The devil lies in details: reply to Stuart Hurlbert

As pointed out in Stuart Hurlbert's recent article, ecologists still at times design their experiments sloppily, creating a situation where various forms of ‘non‐demonic intrusion’ could account for the documented contrasts between treatments and controls. If such contrasts are nevertheless presented to the reader as if they were statistically demonstrated treatment effects, then pseudoreplication is not a pseudoissue and the use of a stigmatizing label of is entirely warranted, as pointed out by Hurlbert. The problems with Hurlbert's concepts start in the context of studies, where the scope of the experiment is to provoke a chain of dramatic and a priori extremely unlikely events, which a given conjecture predicts to happen as a consequence of a given manipulation. As the essence of these experiments is to trigger large dynamical responses in a biological system, they often require much space and/or special conditions, allowing for efficient isolation of the experimental system from potential sources of contamination. These constraints can be incompatible with standard designs (randomization, replication and treatment‐control interspersion). In the context of experiments, where it has been necessary to sacrifice randomization, replication or treatment‐control interspersion, the logic of inferring treatment effects is the same as used when interpreting causes of spontaneous events or events triggered by manipulations with practical purposes. The observed contrasts can be reasonably interpreted as effects of the treatment if and only if their magnitudes and the timing of their emergence makes alternative explanations utterly implausible (which is up to the reader to judge). If the logic of inference is clearly explained and no claim of statistically demonstrated treatment effect is made, the use of stigmatizing labels like ‘pseudoreplication’ is unwarranted. However, it might clarify the literature if such imperfectly designed experiments are referred to as experimental events, to be distinguished from perfectly designed experiments, where mechanical interpretation of contrasts between treatments and controls as treatment effects can be regarded as socially acceptable.     

Does benefit justify research with children?

The inclusion of children in research gives rise to a difficult ethical question: What justifies children's research participation and exposure to research risks when they cannot provide informed consent? This question arises out of the tension between the moral requirement to obtain a subject's informed consent for research participation, on the one hand, and the limited capacity of most children to provide informed consent, on the other. Most agree that children's participation in clinical research can be justified. But the ethical justification for exposing children to research risks in the absence of consent remains unclear. One prevalent group of arguments aims to justify children's risk exposure by appealing to the concept of benefit. I call these ‘benefit arguments’. Prominent versions of this argument defend the idea that broadening our understanding of the notion of benefit to include non‐medical benefits (such as the benefit of a moral education) helps to justify children's research participation. I argue that existing benefit arguments are not persuasive and raise problems with the strategy of appealing to broader notions of benefit to justify children's exposure to research risk.     

Studying the effects of correlation on protein selection in proteomics data

Recently, Efron (2007) provided methods for assessing the effect of correlation on false discovery rate (FDR) in large‐scale testing problems in the context of microarray data. Although FDR procedure does not require independence of the tests, existence of correlation grossly under‐ or overestimates the number of critical genes. Here, we briefly review Efron's method and apply it to a relatively smaller spectrometry proteomics data. We show that even here the correlation can affect the FDR values and the number of proteins declared as critical.     

Paratransgenesis as a potential tool for pest control: review of applied arthropod symbiosis

Research funds for addressing practical plant pest or disease problems are justified by the size of the threat and the financial burden it imposes. When new technology is developed for pest or disease control, regulatory costs to pay for risk assessments make sense when projected income from a new product can be charged to expected income from a future market. When a pest or disease problem affects a minor crop, the research to address regulatory issues does not have such a clear‐cut funding origin. Ironically, a very selective biopesticide designed to address a local pest or disease problem is the ideal form of sustainable pest management, but has the smallest market of any pest control strategy and therefore the smallest amount of financial support. In this sphere of modest financial resources, regulatory needs can force research away from solving the problem at hand to address assessment issues that add considerable cost. When genetic modification is a part of the proposed new strategy, an added burden is placed on the developers. This burden can defy logic and can also come largely from peers, not the public.     

Reciprocal altruism as a felony: Antitrust and the prisoner's dilemma

Biologist study reciprocity. Because U.S. law outlaws cooperative commercial efforts to establish and maintain cartelized prices, for almost a century lawyers and judges also have been interested in the phenomenon of reciprocity. Judges and enforcement officials have set policy based upon intuitive hunches about the likelihood of reciprocity. This law is not consistent. Older court decisions exhibit fear that reciprocity is probable, while more recent doctrine and commentary have disparaged the likelihood of successful cooperation. This antitrust dispute can be understood in game theoretic terms similar to analyses of reciprocity developed by biological theorists. Axelrod's recent research on the repeated prisoner's dilemma game provides an explanation of how cooperative pricing can evolve despite competitive adversity. This research implies both support for the older antitrust fear of collusive reciprocity as well as criticism of recent and supposedly modern skepticism about the older view. But Axelrod's research as it stands is too simplistic for the market context. Before antitrust can use it, this research must be extended to account for three factors: for the existence of more than two equally sized players, for uncertainty in players' communication, and for the manner in which firms learn their managerial strategies.     

Theories and Major Hypotheses in Ethnobotany

Ethnobotany has evolved from a discipline that largely documented the diversity of plant use by local people to one focused on understanding how and why people select plants for a wide range of uses. This progress has been in response to a repeated call for theory-inspired and hypothesis-driven research to improve the rigor of the discipline. Despite improvements, recent ethnobotanical research has overemphasized the use of quantitative ethnobotany indices and statistical methods borrowed from ecology, yet underemphasized the development and integration of a strong theoretical foundation. To advance the field of ethnobotany as a hypothesis-driven, theoretically inspired discipline, it is important to first synthesize the existing theoretical lines of research. We review and discuss 17 major theories and hypotheses in ethnobotany that can be used as a starting point for developing research questions that advance our understanding of people–plant interactions. For each theory or major hypothesis, we identify its primary predictions and testable hypotheses and then discuss how these predictions have been tested. Developing research to test these predictions will make significant contributions to the field of ethnobotany and create the critical mass of primary literature necessary to develop meta-analyses and to advance new theories in ethnobotany.     

Why Early Care and Education Deserves as Much Attention,or More,than Prekindergarten Alone

High-quality early care and education (ECE) programs promote positive child outcomes, allow parents to work, and contribute to the local economy. Although extant research takes into account the ECE sector in its entirety, recent economic and policy interest has centered on part-day prekindergarten for 3- and 4-year-olds only. Using an ecological framework, we review and synthesize the research literature to examine whether the emphasis on pre-k is justified as economically superior to a comprehensive approach. We compare impacts on the macrosystem (regional economy), exosystem (parents), and microsystem (children's long-term human development) and argue that a holistic approach that includes comprehensive ECE services has economic returns as great as or greater than pre-k alone. Finally, we explore the conceptual barriers that have contributed to the narrow focus on pre-k and the policy implications of ignoring the broader ecological context.     

Conceptual biology,hypothesis discovery,and text mining: Swanson's legacy

Innovative biomedical librarians and information specialists who want to expand their roles as expert searchers need to know about profound changes in biology and parallel trends in text mining. In recent years, conceptual biology has emerged as a complement to empirical biology. This is partly in response to the availability of massive digital resources such as the network of databases for molecular biologists at the National Center for Biotechnology Information. Developments in text mining and hypothesis discovery systems based on the early work of Swanson, a mathematician and information scientist, are coincident with the emergence of conceptual biology. Very little has been written to introduce biomedical digital librarians to these new trends. In this paper, background for data and text mining, as well as for knowledge discovery in databases (KDD) and in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a discussion of recent approaches to hypothesis discovery and testing. 'Testing' in the context of text mining involves partially automated methods for finding evidence in the literature to support hypothetical relationships. Concluding remarks follow regarding (a) the limits of current strategies for evaluation of hypothesis discovery systems and (b) the role of literature-based discovery in concert with empirical research. Report of an informatics-driven literature review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's vision of the hidden value in the literature of science and, by extension, in biomedical digital databases, is still remarkably generative for information scientists, biologists, and physicians.     

How We Forgot Who Discovered DNA: Why It Matters How You Communicate Your Results

One hundred and fifty years ago, a hopeful young researcher reported a recent discovery he had made. Working in the bowels of a medieval castle in the German city of Tübingen, he had isolated a then entirely new type of molecule. This was the birth of a field that would fundamentally change the course of biology, medicine, and beyond. His discovery: DNA. His name: Friedrich Miescher. In this article, the authors try to find answers to the question why—despite the fact that virtually everyone nowadays knows DNA—hardly anyone remembers the man who discovered it. In the history of science, the discovery of DNA was a seminal moment. Why then did it not enter into public memory? Ground‐breaking discoveries can occur in a historical context that is not ready to appreciate them. But that's not all that decides who is remembered and who is forgotten. Scientific pioneers sometimes fail to publicize their findings in a way that ensures that they receive the attention they merit. As discussed here, their personalities and habits may cause discoveries to be “overwritten” by more recent researchers, resulting in distorted cultural memories no longer reflecting the initial event.     

Evolutionary games of cooperation: Insights through integration of theory and data

Cooperation is central to the regulation of many ecological processes and the persistence of ecosystems and their associated functions. However, the evolution of cooperation amongst non-kin appears paradoxical. Games such as the prisoner's dilemma, snowdrift and stag hunt have been borrowed from game theory and used extensively to investigate cooperation. Advances in this area have been numerous and have been provided by both empirical and theoretical studies. We outline some of the common games used and review some of the major findings and recent advancements made in this area. We show a clear link between data and theory, and how this link has been key to our understanding of cooperation.     

Motivated research

While Europe is locked in the debate about basic versus applied research, Louis Pasteur solved the problem more than 100 years ago. Antoine Danchin comments on Pasteur''s notion of ‘motivated research'' and how it leads both to new discoveries and to new applications.Three years ago, a senior politician attended his country''s Annual Congress for the Advancement of Science to give the introductory lecture. He asked the attending scientists to make science and research more attractive to young students and the general public, and asked his countrymen to support scientists to address the urgent challenges of global climate change, energy needs and dwindling water resources. It was neither a European nor a US politician, but the Indian Prime Minister Manmohan Singh who made this speech about the relationship between research and its practical applications. This is such an important topic that one might think it deserves appropriate attention in Europe, yet we fail to address it properly. Instead, we just discuss how science should serve society or contribute to the ‘knowledge-based economy'', or how ‘basic'' or ‘fundamental'' research is opposed to ‘applied'' or ‘industrial'' research and how funding for ‘big science'' comes at the expense of ‘little academic'' research.This dichotomy between the research to generate knowledge and the application of that knowledge to benefit humankind seems to be a recent development. In fact, more than 100 years ago Louis Pasteur avoided this debate altogether: one of his major, yet forgotten, contributions to science was the insight that research and its applications are not opposed, but orthogonal to each other (Stokes, 1997). If Niels Bohr ‘invented'' basic academic research—which was nevertheless the basis for many technological inventions and industrial applications—Pasteur developed what we might call ‘motivated'' research.How is research motivated and by what? By definition, scientists are citizens and members of the general public and, like the public, they are motivated by two forces: on the one hand, in Rudyard Kipling''s words, “man''s insatiable curiosity”; on the other hand, a desire for maintaining and improving their well-being. These are not contradictory to one another; curiosity nourishes dreams of a brighter future and leads to discoveries that contribute to well-being.Pasteur understood that it is essential to take account of society''s demands and desires; that science must be motivated by what people want. Still, there are severe misgivings about the nature of research. These stem from the mistaken but popular assumption that the scientists'' main task is to find solutions to current problems or to fulfil our desires. Problems and desires, however, are not enough, because finding solutions also requires creativity and discovery, which, by their very nature, are unpredictable. Often we do not even know what we need or desire and it is only through curiosity and more knowledge that we find new ways to improve our well-being. Motivation by itself is, therefore, not enough to lead to discovery. Motivation simply helps us choose between many different goals and an infinite number of paths to gain novel knowledge. Subsequently, each path, once chosen, must be explored using the scientific method, which is the only way to new discoveries.Motivation helps us to ask relevant questions. For example, why do wine and beer go sour without any apparent reason? Pasteur set out to design experiments that showed that fermentation is caused by microorganisms. A few years later, silkworms were suddenly dying of a terrible disease in the silk factories of southern France. The French government called on Pasteur for help, who eventually found that a parasite had infected silkworm eggs and proposed solutions to eradicate the disease. The original question therefore led to germ theory and bacteriology, helped to develop solutions to infectious diseases, and eventually created the whole field of microbiology.Motivation leads to conceptual and experimental research, which generates discoveries and new technologies. Discoveries, in turn, are the basic resource for the creation of general knowledge and the development of new products, services and other goods that fulfil public demands and generate jobs. The study of the ‘diseases'' of beer and wine also led to the development of fermentation processes that are still in use today. The same motivation that drove Pasteur in the nineteenth century now enables us to tackle current problems, such as pollution, by studying microbial communities that make compost or thrive in garbage dumps. Motivated research therefore reconciles our curiosity with the creation of knowledge and enables us to address pressing needs for humanity.Because it is strongly inspired by—even rooted in—society''s demands and desires, motivated research also raises accompanying ethical, legal, social and safety issues that should be compelling for all research. As mentioned above, scientists are members of the public who share the same concerns and demands as their fellow citizens and therefore participate with a general, public intelligence that, too often, is absent from academic research. This absence of ‘common sense'' or societal expectations generates the misunderstandings concerning research in biology and the development of biotechnology. These misconceptions—whether about the purported risks of genetically modified organisms or the exaggerated expectations for cancer therapies—can create real suffering in society and inefficient allocation of limited resources. It is therefore advisable for researchers to listen more to the public at large in order to find the motivation for their work.     

A Gradualist Theory of Discovery in Ecology

The distinction between the context ofdiscovery and the context of justificationrestricts philosophy of science to the rationalreconstruction of theories, and characterizesscientific discovery as rare, theoreticalupheavals that defy rational reconstruction. Kuhnian challenges to the two contextsdistinction show that non-rational elementspersist in the justification of theories, butgo no further to provide a positive account ofdiscovery. A gradualist theory of discoverydeveloped in this paper shows, with supportfrom ecological cases, that discoveries areroutinely made in ecology by extending modelsto new domains, or by making additions toearlier models. The logic of discovery isphilosophically accessible once it isappreciated that model truth is presumed, evenif counterfactually, in ecologists' applicationof models. A gradualist view shows thatmodels' heuristic power routinely leads todiscoveries.     

Préservation de la fertilité chez les enfants et les adolescents traités pour un cancer. Aspects relationnels et éthiques

Proposing fertility preservation to an adolescent before chemotherapy that may induce sterility raises numerous relational and ethical issues, as it concerns an adolescent, cancer, sexuality, and parenthood. The goal is to preserve fertility without exacerbating confusion and suffering, without triggering a senses of guilt or irretrievable loss in the event of failure, without hampering his relations with the oncologist caregiver, without transforming his self-esteem and existential dynamics, so that later the memory of the illness and its treatment will not be shameful or traumatic. In routine practice, it is importannt to be attentive to two problems: if semen collection is impossible or fails (how will the adolescent react?) and when parents are too reticent or too eager to do so in the adolescent's place. In these situations, and even more so when a rare, innovative procedure is proposed, it is important to take into account the main principles of clinical ethics: respect the patient's autonomy and dignity, the principles of causing no harm and justice. It is also important to determine the adolescent's objectives, expectations and motivations (whether he accepts or refuses the proposal) which are not necessarily the same as those of the clinicians or parents. Dialogue is not always easy because the diagnosis of cancer (and the resulting shock) is recent, the treatment must commence rapidly, and the doctor and patient do not know each other very well. Training in the use of dialogue and relational skills, in issues specific to adolescents and adolescent psychology, and in solving ethical problems in the medical field can be useful.     

In search of certainty in revolutionary India

In this article, I focus on the dilemmas of a friend in Jharkhand who might have joined the revolutionary armed squads of the Maoist insurgency in India. I show how the question of why one supports a revolutionary movement, as well as the nature of that support, can change over time. In particular, I stress the importance of the dialectics between epistemological and ontological uncertainty and certainty, which may be central to the making of a revolutionary in a particular phase of a revolutionary movement. These dialectics are not just the result of an ontological uncertainty of ideological commitment to the movement, but are crucially also about the search for epistemological clarity in social relations imagined to be less opaque and hence more trustworthy. Doubt, an uncertainty about what one knows about one’s social relationships is characteristic of the epistemic murk that accompanies the breakdown of the normative order in the revolutionary situation analysed here. In this context, Maoist terror arises from the creation of epistemic clarity—the possibility that on the other side norms and relationships will be more certain. This is a certainty that is carved out of uncertainty and ambivalence, a certainty that denies or projects away uncertainty. Its weapon is paranoia, an ability to make enemies where there would be doubt, betrayal where there would be benefit of the doubt. The potential revolutionary is therefore not only unsure about his/her ideological commitments, but moreover, a crucial component of their predicament might be an uncertainty about the social relations in which they find themselves and the hope that revolutionary engagement might come with more guarantees. Becoming a revolutionary is also about being in search of certainty.     

Darwin's Galápagos finches in modern biology

One of the classic examples of adaptive radiation under natural selection is the evolution of 15 closely related species of Darwin''s finches (Passeriformes), whose primary diversity lies in the size and shape of their beaks. Since Charles Darwin and other members of the Beagle expedition collected these birds on the Galápagos Islands in 1835 and introduced them to science, they have been the subjects of intense research. Many biology textbooks use Darwin''s finches to illustrate a variety of topics of evolutionary theory, such as speciation, natural selection and niche partitioning. Today, as this Theme Issue illustrates, Darwin''s finches continue to be a very valuable source of biological discovery. Certain advantages of studying this group allow further breakthroughs in our understanding of changes in recent island biodiversity, mechanisms of speciation and hybridization, evolution of cognitive behaviours, principles of beak/jaw biomechanics as well as the underlying developmental genetic mechanisms in generating morphological diversity. Our objective was to bring together some of the key workers in the field of ecology and evolutionary biology who study Darwin''s finches or whose studies were inspired by research on Darwin''s finches. Insights provided by papers collected in this Theme Issue will be of interest to a wide audience.     

MicroRNAs: Potential biomarkers for cancer diagnosis,prognosis and targets for therapy

MicroRNAs have a revolutionary impact on cancer research over recent years. They emerge as important players in tumorigenesis, leading to a paradigm shift in oncology. The widespread and comprehensive use of microRNA microarrays has enabled the identification of a number of microRNAs as potential biomarkers for cancer. It is encouraging to report that microRNAs have remarkable stability in both formalin-fixed tissue and blood. Many microRNAs have been identified to act as oncogenes, tumor suppressors, or even modulators of cancer stem cells and metastasis. Some studies not only reported the identified microRNA biomarkers, but also deciphered their target genes and the underlying mechanisms. The rapid discovery of many microRNA targets and their relevant pathways has contributed to the development of microRNA-based therapeutics, but the developing progress of antisense or siRNA drugs has been hampered by stability, specificity and delivery problems. This review summarizes the most significant and latest findings of original researches on microRNAs involvement in cancer, focusing on the potential of cancer-related microRNAs as biomarkers for diagnosis, prognosis and targets for therapy.     

Darwin,the amphibians,and the natural selection

A critical review of Darwin's publications shows that he did not dissert much about amphibians, in comparison with the other tetrapods. However, in “A Naturalist's Voyage round the World”, Darwin described for the first time several amphibian species and was surprised by their peculiar way of life, terrestrial or euryhaline. These amphibian observations around the world led Darwin to discuss evolutionnary notions, like developmental heterochronies or evolving convergences, and later to illustrate his famous natural selection theory. This is confirmed, for example, by the publication of “On the Origin of Species” where Darwin ironically questioned creation theory, trying to explain the absence of amphibians on oceanic islands. Lamarck also considered amphibians as relevant material to illustrate his theory of acquired character heredity. These historical uses of lissamphibians as evolutionary models have been mostly realized before any amphibian fossil discovery, i.e. out of a palaeontological context.     

城市绿地与居民健康福祉相关性研究进展——基于生态系统服务供需匹配视角

城市绿地耦合了生态系统服务与人类福祉,兼顾公平与效率的城市绿地空间格局,是提升人居环境和改善民生的重要途径。在厘清相关概念内涵的基础上,基于Citespace软件对城市绿地生态系统服务与健康福祉及其相近概念进行关键词共现图谱与聚类分析,可以发现：研究集聚性强、各集群下研究领域重叠度高,研究尺度逐渐精细化,城市绿地与建成环境、休闲性体力活动与健康空间分异成为近几年研究热点。从供给侧：城市绿地绿地生态系统服务类型以及其估与测度方法,需求侧：居民健康福祉需求测度方法及时空表达,供需匹配：城市绿地生态系统服务供需匹配方法与空间公平,提升与调控：城市绿地时空结构优化与高效服务4个方面系统地综述了绿地生态系统服务与居民健康相关性研究,并指出目前城市绿地生态系统服务供需研究在研究内容、研究逻辑、研究方法及研究结果等方面还需进一步深化与提升。未来研究应重点关注城市绿地生态系统服务空间特征关系与居民健康需求层级的供需匹配程度,通过耦合新数据环境下精细化、规范性居民健康时空行为空间研究,总结供需平衡状态下多维度城市绿地高效服务的空间形态、功能结构与要素组织,并将其应用到城市绿地空间格局研究与绿地系统规划实践中,拓展人居环境优化提质的理论与方法。     

ACADEMIC VS. INDUSTRIAL PERSPECTIVES ON SENSORY EVALUATION

The current practice of sensory evaluation occurs in two general settings: the academic environment of a university laboratory and within the foods and consumer products industries. Sensory evaluation programs can differ in orientation, objectives, methodology and context, and viewed from the perspective of Brinberg's tripartite validity theory, focusing on experimental, theoretical and empirical paths. Differences in organizational goals and resources between academia and industry result in different uses of panels, statistics and collaborative efforts. Opportunities for advancement of the field of sensory science exist within the framework of academic training of and industrial demand for sensory professionals.     

Publics and vaccinomics: beyond public understanding of science

Vaccines have been among the most effective tools for addressing global public health challenges. With the advent of genomics, novel approaches for vaccine discovery are opening up new opportunities for vaccine development and applications, particularly with the expectation of personalized vaccines and the possibility of addressing a broader range of infectious diseases. In this context, it is useful to reflect on the social contexts of vaccine development as these have been influenced by social, ethical, political challenges. This article discusses the historical context of vaccine controversies and factors that help explain public acceptance and resistance, illustrating that these challenges go well beyond simple public misunderstandings. The broader vaccine challenges evident along the innovation trajectory, from development to commercialization and implementation include problems in research and development, organizational issues, and legal and regulatory challenges that may collectively contribute to public resistance or confidence. The recent history of genomics provides further lessons that the developing field of vaccinomics can learn from.