Cortical folding exhibits both reproducibility and variability in the geometry and topology of its patterns. These two properties are obviously the result of the brain development that goes through local cellular and molecular interactions which have important consequences on the global shape of the cortex. Hypotheses to explain the convoluted aspect of the brain are still intensively debated and do not focus necessarily on the variability of folds. Here we propose a phenomenological model based on reaction-diffusion mechanisms involving Turing morphogens that are responsible for the differential growth of two types of areas, sulci (bottom of folds) and gyri (top of folds). We use a finite element approach of our model that is able to compute the evolution of morphogens on any kind of surface and to deform it through an iterative process. Our model mimics the progressive folding of the cortical surface along foetal development. Moreover it reveals patterns of reproducibility when we look at several realizations of the model from a noisy initial condition. However this reproducibility must be tempered by the fact that a same fold engendered by the model can have different topological properties, in one or several parts. These two results on the reproducibility and variability of the model echo the sulcal roots theory that postulates the existence of anatomical entities around which the folding organizes itself. These sulcal roots would correspond to initial conditions in our model. Last but not least, the parameters of our model are able to produce different kinds of patterns that can be linked to developmental pathologies such as polymicrogyria and lissencephaly. The main significance of our model is that it proposes a first approach to the issue of reproducibility and variability of the cortical folding. The anatomical variability of the human brain folds remains an unclear and challenging issue. However it is clear that this variability is the product of the brain development. Several hypotheses coexist for explaining the rapid development of cortical sulci and it is of the highest interest that understanding their variability would improve the comparison of anatomical and functional data across cohorts of subjects. In this article we propose to extend a model of cortical folding based on interactions between growth factors that shape the cortical surface. First the originality of our approach lies in the fact that the surface on which these mechanisms take place is deformed iteratively and engenders geometric patterns that can be linked to cortical sulci. Secondly we show that some statistical properties of our model can reflect the reproducibility and the variability of sulcal structures. At the end we compare different patterns produced by the model to different pathologies of brain development. The development of the human brain from the early gestational weeks to the buckling of the first folds at around 20 weeks follows a narrow pathway between determinism and pure randomness. On the one hand normal adult individuals offer quite similar - from a pure qualitative and descriptive point of view - folding structures: gyri and sulci. On the other hand we observe morphological variabilities between different brains Folding or buckling are very general processes in nature and among living organisms. Especially one of the most studied step in the morphogenesis of metazoans is gastrulation which corresponds to a symmetry breaking of the spherical embryo and an invagination. The origin of this folding remains unknown even if mechanical factors are undoubtedly implied In these conditions it raises the issue of realistic modeling of far more complex buckling processes such as the gyrification of mammal brains. In this regard it is important to inspect carrefully previous models of gyrification.Le Gros Clark In the same extra-cortical point of view a recent and very popular model considers that the folding of the brain takes its origin in the mechanical tensions produced by the white matter fibers At the opposite there are numerous hypotheses arguing that the cortical folding has intrinsic origins. In In the intrinsic origins of folding we encounter also purely morphogenetic hypotheses in which cortical convolutions are under genetic control In the next part we will see in detail another hypothesis for the cortical folding which is based on Turing instabilities In this article we investigate the origin of anatomical variability from the early development and we propose a phenomenological model of the folding which is based on the putative existence of Turing morphogens. After recalling briefly some mathematical aspects of the model, we present the numerical schemes used for implementing the equations on a surface and for the deformation of the surface. We show some qualitative and quantitative results of the model. In particular we link sulcal pits maps to the average folding patterns across several realizations of a same noisy initial condition. And we study the variability of our model and demonstrate that it can lead to different modes of variability of one sulcus.Cartwright Very recently the Global Intermediate Progenitor (GIP) model has been proposed to explain the appearance of transversal or sectorial sulci following the Intermediate Progenitor hypothesis We aim at extending the analogy first formulated by Cartwright and the GIP model using a system of reaction-diffusion equations that will modify the surface on which the equations take place. Namely the reaction diffusion system models the non-linear interaction of two morphogens In our model initial conditions of the reaction-diffusion equations have strong similarities with the sulcal roots described in Our choice of the reaction-diffusion equations differs from the one of Cartwright and the GIP model since we have adopted the Gray-Scott model:The mathematical analysis of the model has been previously conducted in Following ideas of Since the surface on which evolve the morphogens is modified with time, we have to adapt the equations (1) and (2) to take into account the geometric changes. The problem of reaction-diffusion on growing domains has been well-studied in the past years. It leads generally to add convective and dilution terms to The model proposed in Since we work on discrete meshes we have used a finite element method to discretize the linear terms in the equations 1 and 2.First we derive a weak formulation of the system onNext we work on a discrete tessellation The weak formulation becomes:It is possible to treat the non-linear term with the following approximation as in At last we need to compute To be exact we should take into account the fact that the finite elements vary along time or in other terms that the mass matrix For the surface deformation step, we translate equation (3) by simply modifying each vertex In our implementation we do not prohibit self-intersection which would increase considerably the computation time. However we can say that we escape this issue by not solving for too long time but also taking a parameter First we can model the growth of a normal brain with the value Note that the evolution specified by the coupled reaction-diffusion equations and the surface deformation leads to a progressive folding of the initial sphere on We can observe on Moreover we propose a simple way to characterize the spatial stability of the folds along time. In other terms we demonstrate that the position of folds formed at different time instants remains relatively stable. We extract a map of the curvature We can see on this figure that the average map In this part we investigate the influence of noise in the spatial position of the folds. In particular we aim at demonstrating that the reaction diffusion mechanism is able to produce reproducible folds at certain specific locations but can also engender variability at other locations. For this we simulate On More generally It is possible to represent directly the influence of one or several parameters of the model (As suggested by So we can see that for Pax6, Ngn2, Id4. Our model supports this hypothesis since mutations in the Pax6 gene for instance can be responsible for polymicrogyria Pax6. We can also mention an alternative scenario for pattern formation that has been recently exposed in Our model extends the initial proposal of Cartwright in In our model we investigate also the variability of folding along the development of one individual and across several individuals - that is several realizations of the model. First we can see that for an unique development the position of the sulci remains stable along time. This result may seem trivial but is required for our model to produce definite patterns of gyrification that can be compared between different realizations of the model. Secondly the study of folding variability among 50 random realizations of the model reveals two important characteristics. The folding does not organize randomly even if we add noise to the initial condition of the reaction diffusion process. We have shown on one example that a main structure emerges that is strongly reproducible among several simulations. We can find a direct analogy between this main fold and the primary folds described in the literature Moreover we have shown that in spite of its strong reproducibility the main fold could be broken in two separate parts by a gyrus. This result echoes previous studies On a more theoretical point of view, our results on the reproducibility of the folds seem to confirm the impact of growth domain on the robust selection of patterns as it has been previously shown in In conclusion we have proposed an extended framework for modelling the cortical folding. It is based on a system of coupled reaction-diffusion equations defined on a surface that evolves through the action of morphogens. We show that for some parameters the model gives rise to geometric patterns that can be related to cortical sulci. We also demonstrate that under the effect of noise the system yields morphological variability in these cortical structures. Moreover changing slightly the values of the parameters of the model can have an important influence on the nature of the created patterns which suggest a link toward pathologies of the brain development such as lissencephaly or polymicrogyria. In future developments we plan to investigate the difficult issue of estimating good values of parameters with respect to a given sequence of cortical surfaces across development.


The current postgraduate psychiatric training programs all over India are psychopharmacology oriented and are essentially based on the medical model of illness. An interesting feature of this change in psychiatric teaching programs is the comfort level of new graduates with typical antipsychotic medications. Most of the institutes and regional medical colleges in India currently emphasize the use of atypical antipsychotics for treatment of schizophrenia as suggested either by the American Psychiatric Association Guidelines or the National Institute of Clinical Excellence or the guidelines suggested by the Indian Psychiatric Society.Among the recently passed postgraduates in Psychiatry, those who are equally comfortable with the use of typical and atypical antipsychotics are very few. The residents passing from leading institutes in India would have difficulty in prescribing Chlorpromazine or pimozide or trifluoperazine or even haloperidol. With new studies questioning the infallibility of the atypical antipsychotics, it should not come as a surprise if typical antipsychotics are again brought to the forefront in the management of schizophrenia.2It may not be long when we would have created a generation of psychiatrists in India who would be poorly trained in psychotherapeutic techniques, as well as prescription of a group of medications which are essential drugs in our armamentarium against schizophrenia. All the Psychiatry program directors in India should be aware of this lacuna in our Psychiatry training, and adequate steps should be taken to rectify this.


Although the population lives in a higher latitude, the incidence of and death rate from skin cancer is approximately the same in Sweden as it is in England and Wales. The proportion of malignant melanoma is higher in the Swedish deaths and the death rate from malignant melanoma is higher in Sweden than in England and Wales.The ratios of male to female cases and deaths from malignant melanoma are higher in Sweden than in England and Wales.These differences do not appear likely to be due to differences in the statistical or medical care systems, and suggest important genetic and occupational effects.Total skin cancer rates and rates summarizing all ages may be poor indicators of the real variations between populations in the epidemiology of malignant skin tumours.


The primary objective of the book is to introduce the subject of epidemiology to medical graduates in a simple and lucid way. The idea is to introduce the fundamentals and applications of epidemiology in such a manner that they are thought provoking and give students an opportunity to learn by themselves. The book provides comprehensive compilation of epidemiology from descriptive and analytic methods to statistical techniques for analysis of those designs and methodologies for measurement. It incorporates the concepts of quantitative and qualitative research methods, decision making of diagnostic tests, screening as well as surveillance and encourages the disciple to endeavor to reach domains of higher learning by inspiring interest in the subject.The book has been organized systematically into five modules, each sub-divided into various chapters. The modules deal with traditional and emerging themes in epidemiology like epidemiologic methods, measurements in epidemiology, statistics in epidemiology, practical epidemiology and applied epidemiology. The chapters are succinctly written with specific objectives and exercises, replete with numerous examples which are very useful and helpful for learning the concepts and methods of epidemiology in a step wise fashion.This book can be an excellent primer for medical graduates for epidemiology. It has all the necessary ingredients to stimulate a graduate's interest in epidemiology as well as enough scientific merit to be recommended as essential reading for undergraduate teaching.The layout of the content in modules and chapter with specific learning objectives is commendable. However, the learning objectives fall short in the context of hierarchy of knowledge and so is the content. The nomenclature of the modules/selection of chapters within the module could have been better: surveillance and investigation could have been under field epidemiology; the module on applied epidemiology could have introduced emerging concepts in infectious disease epidemiology, non-communicable disease epidemiology, genetic epidemiology, etc. The book in its present form is still praise-worthy for presenting the subject in a different perspective and has all the potential to stimulate and kindle the epidemiologist in the medical graduate and hence is more than welcome.


The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types.


There has been a general increase in the incidence of cancer of most major sites during the period 1960-69; this is true even when allowances are made for shifts in the age composition of the population. Improvements in diagnostic procedures may account for some of these increases but it is doubtful that they are solely responsible for the greater incidence recorded.A few sites stand out as being primarily responsible for the increase in the overall cancer incidence. Lung cancer is increasing in both males and females; the rate of increase, however, is much greater among females. It is generally acknowledged that women began smoking cigarettes at a later point in time and to a lesser extent. The pattern which has emerged indicates that females are experiencing a similar trend in lung cancer incidence to that of males. The increase in the incidence of female breast cancer is also noteworthy, although the forces producing this change can only be speculated upon. The high incidence of prostatic cancer among negroes and the increase in the incidence of prostatic cancer in whites are subjects which deserve further investigation, especially since the Alameda County experience is not duplicated in data from the Connecticut Tumour Registry. One of the most encouraging findings is that the incidence of stomach cancer appears to be declining.


Much environmental health research depends on human volunteers participating with biological samples. The perception study explores why and how people participate in a placenta perfusion study in Copenhagen. The participation implies donation of the placenta after birth and some background information but no follow up.Nineteen semi-structured qualitative interviews were conducted with participants in the placenta perfusion study after donation of placenta. Observation studies were made of recruitment sessions.The interviewed participants are generally in favour of medical research. They participated in the placenta perfusion study due to a belief that societal progress follows medical research. They also felt that participating was a way of giving something back to the Danish health care system. The participants have trust in medical science and scientists, but trust is something which needs to be created through "trust-work". Face-to-face interaction, written information material and informed consent forms play important parts in creating trusting relationships in medical research.Medical research ethics do not only amount to specific types of written information material but should also be seen as a number of trust making performances involving researchers as well as research participants. The background of the perception study is a placenta perfusion study undertaken at the Institute of Public Health, University of Copenhagen. The placenta perfusion study uses placentas from women who have given birth by Caesarean section in studies of placental transport of substances from mother to foetus. Sections of the fresh placenta are immediately used in an experimental setup keeping the tissue functional and providing data regarding transport and background concentrations of study compounds of e.g. phthalates -3. The wThe overall research question of the perception study is: Why do people participate in the placenta perfusion study in particular and in environmental health research in general, and what are their perceptions of the ethical and communication practices in the placenta perfusion study? The aim of the perception study is twofold. 1. The study explores the donors' participation in the placenta perfusion study. Is this participation of any importance to the participants and if so, why and how? The perception study thereby also explores the perceived relevance of environmental health research in general and the placenta perfusion study in particular. On a more general level the perception study discusses how and why people participate in the production of medical knowledge and technologies. 2. The perception study also assesses whether the ethical and communication practices in the placenta perfusion project match the needs or expectations of the participants. For instance, do the participants think that they are informed too much or too little, how are the information procedures perceived, and what do participants make of informed consent forms?There is an extensive sociological, anthropological and public health literature on the participation in medical research. Where much of this literature focuses on ethnicity -7 and onThe perception study is structured around the theoretical themes: motives, expectations, altered understandings of self, health and disease in relation to participation, and involvement in science.how people are involved and engaged in environmental health research and to study in what ways the ethical and communication guidelines are practiced and perceived.These themes are inspired by science and technology studies (STS), which is a branch of the social sciences that studies the interdependencies of science and society. A central thesis in STS is that science and society are co-constructed ,15. ThisThe perception study used a method triangulation of observation studies and qualitative interviews. Observation studies were used to get insight into the practices of recruiting donors to the placenta perfusion study (see section on setting and data collection). Qualitative interviews were used to both qualify and problematise the theoretical perspectives of the perception study. When studying science and research from the perspective of STS, science and research become matters of social relations that need to be understood as much as explained, and thus require some kind of access to the perspectives of the actors involved, in this case the placenta donors. In comparison to other methods in the social sciences, observational studies and qualitative interviews are seen to be some of the best ways of getting access to the subject of the study through the privileged position and experiences of the actors involved . QualitaThe research questions were operationalised into an interview guide of 48 questions. The interview guide was used to conduct 19 interviews with donors of placentas to the placenta perfusion study; 5 interviews with both mother and father, 13 interviews with just the mother and 1 interview with just the father. The donors participate in environmental health research at what would seem a very critical moment, namely just before giving birth through Caesarean section. This makes the donors and their involvement in environmental health research an "extreme and critical case"  in the sThe interviewed donors (informants) were recruited at the same time as being recruited to the placenta perfusion study. The recruitment to the placenta perfusion study took place at an information meeting at the hospital the day before the women gave birth. During the information meeting a researcher from the placenta perfusion study would address the possible donors and tell them about the study and ask whether they would want to participate, while handing out information material and informed consent forms. Following this, the possible donors would be asked to participate in the perception study by the sociologist. If so, they were asked to write down their name and number and they would then be contacted about a week after giving birth, and asked if they were still interested in participating in the perception study. Recruiting the informants for the perception study at the same time and place as the recruitment of donors to the perfusion study made it possible to do observation studies, but it may also have been a source of selection bias since the placenta perfusion study and the perception study could be seen as two parts of the same study, which was not the case. The informants signed informed consent forms stating that they would be anonymous to anyone except the interviewer. Permission to conduct the interviews, transcribe and store them was granted by the Danish Data Protection Agency . The participation does not imply any follow-up approaches from the research team.As part of the recruitment strategy, the sociologist offered to interview the informants in their homes, and as a consequence all of the interviews were conducted in the homes of the informants. Interviews were conducted in Danish and range from 20–40 minutes in duration. Quotations in this article are translated into English by the authors. The interview guide included questions about motives, decision making process, practices of information, recruitment procedure, expectations, and relations between environment and health. The study did not include any systematic information about the participants' socio-economic status or educational level since it was not the aim of the perception study to do a representative study of the population. There are no interviews with people who did not wish to participate in the placenta perfusion study. According to the decisions of the Regional Ethics Committee a no must be respected and no other further approach is allowed. Characteristically the people saying no to donate their placenta also seemed to find it annoying or inappropriate to be addressed about other matters than that of their forthcoming birth.Data collection was concluded after 19 interviews with participants in the perfusion study. The original rate of success was 15 interviews. Based on literature on qualitative methods as well as on personal experiences from former qualitative studies 15 in-depth interviews combined with observation studies were judged to give a comprehensive understanding of the social complexities of participating in the placenta perfusion study . After cThe perception study uses an interactionist method of analysis. According to the interactionist perspective, the qualitative interview is seen as a certain social scientific practice with the aim of producing certain forms of knowledge . The intor inductive. It seems more appropriate to characterise the practice of conducting and analysing qualitative interviews and observation studies as a continuous oscillation between deductive and inductive modes of knowing and reasoning. In practice this means that the research questions, the interview guide and the way in which the interviews with the donors from the perfusion study were conducted led to certain forms of knowledge situated in a particular space and time. On the one hand, it is important to take these contextual considerations into account when assessing the results of the perception study. On the other hand this does not mean that the perception study creates types of knowledge that can not lead to general conclusions.The result of the interview is thus not the untouched perspective or hermeneutical truth of the informants' life-world but a negotiation of meaning and reality emerging through the practice of interviewing. When adopting the interactionist approach it would therefore be false to say that the methods of the perception study are either deductive The results of the analysis from the perception study is organised and presented in three parts: reasons for participating, trust in science, and ways of informing.I believe that it is very important to participate in studies of this kind. It advances research and the development, so I think it is a positive thing [...] It is a way in which an enlightened society can progress" and: "You can't just sit and be afraid in your little room. You have to collaborate and by doing that give something to the common good". This sense of duty to participate must be understood in a Danish context. Since the Danish health care system is funded through taxes collected by the Danish state, health care in Denmark is often perceived as both free and as a collective project. Some of the informants thus stressed that participating was a way of giving something back to the Danish health care system. The participants' motivations to participate should also be analysed in relation to the expectations expressed in the interviews. These expectations were about how medical research changes society for the better and that this depends on the participation of "normal people". We may therefore conclude that making society a better place through environmental health research is seen by the informants as a co-operation between scientists and citizens.This part of the analysis is based on the questions and answers about expectations and motivations in relation to the informants' participation in the placenta perfusion study. The overall perception of medical science and research expressed in the interviews is that it is important. When asked to elaborate on this, informants talked about how science and research is synonymous with societal progress and that it is a duty to participate in this progression. Two quotes by two informants illustrate these notions: "The above mentioned motivations could be interpreted as altruistic in a universal sense of the concept, but then motivations are always located in a specific space and time and altruism should therefore be understood as an effect of local circumstances, rather than being a universal explanation. The importance of participating in the placenta perfusion study expressed in the interviews may thus be seen as a result of the direct relevance of this type of research to the donors. The participants easily related to the project since they were pregnant themselves and none of the informants saw themselves as persons seeking out participation in medical research as such.Finally, an important reason for participating was that it was easy. Being asked the day before giving birth was, of course, troublesome for some of the interviewed participants. However, they all stressed that all it really took was to say yes and the placenta would change from being biological waste disposal to becoming raw material in environmental health research. The altruism of the participants should therefore also be seen as an effect of the easiness of participating."You don't want to sit and read...you know, all that ethical stuff...you know what it says already, and you don't bother reading it through [...] And I think that it has something to do with that I trust that they are treating the placenta properly". The relation of trust may therefore be understood as an effect of the face-to-face interaction between the researcher and the participants and not something that solely emerges from reading the written information material and consent form.The participants' perception of the participation as a co-operation underlines the feelings of trust in the placenta perfusion study expressed in the interviews. The trust in the placenta perfusion study is twofold. 1. The informants expressed trust in the meaningfulness of the study. Without knowing many details about the study most of them decided that they would participate and donate their placenta. They also trusted that the researchers would do as they said they would and that the researchers would handle the placenta properly. 2. The informants also trusted that the ethical guidelines would be followed and that these guidelines would protect them sufficiently. Interviews and observation studies showed that far from all of the participants read the information material before signing the consent form, but that they trusted the researcher standing in front of them. One of the informants explains: "I think that it is fundamentally right that you give people the opportunity to say no, because it is in a sense intimate to some people [...] I think just being asked is important because one is already squeezed into a very efficient system such as the health care system. You feel like a piece being moved around, so it is nice that you sometimes feel that you have some rights and can say yes and no". The participants may not have read the information material or consent thoroughly but they nonetheless expressed a need for these documents to be there as a sign of the study being conducted properly. Borrowing from the language of theatre science we might say that written information material and consent forms are important props in the performance of trusting relations between the researchers and the participants. During the observation studies we also witnessed recruitment sessions with critical and clarifying questions posed by the possible participants before deciding to donate. This indicates that the participants did not trust the researchers passively but that trust needed to be produced collectively through "trust-work" where the face-to-face interaction between researcher and participants was crucial.This does not imply, however, that the informants found it superfluous to be asked and give consent. On the contrary, all informants, except one, stressed the importance of giving consent in some form. An informant makes this explicit: The analysis of the interviews and the observation studies has so far shown that the participants are in general favour of medical science and research, and that they trust scientists. However, possible participants still have to be made interested in the specific research project in question. In this process of making possible research participants interested the ways of informing seemingly play an important role. The fact that some of the participants did not read the information material and informed consent forms does not imply that they found information about the study unnecessary, but it implies that what was experienced as suitable ways of informing depended on the space and time in which information was given. According to the interviewed participants both written and oral information is important but the two ways of informing are perceived differently according to the circumstances. If possible, the written information material should be provided to the participants in advance. This would heighten its chances of being read. At the information meeting the oral information given by the researcher in the face-to-face interaction with the possible participants was in the forefront, whereas the written information and consent forms were perceived as mere tokens of the study being conducted properly."You can "sell" the project even better if you tell about already obtained results. You could have said something about some known and debated substance that you had found goes from the mother to the child". The informants were asked if they would the visit the placenta perfusions study website in the future to follow the study and know more about the results. About half of the informants said that they might do that.When talking about the form and substance of both written and oral information the informants stressed that both types should be short and precise and that the purpose of the study should be at the very beginning. The informants wanted to know why they should participate in this particular study and some wanted to become interested and involved in the project. Several of the informants suggested that a way of involving participants and make them interested would be by informing them about already obtained results from the study. One of the informants explains: "If you are not sure, and there are some things that you want to get clear, then it is important that you have the opportunity to ask some questions before you decide. I think that should always be the case". Informants explained that a project would seem less trustworthy if there was no time or space for asking questions. The mere opportunity for asking questions and making suggestions thus signals openness and creates an atmosphere of trust. The involvement and engagement of the participants also shows that they wished to learn from the participation. Some had specific questions about methods or already obtained results which they posed at the information meeting or during the perception study interview, while others expressed a wish to know the results when the perfusion study ends. When asked whether it was negative or positive that participation might have an effect on the ways in which participants think about environment and health in relation to their own lives all of the informants answered that this was positive. They wanted to learn and assess their own ways of living in the light of the research in which they participated.When we understand recruitment as a matter of involvement rather than persuasion it underlines the importance of giving participants an opportunity to ask questions and making suggestions. All of the informants explained that this was essential in their decision to donate, here exemplified by one of the mothers: Medical ethics has traditionally focused on the protection of the autonomy and dignity of research participants. Medical ethics may therefore have lacked focus on how to involve and engage research participants properly and in novel ways in the research projects in which they participate. The interviewed research participants in the placenta perfusion study are in general pro-science and they wished to participate, know results, ask questions and discuss methods. Some of the participants, it must be added, did not care about these matters and participated passively. This calls for flexible and pragmatic research, ethical and information practices that are able to take into account the different ways of participating in research. Table The perception study shows that people participated in the placenta perfusion study because they believed that participating in medical research in general and in the placenta perfusion study in particular would contribute to societal progress through improvements of the health of the population. Improving the health of the population is thus seen as a common project. The participants also felt that participating was a way of giving something back to the Danish health care system, and finally they participated because it was easy. Participants trusted the researchers from the placenta perfusion project and they expressed general trust in medical science and research. The perception study analysis underlines that trust is a social relation that needs to be performed. Face-to-face interaction, written material and informed consent forms, and time for critical and clarifying questions are important properties in the performance of trusting relationships in medical research involving human participants, although the participants may not even read the written information material. According to the interviewed participants the written information material should be short and precise and in both the written and oral material the purpose of the study should be in the forefront. Despite general trust in medical research the participants wished to know why they should participate in this particular study. Oral and written information play different parts according to the circumstances in which they are given. The analysis shows that ethics is not only about the right amount and style of written information material but also about a number of performances and affective relations between humans. In doing trust-work researchers have to put themselves at stake and navigate in the waters of the specific concerns that their research may create.The author(s) declare that they have no competing interests.UL carried out study design, interviews, and analysis of interviews and co-drafted the manuscript. LEK carried out study design and co-drafted the manuscript. TN organised the recruitment and co-drafted the manuscript. All authors have read and approved the final manuscript.


The organ donor shortfall in the UK has prompted calls to introduce legislation to allow for presumed consent: if there is no explicit objection to donation of an organ, consent should be presumed. The current debate has not taken in account accepted meanings of presumption in law and science and the consequences for rights of ownership that would arise should presumed consent become law. In addition, arguments revolve around the rights of the competent autonomous adult but do not always consider the more serious implications for children or the disabled.Any action or decision made on a presumption is accepted in law and science as one based on judgement of a provisional situation. It should therefore allow the possibility of reversing the action or decision. Presumed consent to organ donation will not permit such reversal. Placing prime importance on the functionality of body organs and their capacity to sustain life rather than on explicit consent of the individual will lead to further debate about rights of ownership and potentially to questions about financial incentives and to whom benefits should accrue. Factors that influence donor rates are not fully understood and attitudes of the public to presumed consent require further investigation. Presuming consent will also necessitate considering how such a measure would be applied in situations involving children and mentally incompetent adults.The presumption of consent to organ donation cannot be understood in the same way as is presumption when applied to science or law. Consideration should be given to the consequences of presuming consent and to the questions of ownership and organ monetary value as these questions are likely to arise should presumed consent be permitted. In addition, the implications of presumed consent on children and adults who are unable to object to organ donation, requires serious contemplation if these most vulnerable members of society are to be protected. The controversy about presumed consent has been recently revived in the UK as a consequence of the organ donor shortfall ,2. The dThe understanding of presumption of consent to organ donation may be considered, by some practitioners of law or science, to be an inaccurate and misleading term. This stems from the general understanding of 'presumption' in law and science: as an inference that is made on available fact or evidence with the understanding that vital information that can render the inference invalid may be missing. In law a presumption holds – that of innocence, for example – until a substantial body of evidence is produced to the contrary. Just like a scientific theory or hypothesis, a legal presumption is maintained for as long as no evidence is provided to disprove it or no valid objection is raised against it. A presumption, in law and science, is therefore a 'provisional estimate of facts'  based onUnlike the presumptions in law or the hypotheses of science, presumption of consent for the use of body organs cannot afford any possibility of abandoning the presumption, reversing the decision or of retracting any action based on the decision . The presumption of consent for organ donation cannot therefore be taken as a presumption of donor willingness, with the specific understanding that there will be a provision for changing the course of action should further evidence emerge, but rather as a presumption of state rights to post-mortem body organs, unless an objection by the 'occupant' of the body is raised whilst the 'occupant' is still in 'residence'. Opponents of presumed consent argue that the absence of donor willingness is morally unacceptable because it can be seen as a violation of their wishes .  raises further issues about the right of ownership and hence who should benefit from body organs, and how presumed consent will extend to competent minors and mentally incompetent adults.The debate about presumed consent and importance of optimising the functionality of body organs can extend to ownership and the right to sell these organs -9. It haThe age at which autonomy is granted varies in the UK depending on whether it is with regard to consent to medical treatment or consent to participation in research. In the former case, children are given the status of autonomous adults at the age of sixteen; in the latter the age of consent is eighteen. This distinction has not been properly qualified in the UK and can lead to bizarre situations . Before Decisions on behalf of the mentally incompetent need to be made in cases of medical treatment and in such situations, common law in the UK sets the principle that such decisions should always be made in the best interests of the patient . There hIntroduction of presumed consent into law can take a number of forms, and variations in the application of presumed consent  have beeAccording to one mathematical model, organ availability is likely to be higher when presumed consent measures are introduced, even when other confounding factors are taken into account, but ambiguities in the model are acknowledged . ResultsA recent study  that invUltimately, whether consent is express or presumed, the donor and/or relatives should be fully informed before any consent is obtained. Special attention needs to be given to those for whom others make decisions concerning their health and welfare. The easiest option would be to apply presumed consent only to specified groups (e.g. autonomous adults) and to disallow any vulnerable individuals from being considered as members of these groups. This would ensure that no situation of abuse of the vulnerable, whether intentional or unintentional, occurs. There is no certainty, however, that such a measure would not invoke cries of discrimination from those who may misinterpret the measure as an indication that the body organs of such individuals are of lesser value. It may also create difficulties and lead to complicated legal arguments with cases brought before the courts should a family situation arise that is similar to that of the case of Y , but witThe issues for vulnerable individuals require further analysis and, prior to the introduction of any legislation that allows for presumed consent, there needs to be a thorough re-examination of current laws that treat children and mentally incompetent adults as non-autonomous. With regard to children, reviews of the age of consent and the notion of Gillick competency with better guidelines for practitioners are needed. When deciding on mental impairment or incapacity, there should be an assessment of its scope, its nature, its duration and its durability .To presume consent may or may not alleviate the shortage of donor organs but it will most certainly raise a number of related ethical and legal complexities that will need to be addressed in order to safeguard against unacceptable practices. Fundamentally, what is meant by presumption and how this is applied to the concept of presumed consent to organ donation will have to be determined. It will need to extend beyond the boundaries of current legal and scientific notions and will involve legal and ethical arguments about the sale of body organs, rights of ownership, donation and bequeathing to beneficiaries. More investigation of attitudes towards presumed consent and why and how these may vary is required. Consideration must be given to objections on religious or cultural grounds and whether and how prospective legislation could impinge on beliefs and practices. As always, protection of the most vulnerable, unable to make autonomous decisions, is of paramount importance in any actions taken. Current laws and practices relating to consent and decision-making capacities of children and vulnerable adults need to be reviewed before introducing legislation that permits the presumption of consent.Consent for body organs cannot be presumed in the same way that presumption is used in law or science. Presuming consent for organ donation places the value of body organ function above the requirement for permission from the donor and raises a number of related ethical and legal questions about ownership and sale of body organs, rights of refusal for children and mentally incompetent adults. The factors that influence donation rates and attitudes to presumed consent have not been clearly identified and require further investigation. Measures for the protection of the most vulnerable need to be addressed before legislation to allow for presumed consent can be permitted.The author declares that she has no competing interests.The pre-publication history for this paper can be accessed here:


The coracobrachialis is a muscle of arm has been known for its morphological variations. The variation of the coracobrachialis reported in this case is unique and to the best of our knowledge this variation is not reported in south karnataka population.During routine dissection, we observed an unusual insertion of a coracobrachialis muscle with an accessory slip in the right arm of an old male cadaver. It extended from the superficial fibres of coracobrachialis downwards and medially in front of the median nerve and brachial artery and finally inserted on anteromedial aspect of the medial epicondyle.The existence of abnormal insertion of the coracobrachialis muscle presented in this case should be kept in mind in a patient presenting with high median nerve palsy together with symptoms of brachial artery compression. Coracobrachialis muscle is classically mentioned as taking its origin from the tip of the coracoid process of the scapula, where it is blended with the medial side of the short head of biceps brachii. The tendon is inserted into the medial border of the shaft of the humerus, where the nutrient foramen is located. The musculocutaneous nerve usually pierces the coracobrachialis muscle in man ,2.Morphologic variations of the Coracobrachialis muscle have been known for a long time ,4 and inDuring routine anatomical dissection in our department, we observed an unusual insertion of a coracobrachialis muscle with an accessory slip in the right arm of an old male cadaver. It extended from the superficial fibres of coracobrachialis downwards and medially in front of the median nerve and brachial artery and finally inserted on anteromedial aspect of the medial epicondyle Fig. . The lenThe clinical implication of the accessory slip of coracobrachialis is that it has the potential to cause median nerve entrapment and brachial artery compression. Although we could not detect similar cases described in the available literature, other muscular abnormalities were described, which may lead to a comparable arrangement and injury. Various studies have described the compression of median nerve and brachial artery with anomalous muscles -9. The eThe morphological variations of the coracobrachialis muscle may be due to failure of muscle primordia to disappear during embryological development  and thisThe authors declare that they have no competing interests.BKP did the literature search and wrote the case report and also obtained written consent. MSR conceived the study and helped to draft the manuscript. SRN, VRV, AKM and HT helped in the literature search. All authors had gone through the final manuscript and approved it.Written informed consent was obtained from the subject's relative for publication of this case report.


The year 2008 celebrated 30 years of Primary Health Care (PHC) policy emerging from the Alma Ata Declaration with publication of two key reports, the World Health Report 2008 and the Report of the Commission on the Social Determinants of Health. Both reports reaffirmed the relevance of PHC in terms of its vision and values in today's world. However, important challenges in terms of defining PHC, equity and empowerment need to be addressed.This article takes the form of a commentary reviewing developments in the last 30 years and discusses the future of this policy. Three challenges are put forward for discussion (i) the challenge of moving away from a narrow technical bio-medical paradigm of health to a broader social determinants approach and the need to differentiate primary care from primary health care; (ii) The challenge of tackling the equity implications of the market oriented reforms and ensuring that the role of the State in the provision of welfare services is not further weakened; and (iii) the challenge of finding ways to develop local community commitments especially in terms of empowerment.These challenges need to be addressed if PHC is to remain relevant in today's context. The paper concludes that it is not sufficient to revitalize PHC of the Alma Ata Declaration but it must be reframed in light of the above discussion. In 1978, member States of the World Health Organization (WHO) attending the meeting in Alma Ata supported the policy of Primary Health Care (PHC) . The purPHC analyzed the reasons for health improvements beyond the technical biomedical intervention paradigm. It argued that other factors were equally important determinants. PHC in 1978 was underpinned by the concept of social justice and identified the main principles of equity and social justice as key to health improvements. It also highlighted the role of prevention, multisectoral collaboration, appropriate technology and sustainability. The need to improve the lot of those living in abject poverty was a major emphasis. PHC was a statement of values as much as a strategy for health care. The present call to "revitalize" PHC is to once again bring these values "to life; to animate" them .It can be argued, however, that PHC in the global context of health care and health needs more than revitalization. It is necessary to re-"frame or shape"  PHC so tThe debate continues today. Comprehensive PHC has shown some remarkable successes, although it has not been a history of smooth progression. Notable examples of good programs have been seen in the NGO (non-government organizations) sector. These programs are often small scale projects run by charismatic leaders. Illustrations include Jamkhed in India which became a model for comprehensive PHC. It provided evidence of the value of Community Health Workers (CHWs) and a community development approach to health. Other examples can be found in the book by Taylor-Ide and Taylor .On a national scale evidence is more restricted. The world's two most populated countries returned to PHC principles to address the health needs of the poor. China was the country that inspired PHC thinking through its attention to rural health care and the use of local people called "barefoot doctors" (CHWs) to give first line health care. After a period of market oriented reforms in health care and the resulting deterioration of the health of rural people who are the nation's population, China is now committing huge additional resources to revitalising rural networks based on PHC . India, The year 2008 celebrated 30 years of PHC policy. Two major reports, the World Health Report 2008  and the There is a challenge of getting a consensus among those involved in health care delivery and policy that health improvements must be seen in the context of linking health care and human development. In 1978, the idea of seeing health as a reflection of the wider socio-economic determinants was questioned by many of those working in the field of health. In putting forward the PHC policy, WHO used the personal experiences of people to give evidence of the link between health and development. Drawn mainly from less developed country experiences, those who contributed to this analysis were often charismatic doctors whose leadership and life improved the health of the poor with whom they worked. Coinciding with the widely reported achievements in health improvements in the newly created Peoples' Republic of China that viewed health as integral to development, the arguments that health was more than medicine and services gained credence among providers and policy makers. A book entitled "Health by the People" edited by Dr. Ken Newell, head of the division that crafted the PHC policy published proof of these accomplishments .However, these views and arguments were not shared by the majority of those involved in health care. Many believed that there was little hard evidence to support the view that the socio-economic environment was as critical to health improvements as medicine and service delivery. As a result, although the arguments of social justice and equity were received with sympathy, implementation of policy mostly focused on service provision. One example is selective vs. comprehensive debate discussed above.Another was the confusion of the concepts "Primary Health Care" and "primary care". Those concerned with health care delivery could embrace the PHC vision in the context of service delivery for which they were responsible. As a result their focus became providing first line health services, "primary care", for communities but not engaging in the wider analysis of conditions in which the poor health problems were created nor seriously engaging in activities to promote equity and community participation. The concept of primary care for many of these people was interchangeable with Primary Health Care and has continued to be so. A recent special issue of Lancet on 30 years of celebration of Alma Ata is a good example of the confusion in the understanding of differences between these two concepts . A lack "The Alma Ata Declaration promoted Primary Health Care (PHC) as its central means toward good and fair global health--not simply health services at the primary care level (though that was important) but rather a health system model that acted also on the underlying social, economic and political causes of poor health". [: pg.33].A commitment to reject the duality between Comprehensive PHC and Selective PHC and an agreement for a standard definition of PHC and the attributes it encompasses is necessary to create solid frameworks for policy analysis and health promotion.A second challenge is addressing the equity implications of the market oriented reforms introduced in number of developing countries. The Report of the Commission on the Social Determinants of Health highlighted equity, both in terms of distribution but also in terms of power and politics. Both PHC and the Report of the Commission call for universal coverage. They highlight problem of market oriented approaches and give evidence of its failure to meet objectives for improving health for the poor.The reduced access to health care as a result of the Structural Adjustment Programs (SAP) of the 1980s provides the most graphic example illustrated by the reduction of life expectancy in Africa . In the Equity implications of the market oriented reforms are well documented. A classic example is the introduction of user charges. User charges for health care were introduced as a part of the structural adjustment programs in number of countries. However, the expected benefits in terms of efficiency and equity were not forthcoming. The negative consequences in terms of access and utilisation of health services were observed especially among the lower socio-economic groups across countries. Given the highly regressive nature of user charges and the lack of effective exemption mechanisms, it is therefore not surprising to observe number of countries in Sub-Sahara Africa have abolished user fees or are in the process of doing so .At the global level, the global public private partnerships , Global funds for Aids, TB and Malaria (GFATM) have funded technology for health focusing on profit rather than people and have re-enforced vertical disease program approach. This approach has been criticised for distorting national priorities, weakening the comprehensive integrated health systems approach and supporting re-verticalization of planning  as energA final major challenge is to examine and seek ways forward to develop local community commitments. Community participation was identified as a key principle of PHC. There was little distinction between participation as community mobilisation  and community empowerment . In recent years, recognition of the differences has increased and the term participation has increasingly been replaced by empowerment, calling attention to the importance of power and control over decisions, especially resource allocation.Global Public Health their findings show that community involvement including house to house visits by health staff, group meetings for education and support on health issues, outreach workers providing health services in the community and a community level (CHW) health worker to support community based health management has measurable effects on improvement of child survival. They also highlight empowering communities  as an overarching strategy that underpins these gains.The direct link between community participation and empowerment has not been easy to establish . HoweverIssues around participation and empowerment also have been promoted in the context of governance of health service provision. A growing literature argues that concerns about accountability of public expenditures should be placed in the hands of those intended beneficiaries of those services. These issues centre on both the accountability of services to perform to the satisfaction of the users and the accountability of finances to be used in the way in which they have been allocated. Concerns are developed in discussion about "voice" whereby service users have the ability and capacity to demand the providers perform to user satisfaction. Evidence from the implementation of the Bamako Initiative shows how accountability can catalyze improvement in efficiency and effectiveness of local service delivery .Commitments to meet this challenge continually demand professionals to hold serious dialogues with those for whom they provide service and care. To date this dialogue has often been delayed by several factors. Firstly, there is the existence of attitudes of professionals who tend to disregard opinions and views of those outside the profession. Secondly, there is the historic view that health interventions can only be verified by outcome measures. This view ignores the vital role of process in sustaining the improvements that bio-medicine and technology contribute. The World Health Report 2008 discusses in detail the role of service providers yet does not address the second issue of process. Commitment to addressing both issues is critical to PHC in the present context.Above we have identified the challenges and necessary commitments that need to be addressed if PHC is to remain relevant. Revitalizing PHC principles without developing a framework to address concrete measures for health improvements is not sufficient. The challenges discussed above need to be examined in a systematic and integrated way to produce flexible policy options and solutions that can be implemented. To do this, particularly in a time of financial crisis, requires a willingness to dialogue and appreciate a range of different and often contradictory views working toward consensus. It is clear that more of the same will not answer increasingly risky situations emerging from not only lack of money but also climate change, international political tensions and growing anxiety about resource availability due to rapidly expanding global populations. This does suggest that perhaps revitalizing PHC is not sufficient. What is needed is a reframing of the concept in light of the above discussions around the issues identified.The authors declare that they have no competing interests.Both authors have contributed to the planning, writing and editing of this paper. Both authors have read and approved the final version of this manuscript.


It is increasingly recognised that recessive mutations play an important role in the pathogenesis of many forms of malignancy. Some of the affected loci may prove to be recessively-activated proto-oncogenes, but others are now known to be tumorigenic solely by virtue of their loss or inactivation and therefore form a distinct and novel family of tumour genes. Preliminary evidence suggests that such genes are likely to be functionally heterogeneous and to encode molecules involved in the inhibition of cellular proliferation and/or the induction of differentiation. Their further study is likely to illuminate fundamental mechanisms of normal cellular growth and differentiation as well as having important implications for the pathogenesis and management of cancer.


The rich heritage of Indian mythology has been very little explored and used in psychotherapy in India. The present article deals with the story of Hanuman. How he lost the knowledge about his power to fly due to a childhood curse by Rishis and how he regained his powers when reminded by Jambavan during a crucial mission in search of Queen Sita, is the subject of author′s description of Hanuman complex and its resolution. The author has often used this story in helping patients in psychotherapy as well as in teaching medical doctors and trainees in psychiatry. A plea is made for wider use of stories from Indian mythology in psychiatric practice.


Rapid developments in the medical field in the last century have revolutionized the field of medical practice. It is now possible to diagnose diseases faster and more accurately using advanced diagnostic techniques. Medical management has become more effective with refined medications having more specific actions and fewer side effects. Surgical treatment has moved towards less invasive modes of management with lesser morbidity and faster recovery. Among all these developments, the medical profession in India is at crossroads facing many ethical and legal challenges in the practice of the profession. The medical fraternity is becoming more and more dependent on technology and market forces tend to influence decision making by the doctors. The fundamental values of medicine insist that the doctor's obligation is to keep the patients interest above everything else. The important issues of autonomy, confidentiality, justice, beneficence, and non malefecience are key factors that should guide the daily decision making by the doctor. These decisions may be involving a simple choice of antibiotics for an infection or the best medication for hypertension or hypercholestrolemia. It becomes more complex involving major ethical concerns in organ transplantation, clinical trials, genetic manipulations, end of life issues, or assisted reproductive techniques. However, the principles of ethics remain the same for all the above situations. The ethical guidelines of medical practice provided by The Indian Medical Council  Regulations, 2002 is aimed at strengthening the ethical standards among registered medical practitioners in India.The health sector in India has seen a major transformation with health care becoming a profitable sector attracting investors from diverse and varied backgrounds with profitable motives. There is also an allegation that the practice of modern medicine is becoming more impersonal, and with the increasing dependence on technology, the cost of treatment also rises. It is a fact that cannot be ignored that there is increasing dissatisfaction on the part of the patients who are expecting more and more from the doctors, leading to increasing incidence of litigation. The Medical Council of India has a redressal mechanism that can give punishment to the erring doctor after proper investigative procedures. The unnecessary harassment of doctors who are falsely implicated in criminal negligence issues has been curtailed by the Supreme Court, which has issued guidelines for the criminal charging of a doctor for negligence.The medical profession that was once considered noble is now considered along with other professions in the liability of paying for damages. The patients who wanted monetary compensation for the alleged medical negligence used to resort to the civil courts. This was the only avenue earlier that used to be a lengthy process with its detailed procedural formalities. The confusion about the inclusion of doctors under the Consumer Protection Act, 1986 has been laid to rest by the landmark decision of the Supreme Court in 1996 that puts the services of doctors for consideration under the purview of the Consumer Protection Act. This resulted in an increasing incidence of consumer cases where doctors were implicated for all types of allegations by patients. The recent Supreme Court guidelines that call for stricter evaluation by the Consumer Courts before proceeding with alleged medical negligence cases by the patients will be a boon to the doctors who will not be pulled into unnecessary litigation. However it has to be noted that the judicial bodies favour the patient who has suffered due to the negligent action of the doctors as reiterated by another Supreme Court decision recently confirming the decision of the State Commisison and giving a much higher compensation.It is imperative that the present day medical doctors have continuing medico-legal education. Doctors have a legal duty to comply with the applicable ethical and legal regulations in their daily practice. Ignorance of law and its implications will be detrimental to the doctor even though he treats the patient in good faith for the alleviation of the patient's suffering. All actions that are done in good faith may not stand legal testing. With the increasing number of cases filed by aggrieved patients seeking legal remedy from doctors and medical establishments, it is no longer a matter of choice, but a context-driven legal mandate and necessity for the doctors to be conversant with basic legal issues involved in medical practice. This symposium aims at giving a basic insight into two main areas of medical practice:The ethical issues in medical practice including changing doctor-patient relationships, the need for introducing ethical training in the undergraduate and postgraduate medical training, the modern challenges in urological practice, and the ethical and legal issues in kidney transplantation covered from an Indian perspective.The legal issues covered include the basics of medical negligence, changing concepts of informed consent, and the practical issues of medical negligence cases with representative case decisions from the Indian Courts.


The autologous and allogeneic immunological humoral response of breast cancer patients to breast tumours was investigated by ELISA assay of both the serum and the supernatants of transformed lymphocytes from the patients and controls. No specificity or increased titre relative to the controls was observed in serum antibody. However, when the response was dissected by the use of clones of transformed lymphocytes from the patients, considerable specificity could be demonstrated in certain clones while other clones showed a generalised specificity which contributed to the masking of the specific response in the serum. Some of these clones may have clinical potential as diagnostic and prognostic tools.


A method has been developed for determining the mean volume of breast cancer in women at the time of the involvement of the first, second, third,... nth axillary lymph nodes. It has been found that the proportion of patients with axillary involvement as well as the number of involved nodes increase progressively with tumour size. This orderly involvement of axillary nodes is observed in all patient subsets despite a wide spread of tumour volume at the time of invasion of the axillary nodes. This makes it possible to compute for each patient or subset of patients the size of the tumour at the time of the first node involvement, a parameter which characterises the propensity for nodal involvement. A strong correlation was demonstrated between the propensity to lymphatic involvement and the probability of distant dissemination. During tumour progression the capacity for lymphatic spread is on average acquired much earlier than the capacity for haematogenous spread. For tumours of the outer quadrants, the volume at first axillary involvement is smaller than for tumours located in the inner quadrants, whereas the tumour volumes at the time of distant metastatic initiation are equal for the two tumour sites. The discrepancy between these two observations shows that axillary involvement, while being a good index of the propensity of the tumour cells to acquire the capacity for distant spread, is not the cause of this spread. From a clinical point of view, these data show that the prognostic significance of axillary involvement can be further increased by taking into account the size of the tumour. The data suggest that there is a continuum from slow growing disease with late axillary involvement and late distant dissemination to the most aggressive subtype.


Sir,In response to the communication by Dr. Sanjeev Rastogi we are willing to give our following comments:Apart from the challenges of Ayurveda education that we have recognized in the present study, we have There is an urgent need of establishing a national level body for taking care of the following.Educational research is carried out in Ayurveda and suitable recommendations are put forth from time to time to ensure the relevance of Ayurveda education.Strict regulatory norms are implemented while granting approvals to the institutions.Uniform pay packages and regular promotions are ensured to attract and retain good teachers and clinicians in the education system.NET-like compulsory national level screening test is introduced to assess the quality of the aspiring teachers before declaring them eligible for lectureship.At present, India follows the policy model of "parallel approach", where traditional systems of medicine and Allopathy are segregated. Implemen


Serum lysozyme activity was measured in groups of untreated patients with malignant melanoma, hyperneophroma and breast carcinoma. Significant elevation of serum levels of the enzyme was confined to patients with localized disease. In the presence of metastatic disease such elevation was not detected. The rise in serum lysozyme activity was not due to renal damage or any infective process and in the case of malignant melanoma was shown to be associated with infiltration of the tumour mass by macrophages. In vitro studies demonstrated that the macrophages resident in a tumour mass are responsible for relasing lysozyme in large amounts. It is proposed that the elevation of serum lysozyme in these cases may be an indicator of macrophage-mediated host resistance and that the measurement of macrophage products such as lysozyme in the extracellular fluid may under well defined conditions provide useful clinical information concerning host reactions.


We read the recent article by  with keen interest and would like to congratulate them for a job well done. However, we would like to raise a few points relating to the limitations of the study. Antimalarial use in pregnancy is an important determinant of the level of malaria parasitaemia at delivery but Mokuolu et al. , like thThe authors claimed that they took specific note of those patients who used preventive antimalarial drugs, yet they did not provide the proportion of such patients. These patients are likely to procure the drug from the community pharmacies and are at risk of using counterfeit and adulterated antimalarials which are very abundant in Nigeria . In the The inclusion criteria used in the study appear not to be clearly defined by the authors. We are not sure if pregnant women with HIV infection and unbooked patients were part of the cohorts they studied. Perhaps, it would have been proper to exclude these groups of patients because of the possible bias their inclusion may introduce into the study and this may be better avoided by recruiting patients from antenatal clinics and followed to the time of delivery rather than recruiting at the point of delivery. HIV and malaria coinfection has more adverse effects on pregnancy than malaria alone . The preMokuolu et al. found a significant association between malaria parasitaemia at delivery and maternal age less than twenty years. It may be true that pregnancy associated with acquired immunity is lower in younger women than older ones who have obtained adequate immunity from repeated exposures to malaria infections. Teenage pregnancies are likely to be associated with poverty, lack of good education, and poor nutrition. The necessary proteins needed in the synthesis of antibodies against malaria parasites may therefore be reduced in young pregnant women and may indirectly contribute to the high prevalence of malaria parasitaemia observed by the authors in young parturients.Given that the authors are from various disciplines, a future study that will involve a multidisciplinary approach is therefore suggested. The ability of the contributing authors, who are clinical pharmacologists, to assay blood levels of antimalarial drugs in pregnancy will add novelty to the future study.


Previous work has shown that extensive mammographic dysplasia in women aged less than 50 was strongly associated with breast cancer but that the radiological appearance of ductal prominence was not associated with risk. In the present paper we examine the association between these mammographic signs in the breast and histological patterns in the terminal ductal lobular unit (TDLU), the region of the breast where breast cancer is believed to originate. Surgical biopsies from a consecutive series of women aged less than 50 were reviewed and classified according to the histopathology of the epithelium in the TDLU. Mammograms from the same subjects were independently classified according to the extent of the radiological signs of dysplasia and ductal prominence. Degree of histopathology and the extent of mammographic dysplasia were associated and atypia of the ductal type was found more frequently in patients with extensive dysplasia. However, the strength and statistical significance of the association varied according to the radiologist who classified the mammograms. No association was found between degree of histopathology and ductal prominence. These results add to the evidence that extensive mammographic dysplasia in women aged less than 50 is a risk factor for breast cancer. They do not indicate that the radiological signs of dysplasia are caused by histological changes in the TDLU.


Errors made during the sample preparative process contributesignificantly to the total analytical error of immunoassays. Reduction in the magnitude of these errors have been made by improvements in the manualfluid handling systems and mechanization of the individual steps in the process. The mechanization has been stimulated by developments in both computing hardware and software. A laboratory's workflow and workload will indicate the degree of mechanization required.


Pharmacogenomics is defined as the study of the association between genetics and drug response. This is a rapidly expanding field with the hope that, within a few years, prospective genotyping will lead to patients being prescribed drugs which are both safer and more effective . There are many existing examples in the literature of strong associations between genetic variation and drug response, and some of these even form the basis of accepted clinical tests. The molecular basis for some of these associations is described, and includes examples of variation in genes responsible for absorption and metabolism of the drug, and in target and disease genes. However, there are many issues surrounding the legal, regulatory and ethical framework to these studies that remain unanswered, and a huge amount of education both for the public and haelthcare professionals will be needed bafore the results of this new madicine can be widely accepted.


The creation of effective cancer units is central to the implementation of the report A Policy Framework for Commissioning Cancer Services, produced by the Chief Medical Officers of England and Wales, recently issued by the Department of Health in April 1995. While cancer units are described in this report a range of important questions remain about their nature and how they should be developed. This paper addresses these issues in three ways. A definition of the cancer unit is suggested and its main implications spelt out. The problems of establishing cancer units are covered under three headings. Where should cancer units be? Which cancer sites should the unit cover? What is needed to establish the cancer unit? Finally two checklists are presented, describing the task from the perspectives of the district health authority and hospital(s) concerned. The underlying theme is that real changes in clinical practice and organisation are the goal, and these can only be achieved where there is extensive local dialogue in which the relevant issues are addressed in a structured and rigorous manner. Cosmetic changes in hospital designation will not achieve the consistent quality of cancer service that is the cornerstone of the 'Calman' policy.


Dear Sir,With great interest, I read the case report of Management of a massive thoracoabdominal impalement[Trauma remains a leading cause of death across all age groups, some of the injuries are dynamic and it is crucial for the Anaesthetists to have upto date understanding of Injury patterns, mechanisms, and pathophysiology to facilitate optimal management of these patients because In this published case report the impaled iron angle was projecting in the anterior-posterior direction and the patient and iron angle were supported at all times and the authors decided to intubate the patient in semi-reclining position supported all the time by helpers, anesthetist stood on the stool to gain additional height and even left thoraco-abdominal incision needed to be given instead of conventional midline or paramedian Incision.Peroperative management is very challenging in such cases and the position of patient is very crucial for the safe conduct of such cases. One of the options available is to place the patient in lateral position. DifferePosition of the patient can be modified in such cases for safe peroperative management of patients. Operation theatre tables are composed of different attachments so that various positions can be made for different procedures. I am of the view that in this case the patient could have been placed in the supine postion after transfer from the ward with some additional help from the theatre staff by using gap Figure  in the tTo summarize, the management of massive thoraco-abdominal impalement injuries can be made simpler by modifying the position of patient by making use of gaps in the theatre table attachments and placing the patient in conventional supine postion.SJTREM: The author declares that they have no competing interests.


In the present report a procedure for the isolation of more specific arginine receptors from the soluble fraction of rat liver and Novikoff hepatoma is described. In normal rat liver the specific activity of these receptors from the soluble fraction of rat liver and Novikoff hepatoma is described. In normal rat liver the specific activity of these receptors is fifteen times greater than that of the other proteins whereas in the Novikoff it is only three to four times higher. Attempts to sub-fractionate this class of acceptors would seem to indicate a relative homogeneity.


The language of science should be objective and detached and should place data in the appropriate context. The aim of this commentary was to explore the notion that recent trends in the use of language have led to a loss of objectivity in the presentation of scientific data. The relationship between the value-laden vocabulary and impact factor among fundamental biomedical research and clinical journals has been explored. It appears that fundamental research journals of high impact factors have experienced a rise in value-laden terms in the past 25 years. A recent editorial addressing the care which must be taken in the reporting of clinical results concluded: "The numbers and not their interpretation, must speak for themselves" . This stWe evaluated this hypothesis by examining twelve established biomedical and fundamental clinical and clinical research journals over a twenty year time period for adjectives which modified an otherwise neutral knowledge claim. Our findings indicate that there is an increase in value-laden language in the scientific article from 1985 to 2005. Both high and low impact fundamental research journals exhibit an increase in biased word choice over time, this trend being most marked in high-impact biomedical journals devoted to fundamental research. Comparatively, clinical journals showed a low incidence of biased words and this characteristic has remained consistent over the time period under investigation. We suggest that the increase in incidence of biased language may provide a means through which to view broader changes occurring within the scientific community. Publication practice has evolved over the past twenty years as authors face increasing pressure to publish in high impact journals [To assess the use of value-laden language we began by formulating a list of adjectives we had noticed appearing with increasing frequency in the scientific literature. The list of words compiled, while by no means exhaustive, reflects a general sampling of adjectives which attribute status or significance to an otherwise neutral claim Table . Words wAs the presence or absence of biased language is context dependent, some subjective evaluation was necessary in the tabulation of biased word count. Once OCR identified an adjective, one of the authors (V.F.), used the following guidelines to determine whether a word could be judged to modify the content of the sentence. Selected words Table  were exeA number of clear trends emerged from the analysis. Firstly, for all journals there was an increase in the word score  from 1985 through to 2005 (Figure The use of biased language in clinical journals was infrequent, with no increase in the use of value-laden words over the twenty year interval figure . When thThe Scope and Limits of Scientific Objectivity Joseph F. Hannah states: "It is generally agreed that one of the distinguishing virtues of science is its objectivity. The scope of science is the objective world and the limits of science are determined by the limits of the objective methods of formal and empirical research" [The increasing incidence of adjectives expressing subjective judgments undermines what has traditionally been accepted as the objective nature of the scientific paper. Our argument therefore assumes that objectivity is an integral and necessary component in the quest for scientific progress. Most would tacitly acknowledge that objectivity occupies a unique position within scientific disciplines. In his paper: esearch" . InsofarThe demonstrable increase in the use of adjectives with the potential to bias the reader may indicate that the interpretation of results has come to replace what has traditionally been a more objective stance. This shift towards the somewhat hyperbolic interpretation of data from the more conservative representation of data, raises important questions about the evolution of the scientific article and must be examined in conjunction with changing attitudes within the scientific community regarding the writing and submission of articles, the mounting impact of the impact factor and the pressures currently facing authors seeking publication.Changing attitudes towards scientific publication must be examined in tandem with the changing role of the impact factor in assessing the merits of a body of work and the "impact" this has had on the scientific community. Briefly, the impact factor of a journal reflects the number of citations appearing in indexed publications in a given year to articles published in a given journal in the previous two years, divided by the number of citable papers published within these two years. However, the original purpose of the database developed by the Institute for Scientific Information and used for citation analysis has been somewhat forgotten and the impact factor has taken on a life of its own. Several detailed critiques of the impact factor have been published , highligAlthough the merit of impact factor remains the subject of intense debate, its current influence on scientific papers and publication is not. Impact Factor has extended its reach to be included in the evaluation of academic and medical institutions as well as in the evaluation of researchers for tenure and promotion and the awarding of grants . The latcritical importance to its chances of publication. This trend, when examined in conjunction with the increased use of biased words, raises some fundamental questions. Does a reward-seeking-model of publication – as reflected in the current desire to publish in high impact journals – influence the use of language in scientific manuscripts? For instance, is it possible that authors have discovered that an effective strategy to counter the failure of reviewers to be excited about an article is to create bias through the use of language that exaggerates the importance of the findings? Or, is it merely that language exists in a state of flux and any changes in style or vocabulary merely reflect time-related alterations in writing? Finally, perhaps the biased words are not so much biased as emphatic, though necessary, descriptors of the work which is being presented?The status of scientific journals is measured by the impact factor and journal editors have adopted strategies to enhance the impact factor, e.g. by publishing review articles which tend to be cited frequently. Editorial evaluation of articles and their potential acceptance or rejection based on priority is based on interest to the readership, and not necessarily the quality of the science. Rejection of an article based on being low priority for the journal is often not reflected in the reviews provided to the authors. A judgment of low priority is a subjective opinion and as such is not an issue for debate. How "hot" a topic is, is of At first glance it seems plausible to state that the words under investigation are not reflective of bias, but are rather necessary descriptive terms of what is, in fact, a new and important knowledge claim. A detailed discussion as to whether manuscripts in high impact factor journals are truly more "important" or "novel" than those in low impact journals is beyond the scope of this paper and may be a subject for future investigation. However, we would argue that it is remarkable that the use of biased words has shown an increase over time in both low and high impact journals. That is, it seems unlikely that the ideas posited in scientific articles in 2005 are markedly more valuable or significant than those put forward in 1985. A more plausible explanation is that it is the style, rather than the substance of the articles, which has altered.It is a truism to state that language is constantly evolving and it seems reasonable to consider the possibility that changes in style and vocabulary may simply reflect time-related alterations in writing. Still, it is interesting that the difference between the language used in fundamental and clinical journals is so marked, with biased words more frequently found in high impact fundamental journals. This prompts the question: why is it that language has only "evolved" in fundamental journals? A hypothesis which suggests itself is that the language used in the interpretation of data in clinical journals has the potential to impact upon clinical practice and is therefore more likely to be tempered than language used in fundamental journals. Be that as it may, the question remains as to why the use of biased language is on the rise in fundamental journals and whether this trend should continue unchallenged. Furthermore, what conclusions may be drawn from grandiloquence and high impact factors? Perhaps it is possible that high rejection rates by editors without the use of peer review increases the pressure for hyperbole so as to clear the first hurdleThe increased use of biased words provides an interesting locus for a discussion on the changing trends in publication and the increasing pressure felt by authors today. While we hesitate to suggest that the latter is responsible for the former we are confident in the assertion that the use of biased words in a scientific manuscript does not serve a useful purpose. The readership is unlikely to require orientation to ensure that pivotal and central observations pass unrecognized inadvertently. On the contrary, language that exaggerates the importance of findings may fuel skepticism and alienate the reader. Perhaps journals should encourage more modest claims on the part of the authors and encourage a return to objectivity. To end at the beginning; "The numbers and not their interpretation, must speak for themselves."The authors declare that they have no competing interests.VF contributed to the study design and performed the literature review for the assessment of the vocabulary employed and performed the analysis of the data. She prepared the first draft of the manuscript. JM contributed to the design of the study, assisted with data analysis and presentation, and wrote the final draft of the manuscript.


Arabidopsis is universally acknowledged as the model for dicotyledonous crop plants.Furthermore, some of the information gleaned from this small plant can be used to aidwork on monocotyledonous crops. Here we provide an overview of the current state ofknowledge and resources for the study of this important model plant, with comments onfuture prospects in the field from Professor Pamela Green and Dr Sean May.


However, attempted sensitization and subsequent challenge with DNCB demonstrated that the afferent limb of the responses was impaired in some patients. This did not appear to be related to the morphology of the tumour or to prognosis.Defects in cellular immunocompetence have been sought in 25 patients with Kaposi's sarcoma. Skin tests with recall antigens, and PHA lymphocyte stimulation in vivo and in vitro and these correlated significantly with the morphology and histology. The interpretation of the results for an individual is confounded by the multiplicity of factors influencing the outcome in a particular patient.Tumour specific reactions were demonstrated both