Markov, fractal, diffusion, and related models of ion channel gating. A comparison with experimental data from two ion channels

The gating kinetics of single-ion channels are generally modeled in terms of Markov processes with relatively small numbers of channel states. More recently, fractal (Liebovitch et al. 1987. Math. Biosci. 84:37–68) and diffusion (Millhauser et al. 1988. Proc. Natl. Acad. Sci. USA. 85:1502–1507) models of channel gating have been proposed. These models propose the existence of many similar conformational substrates of the channel protein, all of which contribute to the observed gating kinetics. It is important to determine whether or not Markov models provide the most accurate description of channel kinetics if progress is to be made in understanding the molecular events of channel gating. In this study six alternative classes of gating model are tested against experimental single-channel data. The single-channel data employed are from (a) delayed rectifier K+ channels of NG 108–15 cells and (b) locust muscle glutamate receptor channels. The models tested are (a) Markov, (b) fractal, (c) one-dimensional diffusion, (d) three-dimensional diffusion, (e) stretched exponential, and (f) expo-exponential. The models are compared by fitting the predicted distributions of channel open and closed times to those observed experimentally. The models are ranked in order of goodness-of-fit using a boot-strap resampling procedure. The results suggest that Markov models provide a markedly better description of the observed open and closed time distributions for both types of channel. This provides justification for the continued use of Markov models to explore channel gating mechanisms

Evaluation of Remediation Support in UK Dentistry

BRIEF OF APPELLEES GARLICK, PELTON AND VALLEY BANK AND TRUST APPEAL FROM THE THIRD JUDICIAL DISTRICT COURT OF SUMMIT COUNTY HONORABLE J. DENNIS FREDERICK, DISTRICT JUDG

Readiness to Succeed Preparing the Scholar-Practitioner

This report expands on a previous working group’s effort to clarify the alignment of existing scholarship around doctoral education with how students move through the process at Walden University (Salter et al., 2013). Following up on the recommendations in that report, the current working group was charged with understanding students’ readiness or preparedness to move through these stages/phases across the entire student timeline from prospect to graduate. Additionally, the group attempted to map the services currently in place to support that journey while identifying opportunities to improve it

A systematic review of the subjective wellbeing outcomes of engaging with visual arts for adults (“working-age”, 15-64 years) with diagnosed mental health conditions

The importance of the visual arts in contributing to the wellbeing of adults with mental health conditions has been little documented beyond some insightful and influential interventions and exploratory studies. Initiatives such as Arts on Prescription projects have, in the UK provided examples of the positive effects that engagement in artistic and creative activity can have, and some of these have been documented in small-scale studies of interventions. Most of the evidence has been perceived as positive but of limited scale. In this context, this review was carried out to examine in a more focused way the ‘subjective wellbeing’ (SWB) outcomes of engagement with the visual arts for adults with a background history of mental health conditions. SWB embraces both the positive and negative feelings that arise in individuals based on their view of the world, how they think about themselves and others, and what they do in the interactions and practices of everyday life. Adult subjects in the studies included in this review were of ‘working-age’ (15-64 years). The focus of the review and the precise research question were agreed at inception sessions of the research team, and in collaborative engagement with stakeholders in the areas of policy, service-delivery, project and evaluation commissioning, and research and scholarship in the spheres of the visual arts and mental health. Published studies from the past 10 years were studied for the review, and their findings synthesised and integrated into an evaluation of the state of knowledge in the field, in terms of the specifics of the research questions. We found that there is limited high-quality evidence, though case studies from the UK have provided important and consistent findings, corroborated by grey literature that has reported on interventions and projects. The review includes published findings based on data on/from 163 participants across four countries – Australia, Sweden, the UK, and the USA. Overall, female respondents outnumbered male respondents. A wide variety of wellbeing measures were used in some quantitative, statistical studies. In-depth interviews dominated the qualitative studies, giving voice to the experiences of individual subjects. The visual arts practices that featured in the studies included forms of painting or drawing, art appreciation with selected art forms, artmaking culminating in an exhibition, and more general creative and craft activities that included visual artefacts such as ceramics or sculpture. Evidence we include from recent unpublished reports (grey literature) was produced by or for visual arts organisations since 2014. Participants in the evaluations were both male and female and were engaged in UK-based arts interventions, many via community arts or ‘Arts on Prescription’ types of intervention. Overall, the evidence available in this review has shown that engagement in the visual arts for adults with mental health conditions can reduce reported levels of depression and anxiety; increase self-respect, self-worth and self-esteem; encourage and stimulate re-engagement with the wider, everyday social world; and support in participants a potential renegotiation of identity through practice-based forms of making or doing. The most effective ‘working ways to wellbeing’ are also confirmed in processes of implementation that ensure provision of secure safe-space and havens for interventions; that recognise the value of non-stigmatising settings; and that support and sustain collaborative facilitation of programmes and sessions. 4 Some negative dimensions of engagement with the visual arts were also identified, including stress and pressure felt to complete activities or commit to artmaking, and the very real fear that the end of an intervention would mean the return to a world of anxiety, decreasing confidence and social isolation. The review shows that for adults starting visual arts activities or programmes, the subjective wellbeing outcomes are, for the majority of participants, positive. This applies to men and women alike across the studies. The most convincing evidence has emerged from focused qualitative research designs, and makes clear that the most effective work in the field continues to lack the necessary resources and infrastructure that would ensure sustainable practices and interventions. Overall, there is some evidence of benefit in a weak field that could be strengthened by fuller monitoring of cohorts to evaluate the long-term effects of participants’ engagement with the visual arts

Utility of a next generation framework for assessment of genomic damage: A case study using the industrial chemical benzene

We recently published a next generation framework for assessing the risk of genomic damage via exposure to chemical substances. The framework entails a systematic approach with the aim to quantify risk levels for substances that induce genomic damage contributing to human adverse health outcomes. Here, we evaluated the utility of the framework for assessing the risk for industrial chemicals, using the case of benzene. Benzene is a well‐studied substance that is generally considered a genotoxic carcinogen and is known to cause leukemia. The case study limits its focus on occupational and general population health as it relates to benzene exposure. Using the framework as guidance, available data on benzene considered relevant for assessment of genetic damage were collected. Based on these data, we were able to conduct quantitative analyses for relevant data sets to estimate acceptable exposure levels and to characterize the risk of genetic damage. Key observations include the need for robust exposure assessments, the importance of information on toxicokinetic properties, and the benefits of cheminformatics. The framework points to the need for further improvement on understanding of the mechanism(s) of action involved, which would also provide support for the use of targeted tests rather than a prescribed set of assays. Overall, this case study demonstrates the utility of the next generation framework to quantitatively model human risk on the basis of genetic damage, thereby enabling a new, innovative risk assessment concept. Environ. Mol. Mutagen. 61:94–113, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.JRC.F.3-Chemicals Safety and Alternative Method