Prioritizing a Continuum of Care for Older Orphan Populations: A Qualitative Study from Two Transitional Centers in Armenia

Previous research in residential childcare institutions (RCI) has focused on youth under the age of eighteen. While reaching the age of majority typically signals the end of compulsory childhood institutionalization, age qualifications may deny ministration to young adults whose adolescence was marked by poverty, trauma, violence, or emotional deprivation. To investigate the need for a seamless transition into young adulthood, we interviewed 12 female residents housed in two “transitional centers” (TC) in Armenia. The respondents, while eager for emotional and fiscal autonomy, perceived their previous RCI as integral to their emotional development and thus recognized the need for ancillary care to prepare them for independent living. These findings suggest that Armenia’s TC offer a critical bridge between adolescence and adulthood, providing an environment within which socially vulnerable young adults can prepare for emotional, financial, and intellectual independence. Countries with significant orphan populations should consider integrating a TC component into their continuum of care model to assure that their most vulnerable children populations receive support throughout young adulthood

Efficiency comparison of horizontal axis wind turbines and bladeless turbines

The purpose of this meta study is to determine whether bladeless wind turbines are more efficient than horizontal axis wind turbines. Using resources such as research papers, online articles and academic papers from different academic databases provided by UTS library, a comparison between these wind turbines was constructed. Using Weibull’s equation, it was found that horizontal axis wind turbines are still more efficient. Although bladeless are more cost efficient, offshore horizontal axis wind turbines produce more energy at lower wind speeds, due to the ratio between power usage to power output of approximately 80% for bladed turbines and approximately 70% for bladeless turbines. More research needs to be done on how to increase the efficiency of these wind turbines

Wavelet-based Gaussian-mixture hidden Markov model for the detection of multistage seizure dynamics: A proof-of-concept study

<p>Abstract</p> <p>Background</p> <p>Epilepsy is a common neurological disorder characterized by recurrent electrophysiological activities, known as seizures. Without the appropriate detection strategies, these seizure episodes can dramatically affect the quality of life for those afflicted. The rationale of this study is to develop an unsupervised algorithm for the detection of seizure states so that it may be implemented along with potential intervention strategies.</p> <p>Methods</p> <p>Hidden Markov model (HMM) was developed to interpret the state transitions of the <it>in vitro </it>rat hippocampal slice local field potentials (LFPs) during seizure episodes. It can be used to estimate the probability of state transitions and the corresponding characteristics of each state. Wavelet features were clustered and used to differentiate the electrophysiological characteristics at each corresponding HMM states. Using unsupervised training method, the HMM and the clustering parameters were obtained simultaneously. The HMM states were then assigned to the electrophysiological data using expert guided technique. Minimum redundancy maximum relevance (mRMR) analysis and Akaike Information Criterion (AICc) were applied to reduce the effect of over-fitting. The sensitivity, specificity and optimality index of chronic seizure detection were compared for various HMM topologies. The ability of distinguishing early and late tonic firing patterns prior to chronic seizures were also evaluated.</p> <p>Results</p> <p>Significant improvement in state detection performance was achieved when additional wavelet coefficient rates of change information were used as features. The final HMM topology obtained using mRMR and AICc was able to detect non-ictal (interictal), early and late tonic firing, chronic seizures and postictal activities. A mean sensitivity of 95.7%, mean specificity of 98.9% and optimality index of 0.995 in the detection of chronic seizures was achieved. The detection of early and late tonic firing was validated with experimental intracellular electrical recordings of seizures.</p> <p>Conclusions</p> <p>The HMM implementation of a seizure dynamics detector is an improvement over existing approaches using visual detection and complexity measures. The subjectivity involved in partitioning the observed data prior to training can be eliminated. It can also decipher the probabilities of seizure state transitions using the magnitude and rate of change wavelet information of the LFPs.</p

Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies

Contains fulltext : 88522.pdf (publisher's version ) (Open Access)BACKGROUND: The size of the vertebrate eye and the retina is likely to be controlled at several stages of embryogenesis by mechanisms that affect cell cycle length as well as cell survival. A mutation in the zebrafish out of sight (out) locus results in a particularly severe reduction of eye size. The goal of this study is to characterize the outm233 mutant, and to determine whether mutations in the out gene cause microphthalmia in humans. RESULTS: In this study, we show that the severe reduction of eye size in the outm233 mutant is caused by a mutation in the zebrafish gdf6a gene. Despite the small eye size, the overall retinal architecture appears largely intact, and immunohistochemical studies confirm that all major cell types are present in outm233 retinae. Subtle cell fate and patterning changes are present predominantly in amacrine interneurons. Acridine orange and TUNEL staining reveal that the levels of apoptosis are abnormally high in outm233 mutant eyes during early neurogenesis. Mutation analysis of the GDF6 gene in 200 patients with microphthalmia revealed amino acid substitutions in four of them. In two patients additional skeletal defects were observed. CONCLUSIONS: This study confirms the essential role of GDF6 in the regulation of vertebrate eye size. The reduced eye size in the zebrafish outm233 mutant is likely to be caused by a transient wave of apoptosis at the onset of neurogenesis. Amino acid substitutions in GDF6 were detected in 4 (2%) of 200 patients with microphthalmia. In two patients different skeletal defects were also observed, suggesting pleitrophic effects of GDF6 variants. Parents carrying these variants are asymptomatic, suggesting that GDF6 sequence alterations are likely to contribute to the phenotype, but are not the sole cause of the disease. Variable expressivity and penetrance suggest a complex non-Mendelian inheritance pattern where other genetic factors may influence the outcome of the phenotype

Familial recurrence of SOX2 anophthalmia syndrome:phenotypically normal mother with two affected daughters

The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10–15% of individuals with bilateral anophthalmia. Extra-ocular anomalies are common. The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia /microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband

ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm

The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model system

The ClinGen Epilepsy Gene Curation Expert Panel—Bridging the divide between clinical domain knowledge and formal gene curation criteria

The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes