Differential surface activation of the A1 domain of von Willebrand factor

The clotting protein von Willebrand factor (VWF) binds to platelet receptor glycoprotein Ibα (GPIbα) when VWF is activated by chemicals, high shear stress, or immobilization onto surfaces. Activation of VWF by surface immobilization is an important problem in the failure of cardiovascular implants, but is poorly understood. Here, the authors investigate whether some or all surfaces can activate VWF at least in part by affecting the orientation or conformation of the immobilized GPIbα-binding A1 domain of VWF. Platelets binding to A1 adsorbed onto polystyrene surfaces translocated rapidly at moderate and high flow, but detached at low flow, while platelets binding to A1 adsorbed onto glass or tissue-culture treated polystyrene surfaces translocated slowly, and detached only at high flow. Both x-ray photoelectron spectroscopy and conformation independent antibodies reported comparable A1 amounts on all surfaces. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and near-edge x-ray absorption fine structure spectra suggested differences in orientation on the three surfaces, but none that could explain the biological data. Instead, ToF-SIMS data and binding of conformation-dependent antibodies were consistent with the stabilization of an alternative more activated conformation of A1 by tissue culture polystyrene and especially glass. These studies demonstrate that different materialsurfaces differentially affect the conformation of adsorbed A1 domain and its biological activity. This is important when interpreting or designing in vitro experiments with surface-adsorbed A1 domain, and is also of likely relevance for blood-contacting biomaterials

Beyond the project: building a strategic theory of change to address dementia care, treatment and support gaps across seven middle-income countries

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22–49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process

Equation of state of stishovite and interpretation of SiO 2 shock‐compression data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95606/1/jgrb13349.pd

Typologies of caregiving: Understanding support needs of carers across four continents

Background Caregivers play an essential role in supporting people living with Alzheimer’s disease globally. Cross-country research on caregivers’ experiences of coping is a prerequisite to developing useful trans-cultural guidelines for support organisations. While some coping strategies of caregivers globally have been identified, these are neither well understood or elaborated, nor linked effectively into carer support offerings. Methods In partnership with Alzheimer’s Disease International (ADI) and Roche, we conducted in-depth qualitative interviews with photo-elicitation with 34 caregivers from UK, US, Brazil, and South Africa to understand critical factors in coping during and after the pandemic. Inductive narrative analysis of data and participant generated images coded to dominant themes (Relationships and Caring role) were developed with input from global and national charity and industry sectors. Results We uncovered four caregiving styles: Empaths used emotion-focused strategies to construct their caring role ('put yourself in that person’s shoes’). They tended to develop strong coping skills, but needed psychosocial support and time specific information. Organisers used problem-focused strategies and sought information and training early on ('I’m a pretty good expert now’). They developed strong narratives of organisation, advocacy and expertise. Non-identifiers managed some aspects of the caring role but felt isolated and lacked knowledge and expertise ('do everything I can…there’s nobody else’). They sought others to manage disease related support. Reluctants struggled with unwanted caring duties ('I didn’t sign up for this’). They needed support in coming to terms with their loved one’s diagnosis and professional help with the day-to-day caring role. Conclusion Our findings highlight the need for tailored user-driven support offerings, that begin with the individual carer’s experiences and needs. Our typology will be used in the communication and development of findings and best practice guidelines to inform charities and policy makers about cost effective ways of tailoring support to fit individual carer circumstances globally

Impact and Mortality of COVID-19 on People Living With Dementia: Cross-Country Report

This report brings together international evidence on the impact of the COVID-19 pandemic on people living with dementia and an overview of international policy and practice measures to mitigate the impact of COVID-19 among people living with dementia. Key Findings We have collected data on impact and mortality of COVID-19 in people living with dementia in 9 countries: The United Kingdom (UK), Spain, Ireland, Italy, Australia, the United States (US), India, Kenya and Brazil. The share of people whose deaths were linked to COVID-19 in care homes who had dementia ranges from 29% to 75% across those countries. Within countries, people with dementia account for 25% of all COVID-19 related deaths in England and Wales, 31% in Scotland and 19% in Italy. We did not find nation-level data for the rest of the countries. The high rates of deaths in people living with dementia seem to be linked to death rates in care homes, where many residents have dementia. Direct comparison between countries is not possible due to differences in systems of information: the types of data collected and ways in which they are reported, metrics used and varying definitions of COVID-19 cases and care home facilities. The different approaches to collecting and reporting data across different administrative or autonomous regions within the same nation also hinders the extraction of national-level figures in some countries (e.g. the 4 countries in the UK, the 17 Autonomous Communities in Spain and the different administrative regions in Italy). In many places, the basic human rights of people with dementia may have been compromised during the pandemic. These rights include access to Intensive Care Units, hospital admissions, health care and palliative care. The controversial ban on visits (including spouses and care partners) to care homes across the world, have kept people with dementia detached from essential affective bonds and provision of family care for many months. There is now a pressing need and also an opportunity for innovation, looking at new ways of providing services such as allowing visits to care homes and access to healthcare. Excellent examples of both are contained in this report. Guidelines and tools to support institutions and practitioners to respond better to the needs of people with dementia during the pandemic are needed as a matter of urgency. Confinement, isolation and many of the challenges brought about by the pandemic are detrimental to the cognitive and mental health symptoms in people with dementia across the world, both those living in the community and care homes1 . This report offers a list of short-term and long-term actions needed to ensure that people with dementia are not being left behind in this pandemic or future ones

Outcomes of clinical utility in amyloid-PET studies: state of art and future perspectives

Purpose: To review how outcomes of clinical utility are operationalized in current amyloid-PET validation studies, to prepare for formal assessment of clinical utility of amyloid-PET-based diagnosis. Methods: Systematic review of amyloid-PET research studies published up to April 2020 that included outcomes of clinical utility. We extracted and analyzed (a) outcome categories, (b) their definition, and (c) their methods of assessment. Results: Thirty-two studies were eligible. (a) Outcome categories were clinician-centered (found in 25/32 studies, 78%), patient-/caregiver-centered (in 9/32 studies, 28%), and health economics-centered (5/32, 16%). (b) Definition: Outcomes were mainly defined by clinical researchers; only the ABIDE study expressly included stakeholders in group discussions. Clinician-centered outcomes mainly consisted of incremental diagnostic value (25/32, 78%) and change in patient management (17/32, 53%); patient-/caregiver-centered outcomes considered distress after amyloid-pet-based diagnosis disclosure (8/32, 25%), including quantified burden of procedure for patients’ outcomes (n = 8) (1/8, 12.5%), impact of disclosure of results (6/8, 75%), and psychological implications of biomarker-based diagnosis (75%); and health economics outcomes focused on costs to achieve a high-confidence etiological diagnosis (5/32, 16%) and impact on quality of life (1/32, 3%). (c) Assessment: all outcome categories were operationalized inconsistently across studies, employing 26 different tools without formal rationale for selection. Conclusion: Current studies validating amyloid-PET already assessed outcomes for clinical utility, although non-clinician-based outcomes were inconsistent. A wider participation of stakeholders may help produce a more thorough and systematic definition and assessment of outcomes of clinical utility and help collect evidence informing decisions on reimbursement of amyloid-PET

Outcomes of clinical utility in amyloid-PET studies: state of art and future perspectives.

PurposeTo review how outcomes of clinical utility are operationalized in current amyloid-PET validation studies, to prepare for formal assessment of clinical utility of amyloid-PET-based diagnosis.MethodsSystematic review of amyloid-PET research studies published up to April 2020 that included outcomes of clinical utility. We extracted and analyzed (a) outcome categories, (b) their definition, and (c) their methods of assessment.ResultsThirty-two studies were eligible. (a) Outcome categories were clinician-centered (found in 25/32 studies, 78%), patient-/caregiver-centered (in 9/32 studies, 28%), and health economics-centered (5/32, 16%). (b) Definition: Outcomes were mainly defined by clinical researchers; only the ABIDE study expressly included stakeholders in group discussions. Clinician-centered outcomes mainly consisted of incremental diagnostic value (25/32, 78%) and change in patient management (17/32, 53%); patient-/caregiver-centered outcomes considered distress after amyloid-pet-based diagnosis disclosure (8/32, 25%), including quantified burden of procedure for patients' outcomes (n = 8) (1/8, 12.5%), impact of disclosure of results (6/8, 75%), and psychological implications of biomarker-based diagnosis (75%); and health economics outcomes focused on costs to achieve a high-confidence etiological diagnosis (5/32, 16%) and impact on quality of life (1/32, 3%). (c) Assessment: all outcome categories were operationalized inconsistently across studies, employing 26 different tools without formal rationale for selection.ConclusionCurrent studies validating amyloid-PET already assessed outcomes for clinical utility, although non-clinician-based outcomes were inconsistent. A wider participation of stakeholders may help produce a more thorough and systematic definition and assessment of outcomes of clinical utility and help collect evidence informing decisions on reimbursement of amyloid-PET

Clinical research in dementia: A perspective on implementing innovation

The increasing global prevalence of dementia demands concrete actions that are aimed strategically at optimizing processes that drive clinical innovation. The first step in this direction requires outlining hurdles in the transition from research to practice. The different parties needed to support translational processes have communication mismatches; methodological gaps hamper evidence-based decision-making; and data are insufficient to provide reliable estimates of long-term health benefits and costs in decisional models. Pilot projects are tackling some of these gaps, but appropriate methods often still need to be devised or adapted to the dementia field. A consistent implementation perspective along the whole translational continuum, explicitly defined and shared among the relevant stakeholders, should overcome the "research-versus-adoption" dichotomy, and tackle the implementation cliff early on. Concrete next steps may consist of providing tools that support the effective participation of heterogeneous stakeholders and agreeing on a definition of clinical significance that facilitates the selection of proper outcome measures

Equity and balance in applied dementia research: A charter of conduct and checklist for global collaborations

International audienc