Müller glia activation in response to inherited retinal degeneration is highly varied and disease-specific

Despite different aetiologies, most inherited retinal disorders culminate in photoreceptor loss, which induces concomitant changes in the neural retina, one of the most striking being reactive gliosis by Müller cells. It is typically assumed that photoreceptor loss leads to an upregulation of glial fibrilliary acidic protein (Gfap) and other intermediate filament proteins, together with other gliosis-related changes, including loss of integrity of the outer limiting membrane (OLM) and deposition of proteoglycans. However, this is based on a mix of both injury-induced and genetic causes of photoreceptor loss. There are very few longitudinal studies of gliosis in the retina and none comparing these changes across models over time. Here, we present a comprehensive spatiotemporal assessment of features of gliosis in the degenerating murine retina that involves Müller glia. Specifically, we assessed Gfap, vimentin and chondroitin sulphate proteoglycan (CSPG) levels and outer limiting membrane (OLM) integrity over time in four murine models of inherited photoreceptor degeneration that encompass a range of disease severities (Crb1rd8/rd8, Prph2+/Δ307, Rho-/-, Pde6brd1/rd1). These features underwent very different changes, depending upon the disease-causing mutation, and that these changes are not correlated with disease severity. Intermediate filament expression did indeed increase with disease progression in Crb1rd8/rd8 and Prph2+/Δ307, but decreased in the Prph2+/Δ307 and Pde6brd1/rd1 models. CSPG deposition usually, but not always, followed the trends in intermediate filament expression. The OLM adherens junctions underwent significant remodelling in all models, but with differences in the composition of the resulting junctions; in Rho-/- mice, the adherens junctions maintained the typical rod-Müller glia interactions, while in the Pde6brd1/rd1 model they formed predominantly between Müller cells in late stage of degeneration. Together, these results show that gliosis and its associated processes are variable and disease-dependent

Pain and delirium: mechanisms, assessment, and management

Purpose: Pain and delirium are common problems for older people. Both conditions are prevalent in acute hospital settings. In people living in the community, delirium often precipitates presentation to the emergency department. Pain and delirium are known to interact in a complex and multidirectional way. This can make it challenging for staff to recognize and treat pain in people with delirium. Methods: This paper aims to explore the complex relationship between pain and delirium and on pain assessment in delirium, drawing together evidence from a range of settings including acute medical, cardiac and orthopaedic post-operative cohorts, as well as from aged care. Results: A limited number of studies suggest there is an association between pain and delirium; however, this is a complex, particularly where analgesics which may-themselves cause delirium are prescribed. Factors acting on the pathway between pain and delirium may include depression, sleep deprivation and disturbance of the cholinergic system. Delirium affects the ability to self-report pain. The fluctuating nature of delirium as well as reduced awareness and attention may challenge practitioners in recognizing, assessing and treating pain. Evidence concerning the reliability and validity of current observational and self-assessment tools in people with delirium is unclear but some show promise in this population. Conclusion: The current evidence base regarding assessing pain in people with delirium is lacking. Tentative recommendations, drawing on current guidelines require robust testing. Guidelines for people with pain and dementia require adaptations regarding the unique characteristics of delirium. The complex interplay between dementia, pain and delirium warrants further investigation across a range of settings

Parameterized lower bound and NP-completeness of some HH-free Edge Deletion problems

For a graph $H$, the $H$-free Edge Deletion problem asks whether there exist at most $k$ edges whose deletion from the input graph $G$ results in a graph without any induced copy of $H$. We prove that $H$-free Edge Deletion is NP-complete if $H$ is a graph with at least two edges and $H$ has a component with maximum number of vertices which is a tree or a regular graph. Furthermore, we obtain that these NP-complete problems cannot be solved in parameterized subexponential time, i.e., in time $2^{o(k)}\cdot |G|^{O(1)}$, unless Exponential Time Hypothesis fails.Comment: 15 pages, COCOA 15 accepted pape

Development and psychometric evaluation of a new team effectiveness scale for all types of community adult mental health teams:a mixed-methods approach

Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice

Generalized Tu Formula and Hamilton Structures of Fractional Soliton Equation Hierarchy

With the modified Riemann-Liouville fractional derivative, a fractional Tu formula is presented to investigate generalized Hamilton structure of fractional soliton equations. The obtained results can be reduced to the classical Hamilton hierachy of ordinary calculus.Comment: 12 p

Targets for the MalI repressor at the divergent Escherichia coliK-12malX-malI promoters

Random mutagenesis has been used to identify the target DNA sites for the MalI repressor at the divergent Escherichia coli K-12 malX-malI promoters. The malX promoter is repressed by MalI binding to a DNA site located from position -24 to position -9, upstream of the malX promoter transcript start. The malI promoter is repressed by MalI binding from position +3 to position +18, downstream of the malI transcript start. MalI binding at the malI promoter target is not required for repression of the malX promoter. Similarly, MalI binding at the malX promoter target is not required for repression of the malI. Although the malX and malI promoters are regulated by a single DNA site for cyclic AMP receptor protein, they function independently and each is repressed by MalI binding to a different independent operator site

Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

ゲンショク キョウイン ニ タイスル GIS キョウイク ソノ コウソウ

鳴門教育大学情報処理センターを利用して現職教員に対して提供するGIS教育 (講習会) について計画した (表1)。講習会は2部 (A・B) 構成で、全体として終日 (実質6時間程度) 2日間であるが、A・Bは相対的に独立したものなのでいずれかのみを受講することもできる。Aは現在の地図教育の延長上で学校教育に直ちに適用可能な技能として MANDARA と Kashmir とを取り上げその操作法を説明する。BはGISへの関心を喚起することも含みつつ将来のGIS導入に備えた予備的な技能として ArcVie を用いてGISについて解説する。それぞれ講義と実習とからなる。国立情報学研究所『研究紀要公開支援事業』により電子化

Implications of Mobility Patterns and HIV Risks for HIV Prevention Among Migrant Market Vendors in Kazakhstan

Objectives. We examined the relationships between mobility characteristics and sexual risk behaviors among male and female migrant market vendors in Almaty, Kazakhstan. Methods. Participants completed a structured interview covering sociodemographics, mobility characteristics, sexual behaviors, and biomarkers for HIV, HCV, and syphilis. We used multivariate analyses to examine associations between mobility patterns and HIV risks after adjusting for sociodemographics. Results. Longer duration of a participant's last trip outside Almaty increased the odds of reporting multiple sexual partners. More frequent travel to visit family or friends was associated with multiple sexual partners and unprotected sex with steady partners. More frequent travel to buy goods in the past year was associated with multiple sexual partners. Men who traveled more often to buy goods were more likely to have purchased sex within the previous 90 days. Conclusions. Relationships between mobility patterns and sexual risk behaviors underscore the need for HIV-prevention strategies targeting the specific transmission dynamics that migrant vendors are likely to present

A decision aid to support family carers of people living with dementia towards the end-of-life: Coproduction process, outcome and reflections

BACKGROUND: Family carers of people living with dementia often need support with making decisions about care. Many find end-of-life care decisions particularly difficult. The aim of this article is to present an evidence- and theoretical-based process for developing a decision aid to support family carers of people with dementia towards the end-of-life. METHODS: Following a systematic process, we developed a decision aid using coproduction methods and matrices to synthesize data from a systematic review and qualitative interviews with people living with dementia and family carers. Data were presented to coproduction workshops of people living with dementia, family carers, practitioners and professionals. Development was guided by the Ottawa Decision Support Framework and a modified Interprofessional Shared Decision-Making model. RESULTS: The decision aid covers four decision areas: (1) changes in care; (2) eating and drinking difficulties; (3) everyday well-being; and (4) healthcare, tests and medication. We present an interactive decision aid, using a variety of approaches including written text, Frequently Asked Questions, top tips and illustrative quotes from people living with dementia and family carers. CONCLUSION: This is the first decision aid that focusses on multiple decisions towards the end-of-life in dementia care. The process offers a template for others to develop decision aids or similar interventions, and how to include people living with dementia in coproduction. PATIENT OR PUBLIC CONTRIBUTION: Family carers provided feedback on data collection, data analysis and the decision aid, and one is a coauthor. People living with dementia and family carers were integral to the coproduction workshops