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)

The rubber hand paradigm is used to create the illusion of self-touch, by having the participant administer stimulation to a prosthetic hand while the Examiner, with an identical stimulus , administers stimulation to the participant’s hand. With synchronous stimulation, participants experience the compelling illusion that they are touching their own hand. In the current study, the robustness of this illusion was assessed using incongruent stimuli. The participant used the index finger of the right hand to administer stimulation to a prosthetic (...) hand while the Examiner used a paintbrush to administer stimulation to the participant’s left hand. The results indicate that this violation of tactile expectations does not diminish the illusion of self-touch. Participants experienced the illusion despite the use of incongruent stimuli, both when vision was precluded and when visual feedback provided clear evidence of the tactile mismatch. (shrink)

A simple experimental paradigm creates the powerful illusion that one is touching one’s own hand even when the two hands are separated by 15 cm. The participant uses her right hand to administer stimulation to a prosthetic hand while the Examiner provides identical stimulation to the participant’s receptive left hand. Change in felt position of the receptive hand toward the prosthetic hand has previously led to the interpretation that the participant experiences self-touch at the location of the prosthetic hand, and (...) experiences a sense of ownership of the prosthetic hand. Our results argue against this interpretation. We assessed change in felt position of the participant’s receptive hand but we also assessed change in felt position of the participant’s administering hand. Change in felt position of the administering hand was significantly greater than change in felt position of the receptive hand. Implications for theories of ownership are discussed. (shrink)

Introduction THOMAS C. HELLER AND DAVID E. WELLBERY A he essays that follow originated in a conference entitled "Reconstructing Individualism," held at ...

The acceptance or rejection of computer aids to clinical reasoning is determined not only by the preferences and prejudices of potential users, but also by whether the output generated by the computer aid represents sound clinical judgment. This paper deals with the issue of the appropriate criteria for evaluating the clinical ‘reasoning’ of computer aids. Evaluation of a computer aid should include an assessment of the accuracy or appropriateness of its conclusions and an assessment of the scope of its considerations. (...) In order to use a conclusion generated by a computer aid as a basis for clinical action, information must be available on the alternative conclusions that might have been drawn, the degree of confidence in each conclusion, and the consequences that may result from acting upon the wrong conclusion. If this information is not generated as part of the output of a computer aid, it may be obtained through the use of its explanation and display capabilities, if the aid has such capabilities. Explanation and display capabilities permit the examination of the operations of the computer aid. Examination of a computer's operations is also the most feasible means to evaluate the soundness of its ‘reasoning’. (shrink)

This book presents a theory about the kind of thing a mind is and, on the basis of this theory, a view about how minds are individuated and when two mental states belong to the same mind.

The nonvisual self-touch rubber hand paradigm elicits the compelling illusion that one is touching one’s own hand even though the two hands are not in contact. In four experiments, we investigated spatial limits of distance and alignment on the nonvisual self-touch illusion and the well-known visual rubber hand illusion. Common procedures and common assessment methods were used. Subjective experience of the illusion was assessed by agreement ratings for statements on a questionnaire and time of illusion onset. The nonvisual self-touch illusion (...) was diminished though never abolished by distance and alignment manipulations, whereas the visual rubber hand illusion was more robust against these manipulations. We assessed proprioceptive drift, and implications of a double dissociation between subjective experience of the illusion and proprioceptive drift are discussed. (shrink)

Inattentional blindness studies have shown that an unexpected object may go unnoticed if it does not share the property specified in the task instructions. Our aim was to demonstrate that observers develop an attentional set for a property not specified in the task instructions if it allows easier performance of the primary task. Three experiments were conducted using a dynamic selective-looking paradigm. Stimuli comprised four black squares and four white diamonds, so that shape and colour varied together. Task instructions specified (...) shape but observers developed an attentional set for colour, because we made the black–white discrimination easier than the square–diamond discrimination. None of the observers instructed to count bounces by squares reported an unexpected white square, whereas two-thirds of observers instructed to count bounces by diamonds did report the white square. When attentional set departs from task instructions, you may fail to see what you were told to look for. (shrink)

Few figures of the Middle Ages command the attention of so many modern disciplines as Robert Grosseteste (c. 1170-1253). Theology, Philosophy, History, and Science are all areas which his life and thought continue to have significance and to inspire re-interpretation. Accompanied by a series of original commentaries, this new edition of Grosseteste's work, with English translation, draws together the perspectives of modern scientists and medieval specialists. Volume I of a six volume series, Knowing and Speaking presents two of the earliest (...) of Grosseteste's works, the treatises On the Liberal Arts and On the Generation of Sounds. These are accompanied by a significant Middle English treatise on the Seven Liberal Arts whose anonymous fifteenth-century author translated and excerpted passages from Grosseteste's treatises in a re-imagining of their structure and function.0Each work is treated separately within the volume, which is constructed in three parts. On the Liberal Arts sets Grosseteste's thoughts on the arts subjects and emphasises moral concerns about the purpose of learning. On the Generation of Sounds builds on the theories and statements of On the Liberal Arts in connection to the production of sound, elaborating the earlier position, relating the generation of sounds to human vocal and speech production. (shrink)

Proponents of moral enhancement present this biotechnology as a viable solution to social and political problems. The projected imperative to enhance ourselves morally is a direct response to our p...

Contemporary emphasis on creating culturally relevant and context specific knowledge increasingly drives researchers to conduct their work in settings outside their home country. This often requires researchers to build relationships with various stakeholders who may have a vested interest in the research. This case study examines the tension between relationship development with stakeholders and maintaining study integrity, in the context of potential harms, data credibility and cultural sensitivity. We describe an ethical breach in the conduct of global health research by (...) a arising from the ad-hoc participation of a community stakeholder external to the visiting research group. A framework for reflection is developed from a careful examination of underlying factors and presented with a discussion of consequences and mitigation measures. This framework aims to present lessons learned for researchers working abroad who might face similar situations in their work. (shrink)

Prefrontal cortex is dysregulated in women with restricting anorexia nervosa . It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls completed a dorsolateral PFC working memory task and an anterior cingulate cortex conflict task, while masked subliminal food, aversive and neutral images were presented. During the DLPFC task, accuracy was higher in the RAN compared to the HC group, but superior performance was compromised when subliminal food (...) stimuli were presented: errors positively correlated with self-reported trait anxiety in the RAN group. These effects were not observed in the ACC task. Appetitive activation is intact and anxiogenic in women with RAN, and non-consciously interacts with working memory processes associated with the DLPFC. This interaction mechanism may underlie cognitive inhibition of appetitive processes that are anxiety inducing, in people with AN. (shrink)

The subject of this edited volume is the idea of levels of organization: roughly, the idea that the natural world is segregated into part-whole relationships of increasing spatiotemporal scale and complexity. The book comprises a collection of essays that raise the idea of levels into its own topic of analysis. Owing to the wide prominence of the idea of levels, the scope of the volume is aimed at theoreticians, philosophers, and practicing researchers of all stripes in the life sciences. The (...) volume’s contributions reflect this diversity, and draw from fields such as developmental biology, evolutionary biology, molecular biology, ecology, cell biology, and neuroscience. The book presents wide-ranging novel insights on causation and levels, the hierarchical structure of evolution, the role of levels in biological theory, and more. (shrink)

This paper examines an issue that is becoming increasingly relevant as the pressures of a warming planet, changing climate and changing ecosystems ramp up. The broad context for the paper is the intragenerational, intergenerational, and interspecies equity implications of changing the climate and the value orientations of adapting to such change. In addition, the need to stabilize the planetary climate by urgent mitigation of change factors is a foundational ethical assumption. In order to avoid further animal and plant extinctions, or (...) at the very least, their increased vulnerability to becoming rare and endangered; the systematic assisted colonization of “at risk” species is being seriously considered by scientists and managers of biodiversity. The more practical aspects of assisted colonization have been covered in the conservation biology literature; however, the ethical implications of such actions have not been extensively examined. Our discussion of the value issues, using a novel case study approach, will rectify the limited ethical analysis of the issue of assisted colonization of species in the face of climate change pressures. Beyond sustainability ethics, both animal and environmental ethical approaches will be used and intrinsic versus instrumental value orientations in the literature shall form the basis of our discussion. After the application of all the ethical approaches to the case studies, we conclude that without mitigation and the prospect of a future stable climate, assisted colonization will be involved in an inherently unethical process and a “move and lose it” outcome. With mitigation, there is wide-ranging ethical support for assisted colonization. (shrink)

Preface to Brooks and Nussbaum's edited Rawls's Political Liberalism.

This paper examines the investigations carried out between 1798 and 1834 to determine whether, and how, magnetism affected the rate at which marine chronometers gained or lost time. There were persistent claims that chronometers systematically altered rate between those determined on land and those at sea, and magnetism was thought by some to be the most likely cause. Others disputed any rate difference at all. The experiments carried out to determine the influence of magnetism and those carried out to determine (...) if there was a difference between land and sea rates of chronometers will be considered. The data will be re-analysed in an attempt to extract additional information to clarify the answers to these questions. The influence these experiments had on certain navigational practices will be discussed briefly. (shrink)

Incorporating theoretic insights from ageing biology could advance the “staying alive” hypothesis. Higher male extrinsic mortality can weaken selection against ageing-related diseases and self-preservation, leading to high male intrinsic mortality. This may incidentally result in female-biased longevity-promoting traits, a possibility that will require rigorous testing in order to disentangle from the adaptive self-preservation hypothesis presented in the target article.

Uses modernist and postmodernist theoretical perspectives to examine the formation and reformation of states throughout history and around the globe.

Background While it is generally acknowledged that self-prescribing among physicians poses some risk, research finds such behaviour to be common and in certain cases accepted by the medical community. Largely absent from the literature is knowledge about other activities doctors perform for their own medical care or for the informal treatment of family and friends. This study examined the variety, frequency and association of behaviours doctors report providing informally. Informal care included prescriptions, as well as any other type of personal (...) medical treatment (eg, monitoring chronic or serious conditions). Method A survey was sent to 2500 randomly-selected physicians in Colorado, 600 individuals returned questionnaires with usable data. The authors hypothesised: (1) physicians would prescribe the same types of treatment at home as they prescribed professionally; and (2) physicians who informally prescribed addictive medications would be more likely to engage in other types of informal medical care. Results Physicians who wrote prescriptions for antibiotics, psychotropics and opioids at work were more likely to prescribe these medications at home. Those prescribing addictive drugs outside of the office treated more serious illnesses in emergency situations, more chronic conditions and more major medical/surgical conditions informally than did those not routinely prescribing addictive medications. Physicians reported a variety of informal care behaviour and high frequency of informal care to family and friends. Discussion The frequency and variety of informal care reported in this study strongly argues for profession-wide discussion about ethical and guideline considerations for such behaviour. These areas are discussed in the paper. (shrink)

In this volume Nick C. Ellis, Ute Römer, and Matthew Brook O’Donnell present a view of language as a complex adaptive system that is learned, both in first and second language contexts, through usage. In a series of research studies, they analyze Verb-Argument Constructions (VACs) in language learning, processing, and use. Drawing on diverse epistemological and methodological perspectives, they convincingly demonstrate that language emerges in the development of both mother tongue and additional languages out of multiple experiences of meaning-making following (...) general principles of learning relating to frequency, contingency, and semantic prototypicality. They draw implications from this work that will be of value to students and scholars from a wide range of disciplinary interests in language and learning. (shrink)