Exploitation and community engagement: Can Community Advisory Boards successfully assume a role minimising exploitation in international research?

It has been suggested that community advisory boards (CABs) can play a role in minimising exploitation in international research. To get a better idea of what this requires and whether it might be achievable, the paper first describes core elements that we suggest must be in place for a CAB to reduce the potential for exploitation. The paper then examines a CAB established by the Shoklo Malaria Research Unit under conditions common in resource‐poor settings – namely, where individuals join with a very limited understanding of disease and medical research and where an existing organisational structure is not relied upon to serve as the CAB. Using the Tak Province Border Community Ethics Advisory Board (T‐CAB) as a case study, we assess the extent to which it might be able to take on a role minimising exploitation were it to decide to do so. We investigate whether, after two years in operation, T‐CAB is capable of assessing clinical trials for exploitative features and addressing those found to have them. The findings show that, although T‐CAB members have gained knowledge and developed capacities that are foundational for one‐day taking on a role to reduce exploitation, their ability to critically evaluate studies for the presence of exploitative elements has not yet been strongly demonstrated. In light of this example, we argue that CABs may not be able to perform such a role for a number of years after initial formation, making it an unsuitable responsibility for many short‐term CABs.     

Biobank governance: a lesson in trust

Biobanks are controversial due to their ethical, legal, and social implications. Recent discussion has highlighted a central role for governance in helping to address these controversies. We argue that sustainable governance of biobanks needs to be informed by public discourse. We present an analysis of a deliberative public engagement to explore the public values, concerns, and interests underlying recommendations pertaining to biobank governance. In particular, we identify five themes underlying expressed goals and concerns of participants regarding the development, operation and application of biobank research. Ultimately, we argue that, for the deliberants, governance represented a way to achieve trust in biobanks through accountability, transparency and control. As discussion of biobank governance moves the conceptual to the specific, policy makers and researchers should acknowledge the importance of the public viewpoint in maintaining trust; this acknowledgement is of importance to the ultimate success and longevity of biobanks.     

Power to the people: a wiki-governance model for biobanks

Biobanks are adopting various modes of public engagement to close the agency gap between participants and biobank builders. We propose a wiki-governance model for biobanks that harnesses Web 2.0, and which gives citizens the ability to collaborate in biobank governance and policymaking.     

RECONSIDERING THE VALUE OF CONSENT IN BIOBANK RESEARCH

Biobanks for long‐term research pose challenges to the legal and ethical validity of consent to participate. Different models of consent have been proposed to answer some of these challenges. This paper contributes to this discussion by considering the meaning and value of consent to participants in biobanks. Empirical data from a qualitative study is used to provide a participant view of the consent process and to demonstrate that, despite limited understanding of the research, consent provides the research participants with some level of control and a form of self determination that they value. Participation is framed as a moral act of a responsible citizen providing reinforcement of self identity. Consent symbolizes the trust invested in researchers and research institutions to use the biobank for the public good. The paper argues that consent continues to play an important role in biobank participation and that a participant view should inform proposals to modify consent processes.     

Cloning, characterization, and heterologous expression of the Saccharopolyspora erythraea (Streptomyces erythraeus) gene encoding an EF-hand calcium-binding protein.

The regulatory effects of Ca2+ in eucaryotic cells are mostly mediated by a superfamily of Ca2+-binding proteins (CABs) that contain one or more characteristic Ca2+-binding structural motifs, referred to as EF hands. We have cloned and sequenced the structural gene for an authentic EF-hand CAB from the spore-forming gram-positive bacterium Saccharopolyspora erythraea (formerly Streptomyces erythraeus). When the gene was introduced into Streptomyces lividans on the high-copy plasmid vector pIJ702, CAB was found to be expressed at higher levels than in S. erythraea, with no apparent effects on either growth or sporulation. A more convenient expression system for CAB was obtained by introducing an NdeI site at the initiation codon by using oligonucleotide-directed mutagenesis and placing the gene in the expression vector pT7-7 in Escherichia coli. In this system, CAB was efficiently expressed at levels up to 20 to 30% of total cell protein. When purified to homogeneity from either E. coli or Streptomyces lividans, CAB was found to be identical to the protein previously obtained from S. erythraea.     

Public Opinion about the Importance of Privacy in Biobank Research

Concerns about privacy may deter people from participating in genetic research. Recruitment and retention of biobank participants requires understanding the nature and magnitude of these concerns. Potential participants in a proposed biobank were asked about their willingness to participate, their privacy concerns, informed consent, and data sharing. A representative survey of 4659 U.S. adults was conducted. Ninety percent of respondents would be concerned about privacy, 56% would be concerned about researchers having their information, and 37% would worry that study data could be used against them. However, 60% would participate in the biobank if asked. Nearly half (48%) would prefer to provide consent once for all research approved by an oversight panel, whereas 42% would prefer to provide consent for each project separately. Although 92% would allow academic researchers to use study data, 80% and 75%, respectively, would grant access to government and industry researchers. Concern about privacy was related to lower willingness to participate only when respondents were told that they would receive $50 for participation and would not receive individual research results back. Among respondents who were told that they would receive $200 or individual research results, privacy concerns were not related to willingness. Survey respondents valued both privacy and participation in biomedical research. Despite pervasive privacy concerns, 60% would participate in a biobank. Assuring research participants that their privacy will be protected to the best of researchers'' abilities may increase participants'' acceptance of consent for broad research uses of biobank data by a wide range of researchers.     

Data sharing across biobanks: epistemic values,data mutability and data incommensurability

Despite the centrality of epistemic issues in biobank knowledge generation, there is currently a lacuna in research addressing the epistemic assumptions of biobank science and data sharing. The article addresses this lacuna. Using the insights of philosophical and sociological analysis, we examine standardization and harmonization and central challenges biobank data-sharing faces. We defend two central epistemic values, namely “spatial and temporal translatability” and “epistemic adequacy” which foster effective biobank knowledge generation. The first refers to the way in which biobank data need to be re-usable and re-purposable by bioscience researchers who did not create them. Given the perennial issues of data mutability and incommensurability, we also propose “epistemic adequacy.” In uncovering the social and epistemic foundations of biobank science, we emphasize issues essential for achieving effective and transparent biobank practice and productive communication and engagement with the public about the nature, potential and limits of biobanks.     

Sugar and Chromosome Stability: Clastogenic Effects of Sugars in Vitamin B6-Deficient Cells

Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, has been implicated in preventing human pathologies, such as diabetes and cancer. However, the mechanisms underlying the beneficial effects of PLP are still unclear. Using Drosophila as a model system, we show that PLP deficiency, caused either by mutations in the pyridoxal kinase-coding gene (dPdxk) or by vitamin B6 antagonists, results in chromosome aberrations (CABs). The CAB frequency in PLP-depleted cells was strongly enhanced by sucrose, glucose or fructose treatments, and dPdxk mutant cells consistently displayed higher glucose contents than their wild type counterparts, an effect that is at least in part a consequence of an acquired insulin resistance. Together, our results indicate that a high intracellular level of glucose has a dramatic clastogenic effect if combined with PLP deficiency. This is likely due to an elevated level of Advanced Glycation End-products (AGE) formation. Treatment of dPdxk mutant cells with α-lipoic acid (ALA) lowered both AGE formation and CAB frequency, suggesting a possible AGE-CAB cause-effect relationship. The clastogenic effect of glucose in PLP-depleted cells is evolutionarily conserved. RNAi-mediated silencing of PDXK in human cells or treatments with PLP inhibitors resulted in chromosome breakage, which was potentiated by glucose and reduced by ALA. These results suggest that patients with concomitant hyperglycemia and vitamin B6 deficiency may suffer chromosome damage. This might impact cancer risk, as CABs are a well-known tumorigenic factor.     

生物样本库是生物医学研究的重要基础

在生物医学研究飞速发展的今天,随着对健康和疾病认识的不断深入,传统的单病因、单基因研究模式已难以胜任复杂疾病的研究.医学科学的发展需要一种能提供疾病相关的、具有普遍意义的、全局式的分子信息数据库.生物样本库在其中所能发挥的关键作用得到了越来越多的重视.它从最初的小作坊模式经过100多年,尤其是近30年的快速发展已经演化成为科研院所和政府支持的生物样本库、商业化生物样本库及以人口为基础的生物银行等多种模式.伴随存储样本数据信息的复杂度不断快速增加,生物样本库除了收集样本相关的基本数据和诊断信息外,还延伸到配套信息,包括参加人和病人的多种表型,到目前已经迅速扩展到基因组学、蛋白质组学及其他的组学信息.如何科学地建设和管理这种大型复杂模式的生物样本库成为医学科学领域亟待规范、解决的问题.本文将从生物样本库的发展入手重点讨论其建设、管理和应用.     

Molecular characterization of 5-chlorophyll a/b-binding protein genes from Panax ginseng Meyer and their expression analysis during abiotic stresses

The chlorophyll _a/b-binding protein (CAB) serves in both photosystems (PS), I and II, as a coordinator of antenna pigments in the light-harvesting complex (LHC). The CABs constitute abundant and important proteins in the thylakoid membrane of higher plants. In our study, five CAB genes, which contained full-length cDNA sequences from the 4-year-old ginseng leaves (Panax ginseng Meyer), were isolated and named PgCAB. Phylogenetic comparison of the members of the subfamily between ginseng and higher plants, including Arabidopsis, revealed that the putative functions of these ginseng CAB proteins were clustered into the different family of Arabidopsis CABs; two PgCABs in LHCII family and three PgCABs in LHCI family. The expression analysis of PgCABs consistently showed dark-dependent inhibition in leaves. Expression analysis during abiotic stress identified that PgCAB genes responded to heavy metal, salinity, chilling, and UV stresses differently, suggesting their specific function during photosynthesis. This is the first comprehensive study of the CAB gene family in P. ginseng.     

Banking human tissue for research: vision to reality

Advances in scientific understanding of disease together with introduction of new high throughput technologies have led to increased demand for human tissue in research. In general, patients are willing to donate for research, particularly samples that are surplus to diagnostic or therapeutic requirements. New tissue-specific regulations in the UK are intended to facilitate the use of human tissue in research. Despite this positive environment there are challenges to researcher access. Coordinated, systematic collection and storage, via a biobank can provide easier access. However translating a vision for a biobank into reality whether in the public or private sector, has never been simple. But it can be done.     

The fucoxanthin-chlorophyll proteins from a chromophyte alga are part of a large multigene family: structural and evolutionary relationships to other light harvesting antennae

 A fucoxanthin-chlorophyll protein (FCP) cDNA from the raphidophyte Heterosigma carterae encodes a 210-amino acid polypeptide that has similarity to other FCPs and to the chlorophyll a/b-binding proteins (CABs) of terrestrial plants and green algae. The putative transit sequence has characteristics that resemble a signal sequence. The Heterosigma fcp genes are part of a large multigene family which includes members encoding at least two significantly different polypeptides (Fcp1, Fcp2). Comparison of the FCP sequences to the recently determined three-dimensional structure of the pea LHC II complex indicates that many of the key amino acids thought to participate in the binding of chlorophyll and the formation of complex-stabilizing ionic interactions are well conserved. Phylogenetic analyses of sequences of light-harvesting proteins shows that the FCPs of several chromophyte phyla form a natural group separate from the intrinisic peridinin-chlorophyll proteins (iPCPs) of the dinoflagellates. Although the FCP and CAB genes shared a common ancestor, these lineages diverged from each other prior to the separation of the CAB LHC I and LHC II sequences in the green algae and terrestrial plants. Received: 8 July 1996 / Accepted: 21 August 1996     

Beyond and within public engagement: a broadened approach to engagement in biobanking

Social studies on biobanking have traditionally focused on public engagement, that is, engagement with donors, patients and the general public as an important factor of sustainability. In this article, we claim that, in order to fully understand the way biobanks work, it is necessary to pay attention to a number of other actors, which have an equal, if not greater, impact on their practices and strategies. This means taking a broadened approach to biobank engagement. By using data collected from interviews with different biobank experts based in five different countries (UK, Canada, Finland, Spain and Iceland), we identify seven communities, including the public, that emerge as relevant. Such relationships condition the way biobanks develop, act and plan. The discussion illustrates how the relationships with those seven communities are articulated. We conclude that there is a need for a broadened approach to biobank engagement in order to understand biobank sustainability.     

Combining efficiency and concerns about integrity when using human biobanks

In the debate about human bio-sampling the interests of patients and other sample donors are believed to stand against the interests of scientists and of their freedom of research. Scientists want efficient access to and use of human biological samples. Patients and other donors of blood or tissue materials want protection of their integrity. This dichotomy is reflected in the Swedish law on biobanks, which came into effect 1 January 2003. In this article I argue that if the basic interest of scientists using human biological samples is in increasing knowledge and developing better treatments, and if the concept 'integrity' is properly understood, then sample donors should also be interested in promotion of efficiency as well as in the protection of their integrity. The basic premise of this argument is that donors of samples have interests related to the donation and use of samples as well as to the use of the results of the research, that is, new medical products and treatments. They have a role both as donors or participants in research and as end users of the research. I conclude that if (i) access to information acquired through biobank research is strictly limited to researchers, (ii) the information is protected by secrecy safeguards through coding and (iii) the procedures governing the research are open to public and democratic control, then most research using human biobanks may be carried out on the basis of making general information available when collecting biological samples, without further contact with participants.     

Public Attitudes toward the Use of Animals in Research: Effects of Invasiveness,Genetic Modification and Regulation

ABSTRACT

This study describes an online public engagement experiment aimed at investigating how acceptance of animal-based research is affected by: (a) the presence of regulations that govern the use of nonhuman animals in laboratories, (b) the invasiveness of procedures, and (c) the use of genetically modified (GM) animals. To meet these aims, participants were asked if they were willing to accept the use of pigs in different scenarios involving agricultural research. Two-thirds of the 681 participants were female and the majority (58%) were young (19–29 years old) with college or university level education (62%). Participants came from 26 different countries, with the United States, Canada, and the United Kingdom being the top three countries represented. Participants who self-identified as being vegetarians, familiar with animal welfare, animal advocates, environmental advocates, and familiar with animal research were significantly more likely to be opposed to animal-based research. Older participants were significantly less likely to oppose animal-based research. Support significantly decreased when animal-based research involved an invasive procedure or GM animals. Support for invasive research significantly increased when regulation was in place, but regulation had less effect on acceptance of GM animal use. Comments provided by participants illustrated different decision-making strategies regarding different types of animal-based research. Given the increasing use of GM animals in research, more effort is required to understand people's concerns regarding this type of animal use and to determine how these concerns should be reflected in policy.     

Establishing a neurological-psychiatric biobank: banking, informatics, ethics

The recent development of genetic databases and biobanks in a number of countries reflects scientist's beliefs in the future health benefits to be derived from genetic research. The NEPSYBANK is a national program of the Hungarian Clinical Neurogenetic Society with comprehensive participation of the Neurology and Psychiatry Departments of Medical Universities and the National Institute of Psychiatry and Neurology. The NEPSYBANK forms a part of the national biobank project (www.biobank.hu). The goal is to establish nationwide collaboration and common biobanking standards on quality, access, and protection of integrity in the field of neurology and psychiatry. Biological materials and databases are already collected in stroke, epilepsy, multiple sclerosis, motoneuron diseases, dementia, movement disorders, schizophrenia, and alcohol addiction. In peripheral neuropathies, neuropathic pain syndromes, muscle diseases, migraine, myasthenia gravis, depression, panic disease, anxiety, autism, and software development is in progress. The resources have been expanded by continued prospective collection of samples and data and important bottlenecks in sample purification, sample retrieval, in protection of the integrity of the research participants, as well as in guaranteeing the security and confidentiality of the participant's information have been harmonized. The development of uniform consent management, comprehensive sample overview and quality standards for health care-related biobanking may provide a unique opportunity for Hungary in molecular clinically oriented research. The program is a diseased-based research biobank with comprehensive collection of phenotypic and environmental information as well as biobanking of DNA, RNA or buffy coat, plasma, and erythrocytes stored at -80 degrees C. The biobank has a neuropathological part as well: storing conventional pathology and biopsy specimens. The analytical and informational demands being created by biobanking requires a "connectivity of community" that has not traditionally been present in the life sciences. As you put more resources into something, your silos tend to become taller, and we need to avoid this. The life science and healthcare community should be ignored working in individual "silos."     

Nucleotide sequence and chromosomal location of Cab11 and Cab12, the genes for the fourth polypeptide of the photosystem I light-harvesting antenna (LHCI)

Tryptic peptide sequences from the 22 kDa polypeptide of tomato LHCI were used to construct a probe for gene cloning. The two genes cloned, cab11 and cab12, encode proteins of 251 and 250 residues that are 88% identical in overall amino acid sequence and 93% identical in the deduced mature protein. Each gene is present in a single copy per haploid genome; cab11 on chromosome 3 and cab12 on chromosome 6, and each has 2 introns located in similar positions to introns in other members of the Chl a/b-binding (CAB) protein gene family. Comparison of the amino acid sequences of LHCI, LHCII, CP29 and CP24 polypeptides confirms that all CABs share two regions of very high similarity which include the first and third transmembrane helices and the stroma-exposed sequences preceding them. However, near the N-terminus and between the conserved regions, the LHCI polypeptides have sequence motifs which appear to be PSI-specific.     

Particle-hemodynamics simulations and design options for surgical reconstruction of diseased carotid artery bifurcations

Based on the hypothesis that aggravating hemodynamic factors play a key role in the onset of arterial diseases, the methodology of "virtual prototyping" of branching blood vessels was applied to diseased external carotid artery (ECA) segments. The goals were to understand the underlying particle-hemodynamics and to provide various geometric design options for improved surgical reconstruction based on the minimization of critical hemodynamic wall parameters (HWPs). First, a representative carotid artery bifurcation (CAB) and then CABs with stenosed ECAs, i.e., a distally occluded ECA and an ECA stump, were analyzed based on transient three-dimensional blood flow solutions, employing a user-enhanced commercial finite volume code. Specifically, the HWPs, i.e., oscillatory shear index, wall shear stress angle gradient, near-wall residence time of monocytes, and near-wall helicity angle difference were evaluated to compare the merits of each design option, including a reconstructed near-optimal junction which generates the lowest HWP-values. The results provide physical insight to the biofluid dynamics of branching blood vessels and guide vascular surgeons as well as stent manufacturers towards interventions leading to high sustained patency rates.     

Developing a simplified consent form for biobanking

Background

Consent forms have lengthened over time and become harder for participants to understand. We sought to demonstrate the feasibility of creating a simplified consent form for biobanking that comprises the minimum information necessary to meet ethical and regulatory requirements. We then gathered preliminary data concerning its content from hypothetical biobank participants.

Methodology/Principal Findings

We followed basic principles of plain-language writing and incorporated into a 2-page form (not including the signature page) those elements of information required by federal regulations and recommended by best practice guidelines for biobanking. We then recruited diabetes patients from community-based practices and randomized half (n = 56) to read the 2-page form, first on paper and then a second time on a tablet computer. Participants were encouraged to use “More information” buttons on the electronic version whenever they had questions or desired further information. These buttons led to a series of “Frequently Asked Questions” (FAQs) that contained additional detailed information. Participants were asked to identify specific sentences in the FAQs they thought would be important if they were considering taking part in a biorepository. On average, participants identified 7 FAQ sentences as important (mean 6.6, SD 14.7, range: 0–71). No one sentence was highlighted by a majority of participants; further, 34 (60.7%) participants did not highlight any FAQ sentences.

Conclusions

Our preliminary findings suggest that our 2-page form contains the information that most prospective participants identify as important. Combining simplified forms with supplemental material for those participants who desire more information could help minimize consent form length and complexity, allowing the most substantively material information to be better highlighted and enabling potential participants to read the form and ask questions more effectively.