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)

Cognitive science is currently a rapidly expanding area of research. Much is being written on it, but this collection is notable for its contributors who are extremely eminent and distinguished in the subject . The collection is well-balanced, since it includes the work of both philosophers and scientists . It will therefore appeal to all academics interested in the subject, irrespective of whether they have approached the subject from a philosophical or from a scientific point of view.

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 national ethical guidelines relevant to assisted reproductive technology have recently been reviewed by the National Health and Medical Research Council. The review process paid particular attention to the issue of non-medical sex selection, although ultimately, the updated ethical guidelines maintain the pre-consultation position of a prohibition on non-medical sex selection. Whilst this recent review process provided a public forum for debate and discussion of this ethically contentious issue, the Victorian case of JS and LS v Patient Review Panel [2011] (...) VCAT 856 provides a rare instance where the prohibition on non-medical sex selection has been explored by a court or tribunal in Australia. This paper analyses the reasoning in that decision, focusing specifically on how the Victorian Civil and Administrative Tribunal applied the statutory framework relevant to ART and its comparison to other uses of embryo selection technologies. The Tribunal relied heavily upon the welfare-of-the-child principle under the Assisted Reproductive Treatment Act 2008. The Tribunal also compared non-medical sex selection with saviour sibling selection. Our analysis leads us to conclude that the Tribunal’s reasoning fails to adequately justify the denial of the applicants’ request to utilize ART services to select the sex of their prospective child. (shrink)

The UK Supreme Court in Montgomery v Lanarkshire Health Board adopts an approach to information disclosure in connection with clinical treatment that moves away from medical paternalism towards a more patient-centred approach. In doing so, it reinforces the protection afforded to informed consent and autonomous patient decision making under the law of negligence. However, some commentators have expressed a concern that the widening of the healthcare providers’ duty of disclosure may provide impetus, in future cases, for courts to adopt a (...) more rigorous approach to the application of causation principles. The aim would be to limit liability but, in turn, it would also limit autonomy protection. Such a restrictive approach has recently been adopted in Australia as a result of the High Court decision in Wallace v Kam. This paper considers whether such an approach is likely under English negligence law and discusses case law from both jurisdictions in order to provide a point of comparison from which to scope the post- Montgomery future. (shrink)

How many words is a bilingual 2-year-old supposed to know or say in each of her languages? Speech and language therapists or researchers lack the tools to answer this question, because several factors have an impact on bilingual language skills: gender, amount of exposure, mode of acquisition, socio-economic status and the distance between L1 and L2. Unfortunately, these factors are usually studied separately, making it difficult to evaluate their weight on a unique measure of vocabulary. The present study measures the (...) contribution of the following factors to the vocabulary scores of bilingual toddlers: i) gender; ii) sibling ranking; iii) relative amount of exposure to each language; iv) mode of exposure; v) SES; vi) linguistic distance; vii) language spoken between parents. Close to the child’s second birthday, parents of 278 UK-based bilinguals completed successively: a 100-word version of the Oxford-CDI, the CDI in the child’s Additional Language, a family questionnaire, and the Language Exposure Questionnaire. Thirty-six British-English-AL pairs were considered, with languages contrasted on a second-language-learning scale : for example, Dutch and French are close to British-English, while Polish or Cantonese are more distant. Data from the corpus were included in two mixed-effect models, one with the English scores in comprehension as the dependent variable, and the other with production scores. The seven factors listed above were included as predictors. The amount of English exposure was the strongest predictor of comprehension scores = 9.35, p <.005, β = 0.02, t = 3.08, p <.005), followed by the language that parents speak between themselves = 14.94, p <.001, β = 1.37, t = 3.76, p <.0005), linguistic distance = 6.92, p <.01, β = -0.74, t = -2.66, p <.01) and age = 4.86, p <.05, β = 0.55, t = 2.17, p <.05). In production, gender = 13.57, p <.0005, β = -0.91, t = -03.72, p <.0005), amount of exposure to English = 13.57, p <.0005, β = -0.91, t = -03.72, p <.0005), the language that parents speak between themselves = 11.85, p <.005, β = 1.09, t = 3.41, p <.001), and the mother’s occupation = 4.51, p <.05, β = 0.63, t = 2.13, p <.05) were the significant predictors. The more English parents use to address one another, the more English words the child says and understands. This surprising result could be simply explained by the fact that parents who speak English together are also more likely to speak English to their child. The main results of this study is that linguistic distance is a powerful predictor of toddlers’ vocabulary in English, with children learning two close languages growing their vocabulary faster than those learning distant languages. (shrink)

The House of Lords majority decision in Matthews v. Kent and Medway Towns Fire Authority overturns the narrow interpretation given to key aspects of the Part-Time Workers (Protection of Less Favourable Treatment) Regulations’ core comparator mechanism in the lower tribunals and the Court of Appeal. It is a contextually astute judgment, which recognises the reductionist implications of an overly narrow approach to establishing comparability for the purposes of a less favourable treatment claim on the grounds of part-time work. The positive (...) aspect of this decision remains overshadowed, however, by the fact that this interpretation provides little consolation to the large majority of part-time women workers whose disadvantage and inequality remains outside the scope of the Regulations’ protection. (shrink)

The notion of form is "the most important notion within the Critique of Aesthetic Judgment". The sensible form involved in aesthetic judgment stands in no clear relation to the formal elements of the Transcendental Aesthetic and Logic—neither to the a priori forms of space and time, nor to the categories. It is held to be the same "kind of form" as the intuitable, "empirical form" mentioned infrequently in the Pure Reason. The author attempts to establish only "what Kant meant" as (...) distinct from its "truth." He lays a bold preparation for "the suggestion... that aesthetic experience is a window, so to speak, into the noumenal world". In Ch. I he accepts a widely-held view that Kant is the discoverer of "philosophical aesthetics" or "the autonomy of the aesthetic realm." His concern is not with this historical question. Nonetheless it may be said that he is not sufficiently aware that the autonomy found in Kant is not in understanding aesthetics as a realm of art, but only in understanding aesthetic judgment in its concern with both art and nature. Accordingly the aesthetic form of objects of art and objects of nature is treated without differentiation. The author is little concerned with form in its relation to natural purposiveness, or with the relation of form in the Aesthetic Judgment to form in the Teleological Judgment. Since nature, at least in certain contexts, supplies a kind of norm for art—a "traditional" element in Kant—the author’s exposition of the manner in which art imitates nature is not entirely satisfactory. In Ch. II, the central issue is whether "individual colors and tones are more than mere sensations". If however each may be understood as "a play of sensations" they can be said to possess a "form" and may enter into aesthetic judgments. The assumption here is that only if the parts of a beautiful thing, e.g., the individual colors of a painting, are beautiful, "can the painting as a whole be a beautiful thing". But this atomistic view of the aesthetic part is subsequently modified. In Ch. III, the imagination is said to "function without the categories" in the synthesis of aesthetic forms. The author must then oppose the view of Kemp Smith and others "that there can be no cognitive awareness or consciousness apart from the categories". He relies especially on the "judgments of perception" of the Prolegomena which "require no pure concept of the understanding". The possibility is not considered that although the imagination may indeed function "autonomously"—without the categories—in the synthesis of aesthetic form, that same synthesis may presuppose a synthesis employing the categories, especially in certain types of aesthetic experience. Some valuable clarifications are achieved of the difficult notions of "play," the harmony of form and cognitive faculties, and the universality of aesthetic judgments. The thesis of Ch. IV is that the object of experience, or the phenomenal object, is not a second object, distinct from the thing-in-itself, but an appearance of the thing-in-itself. Ch. V is devoted to Kant’s theory of art and especially to genius as the productive faculty of aesthetic ideas. The harmony of the faculties of imagination and understanding required of the artistic genius is held to be the same as the harmony which "the work of art itself... arouses in the perceiver of that work of art", but is spontaneous and original in the former case. What would be required of the productive agency in the case of natural objects of aesthetic experience lies outside the range of subject matter chosen. Kant’s view, although not entirely lucid, is that "the standard of fine art must be sought in the supersensible substrate of the artist’s faculties and that the production of the accord of the faculties of understanding and imagination ‘is the ultimate end set by the intelligible basis of our nature'". This prepares the conclusion that "the artist, as creative genius, is he who not only produces but expresses in sensible products, forms which are windows into the supersensible substrate of being". The monograph effectively raises this possibility as a central issue in the discussion of Kant’s aesthetics.—R. K. (shrink)

Trait emotional intelligence (“trait EI”) concerns our perceptions of our emotional abilities, that is, how good we believe we are in terms of understanding, regulating, and expressing emotions in order to adapt to our environment and maintain well-being. In this article, we present succinct summaries of selected findings from research on (a) the location of trait EI in personality factor space, (b) the biological underpinnings of the construct, (c) indicative applications in the areas of clinical, health, social, educational, organizational, and (...) developmental psychology, and (d) trait EI training. Findings to date suggest that individual differences in trait EI are a consistent predictor of human behavior across the life span. (shrink)

This work has been selected by scholars as being culturally important and is part of the knowledge base of civilization as we know it. This work is in the public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be (...) preserved, reproduced, and made generally available to the public. To ensure a quality reading experience, this work has been proofread and republished using a format that seamlessly blends the original graphical elements with text in an easy-to-read typeface. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

Trait emotional intelligence concerns people’s perceptions of their emotional functioning. Two studies investigated this construct in surgeons and comparison occupations. We hypothesized that trait EI profiles would differ both within surgical specialties as well as between them and other professions. Study 1 compared the trait EI profiles of four different surgical specialties. There were no significant differences amongst these specialties or between consultant surgeons and trainees in these specialties. Accordingly, the surgical data were combined into a single target sample that (...) was compared against samples of engineers, executives and senior managers, lawyers, junior military managers, nurses, and salespeople. Surgeons scored significantly higher on global trait EI than junior military managers, but lower than executives and senior managers, salespeople, and nurses. There were no significant differences vis-à-vis engineers or lawyers. A MANOVA confirmed a similar pattern of differences in the four trait EI factors. Global trait EI scores correlated strongly with single-question measures of job satisfaction and job performance in the surgical sample. These findings suggest that interventions to optimize the trait EI profiles of surgeons can be helpful in relation to job satisfaction, job performance, and overall psychological wellbeing. (shrink)

1935. A comprehensive text on the understanding and practice of yoga through the study of the nature of man as taught in the Vedas.

Philippe de Mézières est un de ces auteurs du XIVe siècle que l’on estime et étudie volontiers. C’est qu’il est témoin oculaire et participant de bien des hauts moments de l’histoire. Né vers 1327 dans la famille de Mézières, de petite noblesse picarde , il reçoit une formation spirituelle chez les chanoines de la cathédrale d’Amiens. En 1345 il quitte son pays natal et l’année suivante gagne ses éperons de chevalier après la croisade de Humbert II de Dauphiné en Smyrne. (...) Par la suite, il joue plusieurs rôles saillants: nommé en 1361 chancelier de Chypre sous les Lusignan ; ami de Pétrarque; familier de Grégoire XI à Avignon; apologiste des croisades; ami et conseiller de Charles V de France et précepteur du dauphin, le futur Charles VI; écrivain laïque parmi les Célestins de Paris entre 1380 et 1405. Presque octogénaire, Mézières y meurt le 29 mai 1405, et est accordé la distinction d’être enveloppé du manteau de l’ordre à son enterrement. C’est à cette période de retraite que remontent ses écrits importants, tous de caractère religieux et rédigés en latin ou en français. (shrink)

Nobel Laureate in physics Wolfgang Pauli studied philosophy and the history of ideas intensively, especially in his later years, to form an accurate ontology vis-à-vis quantum theory. Pauli's close contacts with the Swiss psychiatrist C.G. Jung gave him special qualifications for also understanding the basic problems of empirical knowledge. After Pauli's sudden death in 1958, this work was maintained mainly in his posthumously published correspondence, which so far extends only to 1939. Because Pauli's view differs essentially from the direction physics (...) research took after the deaths of the founding fathers of quantum theory, this article attempts to describe the main features in Pauli's revolutionary thought, which is based on nature's “epistemological lesson” as revealed by Pauli's atomic research. Pauli's conclusions have important implications for various issues in Western culture, not least with the limits of science and the relation of science to religion. (shrink)

This paper tries to argue that at least some alluring, trendy or fashionable problems to do with thought and language — several of which are discussed in this volume — are in fact alluring, trendy or fashionable red herrings or cul-de-sacs. I shall primarily be concerned with the ascription of thought and intelligence to non-language-users; but, en route to that, will need to brood over our ascriptions of such terms quite generally.