Acidity, generated in hypoxia or hypermetabolic states, perturbs homeostasis and is a feature of solid tumors. That acid peripherally disperses lysosomes is a three‐decade‐old observation, yet one little understood or appreciated. However, recent work has recognized the inhibitory impact this spatial redistribution has on mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of metabolism. This finding argues for a paradigm shift in localization of mTORC1 activator Ras homolog enriched in brain (RHEB), a conclusion several others have now independently (...) reached. Thus, mTORC1, known to sense amino acids, mitogens, and energy to restrict biosynthesis to times of adequate resources, also senses pH and, via dampened mTOR‐governed synthesis of clock proteins, regulates the circadian clock to achieve concerted responses to metabolic stress. While this may allow cancer to endure metabolic deprivation, immune cell mTOR signaling likewise exhibits pH sensitivity, suggesting that suppression of antitumor immune function by solid tumor acidity may additionally fuel cancers, an obstacle potentially reversible through therapeutic pH manipulation. (shrink)

Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Al- though these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances influence (...) moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment. (shrink)

This new translation presents the _Analects_ in a revolutionary new format that, for the first time in any language, distinguishes the original words of the Master from the later sayings of his disciples and their followers, enabling readers to experience China's most influential philosophical work in its true historical, social, and political context.

Integrating concepts of maintenance and of origins is essential to explaining biological diversity. The unified theory of evolution attempts to find a common theme linking production rules inherent in biological systems, explaining the origin of biological order as a manifestation of the flow of energy and the flow of information on various spatial and temporal scales, with the recognition that natural selection is an evolutionarily relevant process. Biological systems persist in space and time by transfor ming energy from one state (...) to another in a manner that generates structures which allows the system to continue to persist. Two classes of energetic transformations allow this; heat-generating transformations, resulting in a net loss of energy from the system, and conservative transformations, changing unusable energy into states that can be stored and used subsequently. All conservative transformations in biological systems are coupled with heat-generating transformations; hence, inherent biological production, or genealogical proesses, is positively entropic. There is a self-organizing phenomenology common to genealogical phenomena, which imparts an arrow of time to biological systems. Natural selection, which by itself is time-reversible, contributes to the organization of the self-organized genealogical trajectories. The interplay of genealogical (diversity-promoting) and selective (diversity-limiting) processes produces biological order to which the primary contribution is genealogical history. Dynamic changes occuring on times scales shorter than speciation rates are microevolutionary; those occuring on time scales longer than speciation rates are macroevolutionary. Macroevolutionary processes are neither redicible to, nor autonomous from, microevolutionary processes. (shrink)

Decades of research conducted in Western, Educated, Industrialized, Rich, & Democratic (WEIRD) societies have led many scholars to conclude that the use of mental states in moral judgment is a human cognitive universal, perhaps an adaptive strategy for selecting optimal social partners from a large pool of candidates. However, recent work from a more diverse array of societies suggests there may be important variation in how much people rely on mental states, with people in some societies judging accidental harms just (...) as harshly as intentional ones. To explain this variation, we develop and test a novel cultural evolutionary theory proposing that the intensity of kin-based institutions will favor less attention to mental states when judging moral violations. First, to better illuminate the historical distribution of the use of intentions in moral judgment, we code and analyze anthropological observations from the Human Area Relations Files. This analysis shows that notions of strict liability—wherein the role for mental states is reduced—were common across diverse societies around the globe. Then, by expanding an existing vignette-based experimental dataset containing observations from 321 people in a diverse sample of 10 societies, we show that the intensity of a society's kin-based institutions can explain a substantial portion of the population-level variation in people's reliance on intentions in three different kinds of moral judgments. Together, these lines of evidence suggest that people's use of mental states has coevolved culturally to fit their local kin-based institutions. We suggest that although reliance on mental states has likely been a feature of moral judgment in human communities over historical and evolutionary time, the relational fluidity and weak kin ties of today's WEIRD societies position these populations' psychology at the extreme end of the global and historical spectrum. (shrink)

The ratio of index- and ring-finger lengths is thought to be related to prenatal androgen exposure, and in many, though not all, populations, men have a lower average digit ratio than do women. In many studies an inverse relationship has been observed, among both men and women, between 2D:4D ratio and measures of athletic ability. It has been further suggested that, in hunter-gatherer populations, 2D:4D ratio might also be negatively correlated with hunting ability, itself assumed to be contingent on athleticism. (...) This hypothesis has been tested using endurance running performance among runners from a Western, educated, and industrialized population as a proximate measure of hunting ability. However, it has not previously been tested among actual hunter-gatherers using more ecologically valid measures of hunting ability and success. The current study addresses this question among Tanzanian Hadza hunter-gatherers. I employ a novel method of assessing hunting reputation that, unlike previous methods, allows granular distinctions to be made between hunters at all levels of perceived ability. I find no statistically significant relationship between digit ratio and either hunting reputation or two important hunting skills. I confirm that Hadza men have higher mean 2D:4D ratios than men in many Western populations. I discuss the notion that 2D:4D ratio may be the consequence of an allometric scaling relationship between relative and absolute finger lengths. Although it is difficult to draw clear conclusions from these results, the current study provides no support for the theorized relationship between 2D:4D ratio and hunting skill. (shrink)

This new translation presents the _Analects_ in a revolutionary new format that, for the first time in any language, distinguishes the original words of the Master from the later sayings of his disciples and their followers, enabling readers to experience China's most influential philosophical work in its true historical, social, and political context.

Culture and Enlightenment are the two words that best characterise the essence of György Markus's career, in whose honour this book is published. Markus devoted the last twenty years of research towards a theory of cultural objectivations and their pragmatics, and the great depth of his knowledge of the history of culture and philosophy informs all his teaching and writing. The pursuit of Enlightenment ideals attains reflective self-consciousness in Markus' works; forged in the knowledge of its own historicity, of the (...) embeddedness of rationalities in culture and in an awareness of the paradoxes that cling to the conscious affirmation of ideals which are no longer self evident or beyond questioning. In taking up the challenge of these paradoxes, Markus spans the whole history of modern philosophy and culture with a matchless authority.This book draws together contributions from leading figures in contemporary philosophy, who are also friends, colleagues and former students of György Markus. The book is divided into two sections: the first presents critical assessments of various aspects of Markus' wide-ranging works; the second presents contributions in celebration of his influence and his wide interests. In their critical assessment of Markus' work and in the demonstration of his influence, the contributors hope to convey something of the breadth and something of the excitement of doing philosophy in the company of György Markus. (shrink)

Both target papers cite evidence from infancy and early childhood to support the notion of human musicality as a somewhat static suite of capacities; however, in our view they do not adequately acknowledge the critical role of developmental timing, the acquisition process, or the dynamics of social learning, especially during later periods of development such as middle childhood.

The purpose of this contemporary history study is to analyse nursing strategy documents produced by NHS Trusts in England in the period 2009–2013, through a process of discourse analysis. In 2013 the Francis Report on the Mid-Staffordshire NHS Foundation Trust was published. The Report highlighted the full range of organisational failures in a Trust that valued financial efficiency over patient care. The analysis that followed, however, dwelt heavily on the failings of the nurses. Nursing strategy documents at that time served (...) to set the future direction for NHS Trusts, prescribing specific value frameworks for each nursing workforce. However, the values chosen frequently conflicted with each other pitting nursing values against a managerial trope. It is argued that documents provided a response to wider NHS concerns and high-profile failures in care, particularly the Francis Report, paying lip service to staff engagement whilst maintaining a corporate focus. Nursing values were placed firmly within a managerialist discourse, one that has needed to be re-evaluated in the current Covid-19 pandemic. Wider implications of the research suggest discussion of value conflict may be beneficial within nursing education and a truly local approach to strategy creation would potentially promote staff buy-in to strategy documents. (shrink)

Current health policy, high‐profile failures and increased media scrutiny have led to a significant focus on patient experience in Britain's National Health Service (NHS). Patient experience data is typically gathered through surveys of satisfaction. The study aimed to support a better understanding of the patient experience and patients' expression of it through consideration of the aspects of the patient experience on NHS wards which are by their nature impossible to capture through patient satisfaction surveys. Existential phenomenology was used to develop (...) an in‐depth exploratory narrative, expressed through the voices of the participants. Data collection involved in‐depth face‐to‐face interviews with 12 purposively sampled participants, with analysis by means of hermeneutics. Though the individuality of each experience was apparent and cannot be overemphasised, common factors emerging from the data included uncertainty and unexpectedness, suffering and finitude, the futility of feedback and bureaucracy and absurdity. Overall, participants demonstrated how their individual personalities and expectations affected their response both to illness or injury and to their hospital admissions, highlighting feelings of vulnerability and voicelessness as a response to hospitalisation. The findings of this study provide useful insight into the patient experience on British hospital wards, and the value of an existential–phenomenological approach is demonstrated. (shrink)