Emerging Ethical, Legal and Social Issues Associated with Stem Cell Research & and the Current Role of the Moral Status of the Embryo

Since its early days, stem cell research, particularly human embryonic stem cell research, has been the focus of intense social debate, and the question of the moral status of the embryo has been a central issue in the controversy. Despite this friction, and while it has yet to obtain widespread success in clinical applications, stem cell research remains a great hope for future advances in healthcare. In this paper, we will discuss the results of our systematic literature review in which we examined recent social science, legal and biomedical discourse, as well as Canadian print media discourse, associated with stem cell research in order to assess the role the question of the moral status of the embryo currently plays in these forums, and to identify what other issues are emerging and receiving attention. This analysis will assist with recognizing the issues which are likely to inform future policy and will facilitate forecasting the probable direction of the continually developing social discourse surrounding stem cell research.

The Stem Cell Research Environment: A Patchwork of Patchworks

Few areas of recent research have received as much focus or generated as much excitement and debate as stem cell research. Hope for the therapeutic promise of this field has been matched by social concern associated largely with the sources of stem cells and their uses. This interplay between promise and controversy has contributed to the enormous variation that exists among the environments in which stem cell research is conducted throughout the world. This variation is layered upon intra-jurisdictional policies that are also often complex and in flux, resulting in what we term a ‘patchwork of patchworks’. This patchwork of patchworks and its implications will become increasingly important as we enter this new era of stem cell research. The current progression towards translational and clinical research among international collaborators serves as a catalyst for identifying potential policy conflict and makes it imperative to address jurisdictional variability in stem cell research environments. The existing patchworks seen in contemporary stem cell research environments provide a valuable opportunity to consider how variations in regulations and policies across and within jurisdictions influence research efficiencies and directions. In one sense, the stem cell research context can be viewed as a living experiment occurring across the globe. The lessons to be gleaned from examining this field have great potential for broad-ranging general science policy application.

Banks, Repositories and Registries of Stem Cell Lines in Europe: Regulatory and Ethical Aspects

To overview banks, repositories and registries of stem cell lines in Europe excluding bone marrow and cord blood banks; to concisely discuss the most important scientific, regulatory and ethical aspects of stem cell banking in a manner understandable to a layperson, but remain detailed enough not to compromise thoroughness of information. Review of scientific publications, laws and ethical guidelines in this field up through September 2008; hearing the opinions of key persons working in stem cell banking. The article discusses the procedure of stem cell banking and related safety issues and reviews the regulation of stem cell banking at the regional (European) and the national level. Stem cell banking can help meet scientific and certain ethical imperatives, but is complicated in the context of heterogeneous laws, guidelines, and ethical standards. In the pluralistic European society with cultural diversity leading to heterogeneous laws, harmonisation of international guidelines and national laws regulating stem cell banking is needed, as well as mapping of implementation at the national level.

Scientists’ Perspectives on the Ethical Issues of Stem Cell Research

This paper describes findings from an ethics education project funded by the Canadian Stem Cell Network (SCN). The project is part of a larger research initiative entitled “The Stem Cell Research Environment: Drawing the Evidence and Experience Together”. The ethics education study began with a series of focus groups with SCN researchers and trainees as part of a “needs assessment” effort. The purpose of these discussions was to identify the main ethical issues associated with stem cell (SC) research from the perspective of the stem cell community. This paper will focus on five prominent themes that emerged from the focus group data including: (1) the source of stem cells; (2) the power of stem cells; (3) working within a charged research environment; (4) the regulatory context; and (5) ethics training for scientists. Additional discussions are planned with others involved in Canadian stem cell research (e.g., research ethics board members, policy makers) to supplement initial findings. These assessment results combined with existing bioethics literature will ultimately inform a web-based ethics education module for the SCN. We believe that our efforts are important for those analyzing the ethical, legal, and social issues (ELSI) in this area because our in depth understanding of stem cell researcher perspectives will enable us to develop more relevant and effective education material, which in turn should help SC researchers address the important ethical challenges in their area.

Randomizing visual feedback in manual aiming: reminiscence of the previous trial condition and prior knowledge of feedback availability

A trial-by-trial analysis was used to systematically examine the influence of switching visual conditions on visual feedback utilization for a manual aiming movement. In experiment one, vision was randomly manipulated from trial to trial with no more than four consecutive trials in the same visual condition. In experiment two, participants were provided with certainty of visual feedback availability prior to every trial. Results of both studies revealed that movement endpoint variability was most associated with visual feedback availability on the previous trial. Furthermore, correlation analyses comparing movement trajectory at 25, 50 and 75% with movement end (i.e. 100%) revealed that the efficiency of online corrections also depends on the availability of visual feedback on the previous trial. These results suggest that the accuracy of an aiming movement is highly dependent on processing of offline visual information from the preceding trial. This study was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) awarded to Luc Tremblay.

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Application of Whole Mouse Embryo Culture System on Stem Cell Research

The normal development of mouse embryo in vivo could be maintained in vitro up to 72 h in the presence of rat serum which is continuously supplied with the appropriate concentration of O₂ and CO₂. There are several applications of the whole mouse embryo culture model for study of cellular dynamics in hematopoiesis and its interaction with vasculogenesis. In this protocol, we have described details of manipulation techniques in combination with the whole embryo culture and also some advance techniques applied to the mouse embryo such as intra-cardiac inoculation of acetylated low density lipoprotein for cell-specific labeling and engraftment of donor yolk-sac from different genotype/phenotype mouse embryo onto the yolk-sac of host mouse for study of the dynamic distribution of hematopoietic cell.

Damage to superior parietal cortex impairs pointing in the sagittal Plane

Neurophysiology and neuroimaging research implicates distinct regions of posterior parietal cortex for reaching versus grasping and for completing these movements in central versus peripheral space. Typically, visuomotor tasks only examine movements made in the frontoparallel plane. We examined a patient with a right superior parietal lesion encompassing the parietal-occipital junction, the intraparietal sulcus and the putative human homologue of V6A on pointing tasks in the sagittal or frontoparallel planes. The patient did not demonstrate a speed-accuracy trade-off, but did show larger times post-peak velocity for all movement directions. Her movements in the sagittal axis were more disordered than movements in the frontoparallel plane. These data indicate a role for superior parietal cortex in fine tuning of visually guided movements and more particularly for movements made back towards the body.

High genetic diversity of Sappinia-like strains (Amoebozoa, Thecamoebidae) revealed by SSU rRNA investigations

Sappinia diploidea is known as a free-living amoeba of worldwide distribution and has also been reported as causative agent of a brain infection in an immunocompetent young man. In the current study, we were able to isolate eight strains of S. diploidea-like amoebae identified by light microscopy from different habitats. Cultures of all strains were established successfully for molecular characterization. The small subunit ribosomal RNA genes of all strains were sequenced and compared to one another, to the neotype of S. diploidea, and to strains of Sappinia pedata, the only other Sappinia species known to date, from GenBank by multiple sequence alignment and cluster analysis. Altogether, the phylogenetic position of the genus Sappinia within the Thecamoebidae was corroborated; however, it was shown that the genus splits into several well-separated clusters making the establishment of new species within this genus inevitable. Furthermore, two of the S. diploidea-like strains were actually more closely related to S. pedata than to S. diploidea, although the diagnostically relevant standing form which seems to be characteristic for S. pedata was not observed in either of the two strains. Claudia Wylezich and Julia Walochnik have contributed equally to this work.

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Dopamine and inhibitory action control: evidence from spontaneous eye blink rates

The inhibitory control of actions has been claimed to rely on dopaminergic pathways. Given that this hypothesis is mainly based on patient and drug studies, some authors have questioned its validity and suggested that beneficial effects of dopaminergic stimulants on response inhibition may be limited to cases of suboptimal inhibitory functioning. We present evidence that, in carefully selected healthy adults, spontaneous eyeblink rate, a marker of central dopaminergic functioning, reliably predicts the efficiency in inhibiting unwanted action tendencies in a stop-signal task. These findings support the assumption of a modulatory role for dopamine in inhibitory action control.

Methodological problems undermine tests of the ideo-motor conjecture

Recent behavioural research has investigated whether viewing someone perform an action results in activation of that action by the observer. Postulated empirical support for this ‘ideo-motor (IM) conjecture’ typically rests upon two types of experimental paradigm (reaction time and movement tracking tasks). These paradigms purport to show movement facilitation when compatible movements are observed and vice versa, but only for biological stimuli. Unfortunately, these paradigms often contain confounding (and unavoidable) generic stimulus–response compatibility effects that are not restricted to observed human movement. The current study demonstrates in three experiments that equivalent compatibility effects can be produced by non-biological stimuli. These results suggest that existing empirical paradigms may not, and perhaps cannot, support the IM-conjecture.

RNAi-dependent and -independent antiviral phenotypes of chromosomally integrated shRNA clones: Role of VASP in respiratory syncytial virus growth

Stable RNA interference (RNAi) is commonly achieved by recombinant expression of short hairpin RNA (shRNA). To generate virus-resistant cell lines, we cloned a shRNA cassette against the phosphoprotein gene of respiratory syncytial virus (RSV) into a polIII-driven plasmid vector. Analysis of individual stable transfectants showed a spectrum of RSV resistance correlating with the levels of shRNA expressed from different chromosomal locations. Interestingly, resistance in a minority of clones was due to mono-allelic disruption of the cellular gene for vasodilator-stimulated phosphoprotein (VASP). Thus, pure clones of chromosomally integrated DNA-directed RNAi can exhibit gene disruption phenotypes resembling but unrelated to RNAi.

Effects of seeing and hearing speech on speech production: a response time study

Research demonstrates that listening to and viewing speech excites tongue and lip motor areas involved in speech production. This perceptual-motor relationship was investigated behaviourally by presenting video clips of a speaker producing vowel-consonant-vowel syllables in three conditions: visual-only, audio-only, and audiovisual. Participants identified target letters that were flashed over the mouth during the video, either manually or verbally as quickly as possible. Verbal responses were fastest when the target matched the speech stimuli in all modality conditions, yet optimal facilitation was observed when participants were presented with visual-only stimuli. Critically, no such facilitation occurred when participants were asked to identify the target manually. Our findings support previous research suggesting a close relationship between speech perception and production by demonstrating that viewing speech can ‘prime’ our motor system for subsequent speech production.

Shared-Environmental Contributions to High Cognitive Ability

Using a combined sample of adolescent twins, biological siblings, and adoptive siblings, we estimated and compared the differential shared-environmentality for high cognitive ability and the shared-environmental variance for the full range of ability during adolescence. Estimates obtained via multiple methods were in the neighborhood of 0.20, and suggest a modest effect of the shared environment on both high and full-range ability. We then examined the association of ability with three measures of the family environment in a subsample of adoptive siblings: parental occupational status, parental education, and disruptive life events. Only parental education showed significant (albeit modest) association with ability in both the biological and adoptive samples. We discuss these results in terms of the need for cognitive-development research to combine genetically sensitive designs and modern statistical methods with broad, thorough environmental measurement.

Factor Structure of Planning and Problem-solving: A Behavioral Genetic Analysis of the Tower of London Task in Middle-aged Twins

We examined the genetic architecture of a Tower of London test of planning and problem-solving in 690 middle-aged male twins. Phenotypic analyses revealed only one general factor, but the best-fitting genetic model indicated two correlated genetic factors: speed and efficiency. One variable—number of attempts required to mentally figure the puzzles—loaded on both factors. Shared environmental effects could be dropped with virtually no reduction in model fit. Despite significant nonshared environmental correlations across measures, there was no discernable nonshared environmental factor structure. The correlation between genetic factors (r = 0.46) and the variable loading on both factors could reflect modulation of planning, testing alternatives, and working memory that are required to perform the test. Such coordinated activity is consistent with the notion of a supervisory attentional system, a central executive, or metacognitive ability. The different phenotypic and genetic factor results suggest that relying solely on the former could obscure genetic associations.

Modelling the human pharyngeal airway: validation of numerical simulations using in vitro experiments

In the presented study, a numerical model which predicts the flow-induced collapse within the pharyngeal airway is validated using in vitro measurements. Theoretical simplifications were considered to limit the computation time. Systematic comparisons between simulations and measurements were performed on an in vitro replica, which reflects asymmetries of the geometry and of the tissue properties at the base of the tongue and in pathological conditions (strong initial obstruction). First, partial obstruction is observed and predicted. Moreover, the prediction accuracy of the numerical model is of 4.2% concerning the deformation (mean quadratic error on the constriction area). It shows the ability of the assumptions and method to predict accurately and quickly a fluid–structure interaction.

Primary immune surveillance: some like it hot

The thermal element of fever has been found to be beneficial in models of infectious disease. The contributions of fever-range temperatures to the efficacy of the adaptive immune response have only begun to be delineated. There is accumulating evidence that fever-range thermal stress bolsters primary immune surveillance of lymph nodes and Peyer patches by augmenting lymphocyte extravasation across specialized vessels termed high endothelial venules. Molecular mechanisms have recently come to light by which the thermal component of fever alone may promote lymphocyte trafficking, and thereby the probability of mounting a defense against microbial infection. Acquired knowledge of the molecular changes associated with thermal stress may allow for the development of novel therapies for a variety of disease processes.

Spontaneous reactions to health risk feedback: a network perspective

Research on the reception of health risk feedback has focused on the analysis of single, researcher-selected cognitive reactions. The full range of spontaneous reactions and their patterns have received little attention. The present paper explores content, interrelations, and adaptivity of spontaneous reactions to health risk feedback from a network perspective. Participants (n = 423) received blood pressure and cholesterol feedback and listed their thoughts afterwards. A network of reactions to health risk feedback was constructed from the responses. Emotions, risk feedback valence, future lifestyle, and expectedness emerged as strong and largely well-connected network nodes, while previously well-researched reactions like feedback acceptance formed small, less connected nodes. The majority of reaction patterns identified through the network appeared adaptive, even after negative feedback. The network provides a potentially useful tool for research and practice, highlighting previously neglected relevant reactions, and providing a group-level background against which individual reactions can be evaluated.

Interaction of intensity and order regarding painful events

While stimulus intensity obviously affects degree of pain responding, presentation order effects of stimuli of different intensities on acute pain responses are under-researched. The present study examined the effects of manipulating presentation order of lower and higher pain stimulus intensity. Using 96 undergraduates, this investigation employed a 2 × 2 mixed research design, with pain stimulus sequence as a between-subjects variable and pain stimulus trial as a repeated measure. When the greater pain stimulus intensity was presented last, verbal report of pain was higher. Also, performance of a cognitive task was interrupted the least when the lower stimulus intensity was presented last. Heart rate, however, was highest when the greater stimulus intensity was presented first, and pain tolerance was greatest when the lower stimulus intensity was presented first. Results are discussed in relation to adaptation-level effects, and implications for pain experienced in clinical settings are suggested.

Role of the lateral prefrontal cortex in visual object-based selective attention

We demonstrate that attention to object representations is vitally dependent on the prefrontal cortex. Object-based selective attention was compared in neurologic patients with unilateral damage to either the dorsolateral prefrontal cortex (DLPFC) or the parietal cortex and in healthy controls. Our task required a top–down attentional modulation of object representations in which spatial location played no role. All groups could invoke top–down object-based selection, but the DLPFC patients showed a selective deficit when target stimuli were in the hemifield contralateral to the lesioned hemisphere. Our findings indicate that in the healthy brain, anterior cortical mechanisms are crucial for attending to object-centered representations, whereas posterior cortical mechanisms are necessary for attending to objects at locations in the visual scene.

VirtualPACS—A Federating Gateway to Access Remote Image Data Resources over the Grid

Collaborations in biomedical research and clinical studies require that data, software, and computational resources be shared between geographically distant institutions. In radiology, there is a related issue of sharing remote DICOM data over the Internet. This paper focuses on the problem of federating multiple image data resources such that clients can interact with them as if they are stored in a centralized PACS. We present a toolkit, called VirtualPACS, to support this functionality. Using the toolkit, users can perform standard DICOM operations (query, retrieve, and submit) across distributed image databases. The key features of the toolkit are: (1) VirtualPACS makes it easy to use existing DICOM client applications for data access; (2) it can easily be incorporated into an imaging workflow as a DICOM source; (3) using VirtualPACS, heterogeneous collections of DICOM sources are exposed to clients through a uniform interface and common data model; and (4) DICOM image databases without DICOM messaging can be accessed.