We analyze the logical form of the domain knowledge that grounds analogical inferences and generalizations from a single instance. The form of the assumptions which justify analogies is given schematically as the "determination rule", so called because it expresses the relation of one set of variables determining the values of another set. The determination relation is a logical generalization of the different types of dependency relations defined in database theory. Specifically, we define determination as a relation between schemata of first (...) order logic that have two kinds of free variables: (1) object variables and (2) what we call "polar" variables, which hold the place of truth values. Determination rules facilitate sound rule inference and valid conclusions projected by analogy from single instances, without implying what the conclusion should be prior to an inspection of the instance. They also provide a way to specify what information is sufficiently relevant to decide a question, prior to knowledge of the answer to the question. (shrink)

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)

Research Ethics Committees (RECs) are frequently a focus of complaints from researchers, but evidence about the operation and decisions of RECs tends to be anecdotal. We conducted a systematic study to identify and compare the ethical issues raised in 54 letters to researchers about the same 18 applications submitted to three RECs over one year. The most common type of ethical trouble identified in REC letters related to informed consent, followed by scientific design and conduct, care and protection of research (...) participants, confidentiality, recruitment and documentation. Community considerations were least frequently raised. There was evidence of variability in the ethical troubles identified and the remedies recommended. This analysis suggests that some principles may be more institutionalized than others, and offers some evidence of inconsistency between RECs. Inconsistency is often treated as evidence of incompetence and caprice, but a more sophisticated understanding of the role of RECs and their functioning is required. (shrink)

Economic models are founded in the idea of taking individuals' preferences as both known and given. This article explores the evolution of personal preferences, within a context of both entrepreneurial discovery and Objectivist philosophy. It begins by formalizing Ayn Rand's theory of Objectivism applied to human values, and continues by modeling preference changes similar to Schumpeter's theory of creative destruction—a process of self-discovery. Next the role of societal factors is examined in forming shared preference sets. Finally, the article describes how (...) the strength of human preferences is used to narrow choice sets in the presence of greater consumption options. (shrink)

Objectives To conduct an independent evaluation of the first phase of the Health Foundation’s Safer Patients Initiative (SPI), and to identify the net additional effect of SPI and any differences in changes in participating and non-participating NHS hospitals. Design Mixed method evaluation involving five substudies, before and after design. Setting NHS hospitals in the United Kingdom. Participants Four hospitals (one in each country in the UK) participating in the first phase of the SPI (SPI1); 18 control hospitals. Intervention The SPI1 (...) was a compound (multi-component) organisational intervention delivered over 18 months that focused on improving the reliability of specific frontline care processes in designated clinical specialties and promoting organisational and cultural change. Results Senior staff members were knowledgeable and enthusiastic about SPI1. There was a small (0.08 points on a 5 point scale) but significant (P<0.01) effect in favour of the SPI1 hospitals in one of 11 dimensions of the staff questionnaire (organisational climate). Qualitative evidence showed only modest penetration of SPI1 at medical ward level. Although SPI1 was designed to engage staff from the bottom up, it did not usually feel like this to those working on the wards, and questions about legitimacy of some aspects of SPI1 were raised. Of the five components to identify patients at risk of deterioration—monitoring of vital signs (14 items); routine tests (three items); evidence based standards specific to certain diseases (three items); prescribing errors (multiple items from the British National Formulary); and medical history taking (11 items)—there was little net difference between control and SPI1 hospitals, except in relation to quality of monitoring of acute medical patients, which improved on average over time across all hospitals. Recording of respiratory rate increased to a greater degree in SPI1 than in control hospitals; in the second six hours after admission recording increased from 40% (93) to 69% (165) in control hospitals and from 37% (141) to 78% (296) in SPI1 hospitals (odds ratio for “difference in difference” 2.1, 99% confidence interval 1.0 to 4.3; P=0.008). Use of a formal scoring system for patients with pneumonia also increased over time (from 2% (102) to 23% (111) in control hospitals and from 2% (170) to 9% (189) in SPI1 hospitals), which favoured controls and was not significant (0.3, 0.02 to 3.4; P=0.173). There were no improvements in the proportion of prescription errors and no effects that could be attributed to SPI1 in non-targeted generic areas (such as enhanced safety culture). On some measures, the lack of effect could be because compliance was already high at baseline (such as use of steroids in over 85% of cases where indicated), but even when there was more room for improvement (such as in quality of medical history taking), there was no significant additional net effect of SPI1. There were no changes over time or between control and SPI1 hospitals in errors or rates of adverse events in patients in medical wards. Mortality increased from 11% (27) to 16% (39) among controls and decreased from 17% (63) to 13% (49) among SPI1 hospitals, but the risk adjusted difference was not significant (0.5, 0.2 to 1.4; P=0.085). Poor care was a contributing factor in four of the 178 deaths identified by review of case notes. The survey of patients showed no significant differences apart from an increase in perception of cleanliness in favour of SPI1 hospitals. Conclusions The introduction of SPI1 was associated with improvements in one of the types of clinical process studied (monitoring of vital signs) and one measure of staff perceptions of organisational climate. There was no additional effect of SPI1 on other targeted issues nor on other measures of generic organisational strengthening. (shrink)

The progression of research and scholarly inquiry does not occur in isolation and is wholly dependent on accurate reporting of methods and results, and successful replication of prior work. Without mechanisms to correct the literature, much time and money is wasted on research based on a crumbling foundation. These guidelines serve to outline the respective responsibilities of researchers, institutions, agencies, and publishers or editors in maintaining the integrity of the research record. Delineating these complementary roles and proposing solutions for common (...) barriers provide a foundation for best practices. (shrink)

Day argues that the meaning of "probable" is partly evaluative and partly descriptive--to say that a proposition is probable is both to recommend its assertion and to say that a certain procedure shows it to be so. The paradigm of an inductive probability judgment, which is the major concern of the book, is "The fact that all observed A's are B's makes it probable that all A's are B's." Several more complex kinds of probability judgments are distinguished and discussed in (...) detail, the author's own theory being illuminated by extensive criticism of the views of other philosophers, including Aristotle, Hume, Whewell, Mill, Peirce, Russell, Braithwaite, Carnap, and Von Wright. Philosophic problems related to induction, such as the existence of other minds and the reliability of memory, are briefly discussed. Ambitious in scope and carefully executed, the book demands, and rewards, close study.--J. R. W. (shrink)

BackgroundKinarm Standard Tests is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior. We have previously used principal component analysis to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab. Here, we performed PCA using data from the Kinarm Exoskeleton Lab, and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction (...) was possible by using PCA across behavioral tasks.MethodsHealthy participants were assessed using the Kinarm EXO and EP. Four behavioral tasks were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching ] and three motor tasks [Visually Guided Reaching, Object Hit, and Object Hit and Avoid ]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type was decided on a per-task basis. To assess agreement, we compared principal components across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments.ResultsBy applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58–75% while accounting for 76–87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance.ConclusionPCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations. (shrink)

Since the publication of Edmund Gettier's challenge to the traditional epistemological doctrine of knowledge as justified true belief, Roberts and Wood claim that epistemologists lapsed into despondency and are currently open to novel approaches. One such approach is virtue epistemology, which can be divided into virtues as proper functions or epistemic character traits. The authors propose a notion of regulative epistemology, as opposed to a strict analytic epistemology, based on intellectual virtues that function not as rules or even as (...) skills but as habits of the heart. To that end, they divide the task of clarifying and expounding their notion in the book's two parts.In the first part, Roberts and Wood examine various components that constitute their notion of regulative epistemology. The first are the epistemic goods or goals that drive the epistemic process. What is needed, claim Roberts and Wood, is an enriched notion of these goods rather than the restricted notion of justified true belief. Epistemic agents are more than calculating devices in that …. (shrink)

Day argues that the meaning of "probable" is partly evaluative and partly descriptive--to say that a proposition is probable is both to recommend its assertion and to say that a certain procedure shows it to be so. The paradigm of an inductive probability judgment, which is the major concern of the book, is "The fact that all observed A's are B's makes it probable that all A's are B's." Several more complex kinds of probability judgments are distinguished and discussed in (...) detail, the author's own theory being illuminated by extensive criticism of the views of other philosophers, including Aristotle, Hume, Whewell, Mill, Peirce, Russell, Braithwaite, Carnap, and Von Wright. Philosophic problems related to induction, such as the existence of other minds and the reliability of memory, are briefly discussed. Ambitious in scope and carefully executed, the book demands, and rewards, close study.--J. R. W. (shrink)

This book's importance is derived from three sources: careful conceptualization of teacher induction from historical, methodological, and international perspectives; systematic reviews of research literature relevant to various aspects of teacher induction including its social, cultural, and political contexts, program components and forms, and the range of its effects; substantial empirical studies on the important issues of teacher induction with different kinds of methodologies that exemplify future directions and approaches to the research in teacher induction.

To contribute to the continuing challenge of explaining how managers identify stakeholders and assess their salience, in this article, we chronicle the history, assess the impact, and evaluate the possibilities opened by Mitchell, Agle, and Wood (MAW-1997). We do so through two types of qualitative analysis, and also through utilizing a quantitative network analysis tool. The first qualitative analysis categorizes the major contributions of the most influential papers succeeding MAW-1997; the second identifies and compares the relevant issues with MAW-1997 (...) at the time of initial publication and today. We apply main path analysis, a quantitative tool, to map how this scholarly domain has evolved. These three analyses robustly depict the impact of MAW-1997 and the ensuing scholarly conversation, and they enable us to illustrate the current state and trajectory of stakeholder identification and salience scholarship. We close by discussing pressing topics related to the broader body of stakeholder theory literature. (shrink)

Samuel Alexander was an important figure in the rise of realism in the early twentieth century. Alongside Moore and Russell he forwarded the cause of realism in England with a systematic exposition of a realist metaphysics in his magnum opus Space, Time and Deity (1920). This volume is a collection of essays on Alexander’s philosophy, ranging from his metaphysics of spacetime, theory of categories, epistemology and account of perception, naturalism, and interpretations of reactions by R.G. Collingwood and John Anderson.

Frank Plumpton Ramsey (1903–30) made seminal contributions to philosophy, mathematics and economics. Whilst he was acknowledged as a genius by his contemporaries, some of his most important ideas were not appreciated until decades later; now better appreciated, they continue to bear an influence upon contemporary philosophy. His historic significance was to usher in a new phase of analytic philosophy, which initially built upon the logical atomist doctrines of Bertrand Russell and Ludwig Wittgenstein, raising their ideas to a new level (...) of sophistication, but ultimately he became their successor rather than remain a mere acolyte. (shrink)