The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Objectives: To investigate the current situation of completing the informed consent for do-not-resuscitate (DNR) orders among the competent patients with terminal illness and the ethical dilemmas related to it. Participants: This study enrolled 152 competent patients with terminal cancer, who were involved in the initial consultations for hospice care. Analysis: Comparisons of means, analyses of variance, Student’s t test, χ2 test and multiple logistic regression models. Results: After the consultations, 117 (77.0%) of the 152 patients provided informed consent for hospice (...) care and DNR orders. These included 21 patients (17.9%) who signed the consent by themselves, and 96 (82.1%) whose consent sheet was signed only by family members. The reasons why patients were not involved in the discussions toward the consent (n = 82) included poor physical or psychological condition (44.9%), concerns of the consultant hospice team (37.2%), and the family’s refusal (28.2%). On a multivariate analysis, patients’ awareness of their poor prognosis (odds ratio = 4.07, 95% confidence interval = 2.05 to 8.07) and their understanding of hospice care (2.27, 1.33 to 3.89) were two independent factors (p<0.01) that influenced their participation in the discussions or their personal signature in the informed consent. Conclusion: The family-oriented culture in Asian countries may violate the principles of the Patient Self-Determination Act and the requirements of the Hospice Care Law in Taiwan, which inevitably poses an ethical dilemma. Earlier truth-telling and continuing education of the public by hospice care workers will be helpful in solving such ethical dilemmas. (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)

Access to legal information is fundamental to access to justice. Yet accessibility refers not only to making legal documents available to the public, but also rendering legal information comprehensible to them. A vexing problem in bringing legal information to the public is how to turn formal legal documents such as legislation and judgments, which are often highly technical, to easily navigable and comprehensible knowledge to those without legal education. In this study, we formulate a three-step approach for bringing legal knowledge (...) to laypersons, tackling the issues of navigability and comprehensibility. First, we translate selected sections of the law into snippets (called CLIC-pages), each being a small piece of article that focuses on explaining certain technical legal concept in layperson’s terms. Second, we construct a _Legal Question Bank_, which is a collection of legal questions whose answers can be found in the CLIC-pages. Third, we design an interactive _CLIC Recommender_. Given a user’s verbal description of a legal situation that requires a legal solution, CRec interprets the user’s input and shortlists questions from the question bank that are most likely relevant to the given legal situation and recommends their corresponding CLIC pages where relevant legal knowledge can be found. In this paper we focus on the technical aspects of creating an LQB. We show how large-scale pre-trained language models, such as GPT-3, can be used to generate legal questions. We compare machine-generated questions against human-composed questions and find that MGQs are more scalable, cost-effective, and more diversified, while HCQs are more precise. We also show a prototype of CRec and illustrate through an example how our 3-step approach effectively brings relevant legal knowledge to the public. (shrink)

Drawing on the behavioral theory, this study examines how the misalignment between a firm's environmental effort and the level of subsidies received from the government in affecting the firm's investment in non-environmental R&D. Based on a sample of Chinese A-share listed firms from 2008 to 2019 and using polynomial regression techniques, our findings reveal that firms in the “low effort-high subsidies” group exhibit lower non-environmental R&D intensity compared to firms in the “high effort-low subsidies” group. This study contributes to the (...) literature by shedding light on the interplay between corporate environmental efforts, government subsidies, and non-environmental R&D investment. The findings suggest the importance of aligning the environmental efforts of firms with subsidy levels from the government to effectively allocate resources for different types of R&D. The implications of this research suggest that firms should carefully consider aligning their environmental efforts with government subsidies to optimize their investment in non-environmental R&D and overall innovation strategy. Furthermore, the study indicates that firms and governments should prudently balance the relationship between environmental R&D and non-environmental R&D to avoid any negative impact on the latter. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

The purpose of this study was to develop a Physician's Spiritual Well-Being Scale (PSpWBS). The significance of a physician's spiritual well-being was explored through in-depth interviews with and qualitative data collection from focus groups. Based on the results of qualitative analysis and related literature, the PSpWBS consisting of 25 questions was established. Reliability and validity tests were performed on 177 subjects. Four domains of the PSpWBS were devised: physician's characteristics; medical practice challenges; response to changes; and overall well-being. The explainable (...) total variance was 65.65%. Cronbach α was 0.864 when the internal consistency of the whole scale was calculated. Factor analysis showed that the internal consistency Cronbach α value for each factor was between 0.625 and 0.794 and the split-half reliability was 0.865. The scale has satisfactory reliability and validity and could serve as the basis for assessment of the spiritual well-being of a physician. (shrink)

© 2016 Regents of the University of California.The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous (...) tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group. The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. (shrink)

Recently implemented Chinese health insurance schemes have failed to achieve a Chinese health care system that is family-oriented, family-based, family-friendly, or even financially sustainable. With this diagnosis in hand, the authors argue that a financially and morally sustainable Chinese health care system should have as its core family health savings accounts supplemented by appropriate health insurance plans. This essay’s arguments are set in the context of Confucian moral commitments that still shape the background culture of contemporary China.

Background: Although ethics consultation has been introduced to clinical practice for many years, the results of empirical studies to evaluate the effectiveness of ethics consultation are still controversial. The design of randomised controlled trials is considered the best research design to evaluate the effect of a clinical practice on the outcomes of interests. In order to understand the effects of ethics consultation, we conducted this search for studies with the design of randomised controlled trials to evaluate ethics consultation.Objective: To provide (...) an integrated review of studies with the design of randomised controlled trials to evaluate the effectiveness of ethics consultation.Methods: PubMed was used to search for studies using the randomised controlled trial design to evaluate the effectiveness of ethics consultation. The search term used was “ethics consultation”. The selection criterion was limited to “randomised controlled trial”.Results: Four articles that met both search criteria were retrieved. One of these articles reported a study that did not actually use the design of a randomised controlled trial and is excluded from the following discussion.Conclusions: To apply randomised controlled trials to evaluate the effectiveness of ethics consultation is extremely difficult as long as two issues are not resolved: the standardisation of ethics consultation and a placebo for ethics consultation to eliminate the placebo effect. Thus, the results generated by the design of randomised controlled trials are always problematic. Furthermore, as long as the two issues exist, the results generated by the design of quantitative research methods always pose problems. (shrink)

A recent series of experiments have demonstrated that a classical fluid mechanical system, constituted by an oil droplet bouncing on a vibrating fluid surface, can be induced to display a number of behaviours previously considered to be distinctly quantum. To explain this correspondence it has been suggested that the fluid mechanical system provides a single-particle classical model of de Broglie’s idiosyncratic ‘double solution’ pilot wave theory of quantum mechanics. In this paper we assess the epistemic function of the bouncing oil (...) droplet experiments in relation to quantum mechanics. We find that the bouncing oil droplets are best conceived as an analogue illustration of quantum phenomena, rather than an analogue simulation, and, furthermore, that their epistemic value should be understood in terms of how-possibly explanation, rather than confirmation. Analogue illustration, unlike analogue simulation, is not a form of ‘material surrogacy’, in which source empirical phenomena in a system of one kind can be understood as ‘standing in for’ target phenomena in a system of another kind. Rather, analogue illustration leverages a correspondence between certain empirical phenomena displayed by a source system and aspects of the ontology of a target system. On the one hand, this limits the potential inferential power of analogue illustrations, but, on the other, it widens their potential inferential scope. In particular, through analogue illustration we can learn, in the sense of gaining how-possibly understanding, about the putative ontology of a target system via an experiment. As such, the potential scientific value of these extraordinary experiments is undoubtedly a significant one. (shrink)

Discourse particles have received a considerable amount of scholarly attention in linguistic research. Although their use in specific text types has been discussed, few studies have actually attempted to look at the effect of text type on their use. Therefore, how the use of discourse particles is related to the situational context in which they are produced remains a largely unexplored area. In this article, the use of one of the most frequently occurring yet often overlooked discourse particles, so, in (...) a number of monologic and dialogic texts is examined. Drawing on data from a spoken corpus of Hong Kong English, the present study shows that the frequency rates and functions of so as a discourse particle vary according to the text type in which it occurs. Findings from the study thus argue that the full range of functions realized by so as a discourse particle cannot be determined without taking into account the wide range of communicative events in which the particle is used. This highlights the fact that contextual cues are indispensable in the interpretation of the pragmatic meanings of discourse particles. (shrink)