Analysis of Toxic Amyloid Fibril Interactions at Natively Derived Membranes by Ellipsometry

There is an ongoing debate regarding the culprits of cytotoxicity associated with amyloid disorders. Although small pre-fibrillar amyloid oligomers have been implicated as the primary toxic species, the fibrillar amyloid material itself can also induce cytotoxicity. To investigate membrane disruption and cytotoxic effects associated with intact and fragmented fibrils, the novel in situ spectroscopic technique of Total Internal Reflection Ellipsometry (TIRE) was used. Fibril lipid interactions were monitored using natively derived whole cell membranes as a model of the in vivo environment. We show that fragmented fibrils have an increased ability to disrupt these natively derived membranes by causing a loss of material from the deposited surface when compared with unfragmented fibrils. This effect was corroborated by observations of membrane disruption in live cells, and by dye release assay using synthetic liposomes. Through these studies we demonstrate the use of TIRE for the analysis of protein-lipid interactions on natively derived lipid surfaces, and provide an explanation on how amyloid fibrils can cause a toxic gain of function, while entangled amyloid plaques exert minimal biological activity

Women’s Prodromal Myocardial Infarction Symptom Perception, Attribution, and Care Seeking

Most women experience several prodromal symptoms prior to myocardial infarction (MI). While investigators have focused on acuteMI symptom perception, attribution, and care seeking, few have studied how women experience and process prodromalMI symptoms and ultimately decide to seek care

A Holistic Exploration of Fatigue Experienced by Women before a Myocardial Infarction

Most women report fatigue in the weeks and months leading to a myocardial infarction (MI). However, fatigue is a complex phenomenon. Dimensions of this MI related fatigue, such as timing, distress, intensity, quality, patterns, and associated characteristics have not been established through focused study of this symptom. A lack of a holistic understanding of this symptom makes clinical decision making difficult, given that fatigue is a frequently reported symptom overall

Excavations and the afterlife of a professional football stadium, Peel Park, Accrington, Lancashire: towards an archaeology of football

Association football is now a multi-billion dollar global industry whose emergence spans the post-medieval to the modern world. With its professional roots in late 19th-century industrial Lancashire, stadiums built for the professionalization of football first appear in frequency in the North of England. While many historians of sport focus on consumerism and ‘topophilia’ (attachment to place) regarding these local football grounds, archaeological research that has been conducted on the spectator experience suggests status differentiation within them. Our excavations at Peel Park confirm this impression while also showing a significant afterlife to this stadium, particularly through children’s play

Physiologically based kinetic (PBK) modelling and human biomonitoring data for mixture risk assessment

Human biomonitoring (HBM) data can provide insight into co-exposure patterns resulting from exposure to multiple chemicals from various sources and over time. Therefore, such data are particularly valuable for assessing potential risks from combined exposure to multiple chemicals. One way to interpret HBM data is establishing safe levels in blood or urine, called Biomonitoring Equivalents (BE) or HBM health based guidance values (HBM-HBGV). These can be derived by converting established external reference values, such as tolerable daily intake (TDI) values. HBM-HBGV or BE values are so far agreed only for a very limited number of chemicals. These values can be established using physiologically based kinetic (PBK) modelling, usually requiring substance specific models and the collection of many input parameters which are often not available or difficult to find in the literature. The aim of this study was to investigate the suitability and limitations of generic PBK models in deriving BE values for several compounds with a view to facilitating the use of HBM data in the assessment of chemical mixtures at a screening level. The focus was on testing the methodology with two generic models, the IndusChemFate tool and High-Throughput Toxicokinetics package, for two different classes of compounds, phenols and phthalates. HBM data on Danish children and on Norwegian mothers and children were used to evaluate the quality of the predictions and to illustrate, by means of a case study, the overall approach of applying PBK models to chemical classes with HBM data in the context of chemical mixture risk assessment. Application of PBK models provides a better understanding and interpretation of HBM data. However, the study shows that establishing safety threshold levels in urine is a difficult and complex task. The approach might be more straightforward for more persistent chemicals that are analysed as parent compounds in blood but high uncertainties have to be considered around simulated metabolite concentrations in urine. Refining the models may reduce these uncertainties and improve predictions. Based on the experience gained with this study, the performance of the models for other chemicals could be investigated, to improve the accuracy of the simulations

Clinical Performance Feedback Intervention Theory (CP-FIT): a new theory for designing, implementing, and evaluating feedback in health care based on a systematic review and meta-synthesis of qualitative research

Background: Providing health professionals with quantitative summaries of their clinical performance when treating specific groups of patients (“feedback”) is a widely used quality improvement strategy, yet systematic reviews show it has varying success. Theory could help explain what factors influence feedback success, and guide approaches to enhance effectiveness. However, existing theories lack comprehensiveness and specificity to health care. To address this problem, we conducted the first systematic review and synthesis of qualitative evaluations of feedback interventions, using findings to develop a comprehensive new health care-specific feedback theory. Methods: We searched MEDLINE, EMBASE, CINAHL, Web of Science, and Google Scholar from inception until 2016 inclusive. Data were synthesised by coding individual papers, building on pre-existing theories to formulate hypotheses, iteratively testing and improving hypotheses, assessing confidence in hypotheses using the GRADE-CERQual method, and summarising high-confidence hypotheses into a set of propositions. Results: We synthesised 65 papers evaluating 73 feedback interventions from countries spanning five continents. From our synthesis we developed Clinical Performance Feedback Intervention Theory (CP-FIT), which builds on 30 pre-existing theories and has 42 high-confidence hypotheses. CP-FIT states that effective feedback works in a cycle of sequential processes; it becomes less effective if any individual process fails, thus halting progress round the cycle. Feedback’s success is influenced by several factors operating via a set of common explanatory mechanisms: the feedback method used, health professional receiving feedback, and context in which feedback takes place. CP-FIT summarises these effects in three propositions: (1) health care professionals and organisations have a finite capacity to engage with feedback, (2) these parties have strong beliefs regarding how patient care should be provided that influence their interactions with feedback, and (3) feedback that directly supports clinical behaviours is most effective. Conclusions: This is the first qualitative meta-synthesis of feedback interventions, and the first comprehensive theory of feedback designed specifically for health care. Our findings contribute new knowledge about how feedback works and factors that influence its effectiveness. Internationally, practitioners, researchers, and policy-makers can use CP-FIT to design, implement, and evaluate feedback. Doing so could improve care for large numbers of patients, reduce opportunity costs, and improve returns on financial investments

COVID-19 impact on social work admissions and education in seven international universities

Inter-country Social Work admissions and educational comparisons are difficult due to variance in policy and practices between Social Work educational providers, even within the same country. However, this paper aims to provide an examination of different levels of impact that COVID-19 ‘lockdown’ had on ‘admissions to social work’ processes and on education, using examples from universities in Australia, England, Finland, Northern Ireland, Norway, Ireland and Sweden. Already we know that across these examples, admissions processes differ significantly. Variances are between selection and entry methodologies with some institutions using academic entry criteria and personal statements and interviews, while others use academic entry criteria and relevant experience or academic entry only. We also know that practicum duration is variable across providers, lasting between seventy-five and two hundred days. Despite all differences, a distinct adjustment to lockdown required a shift to virtual teaching methods for each institution. This paper seeks to explore the range of approaches adopted to lockdown in relation to practice learning placements in each example. We consider the underpinning values and principles that guided responses to these change processes in the various institutions and longer-term implications emerging from the required rapid change processes are discussed

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

<b>Background</b> 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.<p></p> <b>Objectives</b> 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.<p></p> <b>Methods</b> 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.<p></p> <b>Discussion</b> 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

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p> <b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p> <b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts