RESEARCH ON PRISONERS – A COMPARISON BETWEEN THE IOM COMMITTEE RECOMMENDATIONS (2006) AND EUROPEAN REGULATIONS

The Institute of Medicine (IOM) Committee on Ethical Considerations for Revisions to DHHS Regulations for Protection of Prisoners Involved in Research published its report in 2006. It was charged with developing an ethical framework for the conduct of research with prisoners and identifying the safeguards and conditions necessary to ensure that research with prisoners is conducted ethically. The recommendations contained in the IOM report differ from current European regulations in several ways, some being more restrictive and some less so. For example, the IOM report suggests limiting the percentage of prisoners that should be involved in a biomedical study to 50%, a limit that does not exist in Europe. However, the report does not specifically advise against research without a direct benefit to an individual prisoner: the European regulations are more restrictive than the IOM committee recommendations in this respect. The definition of minimal risk varies, as well as the proposed role of the minimal risk requirement and of the principle of subsidiarity (research that can only be done effectively in prisons). The IOM report proposes a number of thoughtful suggestions, which it would be beneficial to implement everywhere, such as registers of research on prisoners. The European regulations offer pragmatic solutions to several thorny issues. In summary, the IOM committee report represents an admirable effort to tackle the present inconsistencies and deficiencies of federal regulations in the US on research on prisoners (45 CFR 46 Subpart C). Nonetheless, before acting on the recommendations, US regulators might consider revisiting international guidelines such as those published by the Council for International Organizations of Medical Science (CIOMS) and the Declaration of Helsinki.     

Ethical Principles for Conducting Fieldwork

Federal regulations to protect human subjects assume a particular relationship between experimenter and subject based upon biomedical research. Because this relationship is not found in every type of research, the regulations are not universally applicable. Relationships between those who study and those who are studied vary with the kind of research. Such variations depend on the relative power and control of the researcher, the direction of interaction, and the level of possible harms and benefits. Measured on these continua, fieldwork is at the opposite end of the spectrum from biomedical research. Consequently, the ethical system on which federal regulations are chiefly based—using utilitarian risk-benefit calculations—becomes ineffective and inappropriate when applied to proposed fieldwork. Here, investigators have relatively little power and less control of the setting and context of research, interaction flows in two directions, and calculable harms and benefits are comparatively low. Various models of fieldwork are described, each having differing relationships between investigators and subjects. It is suggested that the Kantian categorical imperative, with its principle of respect for human autonomy, might be useful in judging the ethical adequacy of these varieties of fieldwork. [fieldwork, ethical principles, research relationships, federal regulations, risk-benefit calculations]     

Bioethics of public commenting: Manipulation,data risk,and public participation in E-Rulemaking

Little scholarly attention has been given to the ethics of public commenting as part of the online federal rule-making process. This essay argues the process of public commenting on federal regulations in the digital era threatens both the integrity of those regulations and the integrity of the individuals they are meant to protect. The ongoing risk is anonymous public commenting is open to manipulation. This risk is particularly salient for eRulemaking with implications for human subjects as was shown in the completed revision process to the Common Rule. Guarding against physical and informational harms requires at least some verification of the identities of public commenters. The burdens of verification access are outweighed by the benefits to authentic participation in e-Rulemaking.     

Ultrastructure of Draparnaldia glomerata (Chaetophorales, Chlorophyceae). 1. The flagellar apparatus of the zoospore

The fine structure of the quadriflagellate zoospores of Draparnaldia glomerata (Vauch.) Agardh is described with emphasis on the flagellar root system and compared with the flagellar apparatus of related green algae. It is demonstrated that the flagellar root system in Draparnaldia is similar to that of the zoospore of Uronema belkae. Common features include presence of a cruciate root system (formula 2–5–2–5), prominent striated distal fibre connecting opposite basal bodies, a system I striated root component associated with the 2–stranded root, association of electron dense material with the 5–stranded root, mode of arrangement of the basal bodies in the absolute configuration model, and presence of four striated peripheral fibres interconnecting adjacent basal bodies. Differences exist in the shape of the striated peripheral fibres, the origin of the 2– and 5– stranded roots in the proximal part of the flagellar apparatus, and the architecture and striation pattern of the proximal part of the system I fibre that detaches from the 2–stranded root between adjacent basal bodies. Both the 2– and 5–stranded roots originate near the basal bodies and descend deeply into the zoospore. One of the 5–stranded roots passes near the eyespot of the chloroplast. The implications of these findings for the taxonomic position of the genus Draparnaldia are discussed. In addition, an evaluation is given of the present status of the order Chaetophorales. Suggestions are given to standardize some aspects of the current terminology of the cruciate flagellar root system in green algae.     

The Misuse of Chayanov: "Chayanov's Rule" and Empiricist Bias in Anthropology

Sahlins's "Chayanov's Rule"–the more consumers each worker has to support the more work each worker does-has characterized Chayanov's analysis for most anthropologists. I examine the relationship between the consumer/worker ratio and product per worker for the Shan community of Thongmakhsan in northwestern Thailand. Since there is no systematic relationship between these variables even when the population is divided into production strategy groups, I go on to examine the relationship between Sahlins's "Chayanov's Rule" and Chayanov's own analysis. In conclusion I raise the issue of the continuing identification of Chayanov with "Chayanov's Rule" and consider a number of possible reasons for this.     

Movement patterns of Common Crossbills Loxia curvirostra in Europe

Over much of Europe, Common Crossbills Loxia curvirostra depend primarily on the seeds of Norway Spruce Picea abies , and their breeding and movement patterns are governed largely by the cropping patterns of this tree species. Good cone crops occur only every few years in particular areas, but in different years in different areas. The main period of movement is in summer, when the previous year's crop is coming to an end, and a new crop is forming in different areas. In years when the Norway Spruce crop is poor over a wide area, and when Common Crossbills are abundant, they leave the boreal forest in large numbers, and appear as irruptive migrants in southwest Europe, with at least 40 invasions reaching Britain in the 120-year period 1881–2000. On irruptions the main migration axis is from northeast to southwest or west. Recoveries of birds ringed mainly in Germany confirm that these birds do not return to the boreal forest in northern Russia in the same calendar year as their irruption, but do so only in a later calendar year, when a new Norway Spruce crop is becoming available. The findings agree with an earlier interpretation of Common Crossbill movements, but not with an alternative hypothesis that irrupting Common Crossbills return to their region of origin in the same calendar year as the outward movement. Recoveries also suggest that some individual Common Crossbills may have bred in widely separated localities in different years (records up to 3170 km apart), and sometimes in localities far removed from their natal sites (records up to 2950 km apart).     

Genetic exchange by recombination or reassortment is infrequent in natural populations of a tripartite RNA plant virus.

Two hundred seventeen field isolates of cucumber mosaic cucumovirus (CMV), sampled from 11 natural populations, were typed by RNase protection assay (RPA) using probes from the genomic RNAs of strains in subgroup I and in subgroup II of CMV strains. Most (85%) of the analyzed isolates belonged to subgroup I. For these subgroup I isolates, only two clearly different RPA patterns, A and B, were found for each of four probes representing RNA1, RNA2, and each of the two open reading frames in RNA3. On the basis of these RPA patterns for each probe, different haplotypes were defined. The frequency composition for these haplotypes differed for the various analyzed populations, with no correlation with place or year of sampling. This genetic structure corresponds to a metapopulation with local extinctions and recolonizations. Most subgroup I isolates (73%) belonged to haplotypes with RPA pattern A (type 1) or B (type 2) for all four probes. A significant fraction of subgroup I isolates (16%) gave evidence of mixed infections with these two main types, from which genetic exchange could occur. Genetic exchange by segment reassortment was seen to occur: the fraction of reassortant isolates was 4%, reassortment did not occur at random, and reassortants did not become established in the population. Thus, there is evidence of selection against reassortment between types 1 and 2 of subgroup I isolates. Aphid transmission experiments with plants doubly infected with type 1 and type 2 isolates gave further evidence that reassortment is selected against in CMV. Genetic exchange by recombination was detected for RNA3, for which two RPA probes were used. Recombinant isolates amounted to 7% and also did not become established in CMV populations. Sequence analyses of regions of RNA1, RNA2, and RNA3 showed that there are strong constraints to maintain the encoded sequence and also gave evidence that these constraints may have been different during divergence of types 1 and 2 and, later on, during diversification of these two types. Constraints to the evolution of encoded proteins may be related to selection against genetic exchange. Our data, thus, do not favor current hypotheses that explain the evolution of multipartite viral genomes to promote genetic exchange.     

Bite-force performance and head shape in a sexually dimorphic crevice-dwelling lizard, the common chuckwalla [Sauromalus ater (= obesus)]

The Common Chuckwalla [ Sauromalus ater (=  obesus )] is a large, sexually dimorphic lizard with a flattened head that takes refuge from predators in rock crevices. Males use their relatively large heads to bite competing males during territorial fights and to restrain females during copulation. Flattened heads with an antipredator function (i.e. seeking refuge in crevices) and enlarged heads with intrasexual competition and reproductive functions suggest possible antagonism between selective pressures on head morphology in males. To examine this hypothesis, we performed a morphometric analysis and measured the bite-force performance of 49 adult chuckwallas. Males had disproportionately wider heads than females, but did not have deeper heads. Males bit with nearly four times the force of females, consistent with the notion of sexual selection for high bite force in males. Although constrained by crevice-wedging behaviour, head depth was a good predictor of bite force in both sexes. In males, however, osteological head width also was a good predictor of bite force. These results are consistent with the hypothesis that head shape in males is under antagonistic selective pressures, which may partly explain the pattern of head shape dimorphism. The disproportionately wide head of males may reflect anatomical modifications to enhance bite force in response to sexual selection in spite of presumed constraints on head shape for crevice-wedging behaviour  © 2006 The Linnean Society of London, Biological Journal of the Linnean Society , 2006, 88 , 215–222.     

Przibram's Rule and male body-size dimorphism in Zygoballus rufipes (Araneae: Salticidae)

Przibram's Rule of growth in hemimetabolous insects is derived from average values for the ratios of mean weights (2–09) and mean lengths (1–29) of successive instars in mantids. Adult males of the jumping spider Zygoballus rufipes Peckham & Peckham (Araneae, Salticidae) were shown to be dimorphic, while adult females were monomorphic. The male body weight distribution was bimodal, with two distinct body-size classes (morphs). A method was developed for testing the null hypothesis that an observed ratio of two means is equivalent to a previously derived null ratio. The observed ratio of mean weights for the two male morphs of Z. rufipes (2–12) was not significantly different from the value for Przibram's Rule for weight (2–09), suggesting that males matured at two different instars. The body-size dimorphism found in males was consistent with the existence of two size-based alternative life-history strategies.     

Evidence for host-associated races in a gall-forming midge: trade-offs in potential fecundity

Abstract. 1. The gall midge, Asphondylia borrichiae , attacks the terminals of three plants in the aster family: Borrichia frutescens , Iva frutescens , and I. imbricata .
2. In the field, Borrichia suffers the highest rate of galling and I. imbricata the lowest. Common garden experiments also revealed highly significant differences in the attack rates of the three host species by Asphondylia . However, these differences depended on the source of the attacking midge population.
3. Midges collected from Borrichia and I. frutescens attacked the host in which they developed almost exclusively, whereas those from I. imbricata attacked both Iva spp.
4. Each Asphondylia larva develops in its own chamber within a gall. Borrichia galls were 2.5–3.5-fold less crowded than those from I. imbricata and I. frutescens , respectively. Consequently, midges that developed in Borrichia were significantly larger and eclosed with 30–40% more eggs than those that developed in I. imbricata and I. frutescens , respectively.
5. Although performance of Asphondylia larvae was lowest on the two Iva spp., especially I. frutescens , these hosts may provide an escape from natural enemies as a trade-off for reduced offspring performance.
6. Differences in host-plant species phenology may reduce gene flow among host-associated populations of Asphondylia , thereby favouring the formation of races at the level of plant genus.     

Reexamining the categorical exclusion of pediatric participants from controlled human infection trials

Controlled human infection (CHI) models have been developed for numerous pathogens in order to better understand disease processes and accelerate drug and vaccine testing. In the past, some researchers conducted highly controversial CHIs with vulnerable populations, including children. Ethical frameworks for CHIs now recommend vulnerable populations be excluded because they cannot consent to high risk research. In this paper we argue that CHI studies span a wide spectrum of benefit and risk, and that some CHI studies may involve minimal risk. The categorical exclusion of children from CHIs therefore departs from the standard approach to evaluating research risks, as international regulations and ethical guidance for pediatric research generally permit non-beneficial research with low risks. The paradigm in research ethics has also shifted from focusing on protecting vulnerable participants to recognizing that inclusion can be important as a matter of justice, providing new reasons to question this default exclusion of children from CHIs. Recognizing that pediatric CHIs can raise complex ethical issues and are easy to sensationalize in ways that may threaten the public’s trust in research and sponsor institutions, we conclude by describing additional complexities that must be addressed before pediatric CHIs beyond licensed vaccine studies might be ethically acceptable.     

Morphological variation in the Common Fiscal Lanius collaris along an altitudinal gradient in southern Africa

Geographic variation among four Common Fiscal subpopulations along an altitudinal gradient in South Africa demonstrated significant variation of 13 morphological features and 38 skeletal characters. Common Fiscals were largest in cooler, less humid, more arid areas and smallest in warmer, wetter, more humid localities, supporting Bergmann's Rule. Patterns of variation in morphology, anatomy and skeletal trends were significantly correlated with 11 climatic trends. Cardiopulmonary organ mass and blood haematocrit increased with altitude and reflected adaptations to low ambient temperatures and decreased oxygen pressures associated with high altitudes. These trends are concordant with those reported in various other avian species.     

Erosion of informed consent in U.S. research

This paper evaluates four recent randomized clinical trials in which the informed consent of participants was either not sought at all, or else was conducted with critical information missing from the consent documents. As these studies have been taking place, various proposals to conduct randomized clinical trials without consent have been appearing in the medical literature. Some of the explanations offered for why it is appropriate to bypass consent or disclosure requirements appear to represent a fundamental misunderstanding of applicable government regulations and even the research enterprise. Others are the result of conceptual disagreements about the importance and application of traditional research ethics norms to ‘comparative effectiveness research’ and modern research environments. Common among these explanations, however, is a failure to appreciate when a research intervention, rather than merely an observation or review of data, is taking place. Review committees and investigators are failing to see, or choosing to ignore, interventions in the lives of research subjects. When these studies have come to light, government agencies with oversight authority have done little or backed down. Prestigious medical journals have published research results knowing that the required consent was not obtained, or they have stood by the published studies even after the inadequacy of consent is discovered. This article critically examines this erosion of consent in theory and practice and calls for restoring the requirement of informed consent to its proper place as a priority in human subjects research.     

Against Harmful Research on Non‐Agreeing Children

The Code of Federal Regulations permits harmful research on children who have not agreed to participate, but I will argue that it should be no more permissive of harmful research on such children than of harmful research on adults who have not agreed to participate. Of course, the Code permits harmful research on adults. Such research is not morally problematic, however, because adults must agree to participate. And, of course, the Code also permits beneficial research on children without needing their explicit agreement. This sort of research is also not problematic, this time because paternalism towards children may be justifiable. The moral problem at the center of this paper arises from the combination of two potential properties of pediatric research, first that it might be harmful and second that its subjects might not agree to participate. In Section 2 of this article I explain how the Code permits harmful research on non‐agreeing children. Section 3 contains my argument that we should no more permit harmful research on non‐agreeing children than on non‐agreeing adults. In Section 4, I argue that my thesis does not presuppose that pediatric assent has the same moral force that adult consent does. In Section 5, I argue that the distinction between non‐voluntary and involuntary research is irrelevant to my thesis. In Section 6, I rebut an objection based on the power of parental permission. In Section 7 I suggest how the Code of Federal Regulations might be changed.     

Computational methods and challenges in analyzing intratumoral microbiome data

The human microbiome is intimately related to cancer biology and plays a vital role in the efficacy of cancer treatments, including immunotherapy. Extraordinary evidence has revealed that several microbes influence tumor development through interaction with the host immune system, that is, immuno–oncology–microbiome (IOM). This review focuses on the intratumoral microbiome in IOM and describes the available data and computational methods for discovering biological insights of microbial profiling from host bulk, single-cell, and spatial sequencing data. Critical challenges in data analysis and integration are discussed. Specifically, the microorganisms associated with cancer and cancer treatment in the context of IOM are collected and integrated from the literature. Lastly, we provide our perspectives for future directions in IOM research.     

The annual cycle of the Toc-toc Foudia sechellarum on Cousin Island, Seychelles

The Seychelles Fody or Toc-toc shows a fairly well-defined annual cycle. A full pre-nuptial moult, lasting 90–100 days, occurs from February to May at the end of the wet season. During this period males enter eclipse plumage and there is little breeding. In most years there is a peak of breeding during the dry southeast monsoon from May to September. The subsequent period of post-fledging parental care is lengthy, up to four months. I suggest that this cycle, which minimizes variation in adult energy requirements through the year, may be particularly advantageous to a generalist feeder like the Toc-toc.
Annual adult mortality is not higher than 17–21%, a figure which agrees reasonably with observed juvenile recruitment of 15–16%. The Cousin population of this globally scarce species is estimated at 1300.     

Heuristic approaches to models and modeling in systems biology

Prediction and control sufficient for reliable medical and other interventions are prominent aims of modeling in systems biology. The short-term attainment of these goals has played a strong role in projecting the importance and value of the field. In this paper I identify the standard models must meet to achieve these objectives as predictive robustness—predictive reliability over large domains. Drawing on the results of an ethnographic investigation and various studies in the systems biology literature, I explore four current obstacles to achieving predictive robustness; data constraints, parameter uncertainty, collaborative constraints and system-scale requirements. I use a case study and the commentary of systems biologists themselves to show that current practices in the field, rather than pursuing these goals, frequently use models heuristically to investigate and build understanding of biological systems that do not meet standards of predictive robustness but are nonetheless effective uses of computation. A more heuristic conception of modeling allows us to interpret current practices as ways that manage these obstacles more effectively, particularly collaborative constraints, such that modelers can in the long-run at least work towards prediction and control.     

Giving addicts their drug of choice: the problem of consent

Researchers working on drug addiction may, for a variety of reasons, want to carry out research which involves giving addicts their drug of choice. In carrying out this research consent needs to be obtained from those addicts recruited to participate in it. Concerns have been raised about whether or not such addicts are able to give this consent. Despite their differences, however, both sides in this debate appear to be agreed that the way to resolve this issue is to determine whether or not addicts have irresistible cravings for drugs – if they do, then they cannot consent to this type of research; if they do not, then they can. This I will argue is a mistake. Determining whether or not addicts can say 'No' to offers of drugs will not help us to make much progress here. Instead we need to look at the various ways in which different types of research may undermine an addict's competence to give consent. What we will find is that the details of the research make a big difference here and that, as such, we need to steer a course between, on the one hand, painting all addicts as being unable to consent to research which involves providing them with drugs, and, on the other, maintaining that there are no problems in obtaining consent from addicts to take part in such research.     

From cell biology to biotechnology in space

In this article I discuss the main results of our research in space biology from the simple early investigations with human lymphocytes in the early eighties until the projects in tissue engineering of the next decade on the international space station ISS. The discovery that T lymphocyte activation is nearly totally depressed in vitro in 0 g conditions showed that mammalian single cells are sensitive to the gravitational environment. Such finding had important implications in basic research, medicine and biotechnology. Low gravity can be used as a tool to investigate complicated and still obscure biological process from a new perspective not available to earth-bound laboratories. Low gravity may also favor certain bioprocesses involving the growth of tissues and thus lead to commercial and medical applications. However, shortage of crew time and of other resources, lack of sophisticated instrumentation, safety constraints pose serious limits to biological endeavors in space laboratories.     

Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity

A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity‐related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration‐approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off‐label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.