition of the majority of biodiversity. The positions taken by so-called compassionate conservationists on particular species and on conservation actions could be extended to hinder other forms of conservation, including translocations, conservation fencing, and fertility control. Animal welfare is incredibly important to conservation, but ironically compassionate conservation does not offer the best welfare outcomes to animals and is often ineffective in achieving conservation goals. Consequently, compassionate conservation may threaten public and governmental support for conservation because of the limited understanding of conservation problems by the general public

X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development.

X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain

Treatment of ocular allergies:nonpharmacologic, pharmacologic and immunotherapy

Ocular allergy is a significant and growing issue worldwide but for many patients, it is often not differentiated from systemic conditions, such as hay fever. Management of seasonal and perennial allergic conjunctivitis is often poor. Management is principally through avoidance measures (blocking or hygiene), nonpharmaceutical (such as artificial tears and cold compresses) and pharmaceutical (such as topical antihistamines and prophylactic mast cell stabilizers). Vernal and atopic keratoconjunctivitis are more severe and generally need treatment with NSAIDs, steroids and immunomodulators. Giant papillary conjunctivitis can be related to allergy but also is often contact lens related and in such cases can be managed by a period of abstinence and replacement of the lens or a change in lens material and/or design. Immunotherapy can be efficacious in severe, persistent cases of contact lens or allergic conjunctivitis