Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants

BACKGROUND: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants. METHODS: We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group. RESULTS: Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning. CONCLUSION: In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed. TRIAL REGISTRATION: PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016

Ethical Issues in the Development of Readiness Cohorts in Alzheimer's Disease Research.

There is growing interest in the development of novel approaches to secondary prevention trials in Alzheimer's disease to facilitate screening and recruitment of research participants and to reduce the time and costs associated with clinical trials. Several international research collaborations are setting up research infrastructures that link existing research cohorts, studies or patient registries to establish 'trial-ready' or 'readiness' cohorts. From these cohorts, individuals are recruited into clinical trial platforms. In setting up such research infrastructures, researchers must make ethically challenging design decisions in at least three areas: re-contacting participants in existing research studies, obtaining informed consent for participation in a readiness cohort, and disclosure of Alzheimer's disease-related biomarkers. These ethical considerations have been examined by a dedicated workgroup within the European Prevention of Alzheimer's Dementia (EPAD) project, a trans-European longitudinal cohort and adaptive proof-of-concept clinical trial platform. This paper offers recommendations for the ethical management of re-contact, informed consent and risk disclosure which may be of value to other research collaborations in the process of developing readiness cohorts for prevention trials in Alzheimer's disease and other disease areas.This work was funded through the Ethical Legal and Social Implications work package of the European Prevention of Alzheimer’s Dementia (EPAD) study EPAD receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115736, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. RM was also funded through the UK National Institute of Health Research grant to the Cambridge Biomedical Research Centre

An analysis of passive earth pressure modification due to seepage flow effects

Using an assumed vertical retaining wall with a drainage system along the soil-structure interface, this paper analyses the effect of anisotropic seepage flow on the development of passive earth pressure. Extremely unfavourable seepage flow inside the backfill, perhaps due to heavy rainfall, will dramatically increase the active earth pressure while reducing the passive earth pressure; thus increasing the probability of instability of the retaining structure. In this paper, a trial and error analysis based on limit equilibrium is applied to identify the optimum failure surface. The flow field is computed using Fourier series expansion, and the effective reaction force along the curved failure surface is obtained by solving a modified Kötter equation considering the effect of seepage flow. This approach correlates well with other existing results. For small values of both the internal friction angle and the interface friction angle, the failure surface can be appropriately simplified with a planar approximation. A parametric study indicates that the degree of anisotropic seepage flow affects the resulting passive earth pressure. In addition, incremental increases in the effective friction angle and interface friction both lead to an increase in the passive earth pressure.National Key Basic Research Program of China (No. 2015CB057801), the National Key R & D program of China (No. 2016YFC0800204), and Natural Science Foundation of China (Nos. 51578499 & 51761130078)

Strategi Dinas Kehutanan dan Perkebunan Kabupaten Kepulauan Meranti dalam Mengkomunikasikan Gerakan Rehabilitasi Hutan dan Lah Mangrove

Damaged forests can cause disasters such as floods and landslides. This also happens in one region of Indonesia, Meranti Islands district have also suffered damage from natural disasters or human activity itself, forest destruction worst that happened in the district of Meranti namely mangrove forests, where the destruction of mangrove forests could impact beach abrasion. The purpose of this study was to determine how the Department of Forestry and Plantation Meranti Islands regency in running communication strategy in the program implementation mangrove forest and land rehabilitation.In this study the authors used a qualitative research method with a phenomenological approach. Data collection techniques are grouped through observation, interviews and documentation. The informant in this research were six people who were taken by purposive sampling techniques, ie 5 civil servants and 1 community. Interactive data analysis type the researchers use to describe the results of research into techniques for data analysis and data validity checking researcher using triangulation techniques.The results in which the communication strategy is executed in accordance with the steps of planning strategies, ie; to identify their communication, communication media selection and assessment destination of the message. From interviews and observations of researchers got field indicates that the Department of Forestry and Plantation Regency Meranti has been doing business in recognizing the target of communication, working with some of the media, both print and electronic media as well as services to create and examine the messages to be conveyed to the public related program mangrove forest and land rehabilitation

Involving research participants in a pan-European research initiative: the EPAD participant panel experience

Abstract: Background: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. Methods: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. Results: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. Conclusions: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations

Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review.

BACKGROUND: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants. METHODS: We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group. RESULTS: Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning. CONCLUSION: In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed. TRIAL REGISTRATION: PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016

A tiered-layered-staged model for informed consent in personal genome testing

In recent years, developments in genomics technologies have led to the rise of commercial personal genome testing (PGT): broad genome-wide testing for multiple diseases simultaneously. While some commercial providers require physicians to order a personal genome test, others can be accessed directly. All providers advertise directly to consumers and offer genetic risk information about dozens of diseases in one single purchase. The quantity and the complexity of risk information pose challenges to adequate pre-test and post-test information provision and informed consent. There are currently no guidelines for what should constitute informed consent in PGT or how adequate informed consent can be achieved. In this paper, we propose a tiered-layered-staged model for informed consent. First, the proposed model is tiered as it offers choices between categories of diseases that are associated with distinct ethical, personal or societal issues. Second, the model distinguishes layers of information with a first layer offering minimal, indispensable information that is material to all consumers, and additional layers offering more detailed information made available upon request. Finally, the model stages informed consent as a process by feeding information to consumers in each subsequent stage of the process of undergoing a test, and by accommodating renewed consent for test result updates, resulting from the ongoing development of the science underlying PGT. A tiered-layered-staged model for informed consent with a focus on the consumer perspective can help overcome the ethical problems of information provision and informed consent in direct-to-consumer PGT.European Journal of Human Genetics advance online publication, 21 November 2012; doi:10.1038/ejhg.2012.237

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Identification of CD8+ cytotoxic T lymphocyte (CTL) epitopes has traditionally relied upon testing of overlapping peptide libraries for their reactivity with T cells in vitro. Here, we pursued deep ligand sequencing (DLS) as an alternative method of directly identifying those ligands that are epitopes presented to CTLs by the class I human leukocyte antigens (HLA) of infected cells. Soluble class I HLA-A*11:01 (sHLA) was gathered from HIV-1 NL4-3-infected human CD4+ SUP-T1 cells. HLA-A*11:01 harvested from infected cells was immunoaffinity purified and acid boiled to release heavy and light chains from peptide ligands that were then recovered by size-exclusion filtration. The ligands were first fractionated by high-pH high-pressure liquid chromatography and then subjected to separation by nano-liquid chromatography (nano-LC)–mass spectrometry (MS) at low pH. Approximately 10 million ions were selected for sequencing by tandem mass spectrometry (MS/MS). HLA-A*11:01 ligand sequences were determined with PEAKS software and confirmed by comparison to spectra generated from synthetic peptides. DLS identified 42 viral ligands presented by HLA-A*11:01, and 37 of these were previously undetected. These data demonstrate that (i) HIV-1 Gag and Nef are extensively sampled, (ii) ligand length variants are prevalent, particularly within Gag and Nef hot spots where ligand sequences overlap, (iii) noncanonical ligands are T cell reactive, and (iv) HIV-1 ligands are derived from de novo synthesis rather than endocytic sampling. Next-generation immunotherapies must factor these nascent HIV-1 ligand length variants and the finding that CTL-reactive epitopes may be absent during infection of CD4+ T cells into strategies designed to enhance T cell immunity