Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

This policy-capturing study, conducted in China, investigated the cognitive basis of managerial decisions to make a corporate charitable donation, a global issue in the context of corporate social responsibility research and practice. Participants responded to a series of scenarios manipulating pressure from the five stakeholders most commonly addressed by CSR research. The independent variables examined included organizational factors and the participants’ personal values. Results indicate a large positive effect of shareholder and governmental pressure on the decision with lesser positive effects (...) from customers and competitors. Surprisingly, employee pressure had a negative effect on the decision to make a charitable donation. Further, personal values and perceived CEO attitudes toward charity were significantly related to the decisions participants made. In line with our theorizing, the findings indicate that a combination of personal, organizational, and institutional factors was salient in the minds of decision makers. (shrink)

In recent years, the construct of character has received substantial attention among developmental scientists, but no consensus exists about the content and structure of character, especially among children and early adolescents. In a study of positive development among racially diverse Cub Scouts in the greater Philadelphia area, we assessed the construct and concurrent validity of a new measure of character, the Assessment of Character in Children and Early Adolescents, among 906 Scouts and 775 non-Scout boys and girls. We identified an (...) eight-correlated-factor model as providing the best fit with our data. We further established measurement invariance and explored latent mean differences for ACCEA scores across two Scout groups, non-Scout boys and non-Scout girls. Girls were generally superior than boys on all character attributes. We further examined concurrent validity of ACCEA by correlating the character attributes with youth sense of school competence, intentional self-regulation and parental perception of youth school performance. We discuss implications for future character research and point to the value of the ACCEA measure being used by practitioners in character development programs. (shrink)

(No abstract is available for this citation).

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)

Aims: To examine the extent of social stigma toward diabetes among Singapore's multi-ethnic general population and determine whether this differs across socio-demographic sub-groups.Methods: Data for this study came from a nationwide cross-sectional study. A diabetes stigma questionnaire comprising Social Distance Scale and Negative Attitudes and Stereotyping Scale was administered to those respondents who had not been diagnosed with diabetes. Exploratory factor analysis was conducted to determine the dimensionality of the instruments and validated using confirmatory factor analysis. Multiple linear regression analysis (...) was conducted to examine associations between socio-demographic factors and measures of diabetes stigma.Results: In all, 2,895 participants were recruited from the general population giving a response rate of 66.2%. Factor analyses found that a one-factor model resulted in an acceptable fit for both stigma scales, which measured social distance and negative attitudes and stereotyping, respectively. Multiple linear regression analyses identified Indian ethnicity, higher personal income and having close friends or family members who had been diagnosed with diabetes to be significantly associated with lower social distance scores while those aged 50–64 years and those with secondary and vocational education were significantly associated with higher social distance scores. Those with a personal income of SG$2,000–3,999 and SGD $6,000 and above, and those with close friends or family members diagnosed with diabetes were significantly associated with lower negative attitudes and stereotyping scores. In contrast those aged 35 years and above, those with primary education and below, and those of Malay ethnicity were significantly associated with higher negative attitudes and stereotyping scores.Conclusions: The study found a relatively low level of stigma toward diabetes in the general population of Singapore, although some stigmatizing beliefs emerged. While greater knowledge of diabetes could reduce stigma, anti-stigma messaging should be incorporated into the “War on Diabetes” programme in Singapore. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

Children with autism spectrum disorder show marked difficulties in reading comprehension, a complex cognitive skill fundamental to successful daily functioning that is associated with core executive functions. However, the neurophysiological mechanisms underlying reading comprehension deficits in these children remain elusive. Twenty-one right-handed males with high-functioning ASD and 23 age-, IQ-, educational level-, sex- and handedness-matched typically developing individuals underwent a reading comprehension test and the semantic verbal fluency test that tapped core executive functions underlying reading comprehension during concurrent prefrontal functional (...) near-infrared spectroscopy measurement. Participants’ information processing efficiency was also assessed. High-functioning ASD children exhibited general reading comprehension [main effect of group: F = 7.58, p = 0.009], selective verbal fluency deficits [Group × category interaction: F = 4.90, p = 0.032] and slower processing speed. Regarding the hemodynamics of the prefrontal cortex, although ASD individuals showed comparable patterns of PFC brain activation to their healthy counterparts, lower PFC intrahemispheric [main effect of group: F = 11.36, p = 0.002] and interhemispheric [main effect of group: F = 7.79, p = 0.008] functional connectivity were evident during the semantic verbal fluency test. At the whole-group level, poorer reading comprehension performance was associated with poorer performance in the semantic verbal fluency test. Moreover, poorer semantic verbal fluency test performance was associated with slower information processing speed, which is associated with reduced left medial PFC functional connectivity. Abnormal intrahemispheric and interhemispheric prefrontal hypoconnectivity is associated with deficits in executive processes essential for reading comprehension in ASD. Our study has provided important implications for the neuropsychological and neurophysiological mechanisms underlying reading comprehension deficits in ASD. (shrink)

This is a collection of papers read at an international logic colloquium held at Oxford in 1963. The first half contains articles on intuitionistic and modal logics, the propositional calculus, and languages with infinitely long expressions by such logicians as Kripke, Bull, Harrop, and Tait. The second part is primarily concerned with recursive functions and features a monograph by Crossley on constructive order types, as well as contributions by Goodstein, Schütte, and Wang, among others. Especially noteworthy is Kripke's paper (...) which applies Cohen's methods to the semantics of intuitionistic logic.—P. J. M. (shrink)

Residency selection is a challenging process for medical students, one further complicated in the USA by the recentDobbs v Jackson Women’s Health Organization(Dobbs) decision over-ruling the federal right to abortion. We surveyed medical students to examine howDobbsis influencing the ideological, personal and professional factors they must reconcile when choosing where and how to complete residency.Between 6 August and 22 October 2022, third-year and fourth-year US medical students applying to US residency programmes were surveyed through social media and direct outreach to (...) medical schools. Analysis of quantitative and qualitative data from 494 responses was performed to assess downstream effects ofDobbson residency applicants’ family, health and career choices.Most respondents said changes in abortion access would likely or very likely influence their decision regarding location of considered residency programme (76.9%), where to start a family (72.2%) and contraceptive planning for them or their partner (57.9%). Cis-gender females were more influenced byDobbsregarding where (5 (4, 5) p<0.001) and when (3 (3, 5) p<0.001) to start a family. In qualitative responses, medical trainees highlighted the importance of abortion access for their patients, themselves and their loved ones.Medical trainees are incorporating state abortion access into their residency programme choices. Future physicians care about both the quality of care they will be able to provide and their own health. For personal and professional reasons, reproductive healthcare access is now a key factor in residency match decisions. (shrink)

BackgroundPhysical activity is known to improve mental health, and is regarded as safe and desirable for uncomplicated pregnancy. In this novel study, we aim to evaluate whether there are associations between maternal physical activity during pregnancy and neonatal brain cortical development.MethodsForty-four mother/newborn dyads were included in this longitudinal study. Healthy pregnant women were recruited and their physical activity throughout pregnancy were documented using accelerometers worn for 3–7 days for each of the 6 time points at 4–10, ∼12, ∼18, ∼24, ∼30, (...) and ∼36 weeks of pregnancy. Average daily total steps and daily total activity count as well as daily minutes spent in sedentary/light/moderate/vigorous activity modes were extracted from the accelerometers for each time point. At ∼2 weeks of postnatal age, their newborns underwent an MRI examination of the brain without sedation, and 3D T1-weighted brain structural images were post-processed by the iBEAT2.0 software utilizing advanced deep learning approaches. Cortical surface maps were reconstructed from the segmented brain images and parcellated to 34 regions in each brain hemisphere, and mean cortical thickness for each region was computed for partial correlation analyses with physical activity measures, with appropriate multiple comparison corrections and potential confounders controlled.ResultsAt 4–10 weeks of pregnancy, mother’s daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn’s cortical thickness in the left caudal middle frontal gyrus (rho = 0.48, P = 0.04), right medial orbital frontal gyrus (rho = 0.48, P = 0.04), and right transverse temporal gyrus (rho = 0.48, P = 0.04); mother’s daily time in moderate activity mode positively correlated with newborn’s cortical thickness in the right transverse temporal gyrus (rho = 0.53, P = 0.03). At ∼24 weeks of pregnancy, mother’s daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn’s cortical thickness in the left (rho = 0.56, P = 0.02) and right isthmus cingulate gyrus (rho = 0.50, P = 0.05).ConclusionWe identified significant relationships between physical activity in healthy pregnant women during the 1st and 2nd trimester and brain cortical development in newborns. Higher maternal physical activity level is associated with greater neonatal brain cortical thickness, presumably indicating better cortical development. (shrink)

An edition of the letters of Erasmus, regarded as one of the greatest humanist writers. All 12 volumes of this work have been reissued, complete with their scholarly apparatus of commentary and notes, as well as plates.

An edition of the letters of Erasmus, regarded as one of the greatest humanist writers. All 12 volumes of this work have been reissued, complete with their scholarly apparatus of commentary and notes, as well as plates.

This volume collects P. M. S. Hacker's papers on Wittgenstein and related themes written over the last decade. Hacker provides comparative studies of a range of topics--including Wittgenstein's philosophy of psychology, conception of grammar, and treatment of intentionality--and defends his own Wittgensteinian conception of philosophy.

The purpose of this essay is to investigate and critically analyse some of the formative factors which led to the spiritual maturation of a leading Vīraśaiva saint, Basava. This inquiry focuses on a single event in the life of this great reformer of medieval times, i.e. his spiritual conflict leading to his rejection of the upanayana ceremony. The study will proceed through an investigation of the earliest and subsequent sources which veil the personality of Basava. The traditional view will be (...) challenged as one-sided. By critically comparing the sources, a more comprehensive and plausible account will be suggested. (shrink)

The desire to see a sign phenomenon in different ways always has a reason to interpret it in an unbiased, panoramic way, and in some places - even allowing for contradictions in its understanding by different participants in the interpretative process. For modern humanities, this disposition is quite understandable, since it follows from its very postmodern nature, thereby defining the semantic semantic fields of the leading humanities. True, it is not so wide-spread, but instead, it is evident that Ukrainian religious (...) thinkers of the Middle Ages and Baroque have interpreted the iconic phenomena more deeply. In the story of Petro Mohyla "On the Wonderful Elder Grigory Mezhyhirsky" the metropolitan Mohyla clearly expresses the need to build before the thinking gaze of the reader his own, immanently religious-philosophical conception of the Divine, which every time would present him not just as an act of manifestation, otherwise he appears before the person, while remaining alone. The contemporary study of this issue in order to integrate its leading concepts in the religious-philosophical and general cultural discourse of the postmodern era has largely determined the relevance of the proposed article. The study of the phenomenon of "leaving" by itself in changing forms of the phenomenon of the Divine is also one of the key ones in the proposed studio, because it expresses the very meaning of the Divine as a religious, and therefore a cultural phenomenon. (shrink)

Bhattacharyya, K. The Advaita concept of subjectivity.--Deutsch, E. Reflections on some aspects of the theory of rasa.--Nakamura, H. The dawn of modern thought in the East.--Organ, T. Causality, Indian and Greek.--Chatterjee, M. On types of classification.--Lacombe, O. Transcendental imagination.--Bahm, A. J. Standards for comparative philosophy.--Herring, H. Appearance, its significance and meaning in the history of philosophy.--Chang Chung-yuan. Pre-rational harmony in Heidegger's essential thinking and Chʼan thought.--Staal, J. F. Making sense of the Buddhist tetralemma.--Enomiya-Lassalle, H. M. The mysticism of Carl Albrecht (...) and Zen.--Parrinder, G. The nature of mysticism.--Cairns, G. E. Axiological contributions of East and West to the spiritual development of mankind.--Mayeda, S. Śaṇkara's view of ethics.--Mercier, A. On peace.--Barlingay, S. S. A discussion of some aspects of Gaudapāda's philosophy. (shrink)

James Conant, a proponent of the ‘New American Wittgenstein’, has argued that the standard inter- pretation of Wittgenstein is wholly mistaken in respect of Wittgenstein’s critique of metaphysics and the attendant conception of nonsense. The standard interpretation, Conant holds, misascribes to Wittgenstein Carnapian views on the illegitimacy of metaphysical utterances, on logical syntax and grammar, and on the nature of nonsense. Against this account, I argue that (i) Carnap is misrepresented; (ii) the so-called standard interpretation (in so far as I (...) have contributed to it) is misrepresented; (iii) Wittgenstein’s views, early and late, are misrepresented. I clarify Wittgen- stein’s conception of logical syntax and of the nonsense that results from transgressing it. (shrink)

In recent years philosophers have given much attention to the ‘ontological problem’ of events. Donald Davidson puts the matter thus: ‘the assumption, ontological and metaphysical, that there are events is one without which we cannot make sense of much of our common talk; or so, at any rate, I have been arguing. I do not know of any better, or further, way of showing what there is’. It might be thought bizarre to assign to philosophers the task of ‘showing what (...) there is’. They have not distinguished themselves by the discovery of new elements, new species or new continents, nor even of new categories, although there has often been more dreamt of in their philosophies than can be found in heaven or earth. It might appear even stranger to think that one can show what there actually is by arguing that the existence of something needs to be assumed in order for certain sentences to make sense. More than anything, the sober reader will doubtlessly be amazed that we need to assume, after lengthy argument, ‘that there are events’. (shrink)

The purpose of this note is to examine the notion of obligations to future generations, a notion that finds increasing use in discussions of social policies and programs, particularly as concerns population distribution and control and environment control. Thus, it may be claimed, the solution of problems in these areas is not merely a matter of enhancing our own good, improving our own conditions of life, but is also a matter of discharging an obligation to future generations.

Background: Hospital nurses are frequently the first care givers to receive a patient’s request for euthanasia or physician-assisted suicide (PAS). In France, there is no consensus over which medical practices should be considered euthanasia, and this lack of consensus blurred the debate about euthanasia and PAS legalisation. This study aimed to investigate French hospital nurses’ opinions towards both legalisations, including personal conceptions of euthanasia and working conditions and organisation. Methods: A phone survey conducted among a random national sample of 1502 (...) French hospital nurses. We studied factors associated with opinions towards euthanasia and PAS, including contextual factors related to hospital units with random-effects logistic models. Results: Overall, 48% of nurses supported legalisation of euthanasia and 29%, of PAS. Religiosity, training in pallative care/pain management and feeling competent in end-of-life care were negatively correlated with support for legalisation of both euthanasia and PAS, while nurses working at night were more prone to support legalisation of both. The support for legalisation of euthanasia and PAS was also weaker in pain treatment/palliative care and intensive care units, and it was stronger in units not benefiting from interventions of charity/religious workers and in units with more nurses. Conclusions: Many French hospital nurses uphold the legalisation of euthanasia and PAS, but these nurses may be the least likely to perform what proponents of legalisation call “good” euthanasia. Improving professional knowledge of palliative care could improve the management of end-of-life situations and help to clarify the debate over euthanasia. (shrink)