Increased Concentration of Polyvalent Phospholipids in the Adsorption Domain of a Charged Protein

We studied the adsorption of a charged protein onto an oppositely charged membrane, composed of mobile phospholipids of differing valence, using a statistical-thermodynamical approach. A two-block model was employed, one block corresponding to the protein-affected region on the membrane, referred to as the adsorption domain, and the other to the unaffected remainder of the membrane. We calculated the protein-induced lipid rearrangement in the adsorption domain as arising from the interplay between the electrostatic interactions in the system and the mixing entropy of the lipids. Equating the electrochemical potentials of the lipids in the two blocks yields an expression for the relations among the various lipid fractions in the adsorption domain, indicating a sensitive dependence of lipid fraction on valence. This expression is a result of the two-block picture but does not depend on further details of the protein-membrane interaction. We subsequently calculated the lipid fractions themselves using the Poisson-Boltzmann theory. We examined the dependence of lipid enrichment, i.e., the ratio between the lipid fractions inside and outside the adsorption domain, on various parameters such as ionic strength and lipid valence. Maximum enrichment was found for lipid valence of about (-3) to (-4) in physiological conditions. Our results are in qualitative agreement with recent experimental studies on the interactions between peptides having a domain of basic residues and membranes containing a small fraction of the polyvalent phosphatidylinositol 4,5-bisphosphate (PIP2). This study provides theoretical support for the suggestion that proteins adsorbed onto membranes through a cluster of basic residues may sequester PIP2 and other polyvalent lipids.Comment: 25 pages, 12 figure

Sheaf theory for stacks in manifolds and twisted cohomology for S^1-gerbes

This is the first of a series of papers on sheaf theory on smooth and topological stacks and its applications. The main result of the present paper is the characterization of the twisted (by a closed integral three-form) de Rham complex on a manifold. As an object in the derived category it will be related with the push-forward of the constant sheaf from a S^1-gerbe with Dixmier-Douady class represented by the three-form. In order to formulate and prove this result we develop in detail the foundations of sheaf theory for smooth stacks.Comment: 39 pages, v2 typos corrected and references added. v3 confusion in 2.2.5 cleaned u

From theory to 'measurement' in complex interventions: methodological lessons from the development of an e-health normalisation instrument

<b>Background</b> Although empirical and theoretical understanding of processes of implementation in health care is advancing, translation of theory into structured measures that capture the complex interplay between interventions, individuals and context remain limited. This paper aimed to (1) describe the process and outcome of a project to develop a theory-based instrument for measuring implementation processes relating to e-health interventions; and (2) identify key issues and methodological challenges for advancing work in this field.<p></p> <b>Methods</b> A 30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring normalisation processes in the context of e-health service interventions was developed on the basis on Normalization Process Theory (NPT). NPT focuses on how new practices become routinely embedded within social contexts. The instrument was pre-tested in two health care settings in which e-health (electronic facilitation of healthcare decision-making and practice) was used by health care professionals.<p></p> <b>Results</b> The developed instrument was pre-tested in two professional samples (N = 46; N = 231). Ratings of items representing normalisation 'processes' were significantly related to staff members' perceptions of whether or not e-health had become 'routine'. Key methodological challenges are discussed in relation to: translating multi-component theoretical constructs into simple questions; developing and choosing appropriate outcome measures; conducting multiple-stakeholder assessments; instrument and question framing; and more general issues for instrument development in practice contexts.<p></p> <b>Conclusions</b> To develop theory-derived measures of implementation process for progressing research in this field, four key recommendations are made relating to (1) greater attention to underlying theoretical assumptions and extent of translation work required; (2) the need for appropriate but flexible approaches to outcomes measurement; (3) representation of multiple perspectives and collaborative nature of work; and (4) emphasis on generic measurement approaches that can be flexibly tailored to particular contexts of study

Ionising radiation exposure from medical imaging – A review of Patient's (un) awareness

Introduction: Medical imaging is the main source of artificial radiation exposure. Evidence, however, suggests that patients are poorly informed about radiation exposure when attending diagnostic scans. This review provides an overview of published literature with a focus on nuclear medicine patients on the level of awareness of radiation exposure from diagnostic imaging. Methods: A review of available literature on awareness, knowledge and perception of ionising radiation in medical imaging was conducted. Articles that met the inclusion criteria were subjected to critical appraisal using the Mixed Methods Appraisal Tool. Results: 140 articles identified and screened for eligibility, 24 critically assessed and 4 studies included in synthesis. All studies demonstrated that patients were generally lacking awareness about radiation exposure and highlighted a lack of communication between healthcare professionals and patients with respect to radiation exposure. Conclusion: Studies demonstrate a need to better inform patients about their radiation exposure, and further studies focusing on nuclear medicine patients are particularly warranted. Implications for practice: Adequate and accurate information is crucial to ensure the principle of informed consent is present

Factors that promote or inhibit the implementation of e-health systems: an explanatory systematic review

OBJECTIVE: To systematically review the literature on the implementation of e-health to identify: (i) barriers and facilitators to e-health implementation, and (ii) outstanding gaps in research on the subject.METHODS: MEDLINE, EMBASE, CINAHL, PSYCINFO and the Cochrane Library were searched for reviews published between 1 January 1995 and 17 March 2009. Studies had to be systematic reviews, narrative reviews, qualitative metasyntheses or meta-ethnographies of e-health implementation. Abstracts and papers were double screened and data were extracted on country of origin; e-health domain; publication date; aims and methods; databases searched; inclusion and exclusion criteria and number of papers included. Data were analysed qualitatively using normalization process theory as an explanatory coding framework.FINDINGS: Inclusion criteria were met by 37 papers; 20 had been published between 1995 and 2007 and 17 between 2008 and 2009. Methodological quality was poor: 19 papers did not specify the inclusion and exclusion criteria and 13 did not indicate the precise number of articles screened. The use of normalization process theory as a conceptual framework revealed that relatively little attention was paid to: (i) work directed at making sense of e-health systems, specifying their purposes and benefits, establishing their value to users and planning their implementation; (ii) factors promoting or inhibiting engagement and participation; (iii) effects on roles and responsibilities; (iv) risk management, and (v) ways in which implementation processes might be reconfigured by user-produced knowledge.CONCLUSION: The published literature focused on organizational issues, neglecting the wider social framework that must be considered when introducing new technologies.<br/

Radiation exposure awareness from patients undergoing nuclear medicine diagnostic 99mTc-MDP bone scans and 2-deoxy-2-(18F) fluoro-D-glucose PET/computed tomography scans

INTRODUCTION: Medical imaging is on average the largest source of artificial radiation exposure worldwide. This study seeks to understand patient's awareness of radiation exposure derived from nuclear medicine diagnostic scans and assess if current information provided by leaflets is adequate. METHODS: Single-centre cross-sectional questionnaire study applied to bone scan and FDG PET/computed tomography patients, at a nuclear medicine and PET/computed tomography department over a 15-week period in 2018. Questionnaires on dose comparators were designed in collaboration with patients, public, and experts in radiation exposure. Qualitative data were analysed using thematic analysis and quantitative data using SPSS (V. 24). RESULTS: A total of 102 questionnaires were completed (bone scan = 50; FDG PET/computed tomography = 52). Across both groups, 33/102 (32.4%) patients reported having a reasonable understanding of nuclear medicine and 21/102 (20.6%) reported a reasonable knowledge of ionising radiations. When asked to compare the exposure dose of respective scans with common comparators 8/50 (16%) of bone scan patients and 11/52 (21.2%) FDG PET/computed tomography answered correctly. On leaflet information, 15/85 (17.6%) patients reported the leaflets do not provide enough information on radiation exposure and of these 10/15 (66.7%) commented the leaflets should incorporate more information on radiation exposure dose. CONCLUSION: More observational and qualitative studies in collaboration with patients are warranted to evaluate patients' understanding and preferences in communication of radiation exposure from nuclear medicine imaging. This will ensure communication tools and guidelines developed to comply with ionising radiation (medical exposure) regulation 2017 are according to patients needs and preferences

Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

&lt;b&gt;Background&lt;/b&gt; Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objectives&lt;/b&gt; The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Discussion&lt;/b&gt; The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices

Statistics of extinction and survival in Lotka-Volterra systems

We analyze purely competitive many-species Lotka-Volterra systems with random interaction matrices, focusing the attention on statistical properties of their asymptotic states. Generic features of the evolution are outlined from a semiquantitative analysis of the phase-space structure, and extensive numerical simulations are performed to study the statistics of the extinctions. We find that the number of surviving species depends strongly on the statistical properties of the interaction matrix, and that the probability of survival is weakly correlated to specific initial conditions.Comment: Previous version had error in authors. 11 pages, including 5 figure

Promiscuity and the Evolution of Sexual Transmitted Diseases

We study the relation between different social behaviors and the onset of epidemics in a model for the dynamics of sexual transmitted diseases. The model considers the society as a system of individual sexuated agents that can be organized in couples and interact with each other. The different social behaviors are incorporated assigning what we call a promiscuity value to each individual agent. The individual promiscuity is taken from a distributions and represents the daily probability of going out to look for a sexual partner, abandoning its eventual mate. In terms of this parameter we find a threshold for the epidemic which is much lower than the classical fully mixed model prediction, i.e. $R_0$ (basic reproductive number) $= 1$. Different forms for the distribution of the population promiscuity are considered showing that the threshold is weakly sensitive to them. We study the homosexual and the heterosexual case as well.Comment: 6 pages, 4 figure

Noise and Correlations in a Spatial Population Model with Cyclic Competition

Noise and spatial degrees of freedom characterize most ecosystems. Some aspects of their influence on the coevolution of populations with cyclic interspecies competition have been demonstrated in recent experiments [e.g. B. Kerr et al., Nature {\bf 418}, 171 (2002)]. To reach a better theoretical understanding of these phenomena, we consider a paradigmatic spatial model where three species exhibit cyclic dominance. Using an individual-based description, as well as stochastic partial differential and deterministic reaction-diffusion equations, we account for stochastic fluctuations and spatial diffusion at different levels, and show how fascinating patterns of entangled spirals emerge. We rationalize our analysis by computing the spatio-temporal correlation functions and provide analytical expressions for the front velocity and the wavelength of the propagating spiral waves.Comment: 4 pages of main text, 3 color figures + 2 pages of supplementary material (EPAPS Document). Final version for Physical Review Letter