Hereditary cancer: family history, diagnosis, molecular genetics, ecogenetics, and management strategies

The translation of knowledge about hereditary breast cancer and its improved control, as well as prevention through prophylactic surgery, has been significantly accelerated through the veritable explosive discoveries in molecular genetics inclusive of BRCA1 and BRCA2 germline mutations. Needed however, among the physician community, medical geneticists, and genetic counselors, is a raised level of knowledge about hereditary breast cancer syndromes. Particular attention needs to be given to their extant genotypic and phenotypic heterogeneity, their natural history, and foremost, the requirement of a sufficiently detailed family history, with knowledge as to how to interpret its significance so that hereditary cancer syndrome can be diagnosed, should it, in fact, exist in the particular family. Collectively, surveillance and management programs can then be developed for the patient and his or her high-risk relatives. We believe very firmly that this knowledge needs to be extended to the individual patient(s), first- and second-degree relatives so that they can benefit from this knowledge.     

消化内科学双语教学问题探讨

目的:了解目前消化内科学双语教学的效果及存在的问题,从而进一步改进教学方法,提高教学质量.方法:对我院2007级七年制的医学生进行了消化专业病历分析双语考试及相关的问卷调查,了解学生医学知识掌握的情况及存在的问题.结果:问卷调查中大部分学生认可双语教学方法,认为其对自身未来的发展、自主学习及沟通交流能力的培养有着重要的作用.双语笔试答卷中,学生对消化内科常见疾病的名称、诊断、并发症等知识均能准确、熟练地双语回答.但同时也暴露了知识掌握的灵活性差、书本知识不能与临床知识有机结合等问题.结论:双语教学值得推广,但为了提高教学质量,应进一步改进教学方法,并调整课堂上英语授课的内容及比例.     

The future of education in the molecular life sciences

The changing landscape of education in biochemistry and molecular biology presents many challenges for the future, for students and educators alike. The exponential increase in knowledge, the genomics, proteomics and computing revolutions, and the merging of once separate fields in biology, chemistry, physics and mathematics, mean that we need to rethink how we should be preparing today's science undergraduates for the future. What do we need to change, and how will we implement it?     

POSTOPERATIVE ESOPHAGEAL COMPLICATIONS—Prevention and Treatment

Postoperative esophagitis and stricture formation may be more serious than the disease for which operation was done.The best treatment is prevention by avoiding use of a nasogastric tube if possible. If it has to be used, the tube should have a small lumen and be removed as soon as possible.When surgical operation is necessary, the cardioesophageal junction should not be sacrificed unless it is absolutely necessary to do so.Conservative treatment if begun early can minimize or prevent the development of esophagitis and subsequent stricture formation.     

Velvetbean: A “new” plant with a history

Velvetbean (Mucuna spp.), a vigorous climbing legume of Asian origin, is prominent among the plants currently promoted for use as a green manure and cover crop in the humid tropics. What is not so well known, however, is that the development and diffusion of cropping systems using velvetbean is the result of experimentation by numerous farmers and scientists spanning four centuries and at least eight countries. This article traces the movement of velvetbean and knowledge of its uses, with a view to identifying some of the conditions under which the crop has waxed and waned in the United States and Mesoamerica. Climatic factors, land and labor constraints, and market forces are discussed. The velvetbean story shows that agricultural innovation is neither static nor the purview of a privileged class of innovators. It also suggests that sustainable cropping practices such as green manuring should not be promoted as static models but rather as dynamic systems responsive to the changing conditions of farmers and the broader environment.     

Fisher'S geometrical model of fitness landscape and variance in fitness within a changing environment

The fitness of an individual can be simply defined as the number of its offspring in the next generation. However, it is not well understood how selection on the phenotype determines fitness. In accordance with Fisher's fundamental theorem, fitness should have no or very little genetic variance, whereas empirical data suggest that is not the case. To bridge these knowledge gaps, we follow Fisher's geometrical model and assume that fitness is determined by multivariate stabilizing selection toward an optimum that may vary among generations. We assume random mating, free recombination, additive genes, and uncorrelated stabilizing selection and mutational effects on traits. In a constant environment, we find that genetic variance in fitness under mutation-selection balance is a U-shaped function of the number of traits (i.e., of the so-called "organismal complexity"). Because the variance can be high if the organism is of either low or high complexity, this suggests that complexity has little direct costs. Under a temporally varying optimum, genetic variance increases relative to a constant optimum and increasingly so when the mutation rate is small. Therefore, mutation and changing environment together can maintain high genetic variance. These results therefore lend support to Fisher's geometric model of a fitness landscape.     

Using provenance to manage knowledge of in silico experiments

This article offers a briefing in one of the knowledge management issues of in silico experimentation in bioinformatics. Recording of the provenance of an experiment-what was done; where, how and why, etc. is an important aspect of scientific best practice that should be extended to in silico experimentation. We will do this in the context of eScience which has been part of the move of bioinformatics towards an industrial setting. Despite the computational nature of bioinformatics, these analyses are scientific and thus necessitate their own versions of typical scientific rigour. Just as recording who, what, why, when, where and how of an experiment is central to the scientific process in laboratory science, so it should be in silico science. The generation and recording of these aspects, or provenance, of an experiment are necessary knowledge management goals if we are to introduce scientific rigour into routine bioinformatics. In Silico experimental protocols should themselves be a form of managing the knowledge of how to perform bioinformatics analyses. Several systems now exist that offer support for the generation and collection of provenance information about how a particular in silico experiment was run, what results were generated, how they were generated, etc. In reviewing provenance support, we will review one of the important knowledge management issues in bioinformatics.     

North-South benefit sharing arrangements in bioprospecting and genetic research: a critical ethical and legal analysis

Most pharmaceutical research carried out today is focused on the treatment and management of the lifestyle diseases of the developed world. Diseases that affect mainly poor people are neglected in research advancements in treatment because they cannot generate large financial returns on research and development costs. Benefit sharing arrangements for the use of indigenous resources and genetic research could only marginally address this gap in research and development in diseases that affect the poor. Benefit sharing as a strategy is conceptually problematic, even if one, as we do, agrees that impoverished indigenous communities should not be exploited and that they should be assisted in improving their living conditions. The accepted concept of intellectual property protection envisages clearly defined originators and owners of knowledge, whereas the concept of community membership is fluid and indigenous knowledge is, by its very nature, open, with the originator(s) lost in the mists of time. The delineation of 'community' presents serious conceptual and practical difficulties as few communities form discrete, easily discernable groups, and most have problematic leadership structures. Benefit sharing is no substitute for governments' responsibility to uplift impoverished communities. Benefit sharing arrangements may be fraught with difficulties but considerations of respect and equity demand that prior informed consent and consultation around commercialisation of knowledge take place with the source community and their government.     

Methodology in prostaglandin and thromboxane assay

Many difficulties encountered in prostaglandin and thromboxane assay can be overcome by metabolic consideration of which compound is the best target for measurement. The following requirements must be fulfilled: the chosen compound should represent a constant and preferably major fraction of the studied pathway; it should not be formed as an artifact during collection and processing of the samples; its half-life in the biological material under study should be long; and it must be chemically stable. Our knowledge of prostaglandin metabolism now enables us to solve most assay problems for prostaglandins of the E and F type and, at least in some cases, also compounds of the D type. In general, either the 15-ketodihydro metabolites or the beta-oxidized end products thereof should be monitored; either as such or as chemically stable degradation products. In the thromboxane area, most assays have so far been directed at TxB2. The present study, however, shows that this compound is a highly unsuitable target for monitoring, since it may be formed in large amounts during sample collection. Metabolic studies indicate that an early metabolite, 11-dehydro-TxB2, is a better alternative. Quantification of this product however presents certain problems: it occurs in two different forms and the equilibrium is highly dependent on for example pH. A recently developed radioimmunoassay was employed in kinetic studies on TxB2 metabolism in the human and confirmed that 11-dehydro-TxB2 gives a more reliable picture of events than its parent compound, TXB2.     

Mathematical description of gene regulatory units

Revealing the control mechanisms responsible for the cell's surprisingly well-organized functions should lead directly to a better understanding of how the cell adapts to extraordinarily changing environments. A general framework for describing models that can represent diverse biochemical regulatory functions systematically would help not only systematic interpretation of the various models proposed for certain systems but also further understanding of the general control mechanism and design principles underlying different biological systems. This article presents a unified mathematical framework for describing gene regulatory units. The proposed framework is fairly compatible with the classical control theoretical framework, so it should serve as a connecting bridge between engineering control theory and biological control mechanisms. It should also provide a unified view of different regulatory units and facilitate systematic comparison of different mathematical models proposed in a variety of literature.     

Rationale for an integrated approach to genetic epidemiology

Conclusion: Genetic knowledge is now in the public domain and its interpretation by the media and the citizens brings the issues into the public forum of discussion for the necessary ethical, legal and socio-cultural evaluation of its application. Science is being perceived by some as dangerous and as requiring international regulation. Others feel that genetic knowledge will be the breakthrough that will permit medical progress and individual autonomy with regards to personal health and lifestyle choices. The mapping of the human genome has already yielded valuable information on an increasing number of diseases and their variants. Prevailing popular and journalistic archetypes ("imaginaires") used in the media are perceived by the producers as slowing down the possible application of genetic knowledge. The answers to these dilemmas are not readily apparent nor are they prescribed by classical philosophy of medicine. Since genetic knowledge eventually resides with the individual who carries the genes of disease and/or susceptibility, a logical approach to integration of this knowledge at a societal level would seem to reside with individual education and decision-making. The politics of the ensuing social debate could transform the current social contract since an individual's interests need to be balanced against those of his or her immediate family in the sharing of information. The ethical foundations of such a contract requires the genetic education of "Everyone" as a matter of urgent priority. Genetic education should not serve ideological power struggles between the medical establishment and the ethical-legal alliance. Instead, it should ensure the transfer of knowledge to physicians, to patients, to users, to planners, to social science and humanities researchers and to politicians, so that they may make "informed" and free decisions....     

On the need to redress an inadequacy in animal welfare science: toward an internally coherent framework

The time is ripe for a greater interrogation of assumptions and commitments underlying an emerging common ground on the ethics of animal research as well on the 3 R (replacement, refinement, reduction) approach that parallels, and perhaps even further shapes, it. Recurring pressures to re-evaluate the moral status of some animals in research comes as much from within the relevant sciences as without. It seems incredible, in the light of what we now know of such animals as chimpanzees, to deny that these animals are properly accorded high moral status. Barring the requirement that they be human, it is difficult to see what more animals such as chimpanzees would have to possess to acquire it. If the grounds for ascribing high moral status are to be non-arbitrary and responsive to our best knowledge of those individuals who possess the relevant features, we should expect that a sound ethical experimental science will periodically reassess the moral status of their research subjects as the relevant knowledge demands. We already can observe this reassessment as scientists committed to humane experimental science incorporate discoveries of enrichment tools and techniques into their housing and use of captive research animals. No less should this reassessment include a critical reflection on the possible elevation of moral status of certain research animals in light of what is discovered regarding their morally significant properties, characteristics or capacities, or so I will argue. To do anything short of this threatens the social and moral legitimacy of animal research.     

The Anaesthetist and Intensive Care

Intensive care and its development is part of an evolutionary process in the general organization of hospital medical practice. No new disease process is involved, and this alone should be sufficient to support our view that intensive care does not call for the creation of a new specialty. The experience, skill, and knowledge of anaesthetists qualify them to fill vital roles in intensive care, but it is of paramount importance that in doing so they should neither neglect nor abdicate from their own special field of medical work from which their unique expertise derives.     

The Biodiversity Discourse: Categorisation of Indigenous People in a Mexican Bio-prospecting Case

Indigenous knowledge is often portrayed as static and traditional, while indigenous people are considered victims of exploitation. In the name of development and empowerment NGOs as well as scientists may run the risk of representing indigenous communities that fit their definition of the “correct” way to be indigenous. However, for indigenous people knowledge is not necessarily a static condition in a binary position to science or the ‘modern’ world. Rather, it is a dynamic condition that draws from experience and adapts to a changing environment. The perspective advanced in this paper is that all forms of knowledge, including indigenous knowledge(s), are situated and hybrid. Our argument draws from research carried out in Chiapas, Mexico, regarding the ICBG-Maya bio-prospecting project that was initiated in the 1990s and later terminated due to accusations of bio-piracy.     

Role of health-seeking behaviour in child mortality in the slums of Karachi,Pakistan

The role of family health-seeking behaviour in under-five-year child mortality was explored through the combined approach of examining health-seeking behaviour regarding treatment generally, and in specific in relation to illness before death. A population-based case control study was carried out during the period 1993-1994 using 222 deaths from diarrhoea and acute respiratory illness (ARI) in children under five years of age in six slums of Karachi as cases, and 419 controls matched on age, disease (diarrhoea and ARI) and slum. Factors significantly associated (p<0.05) with child mortality in the multivariate analysis were: mothers changing healers quickly, using a traditional healer or an unqualified doctor and mothers to whom doctors did not explain the treatment, even when maternal education was controlled for. Seeking effective medical services is highly influential on whether the child survives or succumbs to ARI or diarrhoea. As mothers are the first providers of care, an attempt should be made to try and improve their skills through health education so that they can use simple and effective treatments for minor illnesses. They should also be taught to recognize potentially life-threatening conditions, to seek care early and to persist with treatment.     

Design, Development and Decisions

Evolutionary ideas and modern biological knowledge have important roles to play in the understanding of human behaviour. Nevertheless, it is deeply misleading to regard humans as robots in the grip of their genes. A well designed brain should respond to the consequences of behaviour; if an understanding of the likely consequences can be achieved without actually performing the act, then a person who knows that they will be rewarded or punished for certain acts is bound to be influenced by that knowledge. A brain designed in that way facilitates the evolution of societies with explicit social approval of certain activities and explicit disapproval of others. The evolutionary approach to psychology does not imply that individuals do not make free choices. Individuals clearly do make a big difference to what happens in their lives through their decisions. They may be surprised by the consequences of their own actions. A well designed brain should be able to anticipate the consequences of various courses of action and choose between them on the basis of their likely costs and benefits. Planning before doing is clearly of great advantage. People do make well considered decisions and they benefit from doing so.     

How copying affects the amount, evenness and persistence of cultural knowledge: insights from the social learning strategies tournament

Darwinian processes should favour those individuals that deploy the most effective strategies for acquiring information about their environment. We organized a computer-based tournament to investigate which learning strategies would perform well in a changing environment. The most successful strategies relied almost exclusively on social learning (here, learning a behaviour performed by another individual) rather than asocial learning, even when environments were changing rapidly; moreover, successful strategies focused learning effort on periods of environmental change. Here, we use data from tournament simulations to examine how these strategies might affect cultural evolution, as reflected in the amount of culture (i.e. number of cultural traits) in the population, the distribution of cultural traits across individuals, and their persistence through time. We found that high levels of social learning are associated with a larger amount of more persistent knowledge, but a smaller amount of less persistent expressed behaviour, as well as more uneven distributions of behaviour, as individuals concentrated on exploiting a smaller subset of behaviour patterns. Increased rates of environmental change generated increases in the amount and evenness of behaviour. These observations suggest that copying confers on cultural populations an adaptive plasticity, allowing them to respond to changing environments rapidly by drawing on a wider knowledge base.     

Rawlsian Justice and Palliative Care

Palliative care serves both as an integrated part of treatment and as a last effort to care for those we cannot cure. The extent to which palliative care should be provided and our reasons for doing so have been curiously overlooked in the debate about distributive justice in health and healthcare. We argue that one prominent approach, the Rawlsian approach developed by Norman Daniels, is unable to provide such reasons and such care. This is because of a central feature in Daniels' account, namely that care should be provided to restore people's opportunities. Daniels' view is both unable to provide pain relief to those who need it as a supplement to treatment and, without justice‐based reasons to provide palliative care to those whose opportunities cannot be restored. We conclude that this makes Daniels' framework much less attractive.     

Community-equipoise and the ethics of randomized clinical trials

This paper critically examines a particular strategy for resolving the central ethical dilemma associated with randomized clincial trials (RCTs) -- the "community equipoise" strategy (CE). The dilemma is that RCTs appear to violate a physician's duty to choose that therapy which there is most reason to believe is in the patient's best interest, randomizing patients even once evidence begins to favor one treatment. The community equipose strategy involves the suggestion that our judgment that neither treatment is to be preferred (that there obtains a state of "equipoise") is to be assessed according to a community rather than an individual standard. Thus, though a physician may personally believe that there is some reason to prefer one treatment, patients can legitimately be randomized if there remains disagreement in the community of medical professionals. Rationales in favor of this conception include the following: (i) medical knowledge is best understood as residing in the community, (ii) the judgments of others count as evidence, and so should change one's own opinion, (iii) subjects would not be better off outside the trial, and (iv) the point of any trial is the resolution of dispute in the medical community. I critically examine these rationales and argue that they are insufficient. Amongst the problems are tensions between various of these underlying rationales, and important ambiguities in just what the CE criterion is to amount to. Finally, I argue that even if use of CE was justified, it would not justify carrying out RCTs anywhere near long enough to discharge our duty to gain reliable knowledge on which to base safe and effective medical practice. Hence, we need some different justification for carrying out RCTs.     

‘Merry's Ears’—dispersal of fruits and seeds

Remarkable advances in the treatment of cataract have been made in recent years. Can we teach the eye well enough for these to be understood and appreciated by our students?

After receiving treatment for cataract by intraocular lens implant, the author found out as much as possible about this remarkable operation. Before describing the most recent developments and latest technology, the nature of cataract is discussed together with a brief outline of older methods of treatment. The question is addressed as to whether high-school biology can or should provide sufficient knowledge for pupils to understand this relatively simple defect and appreciate the latest complex remedies. Consideration is given to the possible development of new teaching aids from surgical research materials, for example, introducing pupils to the eye through recent advances in surgery, and so starting them off with the latest applications instead of the conventional ‘naming of parts’.