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)

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 Care homes have been disproportionately affected during the COVID-19 pandemic. Practical challenges of enacting infection control measures in care home settings have been widely reported, but little is known about the ethical concerns of care home staff during the implementation of such measures.. Objectives To understand the ethical challenges perceived by care home staff during the early months of the COVID-19 pandemic. Research design An exploratory qualitative study. Participants and research context A purposive sample of 15 care home staff (...) in different roles and ranks in Hong Kong was recruited to take part in semi-structured interviews between June and August 2020. Ethical considerations Ethical approval for this study was obtained. Participation was voluntary and anonymous. Participants had the right to withdraw from the study at any time without reprisal. Findings Three themes were identified: unclear legitimacy regarding infection control measures, limited autonomy in choices over infection control measures and inevitable harms to residents’ well-being. While the participants expected that they would have legitimated power to implement infection control measures, they were resistant when their right to self-determination of testing and vaccination was infringed. They also felt trapped between ethical duties to protect care home residents from infection risk and the anticipated detrimental effects of infection control measures. Conclusions The findings of this study reveal tensions among the ethical obligations of care home staff in response to a public health emergency. They highlight the importance of strengthening ethical sensitivity and ethical leadership in identifying and resolving the challenges of pandemic responses. (shrink)

Introduction While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand. Methods Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed. Results 525 participants completed the informed consent survey (Heng County, China=255, Xinjiang, China=229, Chiang Mai, Thailand=41). Mean age was (...) 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6–10 yrs vs 0–5 yrs: OR=0.27, p=0.03; more than 11 yrs vs 0–5 yrs: OR=0.18, p=0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR=0.07; p=<0.01), not minding (OR=0.26; p=0.03), being bored (OR=0.25; p=0.01) and not finding the questions easy (OR=0.10; p=<0.01). Conclusions Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent. Trial Registration clinicaltrials.gov number NCT00270257. (shrink)

Can art, religion, or philosophy afford ineffable insights? If so, what are they? The idea of ineffability has puzzled philosophers from Laozi to Wittgenstein. In Ineffability and its Metaphysics: The Unspeakable in Art, Religion and Philosophy, Silvia Jonas examines different ways of thinking about what ineffable insights might involve metaphysically, and shows which of these are in fact incoherent. Jonas discusses the concepts of ineffable properties and objects, ineffable propositions, ineffable content, and ineffable knowledge, examining the metaphysical pitfalls involved in (...) these concepts. Ultimately, she defends the idea that ineffable insights as found in aesthetic, religious, and philosophical contexts are best understood in terms of self-acquaintance, a particular kind of non-propositional knowledge. Ineffability as a philosophical topic is as old as the history of philosophy itself, but contributions to the exploration of ineffability have been sparse. The theory developed by Jonas makes the concept tangible and usable in many different philosophical contexts. (shrink)

This paper uses van Leeuwen’s Authority Legitimation framework to examine government posters published in the 1950s–1980s in Hong Kong, which serve as a means of shaping public opinion and legitimate social action. Martin and White’s Appraisal framework is also applied to provide the study with relevant analytical tools by which to construct evaluatively coherent authorial reading positions propagated by the government in the posters as well as aligning viewers with these desired positions. The government posters being studied are concerned with (...) various aspects of social practices in the domain of public health communication. This paper argues that the representations of these social practices are realized as texts – both visual and verbal – in the posters, as part of a broader recontextualization process where legitimate ways of doing things as stipulated in the government guidelines are recontextualized in these posters and conveyed to members of the public. The aim is two-fold: to provide a systematic analysis of how visual and verbal resources construe evaluation in the government posters and the consequent legitimation discourse as viewers are being persuaded to align with legitimate social practices; to highlight various forms of legitimation, namely, role model authority legitimation, impersonal authority legitimation, and conformity authority legitimation, that are realized in these posters through visual-verbal articulation. (shrink)

: Three major strategies exist for the protection of endangered habitat and species: (1) land acquisition programs, (2) government legislation and regulatory agencies, and (3) "stewardship" programs that are voluntary and community-based. While all of these strategies have merit, we suggest that stewardship holds particular advantages and should be considered more often as a strategy of first choice. In this article, we examine the Municipal Wetland Stewardship program of Newfoundland, a popular and successful Canadian policy for the local protection of (...) wetlands. Important issues are at stake: competing philosophical foundations for managerial ecology, the value of "local ecological knowledge," principles of community-based conservation, the question of whether stewardship empowers local communities or controls them from afar, and ethical conflicts around American colonialism, hunting, and ecotourism. The results suggest that despite some potentially problematic ironies, the Newfoundland program provides a model for a public policy aimed both at the pragmatics of biophysical sustainability and at the ideals of environmental ethics, social justice, and democratic politics. (shrink)

Three major strategies exist for the protection of endangered habitat and species: (1) land acquisition programs, (2) government legislation and regulatory agencies, and (3) "stewardship" programs that are voluntary and community-based. While all of these strategies have merit, we suggest that stewardship holds particular advantages and should be considered more often as a strategy of first choice. In this article, we examine the Municipal Wetland Stewardship program of Newfoundland, a popular and successful Canadian policy for the local protection of wetlands. (...) Important issues are at stake: competing philosophical foundations for managerial ecology, the value of "local ecological knowledge," principles of community-based conservation, the question of whether stewardship empowers local communities or controls them from afar, and ethical conflicts around American colonialism, hunting, and ecotourism. The results suggest that despite some potentially problematic ironies, the Newfoundland program provides a model for a public policy aimed both at the pragmatics of biophysical sustainability and at the ideals of environmental ethics, social justice, and democratic politics. (shrink)

Recent debates within the autism advocacy community have raised difficult questions about who can credibly act as a representative of a particular population and what responsibilities that...

Experiences of discrimination such as everyday racism can negatively affect the mental and physical health of children and adolescents with an immigrant background and impair their integration process in the host societies. Although experiences of racism are part of the everyday life of many minors affected by the process of “Othering”, an overview of empirical findings is missing for this age group worldwide. A systematic review was conducted to identify and analyze international research on the impact of discrimination on the (...) developmental outcomes and integration of immigrant children and adolescents. Three scientific databases were systematically searched up to June 11, 2021. A total of k = 4,769 identified publications were reviewed based on inclusion and exclusion criteria in terms of the PICOS format by independent reviewers. Thirty-four primary studies published between 1998 and 2021 met all inclusion criteria. The samples examined were mainly migrant youth, with only k = 2 studies assessing refugee youth and k = 1 study assessing both migrant and refugee youth. The majority of included studies assessed perceived discrimination, with only k = 1 study directly assessing experiences of racism. The association between discrimination or racism and developmental outcomes was assessed by the included studies within the three main topics of mental and physical health-related outcomes, school-related outcomes, and other developmental outcomes. Data collection procedures were implemented, and findings on minors’ developmental outcomes and integration process who experience discrimination and racism were summarized and discussed. The current review suggests experienced discrimination as a negative predictor of children and adolescents’ health-related outcomes, while no clear results could be found for the association between discrimination and school-related outcomes. A need for more empirical research focusing on the path and indirect link between discrimination and children and adolescents’ school-related outcomes as well as resulting school recommendations and the chosen career path was derived.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260291], identifier [CRD42021260291]. (shrink)

BackgroundTurnover intention, an employee’s intention to voluntarily leave their jobs, affects workforce sustainability. However, scarce data are available about turnover intention and its associated factors among psychiatrists in China, especially during the COVID-19 pandemic. The current research was designed to address this gap.MethodsAn anonymous, nationwide online survey was disseminated to psychiatrists in 41 psychiatric hospitals in China. We collected demographic data, job-related information, and participants’ turnover intention in the next 12 months.ResultsIn total, 3,973 psychiatrists completed the survey. The sample was (...) predominantly female and married, and nearly three-fourths had children. More than one-third had a master’s or doctoral degree in addition to their medical degree. The overall level of job satisfaction was moderate. The rate of turnover intention was 22.0% and was comparable in males and females. Psychiatrists who had participated in the frontline work of COVID-19 were more likely to report an intention to leave their current job. Multiple regression analyses suggested that turnover intention was significantly associated with having insomnia, longer working hours, and more working days per week.ConclusionDuring the pandemic period, approximately one-fifth of psychiatrists in China reported turnover intention. Factors associated with turnover intention included high job-related burdens, low job satisfaction, participation in the frontline work against COVID-19, and insomnia. To improve psychiatric workforce sustainability, policymakers and hospital administrators need to be aware of this potential challenge and address the concerns of psychiatrists in China. (shrink)

ABSTRACTDespite interest in exercise as a treatment for anxiety disorders the mechanism behind the anxiolytic effects of exercise is unclear. Two observations motivate the present work. First, engagement of attention control during increased working memory load can decrease anxiety. Second, exercise can improve attention control. Therefore, exercise could boost the anxiolytic effects of increased WM load via its strengthening of attention control. Anxiety was induced by threat of shock and was quantified with anxiety-potentiated startle. Thirty-five healthy volunteers participated in two (...) types of activity, exercise and control-activity. After each activity, participants completed a WM task at low- and high-load during safe and threat. Results were not consistent with the hypothesis: exercise vs. control-activity increased APS in high-load. However, this incre... (shrink)

A variety of crucial and still most relevant ideas about _nothingness _or _emptiness _have gained profound philosophical prominence in the history and development of a number of South and East Asian traditions—including in Buddhism, Daoism, Neo-Confucianism, Hinduism, Korean philosophy, and the Japanese Kyoto School. These traditions share the insight that in order to explain both the great mysteries and mundane facts about our experience, ideas of "nothingness" must play a primary role. This collection of essays brings together the work of (...) twenty of the world’s prominent scholars of Hindu, Buddhist, Daoist, Neo-Confucian, Japanese and Korean thought to illuminate fascinating philosophical conceptualizations of "nothingness" in both classical and modern Asian traditions. The unique collection offers new work from accomplished scholars and provides a coherent, panoramic view of the most significant ways that "nothingness" plays crucial roles in Asian philosophy. It includes both traditional and contemporary formulations, sometimes putting Asian traditions into dialogue with one another and sometimes with classical and modern Western thought. The result is a book of immense value for students and researchers in Asian and comparative philosophy. (shrink)

Nanotechnology shows great promise in a variety of applications with attractive economic and societal benefits. However, societal issues associated with nanotechnology are still a concern to the general public. While numerous technological advancements in nanotechnology have been achieved over the past decade, research into the broader societal issues of nanotechnology is still in its early phases. Based on the data from the Web of Science database, we applied the main path analysis, cluster analysis and text mining tools to explore the (...) main research fronts and hierarchical structure of these societal issues. We found that the research studies fell into four categories: "General Toxicity and EHS (Environment, Health and Safety)," "Medicine and Cytotoxicity," "Assessment and Regulation," and "Environment and Ecotoxicity." These research studies have disclosed much information about the potential effect of nanotechnology on public health and the environment. Relatively speaking, the studies on the assessment, regulation, preventive solutions, and environmental protection are just emerging. This finding indicates that an abundance of effort should be conducted on these emerging themes to maximize the benefits of nanotechnology while minimizing its potential harm. The implications for various parties in this domain are also presented. (shrink)

The social facilitation of eating plays a significant role in influencing individuals’ eating decisions. However, how social eating cues are processed in health promotion messages is unclear. This study examined individuals’ food craving in response to social cues in images and emotional experiences, perceived threat, perceived efficacy, behavioral intentions, and motivational coactivation elicited by social eating cues in obesity prevention fear appeals. Results suggested that the presence of a group of people eating in an image facilitated food craving for the (...) presented foods. Moreover, fear appeals that presented obesity and its consequences with more social eating cues, versus individual eating cues, generated greater positive emotional responses, perceived threat severity, response and self-efficacy, and motivational coactivation indicating more attention and threat vigilance. However, these cues also generated fewer self-reported intentions to change unhealthy eating behaviors. Implications and suggestions for future research are discussed. (shrink)

A quick mental survey of one's friends or acquaintances reveals an important difference between them. On the one hand, there are seemingly stoic people for whom emotional events (e.g., having a pap...

The human brain does not use more energy than the smaller brains of animals of comparable corporal weight. Uniquely, human functions localized largely in parts of the human brain that show greatest size increase over other animals may be mediated primarily by nonsynaptic neurotransmission, with reduced energy cost per kilogram of brain. This may affect the energetic constraints on evolution.