Little attention has been given in medical ethics literature to issues relating to the truthfulness of patients. Beginning with an actual medical case, this paper first explores truth-telling by doctors and patients as related to two prominent models of the physician-patient relationship. Utilizing this discussion and the literature on the truthfulness and accuracy of the information patients convey to doctors, these models are then critically assessed. It is argued that the patient agency (patient autonomy or contractual) model is inherently and (...) seriously flawed in numerous circumstances, even those involving informed and competent adult patients. (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)

In this chapter we extend earlier work (Vinuesa et al., Nat Commun 11, 2020) on the potential of artificial intelligence (AI) to achieve the 17 Sustainable Development Goals (SDGs) proposed by the United Nations (UN) for the 2030 Agenda. The present contribution focuses on three SDGs related to healthy and sustainable societies, i.e., SDG 3 (on good health), SDG 11 (on sustainable cities), and SDG 13 (on climate action). This chapter extends the previous study within those three goals and goes (...) beyond the 2030 targets. These SDGs are selected because they are closely related to the coronavirus disease 19 (COVID-19) pandemic and also to crises like climate change, which constitute important challenges to our society. (shrink)

Most jurisdictions require that a mental capacity assessment be conducted using a functional model whose definition includes several abilities. In England and Wales and in increasing number of countries, the law requires a person be able to understand, to retain, to use or weigh relevant information and to communicate one’s decision. But interpreting and applying broad and vague criteria, such as the ability ‘to use or weigh’ to a diverse range of presentations is challenging. By examining actual court judgements of (...) capacity, we previously developed a descriptive typology of justifications used in the application of the Mental Capacity Act criteria. We here critically optimise this typology by showing how clear definitions—and thus boundaries—between the criteria can be achieved if the ‘understanding’ criterion is used narrowly and the multiple rationales that fall under the ability to ‘use or weigh’ are specifically enumerated in practice. Such a typology-aided practice, in theory, could make functional capacity assessments more transparent, accountable, reliable and valid. It may also help to create targeted supports for decision making by the vulnerable. We also discuss how the typology could evolve legally and scientifically, and how it lays the groundwork for clinical research on the abilities enumerated by the MCA. No data are available. This paper does not report any original data. (shrink)

Understanding terrestrial carbon metabolism is critical because terrestrial ecosystems play a major role in the global carbon cycle. Furthermore, humans have severely disrupted the carbon cycle in ways that will alter the climate system and directly affect terrestrial metabolism. Changes in terrestrial metabolism may well be as important an indicator of global change as the changing temperature signal. Improving our understanding of the carbon cycle at various spatial and temporal scales will require the integration of multiple, complementary and independent methods (...) that are used by different research communities. Tools such as air sampling networks, inverse numerical methods, and satellite data allow us to study the strength and location of the global- and continental-scale carbon sources and sinks. Bottom-up studies provide estimates of carbon fluxes at finer spatial scales and examine the mechanisms that control fluxes at the ecosystem, landscape, and regional scales. Bottom-up approaches include comparative and process studies that provide the necessary mechanistic information to develop and validate terrestrial biospheric models. An iteration and reiteration of top-down and bottom-up approaches will be necessary to help constrain measurements at various scales. We propose a major international effort to coordinate and lead research programs of global scope of the carbon cycle. (shrink)

Background The use of lengthy, detailed, and complex informed consent forms is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in (...) biomedical research. Methods This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 to 5. Results Of the 2484 questionnaires distributed, 2113 were returned. The majority of respondents considered most elements required in the ICF to be ‘moderately important’ to ‘very important’ for their decision making. Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF. Conclusions Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

Background Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents’ view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. Objective To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese (...) parents. Methods A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0–3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. Results Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an “opt-out” approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. Conclusion Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks. (shrink)

English title: "The early literary education of the young José Gaos in Valencia (1915-1919)"Resumen: Nuestra intención en este texto es investigar acerca de los primeros años de formación del pensamiento de José Gaos (1900-1969); así pues, no parece ser demasiado erróneo pensar que aquél, hacia 1915 no era, aún, puramente “filosófico”: la Filosofía representaba parte de su formación, cumpliendo el mismo papel —eso sí: básico y fundamental— que desempeñó la Literatura. El primer auténtico encuentro con la Filosofía se daría antes (...) de su llegada a Valencia, en ese mismo año de 1915; pero ese también es el año en que Gaos recibirá una sólida formación estético-literaria a través de prensa y revistas filosóficas, especialmente en el grupo que conformó junto con Max Aub, José Medina Echeverría y su hermano Carlos Gaos. Abstract: This paper investigates in detail about the early years of José Gaos (1900-1969) and his education in philosophy and literature. Therefore, we know that their studies (academic or not) were not purely “philosophical” in 1915. Literature and philosophy played in Gaos an equally important role. The first real encounter with philosophy happens before he comes to Valencia in 1915; but in this year Gaos also receives a strong education, in aesthetic and literary, through press and philosophical journals, and especially within the group formed with Max Aub, José Medina Echeverría and his brother Carlos Gaos. Palabras clave: José Gaos, literatura, juventud, formación, Valencia. Keywords: José Gaos, literature, youth, education, Valencia. (shrink)

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

High-spin states have been studied in Pr-135(59), populated through the Cd-116(Na-23,4n) reaction at 115 MeV, using the Gammasphere gamma-ray spectrometer. The negative-parity yrast band has been significantly extended to spin similar to 45 (h) over bar and excitation energy 21.5 MeV, showing evidence for several rotational alignments. The positive-parity yrast band of Ce-135(58), populated through the p4n channel of this reaction, was also populated to spin similar to 38 (h) over bar and excitation energy 18 MeV. Cranking calculations indicate that (...) these nuclei are soft with respect to the triaxiality parameter gamma and that several competing nuclear shapes occur at high spin. (shrink)

Medium- and high-spin states of Pr-134 were populated using the Cd-116(Na-23, 5n) reaction and studied with the GAMMASPHERE spectrometer. Several new bands have been found in this nucleus, one of them being linked to the previously observed chiral-candidate twin-band structure. The ground state of Pr-134 could be determined through establishing a level structure that connects the two previously known long-lived isomeric states. Unambiguous spin-parity assignments for the excited states could be performed based on the known 2(-) spin-parity of the ground (...) state combined with the present experimental data. Intrinsic single-particle configurations have been assigned to the newly observed bands on the basis of the measured B(M1)/B(E2) ratios, alignments, band-crossing frequencies, bandhead spins, the observed single-particle configurations in the neighboring nuclei, and taking into account the predictions of total Routhian surface and tilted-axis cranking calculations. (shrink)

Estudio sobre el alcance de la concepción del pensamiento hispanoamericano en José Gaos, en su obra de los años 40. A History of Latin American Philosophy (s. XVI- XIX): / José Gaos (1900-1969).

Objective: To determine whether a moral reasoning exercise can improve response quality to surveys of healthcare priorities Methods: A randomised internet survey focussing on patient age in healthcare allocation was repeated twice. From 2574 internet panel members from the USA and Canada, 2020 (79%) completed the baseline survey and 1247 (62%) completed the follow-up. We elicited respondent preferences for age via five allocation scenarios. In each scenario, a hypothetical health planner made a decision to fund one of two programmes identical (...) except for average patient age (35 vs 65 years). Half of the respondents (intervention group) were randomly assigned to receive an additional moral reasoning exercise. Responses were elicited again 7 weeks later. Numerical scores ranging from –5 (strongest preference for younger patients) to +5 (strongest preference for older patients); 0 indicates no age preference. Response quality was assessed by propensity to choose extreme or neutral values, internal consistency, temporal stability and appeal to prejudicial factors. Results: With the exception of a scenario offering palliative care, respondents preferred offering scarce resources to younger patients in all clinical contexts. This preference for younger patients was weaker in the intervention group. Indicators of response quality favoured the intervention group. Conclusions: Although people generally prefer allocating scarce resources to young patients over older ones, these preferences are significantly reduced when participants are encouraged to reflect carefully on a wide range of moral principles. A moral reasoning exercise is a promising strategy to improve response quality to surveys of healthcare priorities. (shrink)

AimWhite matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology.MethodsSixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global (...) and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations.ResultsUltra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = −0.34, p = 0.011) and increased sleep fragmentation index (r = −0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses.ConclusionCompromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target. (shrink)

Spanish readers are fortunate in having a publishing house which is committed to reproduce in Spanish the complete works of Georg Lukács. The complete edition will consist of twenty-four, or more, volumes, of which ten are already in print, covering mainly Lukács works on esthetics and literary criticism. The Hegel volume was originally published in German in 1948. The main draft was written as early as the fall of 1938, but the outbreak of World War II delayed publication. Lukács at (...) that time was in the Soviet Union where, following Stalin's lead, Hegel was characterized as an apologist for the Prussian feudal opposition to the French revolution. Considering the winning of the war as more important than provoking a controversy over Hegel, Lukács put his manuscript aside for the duration. In The Young Hegel, Lukács settles his account with Hegel, much as Marx and Engels in The German Ideology--with one significant difference. The objective of Marx and Engels was the abolition of Hegelianism. Their polemic, therefore, was directed against Hegel and the neo-Hegelians. Lukács, on the other hand, sought the restoration of the Hegelian dimension of Marxism, and, while accepting the Marxian critique of Hegelianism, directed his attack against the detractors of Hegel--against the Stalin line within Marxism and against those like Dilthey and Kierkegaard outside of Marxism who transformed Hegel into an "irrationalist." Lukács is consequently much more positive in his treatment of Hegel than Marx and Engels. In History and Class Consciousness, Lukács emphasized the necessity of understanding Hegel in order to properly understand Marx. In The Young Hegel, the emphasis is on the dialectical opposite--Hegel is understood through the eyes of Marx, through the critique of Marx and through a Marxian interpretation by Lukács. Lukács' unique contribution in the present work is the detailed study of the close union of philosophy and economics in the genesis of Hegel's thought. Indeed, the original subtitle of the German edition reads: Über die Beziehungen von Dialektik und Ökonomie. The Spanish edition has a two-and-a-half page preface, written specially for it by Lukács in 1963, in which he states his conviction of the importance in the thought of Hegel and other great philosophers of concern with economic problems, both from the standpoint of economic theory and actual economic conditions. An English edition has been promised by Merlin Press in London, but no date of publication has yet been announced.--H. B. (shrink)

This book is a rare piece of writing in any language. Its first merit is that it puts in 360-odd pages a concise and highly readable history of economic thought from Ricardo and Adam Smith to modern times as seen through the critical spectacles of classical Marxist political economy. Its second merit is that it does not dismiss capitalist economics as mere apologetics or mystification, but--in the genuine spirit of Marx's principles of criticism--it also seeks out the positive aspects of (...) methodology and understanding which can help clarify the workings and malfunctions of late twentieth century capitalism. Nor does the author bow before any mystic infallibility of current Soviet economic theory. Among the most interesting treatments are those of the theories of Böhm-Bawerk, Schumpeter, Marshall, Veblen, Hobson, Hilferding, Kalecki, Keynes, Harrod-Domar, Kaldor, Sraffa, Galbraith, Myrdal, Strachey, and Bettelheim. Aguilar is a professor of economics at the University of Mexico and displays impressive scholarship and perception in his chosen field. His call is for Latin American intellectuals to free themselves from the restrictions of the economic theories of capitalist economics and to dedicate themselves to the development of the theoretical foundations necessary for the liberation of Latin America not only from economic domination, but also from the cultural, social, and political tutelage of their economic masters. Marx's model of capitalism and Lenin's model of imperialism have not lost their power in Latin America as grounds for explaining the continued economic, cultural, social, and political backwardness of this huge area. The present work demonstrates the intellectual sweep of this power. The book is well-footnoted, but, deplorably, lacks an index.--H. B. (shrink)

On one hand, Chinese consumers are well known for conspicuous consumption and the adoption of luxury products and named brands. On the other hand, they also have a bad reputation for buying counterfeit products. Their simultaneous preferences for two contrasting types of product present a paradox that has not been addressed in the literature. This study attempts to present an explanation of this paradox by examining the effects of traditional Chinese cultural values and consumer values on consumers’ deontological judgment of (...) pirated CDs and the amount of social benefits they perceive they gain from them. We interviewed 300 Hong Kong Chinese consumers, and found that face consciousness increased materialism and risk aversion, thereby producing a favorable deontological judgment of pirated CDs. Face consciousness also has a direct effect on the amount of social benefits perceived in pirated CDs. Both favorable deontological judgment and perceived social benefits contributed to a strong intention to buy pirated CDs. The results are discussed in a cultural perspective. (shrink)

We report specific heat and μSR measurements on Th and/or B substituted UBe13. The specific heat data show that either Th or B substitution reduces the Kondo temperature TK and increases the entropy at the superconducting transition by almost 20%, indicating an enhanced density of states. However, whereas μSR shows clear evidence for magnetic correlations for Th substitutions, no magnetism is observed for B substitutions. The enhanced specific heat jump in the B-substituted material is associated with a change in the (...) superconducting properties as TK is reduced. (shrink)