Self-knowledge is the focus of considerable attention from philosophers: Knowing Our Own Minds gives a much-needed overview of current work on the subject, bringing together new essays by leading figures. Knowledge of one's own sensations, desires, intentions, thoughts, beliefs, and other attitudes is characteristically different from other kinds of knowledge: it has greater immediacy, authority, and salience. The contributors examine philosophical questions raised by the distinctive character of self-knowledge, relating it to knowledge of other minds, to rationality and agency, externalist (...) theories of psychological content, and knowledge of language. Together these original, stimulating, and closely interlinked essays demonstrate the special relevance of self-knowledge to a broad range of issues in epistemology, philosophy of mind, and philosophy of language. (shrink)

George Boole collected ideas for the improvement of his Mathematical analysis of logic(1847) on interleaved copies of that work. Some of the notes on the interleaves are merely minor changes in explanation. Others amount to considerable extension of method in his mathematical approach to logic. In particular, he developed his technique in solving simultaneous elective equations and handling hypotheticals and elective functions. These notes and extensions provided a source for his later book Laws of thought(1854).

In vertebrates it is often found that if one considers a group of genes clustered on a certain chromosome, then the homologues of those genes often form another cluster on a different chromosome. There are four explanations, not necessarily mutually exclusive, to explain how such homologous clusters appeared. Homologous clusters are expected at a low probability even if genes are distributed at random. The duplication of a subset of the genome might create homologous clusters, as would a duplication of the (...) entire genome. Alternatively, it may be adaptive for certain combinations of genes to cluster, although clearly the genes must have duplicated prior to rearrangement into clusters. Molecular phylogenetics provides a means to examine the origins of homologous clusters, although it is difficult to discriminate between the different explanations using current data. However, with more extensive sequencing and mapping of vertebrate genomes, especially those of the early diverging chordates, it should soon become possible to resolve the origins of homologous clusters. BioEssays 21:697–703, 1999. © 1999 John Wiley & Sons, Inc. (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)

Some philosophers argue that any attempt to model changing the past will either be contradictory or really model avoiding the past. Using Nicholas Smith's (1997) argument as a basis, I formulate a generic version of this Avoidance Argument. I argue that the Avoidance Argument fails because (i) it involves an equivocation of what is meant by ‘bifurcation of the time of an event’ and (ii) resolving the equivocation results in the falsity of at least one of the premises. Hence, (...) the Avoidance Argument will not support the claim that changing the past is logically impossible. (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)

The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose offspring took part in the Midspan Family study in 1996. There (...) were 286 offspring from 179 families. Parental IQ was related to some, but not all characteristics of offspring. Greater parental IQ was associated with taller offspring. Parental IQ was inversely related to number of cigarettes smoked by offspring. Higher parental IQ was associated with better education, offspring social class and offspring deprivation category. There were no significant relationships between parental IQ and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. Structural equation modelling showed parental IQ associated with offspring education directly and mediated via parental social class. Offspring education was associated with offspring smoking and social class. The smoking finding may have implications for targeting of health education. (shrink)

In recent discussions concerning the definition of argument, it has been maintained that the word ‘argument’ exhibits the process-product ambiguity, or an act/object ambi-guity. Drawing on literature on lexical ambiguity we argue that ‘argument’ is not ambiguous. The term ‘argument’ refers to an object, not to a speech act. We also examine some of the important implications of our argument by considering the question: what sort of abstract objects are arguments?

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Health promotion involves social and environmental interventions designed to benefit and protect health. It often harmfully impacts the environment through air and water pollution, medical waste, g...

A world in which time travel into the past occurred would seem like a most strange world. Nicholas Smith, however, in his ‘Bananas Enough for Time Travel’, argues that time travel is not so strange as we think. In particular, he argues against what he views as the main reason time travel worlds seem so strange – the claim that time travel entails unusual numbers of coincidences. I shall argue that Smith's argument for rejecting the claim is inadequate. (...) Hence, the debate over the consequences of the coincidences of time travel cannot be avoided by denying the coincidences themselves. (shrink)

A world in which time travel into the past occurred would seem like a most strange world. Nicholas Smith, however, in his ‘Bananas Enough for Time Travel’, argues that time travel is not so strange as we think. In particular, he argues against what he views as the main reason time travel worlds seem so strange – the claim that time travel entails unusual numbers of coincidences. I shall argue that Smith's argument for rejecting the claim is inadequate. (...) Hence, the debate over the consequences of the coincidences of time travel cannot be avoided by denying the coincidences themselves. (shrink)

: In her recent paper, “How to Escape Indictment for Impiety: Teaching as Punishment in the Euthyphro,” G. Fay Edwards argues that if Socrates were to become Euthyphro’s student, this should count as the appropriate punishment for Socrates’ alleged crime. In this paper, we show that the interpretation Edwards has proposed conflicts with what Socrates has to say about the functional role of punishment in the Apology, and that the account Socrates gives in the Apology, properly understood, also provides the (...) correct interpretation of what Socrates says in the Euthyphro about the role of instruction for wrongdoers. (shrink)

The fusion of law and equity in common law systems was a crucial moment in the development of the modern law. In this volume leading scholars assess the significance of the fusion of law and equity from comparative, doctrinal, historical and theoretical perspectives.

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)