Green Care: a Conceptual Framework. A Report of the Working Group on the Health Benefits of Green Care

‘Green Care’ is a range of activities that promotes physical and mental health and well-being through contact with nature. It utilises farms, gardens and other outdoor spaces as a therapeutic intervention for vulnerable adults and children. Green care includes care farming, therapeutic horticulture, animal assisted therapy and other nature-based approaches. These are now the subject of investigation by researchers from many different countries across the world

Dyslexia and password usage:accessibility in authentication design

Governments and businesses are moving online with alacrity, driven by potential cost savings, changing consumer and citizen expectations, and the momentum towards general digital provision. Services are legally required to be inclusive and accessible. Now consider that almost every online service, where people have to identify themselves, requires a password. Passwords seem to be accessible, until one considers specific disabilities, one of which can lead to many challenges: dyslexia being a case in point. Dyslexia is associated with word processing and retention difficulties, and passwords are essentially words, phrases or alphanumeric combinations. We report on a literature review conducted to identify extant research into the impact of dyslexia on password usage, as well as any ameliorations that have been proposed. We discovered a relatively neglected field. We conclude with recommendations for future research into the needs of a large population of dyslexics who seem to struggle with passwords, in a world where avoiding passwords has become almost impossible. The main contribution of this paper is to highlight the difficulties dyslexics face with passwords, and to suggest some avenues for future research in this area

Optimizing the use of continuous glucose monitoring in young children with type 1 diabetes with an adaptive study design and multiple randomizations

Parents of young children with type 1 diabetes (T1D) experience unique, developmental challenges in managing their child's T1D, resulting in psychosocial distress. Only a small portion of young children reach glucose goals and adherence to diabetes devices that help improve T1D management have historically been low in this population. The purpose of this study is to test four interventions that couple developmentally tailored behavioral supports with education to optimize use of diabetes devices, improve glucose control, and reduce psychosocial distress for parents of young children with T1D. The study team designed four behavioral interventions, two aimed at improving glucose control and two aimed at optimizing use of diabetes devices. The goal of this paper is to describe the behavioral interventions developed for this study, including the results of a pilot test, and describe the methods and analysis plan to test this intervention strategy with ninety participants in a large-scale, randomized trial using a sequential multiple assignment randomization trial (SMART) design. A SMART design will permit a clinically relevant evaluation of the intervention strategy, as it allows multiple randomizations based on individualized assessments throughout the study instead of a fixed intervention dose seen in most traditional randomized controlled trials

Matrix Orbit Closures

Let $G$ be the group \GL_r(\CC) \times (\CC^\times)^n. We conjecture that the finely-graded Hilbert series of a $G$ orbit closure in the space of $r$-by-$n$ matrices is wholly determined by the associated matroid. In support of this, we prove that the coefficients of this Hilbert series corresponding to certain hook-shaped Schur functions in the \GL_r(\CC) variables are determined by the matroid, and that the orbit closure has a set-theoretic system of ideal generators whose combinatorics are also so determined. We also discuss relations between these Hilbert series for related matrices

A Plan to Facilitate the Early Career Development of Minority Scholars in the Health Sciences

http://dx.doi.org/10.1080/1937191100374817

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test

BACKGROUND: The evolution of alternatively spliced exons (ASEs) is of primary interest because these exons are suggested to be a major source of functional diversity of proteins. Many exon features have been suggested to affect the evolution of ASEs. However, previous studies have relied on the K(A)/K(S )ratio test without taking into consideration information sufficiency (i.e., exon length > 75 bp, cross-species divergence > 5%) of the studied exons, leading to potentially biased interpretations. Furthermore, which exon feature dominates the results of the K(A)/K(S )ratio test and whether multiple exon features have additive effects have remained unexplored. RESULTS: In this study, we collect two different datasets for analysis – the ASE dataset (which includes lineage-specific ASEs and conserved ASEs) and the ACE dataset (which includes only conserved ASEs). We first show that information sufficiency can significantly affect the interpretation of relationship between exons features and the K(A)/K(S )ratio test results. After discarding exons with insufficient information, we use a Boolean method to analyze the relationship between test results and four exon features (namely length, protein domain overlapping, inclusion level, and exonic splicing enhancer (ESE) frequency) for the ASE dataset. We demonstrate that length and protein domain overlapping are dominant factors, and they have similar impacts on test results of ASEs. In addition, despite the weak impacts of inclusion level and ESE motif frequency when considered individually, combination of these two factors still have minor additive effects on test results. However, the ACE dataset shows a slightly different result in that inclusion level has a marginally significant effect on test results. Lineage-specific ASEs may have contributed to the difference. Overall, in both ASEs and ACEs, protein domain overlapping is the most dominant exon feature while ESE frequency is the weakest one in affecting test results. CONCLUSION: The proposed method can easily find additive effects of individual or multiple factors on the K(A)/K(S )ratio test results of exons. Therefore, the system can analyze complex conditions in evolution where multiple features are involved. More factors can also be added into the system to extend the scope of evolutionary analysis of exons. In addition, our method may be useful when orthologous exons can not be found for the K(A)/K(S )ratio test

Fine-Scale Variation and Genetic Determinants of Alternative Splicing across Individuals

Recently, thanks to the increasing throughput of new technologies, we have begun to explore the full extent of alternative pre–mRNA splicing (AS) in the human transcriptome. This is unveiling a vast layer of complexity in isoform-level expression differences between individuals. We used previously published splicing sensitive microarray data from lymphoblastoid cell lines to conduct an in-depth analysis on splicing efficiency of known and predicted exons. By combining publicly available AS annotation with a novel algorithm designed to search for AS, we show that many real AS events can be detected within the usually unexploited, speculative majority of the array and at significance levels much below standard multiple-testing thresholds, demonstrating that the extent of cis-regulated differential splicing between individuals is potentially far greater than previously reported. Specifically, many genes show subtle but significant genetically controlled differences in splice-site usage. PCR validation shows that 42 out of 58 (72%) candidate gene regions undergo detectable AS, amounting to the largest scale validation of isoform eQTLs to date. Targeted sequencing revealed a likely causative SNP in most validated cases. In all 17 incidences where a SNP affected a splice-site region, in silico splice-site strength modeling correctly predicted the direction of the micro-array and PCR results. In 13 other cases, we identified likely causative SNPs disrupting predicted splicing enhancers. Using Fst and REHH analysis, we uncovered significant evidence that 2 putative causative SNPs have undergone recent positive selection. We verified the effect of five SNPs using in vivo minigene assays. This study shows that splicing differences between individuals, including quantitative differences in isoform ratios, are frequent in human populations and that causative SNPs can be identified using in silico predictions. Several cases affected disease-relevant genes and it is likely some of these differences are involved in phenotypic diversity and susceptibility to complex diseases

Intron-loss evolution of hatching enzyme genes in Teleostei

<p>Abstract</p> <p>Background</p> <p>Hatching enzyme, belonging to the astacin metallo-protease family, digests egg envelope at embryo hatching. Orthologous genes of the enzyme are found in all vertebrate genomes. Recently, we found that exon-intron structures of the genes were conserved among tetrapods, while the genes of teleosts frequently lost their introns. Occurrence of such intron losses in teleostean hatching enzyme genes is an uncommon evolutionary event, as most eukaryotic genes are generally known to be interrupted by introns and the intron insertion sites are conserved from species to species. Here, we report on extensive studies of the exon-intron structures of teleostean hatching enzyme genes for insight into how and why introns were lost during evolution.</p> <p>Results</p> <p>We investigated the evolutionary pathway of intron-losses in hatching enzyme genes of 27 species of Teleostei. Hatching enzyme genes of basal teleosts are of only one type, which conserves the 9-exon-8-intron structure of an assumed ancestor. On the other hand, otocephalans and euteleosts possess two types of hatching enzyme genes, suggesting a gene duplication event in the common ancestor of otocephalans and euteleosts. The duplicated genes were classified into two clades, clades I and II, based on phylogenetic analysis. In otocephalans and euteleosts, clade I genes developed a phylogeny-specific structure, such as an 8-exon-7-intron, 5-exon-4-intron, 4-exon-3-intron or intron-less structure. In contrast to the clade I genes, the structures of clade II genes were relatively stable in their configuration, and were similar to that of the ancestral genes. Expression analyses revealed that hatching enzyme genes were high-expression genes, when compared to that of housekeeping genes. When expression levels were compared between clade I and II genes, clade I genes tends to be expressed more highly than clade II genes.</p> <p>Conclusions</p> <p>Hatching enzyme genes evolved to lose their introns, and the intron-loss events occurred at the specific points of teleostean phylogeny. We propose that the high-expression hatching enzyme genes frequently lost their introns during the evolution of teleosts, while the low-expression genes maintained the exon-intron structure of the ancestral gene.</p

Adverse outcomes after colposcopy

Abstract Background Colposcopy is an essential part of the National Health Service Cervical Screening Programme (NHSCSP). It is used for both diagnosis and treatment of pre-cancerous cells of the cervix. Despite colposcopy being a commonly performed and relatively invasive procedure, very little research has explored the potential long-term impacts of colposcopic examination upon patient quality of life. The aim of this study is to investigate and quantify any potential reduction in women's quality of life following a colposcopy procedure. More specifically, the degree of female sexual dysfunction and the excess risk of adverse events in those undergoing colposcopy will be explored. If such risks are identified, these can be communicated to women before undergoing colposcopy. It will also assist in identifying whether there are particular sub-groups at greater risk and if so, this may lead to a re-evaluation of current recommendations concerning colposcopically directed treatments. Methods/design Cohort study using postal surveys to assess sexual function and quality of life in women who have attended for colposcopy (cases), compared with those who have not attended colposcopy (controls). The prevalence and excess risk of female sexual dysfunction will be determined. Logistic regression will identify the predictors of adverse outcomes. Discussion There are more than 400,000 colposcopy appointments each year in England, of which 134,000 are new referrals. There is some evidence that there may be long-term implications for women treated under colposcopy with respect to adverse obstetric outcomes, persisting anxiety, increased rates of sexual dysfunction and reduced quality of life. Reliably establishing whether such adverse outcomes exist and the excess risk of adverse events will facilitate informed decision-making and patient choice.</p