Cancer is a complex disease, necessitating research on many different levels; at the subcellular level to identify genes, proteins and signaling pathways associated with the disease; at the cellular level to identify, for example, cell-cell adhesion and communication mechanisms; at the tissue level to investigate disruption of homeostasis and interaction with the tissue of origin or settlement of metastasis; and finally at the systems level to explore its global impact, e.g. through the mechanism of cachexia. Mathematical models have been proposed (...) to identify key mechanisms that underlie dynamics and events at every scale of interest, and increasing effort is now being paid to multi-scale models that bridge the different scales. With more biological data becoming available and with increased interdisciplinary efforts, theoretical models are rendering suitable tools to predict the origin and course of the disease. The ultimate aims of cancer models, however, are to enlighten our concept of the carcinogenesis process and to assist in the designing of treatment protocols that can reduce mortality and improve patient quality of life. Conventional treatment of cancer is surgery combined with radiotherapy or chemotherapy for localized tumors or systemic treatment of advanced cancers, respectively. Although radiation is widely used as treatment, most scheduling is based on empirical knowledge and less on the predictions of sophisticated growth dynamical models of treatment response. Part of the failure to translate modeling research to the clinic may stem from language barriers, exacerbated by often esoteric model renderings with inaccessible parameterization. Here we discuss some ideas for combining tractable dynamical tumor growth models with radiation response models using biologically accessible parameters to provide a more intuitive and exploitable framework for understanding the complexity of radiotherapy treatment and failure. (shrink)

Mobile devices with health apps, direct-to-consumer genetic testing, crowd-sourced information, and other data sources have enabled research by new classes of researchers. Independent researchers, citizen scientists, patient-directed researchers, self-experimenters, and others are not covered by federal research regulations because they are not recipients of federal financial assistance or conducting research in anticipation of a submission to the FDA for approval of a new drug or medical device. This article addresses the difficult policy challenge of promoting the welfare and interests of (...) research participants, as well as the public, in the absence of regulatory requirements and without discouraging independent, innovative scientific inquiry. The article recommends a series of measures, including education, consultation, transparency, self-governance, and regulation to strike the appropriate balance. (shrink)

Prompted by the development of the Theory of Challenge and Threat States in Athletes (Jones et al, 2009), recent years has witnessed a considerable increase in research examining challenge and threat in sport. This manuscript provides a critical review of the literature examining challenge and threat in sport, tracing its historical development and some of the current empirical ambiguities. In an attempt to reconcile some of these ambiguities, and utilising neurobiological evidence associated with approach- and avoidance-motivation (cf. Elliot & Covington, (...) 2001), this paper draws upon the Evaluative Space Model (ESM: Cacioppo et al., 1997) and considers the implications for understanding challenge and threat in sport. For example, rather than see challenge and threat as opposite ends of a single bipolar continuum, the ESM implies that individuals could be (1) challenged, (2) threatened, (3) challenged and threatened, or (4) neither challenged or threatened by a particular stimulus. From this perspective it could be argued that the appraisal of some sport situations as both challenging and threatening could be advantageous, whereas the current literature seems to imply that the appraisal of stress as a threat is maladaptive for performance. In drawing upon the ESM, we outline the Evaluative Space Approach to Challenge and Threat and provide several testable hypotheses for advancing understanding of challenge and threat (in sport). We also outline a number of cardiovascular and experiential measures that can be used to examine these hypotheses. In sum, this paper provides a significant theoretical, empirical and practical contribution to our understanding of challenge and threat (in sport). (shrink)

In this commentary, the formation of “pre-iconic” visual-prime persistence is described in the context of prime-specific, independent-component activation at prefrontal and posterior EEG-recording sites. Although this activity subserves neural systems that are near identical to those described by Ruchkin and colleagues, we consider priming to be a dynamic process, identified with patterns of coherence and temporal structure of very high precision.

In order to accomplish the transition from avascular to vascular growth, solid tumours secrete a diffusible substance known as tumour angiogenesis factor (TAF) into the surrounding tissue. Endothelial cells which form the lining of neighbouring blood vessels respond to this chemotactic stimulus in a well-ordered sequence of events comprising, at minimum, of a degradation of their basement membrane, migration and proliferation. Capillary sprouts are formed which migrate towards the tumour eventually penetrating it and permitting vascular growth to take place. It (...) is during this stage of growth that the insidious process of invasion of surrounding tissues can and does take place. A model mechanism for angiogenesis is presented which includes the diffusion of the TAF into the surrounding host tissue and the response of the endothelial cells to the chemotactic stimulus. Numerical simulations of the model are shown to compare very well with experimental observations. The subsequent vascular growth of the tumour is discussed with regard to a classical reaction-diffusion pre-pattern model. (shrink)

Virtue and the Moral Life brings together distinguished philosophers and theologians with younger scholars of consummate promise to produce ten essays that engage both academics and students of ethics. This collection explores the role virtues play in identifying the good life and the good society.

There is a long history of cryptographic hash functions, i.e. functions mapping variable-length strings to fixed-length strings, and such functions are also expected to enjoy certain security properties. Hash functions can be effected via modular arithmetic, permutation-based schemes, chaotic mixing, and so on. Herein we introduce the notion of an artificial-life (ALife) hash function (ALHF), whereby the requisite mixing action of a good hash function is accomplished via ALife rules that give rise to complex evolution of a given system. Various (...) security tests have been run, and the results reported for examples of ALHFs. (shrink)

Professor Matthew Kramer is one of the most important legal philosophers of our time - even if the label 'legal philosopher' does not do justice to the breadth of his work. This collection of essays brings together esteemed philosophers, as well as junior scholars, to critically assess Kramer's philosophy. The contributions focus on Kramer's work on legal philosophy, metaethics, normative ethics, and political philosophy. The volume is divided into six parts, each focusing on different aspect of Kramer's work. The first (...) part, Rights and Right-holding, contains five essays addressing Kramer's work on rights and right-holding, including the Hohfeldian analysis and the interest theory of right-holding. The four essays in the second part, General Jurisprudence, focus on Kramer's work in general jurisprudence, from the compatibility of legal positivism with universal legal error, to his robust defense of inclusive legal positivism, concluding with reflections on his writings on the rule of law. The third part, General Matters of Ethics, contains two essays addressing Kramer's metaethical work on moral realism as a moral doctrine. The fourth and fifth parts, Freedom and Liberalism, have four essays falling within political philosophy, probing Kramer's work on negative freedom and political liberalism, respectively. The sixth part, Applied Ethics, contains two essays on Kramer's work on capital punishment and freedom of expression. The collection is rounded off by reflections on, and replies to, the contributions by Kramer himself. (shrink)

Recently Díaz, Hössjer and Marks (DHM) presented a Bayesian framework to measure cosmological tuning (either fine or coarse) that uses maximum entropy (maxent) distributions on unbounded sample spaces as priors for the parameters of the physical models (https://doi.org/10.1088/1475-7516/2021/07/020). The DHM framework stands in contrast to previous attempts to measure tuning that rely on a uniform prior assumption. However, since the parameters of the models often take values in spaces of infinite size, the uniformity assumption is unwarranted. This is known as (...) the normalization problem. In this paper we explain why and how the DHM framework not only evades the normalization problem but also circumvents other objections to the tuning measurement like the so called weak anthropic principle, the selection of a single maxent distribution and, importantly, the lack of invariance of maxent distributions with respect to data transformations. We also propose to treat fine-tuning as an emergence problem to avoid infinite loops in the prior distribution of hyperparameters (common to all Bayesian analysis), and explain that previous attempts to measure tuning using uniform priors are particular cases of the DHM framework. Finally, we prove a theorem, explaining when tuning is fine or coarse for different families of distributions. The theorem is summarized in a table for ease of reference, and the tuning of three physical parameters is analyzed using the conclusions of the theorem. (shrink)

SummaryHuman height is a heritable trait that is known to be influenced by environmental factors and general standard of living. Individual and population stature is correlated with health, education and economic achievement. Strong sexual selection pressures for stature have been observed in multiple diverse populations, however; there is significant global variance in gender equality and prohibitions on female mate selection. This paper explores the contribution of general standard of living and gender inequality to the variance in global female population heights. (...) Female population heights of 96 nations were culled from previously published sources and public access databases. Factor analysis with United Nations international data on education rates, life expectancy, incomes, maternal and childhood mortality rates, ratios of gender participation in education and politics, the Human Development Index and the Gender Inequality Index was run. Results indicate that population heights vary more closely with gender inequality than with population health, income or education. (shrink)

"Central Themes in Early Modern Philosophy is a selection of some of the best work being done in early modern philosophy by Anglo-American philosophers today.... The essays in this collection are historically informed and philosophically challenging. The book is a fitting tribute to Jonathan Bennett." -- Daniel Garber, University of Chicago.

Fossil organisms offer our only direct insight into how the distinctive body plans of extant organisms were assembled. However, realizing the potential evolutionary significance of fossils can be hampered by controversy over their interpretation. Here, as a guide to evaluating palaeontological debates, we outline the process and pitfalls of fossil interpretation. The physical remains of controversial fossils should be reconstructed before interpreting homologies, and choice of interpretative model should be explicit and justified. Extinct taxa lack characters diagnostic of extant clades (...) because the characters had not yet evolved, because of secondary loss, or because they have rotted away. The latter, if not taken into account, will lead to the spurious assignment of fossils to basally branching clades. Conflicting interpretations of fossils can often be resolved by considering all the steps in the process of anatomical analysis and phylogenetic placement, although we must accept that some fossil organisms are simply too incompletely preserved for their evolutionary significance to be realized. (shrink)

A vigorous debate has developed surrounding electronic surveillance in the workplace. This controversial practice is one element of the more general issues of employee dignity and management control, revolving around the use of polygraph and drug testing, integrity exams, and the like. Managers, under pressure from competitors, are making greater use of technologically advanced employee monitoring methods because they are available, and hold the promise of productivity improvement. In this paper, the context of electronic surveillance is described and analyzed from (...) the perspectives of ethics, public policy, and managerial behavior. (shrink)

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from (...) social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic. (shrink)

We describe a novel Internet-based method for building consensus and clarifying con icts in large stakeholder groups facing complex issues, and we use the method to survey and map the scienti c and organizational perspectives of the arti cial life community during the Seventh International Conference on Arti cial Life (summer 2000). The issues addressed in this survey included arti cial life’s main successes, main failures, main open scienti c questions, and main strategies for the future, as well as the (...) bene ts and pitfalls of creating a professional society for arti cial life. By illuminating the arti cial life community’s collective perspective on these issues, this survey illustrates the value of such methods of harnessing the collective intelligence of large stakeholder groups. (shrink)

Essentialists like J. Baird Callicott have argued that one cannot have an environmental ethic unless one adopts the nonanthropocentric principle, which holds that things other than humans can be morally considerable in their own right, typically because they are thought to be intrinsically valuable. Pragmatists like Bryan Norton reject this; they claim that environmental ethics has no core or essence, and hence that the nonanthropocentric principle is not essential to an environmental ethic. Norton advances as an alternative the Convergence Hypothesis, (...) which says that there are many different ways of justifying environmental principles and policies. In this paper I show that pragmatists and essentialists are arguing past one another because they fail to note two crucial points. First, they often propose different accounts of which principles constitute an environmental ethic and so they disagree about which principles must be justified. The nonanthropocentric principle may be required to justify the principles that Callicott believe to be constitutive of an environmental ethic, but it may be unnecessary to justify those principles that pragmatists think are constitutive. Second, essentialists and pragmatists often overlook the distinction to be made between the adequacy of a justification and its epistemic or rhetorical preferability. The nonanthropocentric principle may not be needed to provide an adequate justification of the constitutive principles and judgements, but a justification that contains the nonanthropocentric principle might nevertheless be epistemically preferable. (shrink)

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create (...) new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. (shrink)

The medium surrounding cells either in culture or in tissues contains a chemical mix varying with cell state. As solutes move in and out of the cytoplasmic compartment they set up characteristic signatures in the cellular boundary layers. These layers are complex physical and chemical environments the profiles of which reflect cell physiology and provide conduits for intercellular messaging. Here we review some of the most relevant characteristics of the extracellular/intercellular space. Our initial focus is primarily on cultured cells but (...) we extend our consideration to the far more complex environment of tissues, and discuss how chemical signatures in the boundary layer can or may affect cell function. Critical to the entire essay are the methods used, or being developed, to monitor chemical profiles in the boundary layers. We review recent developments in ultramicro electrochemical sensors and tailored optical reporters suitable for the task in hand. (shrink)

One of the most interesting challenges facing paleobiologists is explaining the Cambrian explosion, the dramatic appearance of most metazoan animal phyla in the Early Cambrian, and the subsequent stability of these body plans over the ensuing 530 million years. We propose that because phenotypic variation decreases through geologic time, because microRNAs (miRNAs) increase genic precision, by turning an imprecise number of mRNA transcripts into a more precise number of protein molecules, and because miRNAs are continuously being added to metazoan genomes (...) through geologic time, miRNAs might be instrumental in the canalization of development. Further, miRNAs ultimately allow for natural selection to elaborate morphological complexity, because by reducing gene expression variability, miRNAs increase heritability, allowing selection to change characters more effectively. Hence, miRNAs might play an important role in shaping metazoan macroevolution, and might be part of the solution to the Cambrian conundrum. (shrink)

Safe stair negotiation is an everyday task that children with developmental coordination disorder are commonly thought to struggle with. Yet, there is currently a paucity of research supporting these claims. We investigated the visuomotor control strategies underpinning stair negotiation in children with and without DCD by measuring kinematics, gaze behavior and state anxiety as they ascended and descended a staircase. A questionnaire was administered to determine parents' confidence in their child's ability to safely navigate stairs and their child's fall history. (...) Kinematics were measured using three-dimensional motion capture, whilst gaze was measured using mobile eye-tracking equipment. The parents of DCD children reported significantly lower confidence in their child's ability to maintain balance on the stairs and significantly more stair-related falls in the previous year compared to the parents of typically developing children. During both stair ascent and stair descent, the children with DCD took longer to ascend/descend the staircase and displayed greater handrail use, reflecting a more cautious stair negotiation strategy. No differences were observed between groups in their margin of stability, but the DCD children exhibited significantly greater variability in their foot-clearances over the step edge, which may increase the risk of a fall. For stair descent only, the DCD children reported significantly higher levels of state anxiety than the TD children and looked significantly further along the staircase during the initial entry phase, suggesting an anxiety-related response that may bias gaze toward the planning of future stepping actions over the accurate execution of an ongoing step. Taken together, our findings provide the first quantifiable evidence that safe stair negotiation is a significant challenge for children with DCD, and that this challenge is reflected by marked differences in their visuomotor control strategies and state anxiety levels. Whilst it is currently unclear whether these differences are contributing to the frequency of stair-related falls in children with DCD, our findings pave the way for future research to answer these important questions. (shrink)

A Companion to Phenomenology and Existentialism is a complete guide to two of the dominant movements of philosophy in the twentieth century. Written by a team of leading scholars, including Dagfinn Føllesdal, J. N. Mohanty, Robert Solomon, Jean–Luc Marion Highlights the area of overlap between the two movements Features longer essays discussing each of the main schools of thought, shorter essays introducing prominent themes, and problem–oriented chapters Organised topically, around concepts such as temporality, intentionality, death and nihilism Features essays on (...) unusual subjects, such as medicine, the emotions, artificial intelligence, and environmental philosophy. (shrink)

Participatory action research (PAR) is a form of community-driven qualitative research which aims to collaboratively take action to improve participants’ lives. This is generally achieved through cognitive, reflexive learning cycles, whereby people ultimately enhance their wellbeing. This approach builds on two assumptions: (1) participants are able to reflect on and prioritize difficulties they face; (2) collective impetus and action are progressively achieved, ultimately leading to increased wellbeing. This article complicates these assumptions by analyzing a two-year PAR project with mothers of (...) disabled children from a South African urban settlement. Participant observation notes, interviews, and a group discussion served as primary data. We found that mothers’ severe psychological stress and the strong intersectionality of their daily challenges hampered participation. Consequently, mothers considered the project ‘inactionable’. Yet, many women quickly started expressing important individual and collective wellbeing transformations. To understand these ‘unlikely’ transformations, a feminist relational account, in particular, that of relational wellbeing, proves essential. We reflect on the consequences of these findings for the dominant PAR methodology and operationalization, and propose to sensitize future PAR with marginalized women by employing relational wellbeing as an overarching ontological awareness. (shrink)

As Dana Villa shows, however, Arendt's thought is often poorly understood, both because of its complexity and because her frame has made it easy for critics to write about what she is reputed to have said rather than what she actually wrote. Villa sets out to change that here, explaining clearly, carefully, and forcefully Arendt's major contributions to our understanding of politics, modernity, and the nature of political evil in our century.(publisher, edited).

In a recent study, Becker and Elliott [Becker, C., & Elliott, M. A. . Flicker induced color and form: Interdependencies and relation to stimulation frequency and phase. Consciousness & Cognition, 15, 175–196] described the appearance of subjective experiences of color and form induced by stimulation with intermittent light. While there have been electroencephalographic studies of similar hallucinatory forms, brain activity accompanying the appearance of hallucinatory colors was never measured. Using a priming procedure where observers were required to indicate the presence (...) of one of eight target colors we compared electrophysiological correlates of hallucinatory color with brain states associated with other visual phenomena. Different target colors were accompanied by different patterns of EEG activation. However, in general, we found that the appearance of hallucinatory colors is preceded by a power decrease in the lower alpha band alongside an increase in gamma band frequencies. We argue that decreasing activity in the lower alpha band acts as a gating mechanism, inducing a switch in perception between different colors. The increasing gamma activation may correlate with the formation of a coherent conscious percept. (shrink)

Political metaphors do more than punch up messages; they can systematically bias observers’ attitudes toward the issue at hand. What, then, is an effective strategy for counteracting a metaphor’s influence? One could ignore or criticize the metaphor, emphasizing strong counterarguments directly pertaining to the target issue. Yet if observers rely on it to understand a complicated issue, they may be reluctant to abandon it. In this case, a “metaphor extension” strategy may be effective: Encourage observers to retain the metaphor but (...) reinterpret its meaning by considering other, less obvious implications. The current studies support this claim. Under conditions where participants gained a strong epistemic benefit from a rhetorical metaphor, they were more persuaded by a rebuttal that extended that metaphor. The studies use converging operational definitions of epistemic benefit and offer insight into how political attitudes are made and unmade. (shrink)

The first of these is not a single disease but a group of three: ‘all the clinical and epidemiological evidence described by Thucydides’ ‘can be attributed to infection with influenza virus complicated by a toxin-producing strain of noninvasive staphylococcus’ . This initial analysis is in fact supplemented by bullous impetigo in an attempt to explain the marked skin symptoms which are not ascribable to the other two diseases: streptococci produce flushes of the skin that end in desquamation – something which (...) Langmuir et al. admit T would have described if present. (shrink)

This paper reports an experiment designed to investigate the potential influence of prior acts of self-control on subsequent prospective memory performance. College undergraduates performed either a cognitively depleting initial task or a less resource-consuming version of that task . Subsequently, participants completed a prospective memory task that required attentionally demanding monitoring processes. The results demonstrated that prior acts of self-control do not impair the ability to execute a future intention in college-aged adults. We conceptually replicated these results in three additional (...) depletion and prospective memory experiments. This research extends a growing number of studies demonstrating the boundary conditions of the resource depletion effect in cognitive tasks. (shrink)

A central characteristic of people with Prader-Willi Syndrome (PWS) is an apparent insatiable appetite leading to severe overeating and the potential for marked obesity and associated serious health problems and premature death. This behaviour may be due to the effects of the genetic defect resulting from the chromosome 15 abnormalities associated with the syndrome. We examine the ethical and legal dilemmas that can arise in the care of people with PWS. A tension exists between a genetic deterministic perspective and that (...) of individual choice. We conclude that the determination of the capacity of a person with PWS to make decisions about his/her eating behaviour and to control that behaviour is of particular importance in resolving this dilemma. If the person is found to lack capacity, the common law principles of acting in a person's "best interests" using the "least restrictive alternative" may be helpful. Allowing serious weight gain in the absence of careful consideration of these issues is an abdication of responsibility. (shrink)