Composite paradigms in medicine: Analysing Gillies' claim of reclassification of disease without paradigm shift in the case of Helicobacter pylori

Since the publication of Kuhn's The Structure of Scientific Revolutions in 1962, the notion of paradigms has shaped the way that philosophy views scientific discovery and how changes in what is regarded as empirical fact occur. This drew heavily on examples from the history of the natural sciences to support Kuhn's hypothesis. However, some argue that medicine is different from the natural sciences. Gillies has proposed another theory of how paradigms apply to medicine; that of composite paradigms. In doing so, Gillies uses the example of Helicobacter pylori and the shift from the excess-acid theory to the current bacterial-infection theory of gastric ulcers to illustrate these fundamental differences between medicine and the natural sciences. Upon analysis of Gillies' claim, it is evident that traditional Kuhnian paradigms are also composite and that the manner in which Gillies proposes disease is classified is insufficient in describing medicine. Furthermore, new local paradigms are demonstrably introduced and the change was accompanied by many of the markers of paradigmatic change including changes in worldview, resistance, incommensurability and the introduction of new questions that could not have existed under the previous paradigm. Whilst this change may not be on the scale of the Chemical revolution, it can still be considered paradigm shift. Thagard also proposes an alternate view of discovery using the case of H. pylori. This has much in common with Kuhnian paradigms but Thagard's theory offers further elucidation and refinement. This allows it to better characterise all of the associated features of discovery relevant in the case of H. pylori, thus provides a preferable tool for examination of this important recent discovery.     

Paradigm change in evolutionary microbiology

Thomas Kuhn had little to say about scientific change in biological science, and biologists are ambivalent about how applicable his framework is for their disciplines. We apply Kuhn's account of paradigm change to evolutionary microbiology, where key Darwinian tenets are being challenged by two decades of findings from molecular phylogenetics. The chief culprit is lateral gene transfer, which undermines the role of vertical descent and the representation of evolutionary history as a tree of life. To assess Kuhn's relevance to this controversy, we add a social analysis of the scientists involved to the historical and philosophical debates. We conclude that while Kuhn's account may capture aspects of the pattern (or outcome) of an episode of scientific change, he has little to say about how the process of generating new understandings is occurring in evolutionary microbiology. Once Kuhn's application is limited to that of an initial investigative probe into how scientific problem-solving occurs, his disciplinary scope becomes broader.     

Humanised models of cancer in molecular medicine: the experimental control of disanalogy

This paper explores the epistemology of extrapolation from model organisms to humans in molecular medicine. We take into account two common views on the issue, the homology view and the disanalogy view. In response to both interpretations, we argue that the foundational basis of extrapolations cannot simply be provided by homology and that relevant disanalogies can, thanks to the techniques of molecular biology, be experimentally controlled and exploited to allow useful and reliable extrapolations. The case of "humanised mice" in the context of cancer stem cell research provides evidence of how animal models can be construed to approximate bona fide causal analogue models of human diseases. To supplement this view we show how the epistemology of model organisms needs to take into account the engineering side of molecular medicine. Model organisms are often manipulated to create analogies or remove disanalogies with the target system. We maintain that highlighting this feature is fundamental to explain what warrants extrapolation in the search for the molecular causes of disease.     

Health as intra-systemic integrity: rethinking the foundations of systems biology and nanomedicine

In current research on systems biology and nanomedicine, we often find an ideal of a new science-based preventive medicine. I consider how disease, cause, explanation, diagnosis, and treatment are understood within this ideal, with special attention to the role of nanoscience and technology in elucidating the "circuit diagram" of a healthy system. I argue that the developmental systems theory that informed George Engel's biopsychosocial model addresses some deficiencies in the current systems ideal, but it needs to be integrated with an ethical analysis that is more attentive to the socioeconomic, cultural, and institutional factors that condition how we understand and manage disease. We also need a richer account of top-down causal paths if we are to appropriately understand diseases as disruptions of inter- and intra-systemic integrity.     

Computational aspects of protein functionality

The purpose of this short article is to examine certain aspects of protein functionality with relation to some key organizing ideas. This is important from a computational viewpoint in order to take account of modelling both biological systems and knowledge of these systems. We look at some of the lexical dimensions of the function and how certain constructs can be related to underlying ideas. The pervasive computational metaphor is then discussed in relation to protein multifunctionality, and the specific case of von Willebrand factor as a 'smart' multifunctional protein is briefly considered. Some diagrammatic techniques are then introduced to better articulate protein function.     

Package inserts for prescribed medicines: what minimum information do patients need?

The information a patient needs about a prescribed medicine can be determined by considering what responsibilities he can assume in relation to taking medicine. When the medicine has been dispensed the patient needs to know how to take the drug; how to store the drug; how it is expected to help; and how to recognise problems and what to do about them. A guide was designed to specify what information is required to meet these needs. Using this guide, a set of minimum information on tetracycline was prepared that aimed at being brief, specific, and readable. The best format for the information remains to be determined. Since leaflets produced by professional organisations are generally unsuitable for these purposes, information sets should be put together by small independent groups consisting of clinical pharmacologists, clinicians, pharmacists, and consumers. Each country should produce its own sets, adapting model sets to the circumstances of local practice.     

The impact of GMOs on poor countries: a threat to the achievement of the Millennium Development Goals?

The first of the Millennium Development Goals - halve the proportion of people who suffer from hunger by 2015 - is essential for eradicating poverty, as most of the poor live in rural areas.The role of agriculture is, therefore, key to the fight against poverty.Nevertheless, over the last years rich countries diminished their official development assistance for agricultural development and some of them proposed and pushed for a new model of agriculture based on biotechnology. Such a new model of agriculture is presented by its supporters as a means to contribute to the elimination of poverty, as it intends to maximise the crop production.However, it does not take into consideration that policies fighting hunger: need a more comprehensive approach; must take into consideration socio-economic and environmental peculiarities, especially local needs and traditional knowledge and practices.Genetically modified technology goes against these basic requirements, as it is designed to suit multinational enterprises in the North.When drafting development policies, rich and poor countries must bear in mind that the framework of the Millennium Development Goals, to which 189 Nations committed, requires a coherent approach to empower the poor, especially women, and promote traditional knowledge of indigenous people and local communities, as well as ensuring environmental sustainability.The fight to poverty and hunger will not be won and people will still go hungry if the fundamental causes of hunger and food insecurity are not tackled, whereas genetically modified technology is not based on this assumption.     

Interactions among biological systems: An analysis of asymptotic stability

An analysis of the interactions among asymptotically stable dynamical systems is formulated by making use of the dynamical system theory. Some results coming from previous mathematical analyses have been slightly modified to take into account some typical biological constraints as the boundedness properties of the solutions. In particular it has been shown that when the “coupling” among the subsystems is “loose” enough (in a sense that has to be made mathematically precise) the asymptotic behaviour of a complex system is the same of that of its individual components. The mathematical theory has been used to analyze two systems of biological significance: the coupling among chemical reactions and the stability properties of a 4-dimensional system describing the kinetics of a chemical transmitter.     

New wine in old bottles? The biotechnology problem in the history of molecular biology

This paper examines the “biotechnology problem” in the history of molecular biology, namely the alleged reinvention of a basic academic discipline looking for the logic of life, into a typical technoscientific enterprise, closely related to agriculture, medicine, and the construction of markets. The dominant STS model sees the roots of this shift in a radical change of the regime of knowledge production. The paper argues that this scheme needs to be historicized to take into account the past in our biotech present. Looking at the development of breast cancer genetic testing and GMOs as examples of mounting issues of intellectual property, risk and regulation, the paper also argues that historians of biology should pay closer attention to the political, the economical and the legal changes of the last thirty years. Solving the biotech problem requires new categories. The notion of “way of regulating” is given as an example of such notions linking the local and the global.     

森林多目标经营单元的时空尺度扩展

森林多目标经营是我国林业发展的重要趋势,而森林本身的特性以及国内外的众多研究证明,森林多目标经营需要考虑多个时空尺度,以满足其生态、经济和社会效益的综合发挥。在界定多功能林业和森林多目标经营的概念及基础上,系统地分析了传统森林经营时空尺度和现代森林多目标经营时空尺度的联系与区别,提出现代森林多目标经营单元空间尺度上应该满足区域、景观和林分多尺度的需要,而在时间尺度上则要综合考虑短期、中期和长期,并以露水河林业局为例给出具体的研究思路,以期为我国开展森林多目标经营提供借鉴。     

Wave intensity analysis of left ventricular filling

Wave intensity analysis (WIA) is a powerful technique to study pressure and flow velocity waves in the time domain in vascular networks. The method is based on the analysis of energy transported by the wave through computation of the wave intensity dI = dPdU, where dP and dU denote pressure and flow velocity changes per time interval, respectively. In this study we propose an analytical modification to the WIA so that it can be used to study waves in conditions of time varying elastic properties, such as the left ventricle (LV) during diastole. The approach is first analytically elaborated for a one-dimensional elastic tube-model of the left ventricle with a time-dependent pressure-area relationship. Data obtained with a validated quasi-three dimensional axi-symmetrical model of the left ventricle are employed to demonstrate this new approach. Along the base-apex axis close to the base wave intensity curves are obtained, both using the standard method and the newly proposed modified method. The main difference between the standard and modified wave intensity pattern occurs immediately after the opening of the mitral valve. Where the standard WIA shows a backward expansion wave, the modified analysis shows a forward compression wave. The proposed modification needs to be taken into account when studying left ventricular relaxation, as it affects the wave type.     

Darwinian psychiatry and the concept of mental disorder

In this paper, we discuss the concept of mental disorder from the perspective of Darwinian psychiatry. Using this perspective does not resolve all of the quandaries which philosophers of medicine face when trying to provide a general definition of disease. However, it does take an important step toward clarifying why current methods of psychiatric diagnosis are criticizable and how clinicians can improve the identification of true mental disorders. According to Darwinian psychiatry, the validity of the conventional criteria of psychiatric morbidity is dependent on their association with functional impairment. Suffering, statistical deviance, and physical lesion are frequent correlates of mental disorders but, in absence of dysfunctional consequences, none of these criteria is sufficient for considering a psychological or behavioral condition as a psychiatric disorder. The Darwinian concept of mental disorder builds from two basic ideas: (1) the capacity to achieve biological goals is the best single attribute that characterizes mental health; and (2), the assessment of functional capacities cannot be properly made without consideration of the environment in which the individual lives. These two ideas reflect a concept of mental disorder that is both functional and ecological. A correct application of evolutionary knowledge should not necessarily lead to the conclusion that therapeutic intervention should be limited to conditions that jeopardize biological adaptation. Because one of the basic aims of medicine is to alleviate human suffering, an understanding of the evolutionary foundations of the concept of mental disorder should translate into more effective ways for promoting individual and social well-being, not into the search for natural laws determining what is therapeutically right or wrong.     

Tumorigenicity Assays,Including Use of the Jackknife

The complexities of long-term tumorigenicity assays are discussed and statistical approaches suggested. Account must be taken of how tumors are discovered, and a reasonable distinction might be made between self-evidencing tumors (palpable tumors and rapidly lethal tumors) and those identified only on necropsy. Tumor autolysis can pose difficulties. The nature of the experimental design must be taken into account-the study can be completely randomized, or may involve litter-matching, or circumstances may require that all members of a litter be treated alike. The use of a logrank procedure or a closely equivalent Mantel-Haenszel procedure can provide a unifying approach, but modification needs to be made so as to take into account-data on non-self-evidencing tumors. Censoring plays a role, whether because of eventual study termination or because losses to competing risks are treated as censored observations. Where there are several non-zero dosage levels, the analysis can be modified according to the dosage metric used. Multiplicity of statistical tests can arise whether because a number of questions are asked or because a multiplicity of tumor sites have to be considered. Some of the kinds of questions raised have been addressed in earlier papers by various of the present authors, to which the reader is referred. Specifically new material is given on use of the jackknife so as to take into account that the unit of observation is the litter or even the group of litters caged together. Various problems were found to attend the application of the jackknife in such situations.     

Virtual labs: a substitute for traditional labs?

Current technologies give us the ability to enhance and replace developmental biology classes with computer-based resources, often called virtual labs. In the process of using these resources, teachers may be tempted to neglect the simpler technologies and lab bench activities, which can be labor intensive. In this paper, I take a critical look at the role of computer-based materials for the teaching of developmental biology in order to aid teachers in assessing their value. I conclude that while digital tools have value, they should not replace all of the traditional laboratory activities. Clearly, both computer-enhanced activities and traditional labs must be included in laboratory exercises. Reliance on only one or the other is inappropriate. In order to determine when it is appropriate to use a particular educational tool, the goals of the course and the needs of biology students for an education that gives them a realistic and engaged view of biology must be understood. In this paper, I dispel some of the myths of computer tools and give specific guidelines for assessing their usage, taking into account the special needs of a developmental biology class and the difficulties of observing all the developmental stages of subject organisms in the timescale of class meetings.     

Mechanical simulation of shear stress on the walls of peripheral arteries

In the last few years many attempts were made to line artificial vascular grafts with in vitro grown endothelial cell layers and thereby to minimize the risk of thromboembolism. However, adherence and resistance against shear stress forces were not tested under physiological pulsatile shear stress forces. In this paper, a mock-circulation apparatus is described, which simulates various forms of pulsatile shear stress, and which at the same time meets the requirements of cell cultivation. It can be sterilized and needs less than 700 ml of culture medium for priming. The generated flow profile can be adapted to a wide range of shear stress and also to different viscosities of used media. To take account of the different viscosities of culture medium and blood, a computerized calculation of the shear stress pattern was performed. Using the results of this computer model, the flow pattern was modified to obtain normal physiological shear stress when using culture medium. Results of pulse generation and simulation for the superficial femoral artery are presented.     

Health,illness, and immigration. East Indians in the United States.

East Indian immigrants to the United States represent the diversity in religion, language, and culture that exists in India, so it is difficult to make unequivocal statements about their health beliefs and behaviors. Despite the diversity, an understanding of Ayurvedic humoral concepts of health and illness provides a key to some pervasive and persistent ideas and practices. India has a pluralistic medical system in which Western medicine, which is increasingly popular for some ailments, is one option among many. Even those who are familiar with the "Western" medical system in India may find American medicine alien.     

The shaping of senescence in the wild

A central prediction of classical theories of senescence states that environments posing a high risk of mortality favor the evolution of rapid intrinsic deterioration, or ageing. Although widely cited as being largely corroborated by existing data, empirical support for this prediction has been mixed. Recent theory suggests that this expectation should only be realized under particular circumstances, and this could account for the equivocal empirical findings. Here, we highlight the salient features of some of the recent developments in this field and suggest some ways in which progress might be made. We argue that it is necessary to move beyond the simplistic classical expectation and to take a more comprehensive and precise approach to studies of senescence, both theoretically and empirically.     

On Scott-Phillips’ General Account of Communication

The purpose of this paper is to critically engage with a recent attempt by Thom Scott-Phillips to offer a general account of communication. As a general account, it is intended to apply equally well to both non-human and human interactions which are prima facie communicative in character. However, so far, Scott-Phillips has provided little detail regarding how his account is supposed to apply to the latter set of cases. After presenting what I take to be the most plausible way of filling in those details, I argue that his account would appear to be too narrow: it (minimally) fails to capture a range of human interactions which strike us as instances of communication. To wit, these are cases in which some but not all of the information an act is designed to convey to a reactor actually reaches that reactor. An alternative account incorporating Scott-Phillips’ main insights is then sketched, and it is suggested that this account, or something like it, would accommodate the full range of non-human and human interactions that are intuitively communicative.     

The Evolution of Sex: Domains and Explanatory Pluralism

The evolution of sexual reproduction is a striking case of explanatory pluralism, meaning that one needs to refer to more than one explanation in order to adequately account for it. I develop the concept a domain of phenomena in order to analysis this pluralism. Pluralism exists when a phenomenon can be included in more that one homogeneous domain or in a heterogeneous domain. I argue that in some cases domain partitioning can be used to decrease pluralism, but that in the case of sex domains are overlapping and interconnecting, or in other words bear an orthogonal relationship to one another, and hence cannot be partitioned in such a way as to eliminate pluralism.     

Cumulative logit modelling for ordinal response variables: applications to biomedical research

Incorrect statistical methods are often used for the analysisof ordinal response data. Such data are frequently summarizedinto mean scores for comparisons, a fallacious practice becauseordinal data are inherently not equidistant. The ubiquitousPearson chi-square test is invalid because it ignores the rankingof ordinal data. Although some of the non-parametric statisticalmethods take into account the ordering of ordinal data, thesemethods do not accommodate statistical adjustment of confoundingor assessment of effect modification, two overriding analyticgoals in virtually all etiologic inference in biology and medicine.The cumulative logit model is eminently suitable for the anlaysisof ordinal response data. This multivariate method not onlyconsiders the ranked order inherent in ordinal response data,but it also allows adjustment of confounding and assessmentof effect modification based on modest sample size. A non-technicalaccount of the cumulative logit model is given and its applicationsare illustrated by two research examples. The SAS programs forthe data analysis of the research examples are available fromthe author.