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)

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.

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)

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)

There are many things—call them ‘experts’—that you should defer to in forming your opinions. The trouble is, many experts are modest: they’re less than certain that they are worthy of deference. When this happens, the standard theories of deference break down: the most popular (“Reflection”-style) principles collapse to inconsistency, while their most popular (“New-Reflection”-style) variants allow you to defer to someone while regarding them as an anti-expert. We propose a middle way: deferring to someone involves preferring to make any decision (...) using their opinions instead of your own. In a slogan, deferring opinions is deferring decisions. Generalizing the proposal of Dorst (2020a), we first formulate a new principle that shows exactly how your opinions must relate to an expert’s for this to be so. We then build off the results of Levinstein (2019) and Campbell-Moore (2020) to show that this principle is also equivalent to the constraint that you must always expect the expert’s estimates to be more accurate than your own. Finally, we characterize the conditions an expert’s opinions must meet to be worthy of deference in this sense, showing how they sit naturally between the too-strong constraints of Reflection and the too-weak constraints of New Reflection. (shrink)