A Role for Research Ethics Committees in Exchanges of Human Biospecimens Through Material Transfer Agreements

International transfers of human biological material (biospecimens) and data are increasing, and commentators are starting to raise concerns about how donor wishes are protected in such circumstances. These exchanges are generally made under contractual material transfer agreements (MTAs). This paper asks what role, if any, should research ethics committees (RECs) play in ensuring legal and ethical conduct in such exchanges. It is recommended that RECs should play a more active role in the future development of best practice MTAs involving exchange of biospecimens and data and in monitoring compliance.     

Practical Use of MCMC Methods: Lessons from a Case Study

This paper uses the analysis of a data set to examine a number of issues in Bayesian statistics and the application of MCMC methods. The data concern the selectivity of fishing nets and logistic regression is used to relate the size of a fish to the probability it will be retained or escape from a trawl net. Hierarchical models relate information from different trawls and posterior distributions are determined using MCMC. Centring data is shown to radically reduce autocorrelation in chains and Rao‐Blackwellisation and chain‐thinning are found to have little effect on parameter estimates. The results of four convergence diagnostics are compared and the sensitivity of the posterior distribution to the prior distribution is examined using a novel method. Nested models are fitted to the data and compared using intrinsic Bayes factors, pseudo‐Bayes factors and credible intervals.     

Moving from Rabies Research to Rabies Control: Lessons from India

BACKGROUND: Despite the availability of effective interventions and public recognition of the severity of the problem, rabies continues to suffer neglect by programme planners in India and other low and middle income countries. We investigate whether this state of 'policy impasse' is due to, at least in part, the research community not catering to the information needs of the policy makers. METHODS #ENTITYSTARTX00026; FINDINGS: Our objective was to review the research output on rabies from India and examine its alignment with national policy priorities. A systematic literature review of all rabies research articles published from India between 2001 and 2011 was conducted. The distribution of conducted research was compared to the findings of an earlier research prioritization exercise. It was found that a total of 93 research articles were published from India since 2001, out of which 61% consisted of laboratory based studies focussing on rabies virus. Animals were the least studied group, comprising only 8% of the research output. One third of the articles were published in three journals focussing on vaccines and infectious disease epidemiology and the top 4 institutions (2 each from the animal and human health sectors) collectively produced 49% of the national research output. Biomedical research related to development of new interventions dominated the total output as opposed to the identified priority domains of socio-politic-economic research, basic epidemiological research and research to improve existing interventions. CONCLUSION: The paper highlights the gaps between rabies research and policy needs, and makes the case for developing a strategic research agenda that focusses on rabies control as an expected outcome.     

Misuse of anecdotes in primatology: lessons from citation analysis

This study analyzes the accuracy of anecdotes cited in behavioral primatology publications. Anecdotes (n=1 cases) recounting tool use were sought in the four main primatological journals. Citations of anecdotes in the scientific literature that met three criteria were systematically coded for recognition and accuracy. The results showed that 60% of the time, authors who cited anecdotes did not explicitly acknowledge them as such. To a lesser extent, the citations exaggerated the frequency of anecdotal events or misrepresented their status. For tool use specifically, the actor was misreported more often than the tool or its target. Multiple citations were incorrect more often than single citations. Overall, it seems that citation of anecdotes is problematic and may have far-reaching implications in terms of misleading overgeneralizations. Primatologists should take care in citing singular or rare events.     

Habitat Use by Waterbirds in Relation to Pond Size,Water Depth,and Isolation: Lessons from a Restoration in Southern Spain

Wetland restoration is increasingly important to reverse habitat degradation, recover ecosystem services, and maintain biodiversity. To aid project design, more information is required on the influence of wetland size, depth of water, and isolation on the waterbird communities that become established. During a restoration project in Doñana, one of the Europe's most important wetland complexes, an experimental network of 96 temporary ponds with standard shape but variable size, water depth, and isolation was created. We surveyed the waterbird community in spring from 2006 to 2008 and related species abundance and richness to abiotic pond characteristics. We also performed analyses pooling species by foraging guilds or body size. Waterbird abundance and species richness were highest in 2007, the wettest year when the ponds had longer hydroperiods. Larger ponds had consistently higher abundance and species richness for the entire community and for different guilds and body sizes. Moreover, the density of birds per hectare was higher in large ponds than in the smaller ones. Pond isolation and excavated depth did not affect overall abundance and richness, although opposing effects of depth were observed on some size classes, and ducks and large birds preferred isolated ponds. Some bird groups preferred ponds at a particular location. This is the first waterbird study to address the importance of pond size, depth, and isolation independently of confounding variables such as pond shape. It illustrates the varied responses from different bird groups and demonstrates the importance of varying depth, location, and isolation to enhance community abundance and diversity .     

Off-Label Use and Misuse of Testosterone,Growth Hormone,Thyroid Hormone,and Adrenal Supplements: Risks and Costs of a Growing Problem

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to “adrenal fatigue,” an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements.Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

The Use (and Misuse) of Phylogenetic Trees in Comparative Behavioral Analyses

Phylogenetic comparative methods play a critical role in our understanding of the adaptive origin of primate behaviors. To incorporate evolutionary history directly into comparative behavioral research, behavioral ecologists rely on strong, well-resolved phylogenetic trees. Phylogenies provide the framework on which behaviors can be compared and homologies can be distinguished from similarities due to convergent or parallel evolution. Phylogenetic reconstructions are also of critical importance when inferring the ancestral state of behavioral patterns and when suggesting the evolutionary changes that behavior has undergone. Improvements in genome sequencing technologies have increased the amount of data available to researchers. Recently, several primate phylogenetic studies have used multiple loci to produce robust phylogenetic trees that include hundreds of primate species. These trees are now commonly used in comparative analyses and there is a perception that we have a complete picture of the primate tree. But how confident can we be in those phylogenies? And how reliable are comparative analyses based on such trees? Herein, we argue that even recent molecular phylogenies should be treated cautiously because they rely on many assumptions and have many shortcomings. Most phylogenetic studies do not model gene tree diversity and can produce misleading results, such as strong support for an incorrect species tree, especially in the case of rapid and recent radiations. We discuss implications that incorrect phylogenies can have for reconstructing the evolution of primate behaviors and we urge primatologists to be aware of the current limitations of phylogenetic reconstructions when applying phylogenetic comparative methods.     

Misuse,perceived risk,and safety issues of household insecticides: Qualitative findings from focus groups in Arequipa,Peru

BackgroundThe current body of research on insecticide use in Peru deals primarily with application of insecticides offered through Ministry of Health-led campaigns against vector-borne disease. However, there is a gap in the literature regarding the individual use, choice and perceptions of insecticides which may influence uptake of public health-based vector control initiatives and contribute to the thousands of deaths annually from acute pesticide poisoning in Peru.MethodsResidents (n = 49) of the Alto Selva Alegre and CC districts of peri-urban Arequipa participated in seven focus group discussions (FGD). Using a FGD guide, two facilitators led the discussion and conducted a role-playing activity. this activity, participants insecticides (represented by printed photos of insecticides available locally) and pretended to “sell” the insecticides to other participants, including describing their qualities as though they were advertising the insecticide. The exercise was designed to elicit perceptions of currently available insecticides. The focus groups also included questions about participants’ preferences, use and experiences related to insecticides outside the context of this activity. Focus group content was transcribed, and qualitative data were analyzed with Atlas.ti and coded using an inductive process to generate major themes related to use and choice of insecticides, and perceived risks associated with insecticide use.ResultsThe perceived risks associated with insecticides included both short- and long-term health impacts, and safety for children emerged as a priority. However, in some cases insecticides were reportedly applied in high-risk ways including application of insecticides directly to children and bedding. Some participants attempted to reduce the risk of insecticide use with informal, potentially ineffective personal protective equipment and by timing application when household members were away. Valued insecticide characteristics, such as strength and effectiveness, were often associated with negative characteristics such as odor and health impacts. “Agropecuarios” (agricultural supply stores) were considered a trusted source of information about insecticides and their health risks.ConclusionsIt is crucial to characterize misuse and perceptions of health impacts and risks of insecticides at the local level, as well as to find common themes and patterns across populations to inform national and regional programs to prevent acute insecticide poisoning and increase community participation in insecticide-based vector control campaigns. We detected risky practices and beliefs about personal protective equipment, risk indicators, and safety levels that could inform such preventive campaigns, as well as trusted information sources such as agricultural stores for partnerships in disseminating information.     

Research for Change versus Research as Change: Lessons from a Mujerista Participatory Research Team

In this article, I aim to further the discussion of engaged research in anthropology and education by examining the unique changes promoted by participatory research in contrast to policy-oriented activist research models. Drawing on my work with Latina immigrant mothers in a school reform movement, I argue for a Latina feminist view of participatory research that illuminates and builds on Latina women's capacities for social critique and transformative resistance.  [participatory research, activist anthropology, Latino parents, school reform]     

Aging,Stem Cells and Tissue Regeneration: Lessons from Muscle

With age, there is a gradual decline in the regenerative properties of most tissues due to a combination of age-dependent changes in tissue-specific stem cells and in the environmental cues that promote those cells to participate in tissue maintenance and repair. In adult skeletal muscle, where the resident dedicated stem cells (“satellite cells”) are capable of rapid and highly effective regeneration in response to injury, there is just such a loss of regenerative potential with age. Satellite cell activation and cell fate determination are controlled by the Notch signaling pathway that is initiated by the rapid increase in expression of the Notch ligand, Delta, following injury. In old muscle, this upregulation of Delta is blunted and thus satellite cell activation is markedly diminished. However, by indirectly inducing Notch activity, the regenerative potential of aged satellite cells can be restored. Furthermore, exposure of aged satellite cells to serum from young mice, either in vivo by heterochronic parabiotic pairings or in vitro, rejuvenates the satellite cell response. This restorative potential suggests that tissue-specific stem cells do not lose their ability to participate in tissue maintenance and repair. Therefore, it may be that even very old stem cells may be capable of maintaining and repairing aged tissues if provided with optimal environmental cues.     

Kinases and Pseudokinases: Lessons from RAF

Protein kinases are thought to mediate their biological effects through their catalytic activity. The large number of pseudokinases in the kinome and an increasing appreciation that they have critical roles in signaling pathways, however, suggest that catalyzing protein phosphorylation may not be the only function of protein kinases. Using the principle of hydrophobic spine assembly, we interpret how kinases are capable of performing a dual function in signaling. Its first role is that of a signaling enzyme (classical kinases; canonical), while its second role is that of an allosteric activator of other kinases or as a scaffold protein for signaling in a manner that is independent of phosphoryl transfer (classical pseudokinases; noncanonical). As the hydrophobic spines are a conserved feature of the kinase domain itself, all kinases carry an inherent potential to play both roles in signaling. This review focuses on the recent lessons from the RAF kinases that effectively toggle between these roles and can be “frozen” by introducing mutations at their hydrophobic spines.     

Habitat Selection and Use of Space by Bald-Faced Sakis (Pithecia irrorata) in Southwestern Amazonia: Lessons from a Multiyear, Multigroup Study

Population density and distribution in tropical forest vertebrates are directly linked to patterns of use of space relative to habitat structure and composition. To examine how forest type may explain the ranging behavior and high variance in group density observed within the geographic range of bald-faced saki monkeys (Pithecia irrorata), we monitored habitat use of 5 neighboring focal groups of this species in southwestern Amazonia over 3 yr. To test whether sakis are unflooded (terra firme) forest specialists, we compared home range (HR) use to the corresponding availability of 4 main forest types and quantified HR size and activity budgets as a function of forest type. HR size varied from 16 to 60 ha, and saki population density at this scale (12.5 ± 6.4 SD individuals/km²) was more closely related to forest type than to group size. Although sakis were not obligate habitat specialists, groups clearly avoided bamboo forest and preferred terra firme forest. Terra firme forests were associated with small HRs, intensive use, high HR overlap, and territorial defense, all of which suggest that saki densities will be higher in areas dominated by terra firme forest where large patches of bamboo (Guadua spp.) are absent. The increased desiccation and subsequent forest fires expected in this region from the combined impacts of climate change and human land use potentially threaten the long-term viability of old-growth terra firme forest specialists such as sakis. Regional-scale conservation efforts should ensure that extensive blocks of terra firme forest are protected in areas that remain relatively free of bamboo.     

Lessons from microRNA mutants in worms,flies and mice

It is apparent that microRNAs (miRNAs) are important components in the regulation of genetic networks in many biological contexts. Based on computational analysis, typical miRNAs are inferred to have tens to hundreds of conserved targets. Many miRNA-target interactions have been validated by various means, including heterologous tests in cultured cells and gain-of-function approaches that can yield striking phenotypes in whole animals. However, these strategies do not report on the endogenous importance of such miRNA activities. Likewise, studies of miRNA pathway mutants can suggest an endogenous role for miRNAs in a given setting, but do not identify roles for specific miRNAs. Therefore, these approaches must be complemented with the analysis of miRNA mutant alleles. In this review, we describe some of the lessons learned from studying miRNA gene deletions in worms, flies and mice, and discuss their implications for the control of endogenous regulatory networks.     

Trends in Austrian Resource Efficiency: An Exergy and Useful Work Analysis in Comparison to Material Use,CO2 Emissions,and Land Use

In the past few years, resource use and resource efficiency have been implemented in the European Union (EU) environmental policy programs as well as international sustainable development programs. In their programs, the EU focuses on four resource types that should be addressed: materials, energy (or carbon dioxide [CO₂] emissions), water, and land. In this article, we first discuss different perspectives on energy use and present the results of a long‐term exergy and useful work analysis of the Austrian economy for the period 1900–2012, using the methodology developed by Ayres and Warr. Second, we discuss Austrian resource efficiency by comparing the presented exergy and useful work data with material use, CO₂ emissions, and land‐use data taken from statistical sources. This comparison provides, for the first time, a long‐term analysis of Austrian resource efficiency based on a broad understanding thereof and evaluates Austrian development in relation to EU and Austrian policy targets.     

Community Members' Engagement with and Involvement in Genomic Research: Lessons to Learn from the Field

In this paper, we describe the potential role laypersons on ethics committees can play in ensuring community concerns are addressed in the design and implementation of genomic research. We draw inferences from the outcome of an empirical study of the impact of training of laypersons to address community engagement issues in ethics review of research protocol. While this paper does not advocate a particular solution, it describes the importance of community engagement in genomic research, the current limitations there are in engaging communities in the design of these research projects and how communities can be indirectly engaged in the design and implementation of genomic research through the engagement of laypersons on ethics committees. However, to ensure that these laypersons can play this role, their capacity needs to be built to play this role appropriately. There is evidence to show that where resources are invested in building the capacity of laypersons to play their role as community ‘watchdogs’ in research, they play this role aptly. Community engagement is important in genomic research as genomic researchers will increasingly require community perspectives in critical ethics decision making.     

TERRA,CpG methylation,and telomere heterochromatin: Lessons from ICF syndrome cells

Self-reinforcing negative feedback loops are commonly observed in biological systems. RNA-mediated negative feedback loops have been described in the formation of heterochromatin at centromeres in fission yeast and the inactive X chromosome in mammalian cells. The telomere repeat-containing RNA (TERRA) has also been implicated in the formation of telomeric heterochromatin through a self-reinforcing negative feedback loop. In cells derived from human ICF syndrome, TERRA levels are abnormally elevated and telomeres are abnormally shortened. We now show that telomere heterochromatin is also abnormal in ICF cells. We propose that ICF cells fail to reinforce the TERRA-dependent negative feedback loop as a result of the inability to establish heterochromatin at subtelomeres. This failure is likely due to the lack of DNMT3b and DNA methylation, which is a genetic lesion associated with ICF syndrome. Failure of this feedback mechanism leads to catastrophic telomere dysfunction and chromosome instability.