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Objective: To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).Design: Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.Setting: Melbourne, Australia.Participants: A cohort of 20 926 participants (62 % women) aged 40-59 years at recruitment between 1990 and 1994.Results: For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.Conclusions: Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation. [ABSTRACT FROM AUTHOR]

Bone conduction implant systems utilize osseointegrated fixtures to transmit sound through the bones of the skull. They allow patients with hearing loss to receive acoustic signals directly to the inner ear, bypassing the outer and middle ear. The new Cochlear™ Baha® Attract System (Cochlear Bone Anchored Solutions AB, Mölnlycke, Sweden) has been designed as a non-skin penetration hearing implant. The system uses magnetic coupling to hold the external sound processor in place and transmit acoustic energy. An implantable magnet is anchored to the skull via a single osseointegrated fixture, maximizing the efficiency of energy sound transfer. The interposed soft tissue is protected by a SoftWear pad that evenly distributes pressure in order to minimize the risk of pressure necrosis. This article summarizes the design features and early clinical results of the Baha 4 Attract System and provides context as to its place in the broader hearing aid market. [ABSTRACT FROM AUTHOR]

Biobanks are currently archiving human materials for medical research at a hitherto unprecedented rate. These valuable resources will be essential for developing ‘personalized’ medicines and for a better understanding of disease susceptibilities. However, for such scientific advances to benefit everyone, it is crucial that biobanks recruit donations from all sections of the community. Unfortunately, other initiatives, such as transplant programmes, have clearly demonstrated that ethnic minorities are under-represented. Here we suggest that this issue deserves serious consideration to avoid biobanks evolving into ethnically biased archives which unwittingly promote race-specific research. Specifically, this necessitates research ethics committees engaging in a re-assessment of the relative merits of individual personal sovereignty and the common good. [ABSTRACT FROM AUTHOR]

Many research ethics guidelines now oblige researchers to offer research participants the results of research in which they participated. This practice is intended to uphold respect for persons and ensure that participants are not treated as mere means to an end. Yet some scholars have begun to question a generalised duty to disclose research results, highlighting the potential harms arising from disclosure and questioning the ethical justification for a duty to disclose, especially with respect to individual results. In support of this view, we argue that current rationales for a duty of disclosure do not form an adequate basis for an ethical imperative. We review policy guidance and scholarly commentary regarding the duty to communicate the results of biomedical, epidemiological and genetic research to research participants and show that there is wide variation in opinion regarding what should be disclosed and under what circumstance. Moreover, we argue that there is fundamental confusion about the notion of 'research results,' specifically regarding three core concepts: the distinction between aggregate and individual results, amongst different types of research, and across different degrees of result veracity. Even where policy guidance and scholarly commentary have been most forceful in support of an ethical imperative to disclose research results, ambiguity regarding what is to be disclosed confounds ethical action. [ABSTRACT FROM AUTHOR]

The complexities of modern science are not adequately reflected in many bioethical discussions. This is especially problematic in highly contested cases where there is significant pressure to generate clinical applications fast, as in stem cell research. In those cases a more integrated approach to bioethics, which we call systems bioethics, can provide a useful framework to address ethical and policy issues. Much as systems biology brings together different experimental and methodological approaches in an integrative way, systems bioethics integrates aspects of the history and philosophy of science, social and political theory, and normative analysis with the science in question. In this paper we outline how a careful analysis of the science of stem cell research can help to refocus the discussions related to the clinical applications of stem cells. We show how inaccurate or inadequate scientific assumptions help to create a set of unrealistic expectations and badly inform ethical deliberations and policy development. Systems bioethics offers resources for moving beyond the current impasse. [ABSTRACT FROM AUTHOR]

This paper critically examines the biology of species identity and the morality of crossing species boundaries in the context of emerging research that involves combining human and nonhuman animals at the genetic or cellular level. We begin with the notion of species identity, particularly focusing on the ostensible fixity of species boundaries, and we explore the general biological and philosophical problem of defining species. Against this backdrop, we survey and criticize earlier attempts to forbid crossing species boundaries in the creation of novel beings. We do not attempt to establish the immorality of crossing species boundaries, but we conclude with some thoughts about such crossings, alluding to the notion of moral confusion regarding social and ethical obligations to novel interspecies beings. [ABSTRACT FROM AUTHOR]

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage.Methods/design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality.Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma.Trial Registration: Netherlands Trial Register [ NTR4243 , 11 October 2013]. [ABSTRACT FROM AUTHOR]

Background: Research ethicists have recently declared a new ethical imperative: that researchers should communicate the results of research to participants. For some analysts, the obligation is restricted to the communication of the general findings or conclusions of the study. However, other analysts extend the obligation to the disclosure of individual research results, especially where these results are perceived to have clinical relevance. Several scholars have advanced cogent critiques of the putative obligation to disclose individual research results. They question whether ethical goals are served by disclosure or violated by non-disclosure, and whether the communication of research results respects ethically salient differences between research practices and clinical care. Empirical data on these questions are limited. Available evidence suggests, on the one hand, growing support for disclosure, and on the other, the potential for significant harm.Methods: This paper explores the implications of the disclosure of individual research results for the relationship between research and clinical care through analysis of research-based cancer genetic testing in Ontario, Canada in the late 1990s. We analyze a set of 30 interviews with key informants involved with research-based cancer genetic testing before the publicly funded clinical service became available in 2000.Results: We advance three insights: First, the communication of individual research results makes research practices seem like clinical services for our respondents. Second, while valuing the way in which research enables a form of clinical access, our respondents experience these quasi-clinical services as inadequate. Finally, our respondents recognize the ways in which their experience with these quasi-clinical services is influenced by research imperatives, but understand and interpret the significance and appropriateness of these influences in different ways.Conclusion: Our findings suggest that the hybrid state created through the disclosure of research results about individuals that are perceived to be clinically relevant may produce neither sufficiently adequate clinical care nor sufficiently ethical research practices. These findings raise questions about the extent to which research can, and should, be made to serve clinical purposes, and suggest the need for further deliberation regarding any ethical obligation to communicate individual research results. [ABSTRACT FROM AUTHOR]

This essay assesses the rationale for regulating research administrators as carefully as they regulate researchers. The reasons for such regulation are identical: protecting scientific integrity, ensuring responsible use of public funds, addressing the lack of effective recourse for victims, creating negative consequences for misbehaving actors, and addressing high incentives for misconduct. Whereas the reasons compelling us to regulate research administrators are obvious, counterarguments to administrative oversight are based on suggestions that the incidence and prevalence of cases of administrative misconduct are too low to warrant formal regulation. I briefly describe examples of the phenomenon drawn from publicly available records. My analysis suggests that the misconduct of research administrators is both serious and worthy of better oversight. Improved oversight of research administration will help steward tax dollars appropriately and enhance the overall integrity of the scientific record and of the free pursuit of knowledge more generally., (© 2024 Wiley Periodicals LLC.)

Background: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation., Methods: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs)., Findings: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4)., Interpretation: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established., Funding: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust)., Competing Interests: Declaration of interests MEB reports personal fees from GRAIL Bio UK Ltd, for Independent Data Monitoring Committee (IDMC) membership unrelated to this study. OB and GM report salary compensation for analysis of trial data in preparation for review by the Data Safety Monitoring Board for the POWERRANGER trial (NCT01404156), unrelated to this project. DWH reports grant support by Moondance Cancer Initiative (to institution) in relation to exploring bowel cancer audit data. YN reports grant support to The Cancer Registry of Norway by the Norwegian Cancer Society on standardised cancer pathways (no direct payment). RRW reports research grant funding by the Michael Smith Foundation for Health Research, the First Nations Health Authority/Canadian Partnership Against Cancer, and the BC Cancer Foundation for unrelated to the present study public health research projects. GL declares research grant funding by the study sponsors to his employer (University College London)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

A cell's ability to secrete extracellular vesicles (EVs) for communication is present in all three domains of life. Notably, Gram-negative bacteria produce a specific type of EVs called outer membrane vesicles (OMVs). We previously observed the presence of OMVs in human blood, which could represent a means of communication from the microbiota to the host. Here, in order to investigate the possible translocation of OMVs from the intestine to other organs, the mouse was used as an animal model after OMVs administration. To achieve this, we first optimized the signal of OMVs containing the fluorescent protein miRFP713 associated with the outer membrane anchoring peptide OmpA by adding biliverdin, a fluorescence cofactor, to the cultures. The miRFP713-expressing OMVs produced in E. coli REL606 strain were then characterized according to their diameter and protein composition. Native- and miRFP713-expressing OMVs were found to produce homogenous populations of vesicles. Finally, in vivo and ex vivo fluorescence imaging was used to monitor the distribution of miRFP713-OMVs in mice in various organs whether by intravenous injection or oral gavage. The relative stability of the fluorescence signals up to 3 days post-injection/gavage paves the way to future studies investigating the OMV-based communication established between the different microbiotas and their host.

Virtually all of the scholarly literature on responsible conduct in research (RCR) focuses on the integrity of scientists - including why scientists misbehave, and how to improve training and enhance compliance with institutional and federal policies and regulations to prevent research misconduct. What this literature does not yet address is the integrity of those responsible for research administration. This article explores the responsible conduct of research administration and the potential for administrative misconduct. I highlight ways in which a lack of integrity in research administration can jeopardize the progress of science, the careers of researchers, and the reputation of institutions just as much as research misconduct can. Accordingly, I call for policies and appropriate oversight of research administration that are on par with policies governing research misconduct by scientists.

Extracellular vesicles (EVs) are critical elements of cell-cell communication. Here, we characterized the outer membrane vesicles (OMVs) released by specific clones of Escherichia coli isolated from the Long-Term Evolution Experiment after 50,000 generations (50K) of adaptation to glucose minimal medium. Compared with their ancestor, the evolved clones produce small OMVs but also larger ones which display variable amounts of both OmpA and LPS. Tracking ancestral, fluorescently labelled OMVs revealed that they fuse with both ancestral- and 50K-evolved cells, albeit in different proportions. We quantified that less than 2% of the cells from one 50K-evolved clone acquired the fluorescence delivered by OMVs from the ancestral strain but that one cell concomitantly fuses with several OMVs. Globally, our results showed that OMV production in E. coli is a phenotype that varies along bacterial evolution and question the contribution of OMVs-mediated interactions in bacterial adaptation.

It now seems technically feasible to culture human embryos beyond the "fourteen-day limit," which has the potential to increase scientific understanding of human development and perhaps improve infertility treatments. The fourteen-day limit was adopted as a compromise but subsequently has been considered an ethical line. Does it remain relevant in light of technological advances permitting embryo maturation beyond it? Should it be changed and, if so, how and why? What justifications would be necessary to expand the limit, particularly given that doing so would violate some people's moral commitments regarding human embryos? Robust stakeholder engagement preceded adoption of the fourteen-day limit and should arguably be part of efforts to reassess it. Such engagement could also consider the need for enhanced oversight of human embryo research. In the meantime, developing and implementing reliable oversight systems should help foster high-quality research and public confidence in it., (© 2021 The Hastings Center.)

Biomedical research is at a critical juncture, with an aging population increasingly beset by chronic illness and prominent failures to translate research from "bench to bedside." These challenges emerge on a background of increasing "silo-ing" of experiments (and experimenters)-many investigators produce and consume research conducted in 1, perhaps 2, species-and increasing pressure to reduce or eliminate research on so-called "higher" mammals. Such decisions to restrict species diversity in biomedical research have not been data-driven and increase the risk of translational failure. To illustrate this problem, we present a case study from neuroscience: cholinergic suppression in the cortex. In all mammals studied so far, acetylcholine reduces activity in some cortical neurons. Comparative anatomical studies have shown that the mechanism behind this suppression differs between species in a manner that would render drug treatments developed in nonprimate species entirely ineffective if applied to primates (including humans). Developing clinical interventions from basic research will always require translation, either between species (e.g., using a mouse model of a human disease) or within a species (using a subset of humans as a representative sample for all humans). We argue that successful translation will require that we 1) be data-driven in our selection of species for study; 2) use (with careful attention to welfare) animals that minimize the translation gap to humans; and 3) become agile at translation, by resisting the pressures to narrow our focus to a small number of organisms, instead using species diversity as an opportunity to practice translation.

As we reread Mary Shelley's Frankenstein at two hundred years, it is evident that Victor Frankenstein is both a mad scientist (fevered, obsessive) and a bad scientist (secretive, hubristic, irresponsible). He's also not a very nice person. He's a narcissist, a liar, and a bad "parent." But he is not genuinely evil. And yet when we reimagine him as evil-as an evil scientist and as an evil person-we can learn some important lessons about science and technology, our contemporary society, and ourselves., (© 2018 The Hastings Center.)

Background: Discrepancies are often noted between management of perihilar cholangiocarcinoma (PHC) in regional hospitals and the eventual treatment plan in specialized centers., Objective: The objective of this article is to evaluate whether regional centers adhere to guideline recommendations following implementation in 2013., Methods: Data were analyzed from all consecutive patients with suspected PHC referred to our academic center between June 2013 and December 2015. Frequency and quality of biliary drainage and imaging at referring centers were assessed as well as the impact of inadequate initial drainage., Results: Biliary drainage was attempted at regional centers in 83 of 158 patients (52.5%), with a technical and therapeutic success rate of 79.5% and 50%, respectively, and a complication rate of 45.8%. The computed tomography protocol was not in accordance with guidelines in 52.8% of referrals. In 45 patients (54.2%) who underwent drainage in regional centers, additional drainage procedures were required after referral. Initial inadequate biliary drainage at a regional center was significantly associated with more procedures and a prolonged waiting time until surgery. A trend toward more drainage-related complications was observed among patients with inadequate initial drainage (54.7% vs. 39.0%, p  = 0.061)., Conclusion: Despite available guidelines, suboptimal management of PHC persists in many regional centers and affects eventual treatment strategies.

Objective: To explore the self-expressed desire for, envisioned reaction to, and basic understanding of presymptomatic Alzheimer disease (AD)-related genetic and biomarker tests., Patients and Methods: The Alzheimer's Prevention Registry is an online community of people at least 18 years of age who are interested in AD prevention research for purely informational purposes or to be considered for possible research participation in future studies. Information about presymptomatic testing and an online multiple choice format survey were posted from November 1, 2012, through June 20, 2013, on the registry website., Results: Of 4036 respondents, 80.8% (3195/3952) wanted genetic testing if paid by insurance and 58.7% (2261/3851) if it would cost them at least $100. A total of 80.2% (3112/3879) wanted biomarker testing. If at high risk for AD, 90.5% (3478/3841) endorsed that they would "pursue a healthier lifestyle," but 11.6% (427/3706) endorsed "seriously consider suicide." The implication of a positive genetic test result was incorrectly understood by 13.1% (500/3812) and 32.6% (1255/3848) failed to view a positive biomarker test result as evidence of increased risk for or the presence of AD., Conclusion: Despite efforts to increase public awareness of AD, our survey results suggest that greater education of the public is needed. Interested patients should probably undergo psychological screening to identify those at high risk of adverse psychological outcomes, and disclosure of presymptomatic test results should be anchored to tangible constructive action plans, such as healthy lifestyle changes, long-term care planning, and, when available and appropriate, participation in research trials., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The nature of compensation for women who donate eggs (oocytes) for research remains a contentious issue internationally. This position paper lays out the arguments for, and discusses the arrangements in which, a modest payment might be ethically justifiable., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Three children with keratitis-ichthyosis-deafness (KID) syndrome received cochlear implants at the Royal Victorian Eye and Ear Hospital. KID syndrome is a rare genodermatosis associated with mutation of the connexin-26 gene with characteristics affecting skin, hair, vision and hearing. Ichthyotic involvement of the ear canal epithelium and associated non-erosive keratosis obturans complicate hearing assessment and aid fitting. The tendency to eczematous dermatitis and otitis media is an additional problem with cochlear implantation. All cases have required additional medical management, however the outcomes show that the cochlear implant can be effective in these patients.

It has been argued that bioethicists too often tend to represent the interests of scientists and not of the broader polity. Indeed, bioethicists seem predisposed to discard the voices and viewpoints of all but the cognoscenti. Focusing particularly on human pluripotent stem cell research, this commentary explores a variety of characterizations of bioethics and bioethicists in relation to forbidding science. Rather than proselytizing or prohibiting, bioethicists should work in partnership with scientists and publics to craft scientifically well-informed and morally sophisticated debates about forbidding science.

An apparent consensus governs the management of carrier status information generated incidentally through newborn screening: results cannot be withheld from parents. This normative stance encodes the focus on autonomy and distaste for paternalism that characterize the principles of clinical bioethics. However, newborn screening is a classic public health intervention in which paternalism may trump autonomy and through which parents are-in effect-required to receive carrier information. In truth, the disposition of carrier results generates competing moral infringements: to withhold information or require its possession. Resolving this dilemma demands consideration of a distinctive body of public health ethics to highlight the moral imperatives associated with the exercise of collective authority in the pursuit of public health benefits.

Calls for the "translation" of research from bench to bedside are increasingly demanding. What is translation, and why does it matter? We sketch the recent history of outcome-oriented translational research in the United States, with a particular focus on the Roadmap Initiative of the National Institutes of Health (Bethesda, MD). Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice. We explore the nature of and obstacles to translational research and assess the ethical and biomedical challenges of embracing a translational ethos.

The US National Academy of Sciences (NAS) recently published voluntary guidelines for human embryonic stem (hES) cell research. The NAS guidelines propose two levels of oversight. AT the local level, research institutions are to create Embryonic Stem Cell Research Oversight (ESCRO) committees with a mandate to assess the scientific merit and ethical acceptability of hES cell research. At the national level, a new committee is to be created, not to review specific research proposals, but rather to periodically assess, and as needed revise, the NAS guidelines. In this article, we critically assess this proposal. In particular, we review the benefits and limitations of local research review. On this basis, we argue that local review is insufficient for hES cell research and that while there are obvious pragmatic and political reasons for the NAS to favor local research review, there are more compelling reasons for the NAS to have recommended national review of hES cell research proposals.

As compared with conventional vaccine production systems, plant-made vaccines (PMVs) are said to enjoy a range of advantages including cost of production and ease of storage for distribution in developing countries. In this article, we introduce the science of PMV production, and address ethical issues associated with development and clinical testing of PMVs within three interrelated domains: PMVs as transgenic plants; PMVs as clinical research materials; and PMVs as agents of global health. We present three conclusions: first, while many of the ethical issues raised by PMVs are familiar, PMVs add a new dimension to old issues, and raise some novel issues for ethicists and policy-makers; secondly, it is premature to promise broad applicability of PMVs across the developing world without having demonstrated their feasibility; thirdly, in particular, proponents of PMVs as a solution to global health problems must, as a condition of the ethical conduct of their research, define the commercial feasibility of PMVs for distribution in the developing world.

The National Academy of Sciences recently issued voluntary guidelines to govern human embryonic stem cell research. Among other restrictions, these guidelines prohibit certain kinds of combinations of human and nonhuman animal cells, and call for ethics review and oversight of any protocol involving the transfer of human embryonic stem cells into nonhuman animals. In this essay, I discuss the history of and scientific rationales for combining human cells with cells of nonhuman animals, and critically assess the most recent attempts to limit such research on moral grounds--and find them lacking. Nonetheless, as I show, this research remains scientifically and morally contested. I then explore whether and how the NAS's recommended Embryonic Stem Cell Research and Oversight committees will allow for scientifically well-informed moral assessment of this controversial, but possibly important, research.

This article proposes that an assessment of commercial feasibility should be integrated as a prerequisite for human clinical testing to improve the quality and relevance of materials being investigated, as an ethical aspect for human subject protection, and as a means of improving accountability where clinical development is funded on promises of successful translational research. A commercial feasibility analysis is not currently required to justify human clinical testing, but is assumed to have been conducted by industry participants, and use of public funds for clinical trials should be defensible in the same manner. Plant-made vaccines (PMVs) are offered in this discussion as a model for evaluating the relevance of commercial feasibility before human clinical testing. PMVs have been proposed as a potential solution for global health, based on a vision of immunizing the world against many infectious diseases. Such a vision depends on translating current knowledge in plant science and immunology into a potent vaccine that can be readily manufactured and distributed to those in need. But new biologics such as PMVs may fail to be manufactured due to financial or logistical reasons--particularly for orphan diseases without sufficient revenue incentive for industry investment--regardless of the effectiveness which might be demonstrated in human clinical testing. Moreover, all potential instruments of global health depend on translational agents well beyond the lab in order to reach those in need. A model compromising five criteria for commercial feasibility is suggested for inclusion by regulators and ethics review boards as part of the review process prior to approval of human clinical testing. Use of this model may help to facilitate safe and appropriate translational research and bring more immediate benefits to those in need.

Some psychiatrists anticipate a revolution in psychiatric nosology, on the basis of emerging data from genetics and genomics. There are, however, good empirical and conceptual reasons to resist any such revolution. Basing an understanding of psychiatric entities on one of multiple biological (not to mention sociocultural and psychological) considerations is a specious method of approaching the project of psychiatric taxonomy. A classification system that lacks sufficient consensus on the phenomenology of those classified cannot be adequately buttressed by exclusively genetic accounts. This paper advocates a more diversely informed nosology that, in turn, fosters attention to broader diagnostic considerations. We explore more plausible ways in which genetics and genomics, in conjunction with neuroscience and other biological disciplines, can help to shape diagnostic classification in psychiatry. There are, of course, differing views on the degree of prominence that genetics should take in psychiatric diagnosis and classification. We outline these accounts in illustration of this continuum. Drawing on Wimsatt's work on robustness analysis, we dismiss optimistic scenarios about the potential nosological advantages of psychiatric genetics and genomics, and offer a novel defense of realism about psychiatric entities. We also briefly sketch an integrative methodology for psychiatric research and classification., (Copyright 2005 S. Karger AG, Basel.)