The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

Ex-vivo tissue engineering is a quickly developing medical technology aiming to regenerate tissue through the introduction of an ex-vivo created tissue construct instead of restoring the damaged tissue to some level of functionality. Tissue engineering is considered by some as a new medical paradigm. We analyse this claim and identify tissue engineering’s fundamental characteristics, focusing on the aim of the intervention and on the complexity and continuity of the process. We inquire how these features have an impact not only on (...) the scientific research itself but also on the ethical evaluation of this research. We suggest that viewing tissue engineering as a new medical paradigm allows us to develop a wider perspective for successful investigation instead of focusing on isolated steps of the tissue engineering process in an anecdotal way, which may lead to an inadequate ethical evaluation. We argue that the concept of tissue engineering as a paradigm may benefit the way we address the ethical challenges presented by tissue engineering. (shrink)

More and more areas of medicine involve subjects donating tissues to another — blood, organs, bone marrow, sperm, ova and embryos can all be transferred from one person to another. Within the technical frameworks of biomedicine, such fragments are generally treated as detachable things, severed from social identity once they are removed from a particular body. However an abundant anthropological and sociological literature has found that, for donors and patients, human tissues are not impersonal. They retain some of (...) the values of personhood and identity, and their incorporation often has complex effects on embodied identity. This article draws on feminist philosophy of the body to think through the implications of some of these practices. Specifically, it draws on the idea of intercorporeality, wherein the body image is always the effect of embodied social relations. While this approach is highly productive for considering the stakes involved in tissue transfer, it is argued that the concept of body image has been too preoccupied with the register of the visual at the expense of introceptive data and health/illness events. Empirical data around organ transplant and sperm donation are used to demonstrate that the transfer of biological fragments involves a profound kind of intercorporeality, producing identifications and disidentifications between donors and recipients that play out simultaneously at the immunological, psychic and social levels. (shrink)

Testicular tissue cryopreservation aims to preserve the future option of genetic reproduction for prepubescent cancer patients who are at risk of infertility as a result of their cancer therapies. This technology is experimental and currently only offered in the research context. As TTCP moves towards becoming more widely available, it is imperative that healthcare providers recognize the complex ethical issues surrounding this technology. This scoping review study identifies and assesses the range and depth of ethical concerns related to this testicular (...) tissue cryopreservation technology. At present, no such scoping review of ethical concerns exists in the TTCP literature. The forty-three full-text articles included in this study yielded twenty-two different ethical considerations discussed in relation to TTCP. It was observed that these ethical considerations fit within a mainstream Principlism approach to bioethics. Accordingly, there are ethical gaps in the TTCP literature that can be identified with alternative moral lenses. In particular, it was found that ethical concerns related to context and relational aspects of identity were absent in nearly all ethical examinations of TTCP. Furthermore, only 9 per cent of articles reviewed in this study focused primarily on the ethics of TTCP, thus demonstrating a need for further in depth ethical analyses of this technology. The results of this study are important for supporting the ethical provision of TTCP and can contribute to policy and guideline development. The findings of this study demonstrate the need for greater depth and diversity in analyses of ethical considerations related to this technology. (shrink)

Health research is increasingly being conducted on a global scale, particularly in the developing world to address leading causes of morbidity and mortality. While research interest has increased, building scientific capacity in the developing world has not kept pace. This often leads to the export of human tissue (defined broadly) from the developing to the developed world for analysis. These practices raise a number of important ethical issues that require attention.

Age‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase in (...) phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis. (shrink)

There are complex unresolved ethical, legal and social issues related to the use of human tissues obtained in the course of research or diagnostic procedures and retained for further use in research. The question of intellectual property rights over commercially viable products or procedures that are derived from these samples and the suitability or otherwise of participants relinquishing their rights to the samples needs urgent attention. The complexity of these matters lies in the fact that the relationship between intellectual (...) property rights and ownership or rights pertaining to the samples on which the intellectual property right is based may either be overlooked or taken for granted. What equally makes the matter complex is that samples may be obtained from participants in developing countries and exported to developed countries for analysis and research. It is important for research ethics committees to tread carefully when reviewing research protocols that raise such issues for purposes of ensuring that appropriate benefit sharing agreements, particularly with developing countries, are in place.This paper attempts to analyse the key questions related to ownership and intellectual property rights in commercially viable products derived from human tissue samples. Patent law is used as a point of reference as opposed to other forms of intellectual property rights such as industrial designs because it is the right that most inventors apply for in respect of human tissue-related inventions. The key questions are formulated following a systematic analysis of peer reviewed journal articles that have reported original investigations into relevant issues in this field. Most of the cases and reported studies that are referred to in this paper do not directly deal with HIV/AIDS research but the underlying principles are helpful in HIV/AIDS research as well. Pertinent questions, which members of ethics review committees should focus on in this regard are discussed and suggestions on appropriate approaches to the issues are proposed in the form of specific questions that an ethics review committee should consider. Specific recommendations regarding areas for further research and action are equally proposed. (shrink)

Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT‐mediated NAD+ biosynthesis, together with its key downstream mediator, namely the NAD+‐dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue‐dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such (...) as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT‐mediated NAD+ biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD+ biology. (shrink)

One important sense of 'global ethics' concerns the applied ethical issues arising in the context of economic globalisation. This article contends that we are beginning to witness the economic commodification and, concomitantly, the globalisation, of human tissue and the human genome. Policy-makers and local research ethics committees need to be aware that the relevant ethical questions are no longer confined to their old national or subnational context. A shift from questions of personal autonomy and identity can therefore be expected-towards the (...) more problematic issues of justice, exploitation and distribution. Here we can learn from the distinctions drawn in legal philosophy, such as the notion of property as a 'bundle' of rights, from which we may choose rights favouring the interests of vulnerable populations. We may also wish to apply the distinctions drawn by Calabresi and Melamed between pure property rules, modified alienability rules, and pure non-property regimes. Global ethics also concerns issues of value disparity across cultures, directing our attention to the moral beliefs of indigenous peoples, for example, whose DNA or tissue is increasingly of commercial importance. In examining case examples from Tonga and Aotearoa/new Zealand, I will consider the impact of indigenous belief systems and of neo-colonialism on indigenous peoples' perceptions of Western researchers. It is clear that many indigenous peoples reject both the pure property system and any modifications, insisting on a pure non-property regime. How can they then be protected in a globalised market system that so far favours the opposite end of the spectrum? (shrink)

The controversies in Bristol, Alder Hey and elsewhere in the UK surrounding the removal and retention of human tissue and organs have led to extensive law reform in all three UK legal systems. This paper reports a short study of the reactions of a range of health professionals to these changes. Three main areas of ethical concern were noted: the balancing of individual rights and social benefit; the efficacy of the new procedures for consent; and the helpfulness for professional practice (...) of the new legislation and regulation. Recognition of these concerns may help in forging a new partnership between professionals and patients and their families. (shrink)

Ethical controversy over transplantation of human fetal tissue has arisen because the source of tissue is induced abortions. Opposition to such transplants has been based on various arguments, including the following: rightful informed consent cannot be obtained for use of fetal tissue from induced abortions, and fetal tissue transplantation might result in an increase in the number of abortions. These arguments were not accepted by the National Institutes of Health (NIH) Human Fetal Tissue Transplantation Research Panel. The majority opinion of (...) the panel stated that abortion and fetal tissue use are entirely separate issues, and that tissue use is ethically acceptable because it can be morally insulated from the issue of abortion. In support of this view, panel members and others have replied to the arguments put forward by opponents of fetal tissue use. However, replies to the two arguments mentioned above have been unsatisfactory, and the shortcomings of those replies are identified herein. Examination of the arguments pro and con suggests that fetal tissue use cannot be completely insulated from the issue of abortion. Thus, in seeking an ethical justification for fetal tissue transplantation we must consider reasons other than those put forward by the NIH panel. In this paper it is argued that whatever wrong is involved in using fetal tissue from induced abortions must be balanced against the benefits for patients, and it is on this basis that fetal tissue transplantation can be ethically justified. (shrink)

Tissue typing (TT) is a recent and controversial scientific advance. Whilst its current applications can easily be described as protherapeutic and within the realms of preventative medicine,1 its specificity and potential are often characterized as the tip of the eugenic iceberg: undermining the very basis of individual autonomy and identity in an inevitable march towards the perfect society:2 In addition to arguments concerning societal harms flowing from TT, significant concerns have also been raised concerning harms to the future child born (...) as a result. In the context of current legislation and policy, this article examines two aspects of arguments concerning harm to the future child: those relating to psychological harms, and those arguing that TT is contrary to the future child’s best interests.3The article examines the moral basis for arguments concerning harm to the future child. It proposes that arguments concerning psychological harm may overlook or minimise the potential benefits flowing from the broader social, familial context into which the child is born. These arguments may be countered, or at least balanced, by considering the future child in this context. In relation to arguments that TT is contrary to the future child’s best interests, the paper examines a non-standard consideration of best interests. It argues that this standard should be used in considering whether or not TT for bone marrow transplant is harmful to the future child, thereby extending moral consideration of interests to intra-familial interests and outcomes. On this basis, it can be argued that TT is not contrary to the interests of the future child. The paper concludes by noting a potential tension between the first guiding principle of the Infertility Treatment Act 1995 (Vic) and the current Victorian policy on TT. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal tissue from induced abortion (...) slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)

Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non‐model organisms has revealed that a common set of genes underlie tooth‐forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints act (...) in parallel to shape the tooth throughout development. Here recent advances in understanding dental development from these studies are reviewed and important gaps that can be filled through continued application of evolutionary and biomechanical approaches are discussed. (shrink)

Cadaveric donation comprises organ donation—that is, taking organs from brain dead people, as well as tissue donation, meaning taking tissues from brain dead as well as heart dead people. The organ transplant procedure from brain dead patients is beyond the scope of the pathologist, as it is done by surgeons in the operating theatre. In a broader sense, however, pathologists are involved in cadaveric tissue donation as well as taking tissues from cadavers for diagnostic procedures within the framework (...) of the autopsy , and to gather material for research and training students and pathology residents . For cadaveric tissue donation, different ethical and practical issues must be considered, which we will try to review in this paper from the perspective of the pathologist.CADAVERIC TISSUE SAMPLING FOR TRANSPLANTATION PURPOSESSeveral tissues can be taken from “true” cadavers that may still be used for transplantation such as skin, corneas, tendons, bone. This is usually done in collaboration with the pathologist, who is in most countries responsible for the body after the death of the patient in the hospital. All these tissues can be harvested several hours after death, as they undergo only slow degradation. In The Netherlands, as dictated by law, patients must actively have given permission for donation during life by registering with the Transplantation Register. Since this procedure was implemented, the number of organs available for donation has not increased but decreased somewhat, while the number of tissues has increased. A great obstacle to the increase in the number of donations is that only 37% of the population is registered …. (shrink)

The bill to restore federal funding for human fetal tissue research has been passed by the House and awaits Senate approval. But it requires women who are willing to donate fetal tissue to certify that they did not have an abortion with the intent to donate. It further requires researchers to keep the certifications on file and available for government audit. Both requirements spell trouble.

The importance of inductive phenomena in the development of new tissues and organs in animal development has long been known. Genetic experiments in plants, involving the creation of plants with distinctively marked cell populations, are now establishing the existence and importance of induction during the development of plants as well.

In mammals, a network of cellular circadian clocks organizes physiology and behavior along the 24‐h day cycle. The traditional hierarchical model of circadian clock organization with a central pacemaker and peripheral slave oscillators has recently been challenged by studies combining tissue‐specific mouse mutants with transcriptome analyses. First, a surprisingly small number of tissue rhythms are lost when only local clocks are ablated and, second, transcriptional circadian rhythms appear to be regulated by a complex mix of local and systemic factors. As (...) reviewed here, these findings suggest a more integrated model of clock network interaction with the central pacemaker as the main source of behavioral and systemic–physiological rhythms and peripheral clocks controlling some local rhythms while at the same time acting as gatekeepers that temporally adjust cellular responses to external stimuli. (shrink)

In many animal species, the early development of the embryo follows a stereotypic pattern of cell cleavage, lineage allocation and generation of tissue asymmetry leading to delineation of the body plan with three primary embryonic axes. The mammalian embryo has been regarded as an exception and primary body axes of the mouse embryo were thought to develop after implantation. However, recent findings have challenged this view. Asymmetry in the fertilised oocyte, as defined by the position of the second polar body (...) and the sperm entry point, can be correlated with the orientation of the animal–vegetal and the embryonic–abembryonic axes in the preimplantation blastocyst. Studies of the pattern of morphogenetic movement of cells and genetic activity in the peri‐implantation embryo suggest that the animal–vegetal axis of the blastocyst might presage the orientation of the anterior–posterior axis of the gastrula. This suggests that the asymmetry of the zygote that is established at fertilisation and early cleavage has a lasting impact on the delineation of body axes during embryogenesis. BioEssays 23:508–517, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Biobanks are currently archiving human materials for medical research at a hitherto unprecedented rate. These valuable resources will be essential for developing ‘personalized’ medicines and for a better understanding of disease susceptibilities. However, for such scientific advances to benefit everyone, it is crucial that biobanks recruit donations from all sections of the community. Unfortunately, other initiatives, such as transplant programmes, have clearly demonstrated that ethnic minorities are under-represented. Here we suggest that this issue deserves serious consideration to avoid biobanks evolving (...) into ethnically biased archives which unwittingly promote race-specific research. Specifically, this necessitates research ethics committees engaging in a re-assessment of the relative merits of individual personal sovereignty and the common good. (shrink)

In this article Mr Tam Dalyell mp uses extracts from the speech1 he made in the House of Commons on 11 December 1974 to reiterate his reasons for persisting in his attempts to have formulated in law the right of hospitals to take such organs from a dead person as might be useful unless before death potential donors (all of us) had stated that they did not consent. Details of those objecting would be registered on a central computer.

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy (...) domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain. (shrink)

Three-dimensional ‘bioprinting’ is under development, which may produce living human organs and tissues to be surgically implanted in patients. Like tissue engineering and regenerative medicine generally, the process of bioprinting potentially disrupts experience of the human body by redefining understandings of, and becoming actualised in new practices and regimes in relation to, the body. The authors consider how these novel sociotechnical imaginaries may emerge, having regard to law’s contribution to, as well as its possible transformation by, the process of (...) 3D bioprinting. The authors draw on Gilbert Simondon and corporeal, material feminists to account for these disruptions as ‘ontogenetic,’ in the sense that technology can produce new ontologies or beings. The authors focus namely on ontogenesis, individuation and the pre-individual forces that comprise, and yet remain inexhausted by, the process of 3D bioprinting. The authors argue legal phenomena are pre-individual forces that ‘in-form’ ontogenesis. These pre-individual forces are indistinguishable from those implicated in the individuation of the body’s physical form; thereby, the individuation of the bodily material through 3D bioprinting may be expressive and generative of sociolegal phenomena, at least as those relate to the body. The authors conclude that 3D bioprinting shores up conventional, liberal conceptions in law of the human body as individual, bounded and primarily contractual. Three-dimensional bioprinting may introduce ontological difference to the extent it promises and realises a new temporality of the human as a species- and legal-subject, although such a development would only seem to expand, rather than attenuate, a biopolitical regime. (shrink)

Purpose: To survey the attitudes of the general public in Sweden to biobank research and to discuss the findings in the light of some well-known ethical principles.Methods: A questionnaire was used to survey the opinions of the general public in Sweden, and an ethical analysis (using the principles of autonomy, non-maleficence, beneficence and justice) was performed to discuss the possible conditions of such research.Findings: Between 3 and 9% answered that they did not want their samples to be collected and stored (...) in a biobank. Many respondents required information about the purpose of the research and wanted to be able to consent or refuse. About one third of the respondents said they would have answered differently if financial gain was involved and those who commented indicated a more negative attitude. The principle of autonomy maintains that the right to self-determination should be respected, and the principles of non-maleficence and beneficence that the probable harms and benefits resulting from a particular project by using samples from a biobank should be balanced. The general public disagree about how these principles are to be balanced. Interpretation: In the light of the findings different interpretations of the situation as well as possible alternatives are discussed in this paper. (shrink)

The prospect for widespread therapeutic use of human fetal tissues has aroused strong emotions and prompted several objections. Fetal tissue transplantation circumscribed by medical and moral limits will not erode important ethical values, but the pace of scientific research must not preempt public debate and a verdict consistent with societal values.

Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body fluids. Yet, (...) its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter. (shrink)

Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body fluids. Yet, (...) its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter. (shrink)

The following three points are made. One must consider not only the levels of circulating hormone but the target tissue upon which the hormone acts. Increased testosterone levels alone do not account for differences in displayed intermale aggression, because testosterone and social environment interact in complex ways to influence behavior. A given behavior can be triggered by multiple motivational systems.

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy (...) domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain. (shrink)

Based on a general review of international, representative tissue banking policies that were described in the medical, ethics, and legal literature, this paper reviews the range of standards, both conceptually and in existing regulations, relevant to four main factors:(1) commercialization, (2) confidentiality, (3) informed consent, and (4) quality of research. These four factors were selected as reflective of some of the major ethical considerations that arise in the conduct of tissue banking research. The authors emphasize that any policy or ethical (...) guidelines designed to regulate tissue bank research should address all four factors. Whenever this sort of research is conducted between several institutions or several countries, the paper suggests that the relevant entities work collaboratively to harmonize their standards. (shrink)

Paleoneuranatomy is an emerging subfield of paleontological research with great potential for the study of evolution. However, the interpretation of fossilized nervous tissues is a difficult task and presently lacks a rigorous methodology. We critically review here cases of neural tissue preservation reported in Cambrian arthropods, following a set of fundamental paleontological criteria for their recognition. These criteria are based on a variety of taphonomic parameters and account for morphoanatomical complexity. Application of these criteria shows that firm evidence for (...) fossilized nervous tissues is less abundant and detailed than previously reported, and we synthesize here evidence that has stronger support. We argue that the vascular system, and in particular its lacunae, may be central to the understanding of many of the fossilized peri‐intestinal features known across Cambrian arthropods. In conclusion, our results suggest the need for caution in the interpretation of evidence for fossilized neural tissue, which will increase the accuracy of evolutionary scenarios. Also see the video abstract here: https://youtu.be/2_JlQepRTb0. (shrink)

Legislation that authorises controversial organ procurement strategies but ignores respect for autonomy is flawed in principle and predictably unworkable in practiceThe UK Human Tissue Act 2004,1 designed to regulate all activity involving human tissue, organs, or bodies, was introduced in the House of Commons in December 2003, received Royal Assent on 15 November 2004,2 and has been partially implemented by Commencement Orders from April 2005. The new act, which repeals and replaces the Human Tissue Act 1961, the Anatomy Act 1984, (...) and the Human Organ Transplants Act 1989, has its origins in events of serious public concern, namely the retained organs scandals at Bristol Royal Infirmary3 and the Royal Liverpool Childrens’ Hospital.4 The act is correspondingly dominated by regulation of postmortem examinations and retention of human tissue, with consistent emphasis on the need for fully informed consent. Compliance with these requirements is now mandatory with the threat of up to three years’ imprisonment and/or fines for any deviation.The impact of the original proposals within the bill on research and the clinical practice of pathology have been carefully considered and documented,5 with subsequent amendments to ameliorate professional concerns.6 The act, however, also carries significant implications for medical practice in areas where donor recruitment for transplantation can take place, and representations on these aspects during readings of the bill7 have produced neither clarification, justification, nor amendment within the final legislation.Section 43 will make it lawful for hospital authorities “to take steps for the purpose of preserving the part for use for transplantation and to retain the body for that purpose”. The original explanatory notes for the bill8 while it proceeded through parliament implied that such action, prior to consent to transplantation being sought, was then lawful, clause 44 as section 43 …. (shrink)