The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

The tsunami effect of the COVID-19 pandemic is affecting many aspects of scientific activities. Multidisciplinary experimental studies with international collaborators are hindered by the closing of the national borders, logistic issues due to lockdown, quarantine restrictions, and social distancing requirements. The full impact of this crisis on science is not clear yet, but the above-mentioned issues have most certainly restrained academic research activities. Sharing innovative solutions between researchers is in high demand in this situation. The aim of this paper is (...) to share our successful practice of using web-based communication and remote control software for real-time long-distance control of brain stimulation. This solution may guide and encourage researchers to cope with restrictions and has the potential to help expanding international collaborations by lowering travel time and costs. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: (...) DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom. (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)

The regulatory effect of embodied emotion on one’s general emotion and the impact of the compatibility or incompatibility of the two types of emotion on creative thinking are still debatable. The purpose of this study is to investigate these issues experimentally. In Experiment 1, participants completed an explicit positive and negative emotion test [Positive and Negative Affect Schedule (PANAS)] and an implicit positive and negative emotion test [Implicit Positive and Negative Affect Test (IPANAT)] twice on a computer after emotional video (...) priming was used to induce negative emotions and facial expression manipulation was performed to induce embodied positive or negative emotions. It was found that maintaining the expression of a suppressed smile was helpful in regulating negative emotions ( p = 0.047). Specifically, the implicit negative emotions induced by facial expression manipulation had a positive regulating effect on the implicit negative emotions induced by the video (T1, M = 47.813; to T2, M = 44.188). In Experiment 2, the positive or negative emotions of the participants were induced using emotional videos, and facial expression manipulation was used to induce their embodied positive or negative emotions. Then, the participants completed a creative test by completing alternative use tasks (AUTs) and Chinese character riddles. The AUT fluency score in the emotionally compatible group was significantly higher than that in the emotionally incompatible group ( p = 0.032), but while experiencing negative emotions, the emotionally compatible group had a significantly higher originality score and insight in Chinese character riddle score than the emotionally incompatible group ( p = 0.017, p = 0.004). Therefore, embodied negative emotion has a significant regulating effect on implicit negative emotion. The compatibility of emotion activated by facial expression and viewing a video contributes to creative thinking, whereas the incompatibility of emotion hinders creative thinking. The compatibility of emotion under positive emotions improved thinking fluency, whereas under negative emotions, it activated originality and insight in creative thinking. The influence of such emotional compatibility on creative thinking may be due to the regulating effect of embodied emotions on implicit emotions induced by emotional stimuli. (shrink)

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and (...) mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability. (shrink)

Primary progressive aphasia is a clinical syndrome in which patients progressively lose speech and language abilities. Three variants are recognized: logopenic, associated with phonology and/or short-term verbal memory deficits accompanied by left temporo-parietal atrophy; semantic, associated with semantic deficits and anterior temporal lobe atrophy; non-fluent associated with grammar and/or speech-motor deficits and inferior frontal gyrus atrophy. Here, we set out to investigate whether the three variants of PPA can be dissociated based on error patterns in a single language task. We (...) recruited 21 lvPPA, 28 svPPA, and 24 nfvPPA patients, together with 31 healthy controls, and analyzed their performance on an auditory noun-to-verb generation task, which requires auditory analysis of the input, access to and selection of relevant lexical and semantic knowledge, as well as preparation and execution of speech. Task accuracy differed across the three variants and controls, with lvPPA and nfvPPA having the lowest and highest accuracy, respectively. Critically, machine learning analysis of the different error types yielded above-chance classification of patients into their corresponding group. An analysis of the error types revealed clear variant-specific effects: lvPPA patients produced the highest percentage of “not-a-verb” responses and the highest number of semantically related nouns ; in contrast, svPPA patients produced the highest percentage of “unrelated verb” responses and the highest number of light verbs. Taken together, our findings indicate that error patterns in an auditory verb generation task are associated with the breakdown of different neurocognitive mechanisms across PPA variants. Specifically, they corroborate the link between temporo-parietal regions with lexical processing, as well as ATL with semantic processes. These findings illustrate how the analysis of pattern of responses can help PPA phenotyping and heighten diagnostic sensitivity, while providing insights on the neural correlates of different components of language. (shrink)

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The (...) animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions. (shrink)

Research investigating the underlying mechanisms and boundary conditions under which leader humility influences employee voice remains underdeveloped. Drawing from approach–inhibition theory of power and leader humility literature, we developed a moderated-mediation model in which personal sense of power was theorized as a unique mechanism underlining why employees feel motivated to speak up under the supervision of humble leaders. Additionally, the cultural value of power distance was proposed to be a relevant boundary condition to influence such relationship. We tested the model (...) using time-lagged supervisor–subordinate matched data. Results of mixed models analyses provided support for our hypotheses confirming that employees’ personal sense of power mediates the relationship between leader humility and employee voice, and such relationship was found to be stronger when employees’ power distance was lower rather than higher. (shrink)

The paper is devoted to modelling of cell differentiation in an initially homogeneous cell population. The mechanism which provides coexistence of two cell lineages in the initially homogeneous cell population is suggested. If cell differentiation is initiated locally in space in the population of undifferentiated cells, it can propagate as a travelling wave converting undifferentiated cells into differentiated ones. We suggest a model of this process which takes into account intracellular regulation, extracellular regulation and different cell types. They include undifferentiated (...) cells and two types of differentiated cells. When a cell differentiates, its choice between two types of differentiated cells is determined by the concentrations of intracellular proteins. Differentiated cells can either stimulate differentiation into their own cell lineage or into another cell lineage. In the case of the positive feedback, only one lineage of differentiated cells will finally appear. In the case of negative feedback, both of them can coexist. In this case a periodic spatial pattern emerges behind the wave. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Books ReceivedThe Ambitions of Curiosity: Understanding the World in Ancient Greece and China. By G.E.R. Lloyd. Cambridge: Cambridge University Press, 2002. Pp. xvi + 175. Price not given.The Art of the Han Essay: Wang Fu's Ch'ien-Fu Lun. By Anne Behnke Kinney. Tempe: Center for Asian Studies, Arizona State University, 1990. Pp. xi + 154. Paper $10.00.The Autobiography of Jamgön Kongtrul: A Gem of Many Colors. By Jamgön Kongtrul Lodrön (...) Thayé and translated by Richard Barron (Chökyi Nyima). Ithaca, New York: Snow Lion Publications, 2003. Pp. xxii + 549. Price not given.Awesome Nightfall: The Life, Times, and Poetry of Saigyō. By William R. LaFleur. Boston: Wisdom Publications, 2003. Pp. xiii + 173. Paper $14.95.Becoming the Compassion Buddha: Tantric Mahamudra for Everyday Life. By Lama Thubten Yeshe, edited by Robina Courtin, and foreword by Geshe Lhundub Sopa. Boston: Wisdom Publications, 2003. Pp. xi + 194. Paper $14.95.Between Two Worlds East and West: An Autobiography. By J. N. Mohanty. New Delhi: Oxford University Press, 2002. Pp. ix + 134. Hardcover RS 525.00.The Chinese Face of Jesus Christ. Edited by Roman Malek, S.V.D. Sankt Augustin, Germany: Institut Monumenta Serica and China-Zentrum; and Nettetal, Germany: Steyler Verlag, 2002. Pp. 391. EUR 40.00.Chinese Medicine in Contemporary China: Plurality and Synthesis. By Volker Scheid. Durham and London: Duke University Press, 2002. Pp. xiv + 407. Hardcover $69.95. Paper $23.95.Confucian Feminist: Memoirs of Zeng Baosun (1893-1978). Translated and adapted by Thomas L. Kennedy. Philadelphia: American Philosophical Society, 2002. Pp. xxi + 170. Price not given.Consciousness Studies: Cross-Cultural Perspectives. By K. Ramakrishna Rao. Jefferson (North Carolina) and London: McFarland and Company, 2002. Pp. 367. Hardcover $65.00.Constituting Communities: Theravāda Buddhism and the Religious Cultures of South and Southeast Asia. Edited by John Clifford Holt, Jacob N. Kinnard, and Jonathan S. Walters. Albany: State University of New York Press, 2003. Pp. viii + 224. Hardcover $65.50. Paper $21.95.Developments in Indian Philosophy from Eighteenth Century Onwards: Classical and Western. By Daya Krishna. Volume X Part 1 of History of Science, Philosophy and Culture in Indian Civilization, edited by D. P. Chattopadhyaya. New [End Page 110] Delhi: Centre for Studies in Civilizations, 2001. Pp. xxiii + 417. Hardcover RS 1200.East and West: Identità e dialogo interculturale. By Giangiorgio Pasqualotto. Venezia: Marsilo Editori, 2003. Pp. 210. EUR 16.00.Effortless Action: Wu-wei as Conceptual Metaphor and Spiritual Ideal in Early China. By Edward Slingerland. New York: Oxford University Press, 2003. Pp. xii + 352. Price not given.Encountering Kā lī: In the Margins, at the Center, in the West. Edited by Rachel Fell McDermott and Jeffrey J. Kripal. Berkeley and Los Angeles: University of California Press, 2003. Pp. xviii + 321. Hardcover $55.00, £37.95. Paper $21.95, £15.95.Encyclopedia of Chinese Philosophy. Edited by Antonio S. Cua. New York and London: Routledge, 2003. Pp. xx + 1020. Hardcover $150.00.Essays on Indian Philosophy. By J. N. Mohanty and edited by Purushottama Bilimoria. New Delhi: Oxford University Press, 2002. Pp. xxxvii + 347. Paper RS 525.00.Faith, Humor, and Paradox. By Ignacio L. Götz. Westport, Connecticut: Praeger Publishers, 2002. Pp. 136. Hardcover $61.95.Four Illusions: Candrakīrti's Advice for Travelers on the Bodhisattva Path. Translated by Karen C. Lang. New York: Oxford University Press, 2003. Pp. xv + 240. Price not given.The Great Awakening: A Buddhist Social Theory. By David R. Loy. Boston: Wisdom Publications, 2003. Pp. 223. Paper $16.95.The Hidden History of The Tibetan Book of the Dead. By Bryan J. Cuevas. New York: Oxford University Press, 2003. Pp. xi + 328. Price not given.Huang Di nei jing su wen: Nature, Knowledge, Imagery in an Ancient Chinese Medical Text. By Paul U. Unschuld. Berkeley and Los Angeles: University of California Press, 2003. Pp. xii + 520. Hardcover $75.00, £52.00.In Dewey's Wake: Unfinished Work of Pragmatic Reconstruction. Edited by William J. Gavin. Albany: State University of New York Press, 2003. Pp. vi + 249. Hardcover $71.50. Paper $23.95.Knowledge and Freedom in Indian Philosophy. By Tara Chatterjea. Lanham, Maryland: Lexington Books, 2002. Pp. xvi + 159. Hardcover... (shrink)

Community-based interventions (CBIs) show promise as effective and cost-effective obesity prevention initiatives. CBIs are typically complex interventions, including multiple settings, strategies and stakeholders. Cost-effectiveness evidence, however, generally only considers a narrow range of costs and benefits associated with anthropometric outcomes. While it is recognised that the complexity of CBIs may result in broader non-health societal and community benefits, the identification, measurement, and quantification of these outcomes is limited. This study aimed to understand the perspectives of stakeholders on the broader benefits (...) of CBIs and their measurement, as well as perceptions of CBI cost-effectiveness. Purposive sampling was used to recruit participants from three stakeholder groups (lead researchers, funders, and community stakeholders of CBIs). Online semi-structured interviews were conducted, taking a constructivist approach. Coding, theme development and analysis were based on published guidance for thematic analysis. Twenty-six stakeholders participated in the interviews (12 lead researchers; 7 funders; 6 community stakeholders). Six key themes emerged; (1) Impacts of CBIs (health impacts and broader impacts); (2) Broader benefits were important to stakeholders; (3) Measurement of benefits are challenging; (4) CBIs were considered cost-effective; (5) Framing CBIs for community engagement (6) Making equitable impacts and sustaining changes—successes and challenges. Across all stakeholders, broader benefits, particularly the establishment of networks and partnerships within communities, were seen as important outcomes of CBIs. Participants viewed the CBI approach to obesity prevention as cost-effective, however, there were challenges in measuring, quantifying and valuing broader benefits. Development of tools to measure and quantify broader benefits would allow for more comprehensive evaluation of the cost-effectiveness of CBIs for obesity prevention. (shrink)

Food safety problems in China, such as deadly tainted milk, have attracted growing attention from a corporate social responsibility perspective. To examine the forces that potentially drive CSR behavior within the Chinese food industry, our study is organized as follows. First, a review is conducted on the unique history of CSR in China as well as some of the major Chinese food scandals that have taken place. The primary drivers of CSR in China that have been suggested in the literature (...) are then summarized. Next, new institutional theory perspectives are drawn upon to analyze three forces that potentially affect the behavior of Chinese firms: coercive isomorphism, mimetic processes, and normative pressures. Based on a questionnaire survey of 164 Chinese managers and employees, the CSR behavior of firms operating in the Chinese food industry is found to only be significantly affected by the institutional factor of normative pressures. The study concludes with its limitations as well as the implications of the findings. (shrink)

Explanation of terms in Mīmāṃsā, an orthodox school in Hindu philosophy.