This article reviews the strengths and limitations of five major paradigms of medical computer-assisted decision making (CADM): (1) clinical algorithms, (2) statistical analysis of collections of patient data, (3) mathematical models of physical processes, (4) decision analysis, and (5) symbolic reasoning or artificial intelligence (Al). No one technique is best for all applications, and there is recent promising work which combines two or more established techniques. We emphasize both the inherent power of symbolic reasoning and the promise of artificial intelligence (...) and the other techniques to complement each other. (shrink)

It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi‐unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular‐to‐unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one‐off multicellular‐to‐unicellular reversion, and are (...) better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular‐eukaryote‐to‐multicellular‐eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ. (shrink)

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

BackgroundClinical Ethics Support (CES) services are offered to support healthcare professionals in dealing with ethically difficult situations. Evaluation of CES is important to understand if it is indeed a supportive service in order to inform and improve future implementation of CES. Yet, methods to measure outcomes of CES are scarce. In 2014, the European Moral Case Deliberation Outcomes Instrument (Euro-MCD) was developed to measure outcomes of Moral Case Deliberation (MCD). To further validate the instrument, we tested it in field studies (...) and revised it. This paper presents the Euro-MCD 2.0 and describes the revision process.MethodsThe revision process comprised an iterative dialogue among the authors as Euro-MCD-project team, including empirical findings from six Euro-MCD field-studies and input from European experts in CES and theory. Empirical findings contained perceptions and experiences of MCD outcomes among healthcare professionals who participated in MCDs in various settings in Norway, Sweden and the Netherlands. Theoretical viewpoints on CES, literature on goals of CES and MCD and ethics theory guided the interpretation of the empirical findings and final selection of MCD outcomes.ResultsThe Euro-MCD 2.0 Instrument includes three domains: Moral Competence, Moral Teamwork and Moral Action. Moral Competence consists of items about moral sensitivity, analytical skills and virtuous attitude. Moral Teamwork includes open dialogue and supportive relationships and Moral Action refers to moral decision-making and responsible care. During the revision process, we made decisions about adding and reformulating items as well as decreasing the number from 26 to 15 items. We also altered the sentence structure of items to assess the current status of outcomes (e.g. ‘now’) instead of an assumed improvement over time (e.g. ‘better’) and we omitted the question about perceived importance.ConclusionsThe Euro-MCD 2.0 is shorter, less complex and more strongly substantiated by an integration of empirical findings, theoretical reflections and dialogues with participants and experts. Use of the Euro-MCD 2.0 will facilitate evaluation of MCD and can thereby monitor and foster implementation and quality of MCD. The Euro-MCD 2.0 will strengthen future research on evaluation of outcomes of MCD. (shrink)

Ethics support services like Moral Case Deliberation intend to support healthcare professionals in ethically difficult situations. To assess outcomes of MCD, the Euro-MCD Instrument has been developed. Field studies to test this instrument are needed and have been conducted, examining important outcomes before MCD participation and experienced outcomes. The current study aimed to describe how participants’ perceive the importance of MCD outcomes after MCD; compare these perceptions with those before MCD participation; and test the factor structure of these outcomes. Swedish, (...) Norwegian and Dutch healthcare professionals rated the importance of outcomes in the Euro-MCD Instrument after four and eight MCDs. Ratings were compared with those before MCD participation using paired and independent samples t-tests. The factor structure was tested using exploratory factor analyses. After 4 and 8 MCDs, 443 respectively 247 respondents completed the instrument. More than 69% rated all MCD outcomes as ‘quite’ or ‘very’ important, especially outcomes from Enhanced Collaboration, Improved Moral Reflexivity and Improved Moral Attitude. Significant differences for 16 outcomes regarding ratings before and after MCD participation were not considered meaningful. Factor analyses suggested three categories, which seemingly resemble the domains Improved Moral Reflexivity, Enhanced Collaboration and a combination of Improved Moral Attitude and Enhanced Emotional Support. After participation in MCDs, respondents confirmed the importance of outcomes in the Euro-MCD Instrument. The question on perceived importance and the categorization of outcomes need reconsideration. The revised instrument will be presented elsewhere, based on all field studies and theoretical reflections. (shrink)

'Uncertainty and chance' is a subject with a broad span, in that there is no academic discipline or walk of life that is not beset by uncertainty and chance. In this book a range of approaches is represented by authors from varied disciplines: natural sciences, mathematics, social sciences and medical sciences. At one extreme, this volume is concerned with the foundations of probability. At the other extreme, we have scholars who acknowledge the concept of chance and uncertainty but do not (...) cope with it by means of systematic measurement or quantative analysis. (shrink)

In this article, the manuscript of Codex Madrid I, Leonardo da Vinci's workshop drawings collection, is reviewed and the main mechanisms that appear in the aforesaid codex are analysed. It begins with a short reference to Leonardo da Vinci works and, subsequently, Leonardo's manuscripts and Codex Madrid I, in particular, are placed in their historical context. After analysing the historical scope of Codex Madrid I, a compilation of the 100 main drawings of the manuscript is made, composing nine Mechanisms Drawings (...) Boxes. Each Mechanisms Drawings Box is a collage made up of 10 to 14 drawings of mechanical elements that appear in Codex Madrid I, with a brief description of each drawing. This compilation illustrates the wide range of mechanical elements and simple mechanisms of Codex Madrid I, forming, as a whole, a complete treatise on mechanisms, understanding mechanisms as basic elements of machines. (shrink)

In a study of the kin investment of aunts and uncles we show that the laterality effect expected as a result of paternity uncertainty is statistically reliable but somewhat smaller than the sex effect. Matrilateral aunts invest significantly more than patrilateral aunts, and the same is true for uncles. Regardless of laterality, however, aunts invest significantly more than uncles. Multivariate controls show that the matrilateral bias is fully independent of any age or distance confounds that might result from sex differences (...) in age at marriage or dispersal. We discuss our results in relation to recent findings on the kin investment of grandparents (Euler and Weitzel 1996). In addition, we propose a simple method for estimating the level of paternity uncertainty from kin investment data; application of this method to our data on aunts and uncles suggests that between 13% and 20% of children are not the offspring of their putative father. Our parallel analyses of Euler and Weitzel’s (1996) data on grandparental investment suggest a similar estimate, that paternity uncertainty lies between 9% and 17%. (shrink)

This is the first book to offer the best essays, articles, and speeches on ethics and intelligence that demonstrate the complex moral dilemmas in intelligence collection, analysis, and operations. Some are recently declassified and never before published, and all are written by authors whose backgrounds are as varied as their insights, including Robert M. Gates, former Director of the Central Intelligence Agency; John P. Langan, the Joseph Cardinal Bernardin Professor of Catholic Social Thought at the Kennedy Institute of Ethics, Georgetown (...) University; and Loch K. Johnson, Regents Professor of Political Science at the University of Georgia and recipient of the Owens Award for contributions to the understanding of U.S. intelligence activities. Creating the foundation for the study of ethics and intelligence by filling in the gap between warfare and philosophy, this is a valuable collection of literature for building an ethical code that is not dependent on any specific agency, department, or country. (shrink)

In orthodox quantum mechanics, it has virtually become the custom to identify properties of a physical system with operationally testable propositions about the system. The causes and consequences of this practice are explored mathematically in this paper. Among other things, it is found that such an identification imposes severe constraints on the admissible states of the physical system.

Background The use of lengthy, detailed, and complex informed consent forms is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in (...) biomedical research. Methods This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 to 5. Results Of the 2484 questionnaires distributed, 2113 were returned. The majority of respondents considered most elements required in the ICF to be ‘moderately important’ to ‘very important’ for their decision making. Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF. Conclusions Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF. (shrink)

Originally published in 1933, this volume contains the emended text of the Adamson Lecture for 1930, delivered by H. J. C. Grierson under the title 'Carlyle and the Hero'. This book will be of value to anyone with an interest in the modern and possibly controversial applications of Carlyle's philosophy.

Introduction: The Dutch Euthanasia Act states that euthanasia is not punishable if the attending physician acts in accordance with the statutory due care criteria. These criteria hold that: there should be a voluntary and well-considered request, the patient’s suffering should be unbearable and hopeless, the patient should be informed about their situation, there are no reasonable alternatives, an independent physician should be consulted, and the method should be medically and technically appropriate. This study investigates whether physicians experience problems with these (...) criteria in medical practice.Methods: In 2006, questionnaires were sent to a random, stratified sample of 2100 Dutch physicians . Physicians were asked about problems in their decision-making related to requests for euthanasia or assisted suicide after enforcement of the 2002 Euthanasia Act.Results: Of all physicians who had received a request for euthanasia or assisted suicide , 25% had experienced problems in the decision-making with regard to at least one of the criteria of due care. Physicians who had experienced problems mostly indicated to have had problems related to evaluating whether or not the patient’s suffering was unbearable and hopeless and whether or not the patient’s request was voluntary or well considered .Discussion: Physicians in The Netherlands most frequently reported problems related to aspects in which they have to evaluate the patient’s subjective perspective. However, it can be questioned whether placing emphasis on these subjective aspects is an adequate fulfilment of the duties imposed on physicians, as laid down in the Dutch Euthanasia Act. (shrink)

The sequencing of the human genome and decreasing costs of sequencing technology have led to the notion of ‘personalized medicine’. This has been taken by some authors to indicate that personalized medicine will provide individualized treatments solely based on one’s DNA sequence. We argue this is overly optimistic and misconstrues the notion of personalization. Such interpretations fail to account for economic, policy and structural constraints on the delivery of healthcare. Furthermore, notions of individualization based on genomic data potentially take us (...) down the road of genetic reductionism obscuring the role of environmental factors in disease and ill health. We propose that one should see personalized medicine as a way of using personal genomic information to stratify individuals into subpopulations and suggest that personalized medicine be seen within a broader idea of personalized healthcare, reflecting healthcare that integrates personal genomic data into cultural, environmental and personal contexts. (shrink)

Corporate social responsibility involvement and disclosure has been becoming increasingly popular among US public firms, including those that qualify as real estate investment trusts. This paper aims to discover the relationship between CSR involvement and potential determinants such as growth opportunities, profitability, visibility, and agency costs. Types of CSR involvement are assessed in terms of environmental, community, and governance disclosures and are quantified using word count from the company’s voluntary disclosure. Our results support the hypothesis that CSR has a strategic (...) element and that REITs have greater CSR involvement when they have greater growth and investment opportunities. When the type of disclosure is broken into subcategories, the results show that not all dimensions of CSR are alike: environmental, community, and governance CSR disclosures appear to be motivated by different sets of incentives and reasons. (shrink)

Gaulin, McBurney, and Brakeman-Wartell (1997) found that college students reported both matrilateral and sex biases in the investment of aunts and uncles (aunts invested more than uncles). They interpreted the matrilateral bias as a consequence of paternity uncertainty. We replicated that study with Orthodox Jewish college students, selected because they come from a population we presume to have higher paternity certainty than the general population. The Orthodox sample also showed matrilateral and sex biases. Comparing the two data sets, the Orthodox (...) sample reported more investment, and slightly less matrilateral and sex biases, but the differences were not statistically significant. We did find an interaction between sex of relative and group membership, resulting from greater investment by Orthodox uncles. We interpret the results as reflecting the operation of a facultative investment mechanism whose upper limit is tuned to the maximum levels of paternity certainty found in ancestral environments. Lack of a difference in matrilateral bias between groups may result from levels of paternity certainty near to, or above, that maximum in both groups. (shrink)

Decisions related to animal welfare standards depend on farmer’s multiple goals and values and are constrained by a wide range of external and internal forces. The aim of this paper is twofold, i.e., to develop a theoretical framework for farmers’ AW decisions that incorporates farmers’ goals, use and non-use values and to present an approach to empirically implement the theoretical framework. The farmer as a head of the farm household makes choices regarding production to maximize the utility of the household. (...) The overall utility of the farmer is determined by his multiple objectives. For the analysis of multi-objective problems, the multiple criteria decision - making paradigm provides an appropriate theoretical framework. However, theories from the field of social-psychology are needed to facilitate the identification of all relevant aspects in the decision making. The practical use of the conceptual framework is demonstrated using a simple numerical application of a multi-objective programming model. Two workshops were devoted to examining the scientific consistency and the practical usefulness of the approach. Implementing this approach will increase knowledge of the main factors and barriers that determine farmers’ decisions with regard to AW standards. This knowledge is relevant during the development of new AW concepts that aims to supply products that comply with above-legal AW standards for middle-market segments. (shrink)

The acceleration of the market globalisation process over the last three decades has internationalised clinical research and influenced both the way in which it is funded and the development and application of research practices. In addition, in recent years international multicentre randomised clinical trials have become the model par excellence for research on new medicines. The neoliberal model of globalisation has induced a decline in state power, both with regard to establishing national research for health priorities and to influencing the (...) development of adequate ethical guidelines to protect human beings that participate in multinational research. In this respect, poor and low-income countries, which lack sustainable control and review systems to deal with the ethical and methodological challenges of complex studies conducted by researchers from affluent countries and funded by large multinational pharmaceutical companies, are particularly vulnerable. The aim of the present paper is to explore critically some of the actual and possible ethical pitfalls of globalisation of clinical research and propose mechanisms for turning transnational clinical research into a more cooperative and fairer enterprise. (shrink)

Recognition that biological systems are stabilized far from equilibrium by self-organizing, informed, autocatalytic cycles and structures that dissipate unusable energy and matter has led to recent attempts to reformulate evolutionary theory. We hold that such insights are consistent with the broad development of the Darwinian Tradition and with the concept of natural selection. Biological systems are selected that re not only more efficient than competitors but also enhance the integrity of the web of energetic relations in which they are embedded. (...) But the expansion of the informational phase space, upon which selection acts, is also guaranteed by the properties of open informational-energetic systems. This provides a directionality and irreversibility to evolutionary processes that are not reflected in current theory.For this thermodynamically-based program to progress, we believe that biological information should not be treated in isolation from energy flows, and that the ecological perspective must be given descriptive and explanatory primacy. Levels of the ecological hierarchy are relational parts of ecological systems in which there are stable, informed patterns of energy flow and entropic dissipation. Isomorphies between developmental patterns and ecological succession are revealing because they suggest that much of the encoded metabolic information in biological systems is internalized ecological information. The geneological hierarchy, to the extent that its information content reflects internalized ecological information, can therefore be redescribed as an ecological hierarchy. (shrink)

Successful applications of a conceptually novel setup of Quantum Field Theory, that accounts for all subtheories of the Standard Model (QED, Electroweak Interaction and Higgs, Yang–Mills and QCD) and beyond (Helicity 2), call for a perspective view in a broader conceptual context. The setting is “autonomous” in the sense of being intrinsically quantum. Its principles are: Hilbert space, Poincaré symmetry and causality. Its free quantum fields are obtained from Wigner’s unitary representations of the Poincaré group, with only physical and observable (...) degrees of freedom. A “quantization” of an “underlying” classical theory is not needed. It allows renormalizable perturbation theory with interactions whose detailed structure, and in some cases even the particle content, is predicted by internal consistency. The results confirm and extend observable predictions for the interactions of the Standard Model without assuming a “principle” of gauge invariance. (shrink)

ABSTRACT:This manuscript develops the concept of organizational virtue orientation (OVO) and examines differences between family and non-family firms on the six organizational virtue dimensions of Integrity, Empathy, Warmth, Courage, Conscientiousness, and Zeal. Using content analysis of shareholder letters fromS&P 500companies, our analyses find that there are significant differences between family and non-family firms in their espoused OVO, with family firms generally being higher. Specifically, family firms were significantly higher on the dimensions of Empathy, Warmth, and Zeal, but lower on Courage. (...) Based on these findings we further develop the OVO concept through the discussion of implications and areas for future research. (shrink)

Experiments are described, using electroencephalography (EEG) and simple tests of performance, which support the hypothesis that collapse of a quantum field is of importance to the functioning of the brain. The theoretical basis of our experiments is derived from Penrose (1989) who suggested that conscious decision-making is a manifestation of the outcome of quantum computation in the brain involving collapse of some relevant wave function. He also proposed that collapse of any wave function depends on a gravitational criterion. As different (...) brain areas are known to subserve different functions, we argue that `Penrose collapse' must occur in a particular brain area when performing a task that uses it. Further, taking an EEG from the area should amplify the gravitational prerequisite for collapse, so affecting task performance. There are no non-quantum theories which could lead one to expect that taking an EEG could directly affect task performance by subjects. The results of both pilot and main experiments indicated that task performance was indeed influenced by taking an EEG from relevant brain areas. Control experiments suggested that the influence was quantum mechanical in origin, and was not due to any experimental artefact. The results are statistically significant and merit attempts at replication in an independent laboratory, preferably with more sophisticated equipment than was available to us. (shrink)

The neural correlates of rapid eye movements (REMs) in sleep are extraordinarily robust; including REM-locked activation in the retrosplenial cortex, the supplementary eye field and areas overlapping cholinergic basal nucleus. The phenomenology of REMs speaks to the notion that perceptual experience in both sleep and wakefulness is a constructive process – in which we generate predictions of sensory inputs and then test those predictions through actively sampling the sensorium with eye movements. On this view, REMs during sleep may index an (...) internalized active sampling or ‘scanning’ of self-generated visual constructs that are not constrained by visual input. If this view is correct, it renders REMs an ideal probe to study consciousness as “an exclusively internal affair” (Metzinger 2009). In other words, REMs offer a probe of active inference – in the sense of predictive coding – when the brain is isolated from the sensorium in virtue of the natural blockade of sensory input during REM sleep. REMs are temporally precise events that enable powerful inferences based on timeseries analyses. As a natural, task-free probe, [REMs] could be used in non-compliant subjects, including infants and animals. In short, REM constitutes a promising probe to study the ontogenetic and phylogenetic development of consciousness and perhaps its abnormal development in schizophrenia and autism, which have been considered in terms of aberrant predictive coding. (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)