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)

Objectives The objectives of the study are to understand the current practice of informed consent in medical research in public hospitals in Shanghai, and to share our views with other countries, especially developing countries. Methods In the study, 145 consent forms (CFs) of the selected research projects in eight public hospitals with ethics committees in Shanghai were audited, and the principle investigators (PIs) of these research projects and 40 student subjects who had participated in clinical drug tests were surveyed by (...) questionnaires. Results The CFs of medical researches in public hospitals with ethics committees in Shanghai were generally acceptable. However, there were some defects in the CFs. Although most of the surveyed PIs had correct recognition of informed consent, some processes of informed consent were not in accordance with generally accepted requirements. A large number of the PIs considered the greatest difficulty with informal consent was lack of correct recognition of subjects or legally authorised representatives on medical research. Discussion Informed consent in medical research should consider the research ethics, the background of potential subjects, the local resources and culture of medical research. In addition, special protection is needed for student subjects in informed consent as well as efforts for building and restoring the public's trust in biomedical research. Conclusion The informed consent in Shanghai's public hospitals with ethics committees was generally acceptable and the achievement of adequate informed consent is influenced by many factors. (shrink)

Objectives The objective of this research was to develop ethics accreditation standards for hospitals. Research design Our research methods included a literature review, an expert focus group, the Delphi technique and a hospital survey. The entire process was separated into two stages: (1) the development of a draft of hospital ethics accreditation standards; and (2) conducting a nationwide hospital survey of the proposed standards. Results This study produced a tentative draft of hospital ethics accreditation standards comprised of six chapters and (...) 62 standards based on the expert focus group and Delphi technique. The six chapters are: Medical ethics policies, regulations and leadership; The establishment and operation of a medical ethics committee; The establishment and operation of research-related ethics committees; Medical ethics education; Organisational ethical climate; and Respect for patients' rights and establishment of good hospital-patient relationships. The hospital survey indicated that the concept of an organisational ethical climate was new to most hospital managers, most hospitals disliked the idea of having a separate hospital ethics accreditation system, and small hospitals were concerned about their ability to comply with all of the standards. Conclusions Regardless of whether hospital ethics accreditation can be a stand-alone accreditation or just part of existing hospital accreditation programmes, we hope this draft can serve as a good reference for future endeavours by hospital accreditation authorities. (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)

The aim of this paper is to explore the conditions under which generalisation from single case studies, in the sense of making inferences concerning a wider class of phenomena beyond a case, is reasonable. Two sets of conditions, in particular, provide the basis for our consideration of this issue. The first is an exploration of the impressive amount of empirical knowledge that is contained within the theories that are used to make observations, to classify phenomena, and to understand and interpret (...) cases. The second is recognition of the role of a pattern of inference known as abduction, or inference to the best explanation, in drawing conclusions from case studies. It is argued that these two conditions, when applied to the procedures for conducting case studies, can be used to defend, as reasonable, the making of certain provisional generalisations from single cases. An epistemological procedure for testing and further justifying these generalisations, with a particular emphasis on dealing with the problem of confirmation bias, is then discussed and recommended. (shrink)

Objective: The objectives of this study are to understand the current functions, structure and operation of hospital ethics committees (HECs) in Shanghai and to facilitate their improvement. Methods: (1) A questionnaire survey, (2) interviews with secretaries and (3) on-site document reviews of HECs in Shanghai were used in the study, which surveyed 33 hospitals. Results: In Shanghai, 57.56% of the surveyed hospitals established HECs from 1998 to 2005. Most HECs used bioethical review of research involving human subjects as well as (...) bioethical review or consultation regarding medical care services and administrative decision- making. Of the surveyed HECs, 14.3% did not provide any formal bioethical training to the HECs’ members and many HECs had no standard operating procedures. Some HECs had no clear definition of what was “conflict of interest” that should be considered by the HECs, while 44.4% of the HECs did not perform continuing review. Discussion: After the issues of related national regulations, more and more hospitals established HECs in Shanghai, but the functions of HECs need to be further developed and formal training on bioethics should be provided to HEC members. To assure the independence and good performance of HECs, the conflict of interest procedure, the standard operating procedures and bioethical review should be improved. Conclusion: HECs in Shanghai had developed in the preceding 10 years and they played great roles in protecting the rights and welfare of human subjects and patients; some areas need improvement. (shrink)

Objectives: To study the attitudes of both medical and non-medical students towards the do-not-resuscitate decision in a university in Hong Kong, and the factors affecting their attitudes.Methods: A questionnaire-based survey conducted in the campus of a university in Hong Kong. Preferences and priorities of participants on cardiopulmonary resuscitation in various situations and case scenarios, experience of death and dying, prior knowledge of DNR and basic demographic data were evaluated.Results: A total of 766 students participated in the study. There were statistically (...) significant differences in their DNR decisions in various situations between medical and non-medical students, clinical and preclinical students, and between students who had previously experienced death and dying and those who had not. A prior knowledge of DNR significantly affected DNR decision, although 66.4% of non-medical students and 18.7% of medical students had never heard of DNR. 74% of participants from both medical and non-medical fields considered the patient’s own wish as the most important factor that the healthcare team should consider when making DNR decisions. Family wishes might not be decisive on the choice of DNR.Conclusions: Students in medical and non-medical fields held different views on DNR. A majority of participants considered the patient’s own wish as most important in DNR decisions. Family wishes were considered less important than the patient’s own wishes. (shrink)

Background: Discussions about medical errors facilitate professional learning for physicians and may provide emotional support after an error, but little is known about physicians’ attitudes and practices regarding error discussions with colleagues.Methods: Survey of faculty and resident physicians in generalist specialties in Midwest, Mid-Atlantic and Northeast regions of the US to investigate attitudes and practices regarding error discussions, likelihood of discussing hypothetical errors, experience role-modelling error discussions and demographic variables.Results: Responses were received from 338 participants . In all, 73% of (...) respondents indicated they usually discuss their mistakes with colleagues, 70% believed discussing mistakes strengthens professional relationships and 89% knew at least one colleague who would be a supportive listener. Motivations for error discussions included wanting to learn whether a colleague would have made the same decision , wanting colleagues to learn from the mistake and wanting to receive support . Given hypothetical scenarios, most respondents indicated they would likely discuss an error resulting in no harm , minor harm or major harm . Fifty-seven percent of physicians had tried to serve as a role model by discussing an error and role-modelling was more likely among those who had previously observed an error discussion .Conclusions: Most generalist physicians in teaching hospitals report that they usually discuss their errors with colleagues, and more than half have tried to role-model discussions. However, a significant number of these physicians report that they do not usually discuss their errors and some do not know colleagues who would be supportive listeners. (shrink)

Wisdom is a multi-component trait that is important for mental health and well-being. In this study, we sought to understand gender differences in relative strengths in wisdom. A total of 659 individuals aged 27–103 years completed surveys including the 3-Dimensional Wisdom Scale and the San Diego Wisdom Scale. Analyses assessed gender differences in wisdom and gender’s moderating effect on the relationship between wisdom and associated constructs including depression, loneliness, well-being, optimism, and resilience. Women scored higher on average on the 3D-WS (...) but not on the SD-WISE. Women scored higher on compassion-related domains and on SD-WISE Self-Reflection. Men scored higher on cognitive-related domains and on SD-WISE Emotion Regulation. There was no impact of gender on the relationships between wisdom and associated constructs. Women and men have different relative strengths in wisdom, likely driven by sociocultural and biological factors. Tailoring wisdom interventions to individuals based on their profiles is an important next step. (shrink)

Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, from the (...) +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. RESULTS: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 , nm23 nucleoside diphosphate kinase/metastatic inhibitory protein , and specificity protein 1 . These sites crossed a known single nucleotide polymorphism . EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. CONCLUSIONS: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging. (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)

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)

The target article retains the traditional account of saccades as conjugate eye movements. However, recent single-unit recordings of premotor cells in the saccade pathway (excitatory burster neurons [EBNs]) found that they do not encode conjugate eye velocity, but rather, monocular eye velocity. These data argue against the traditional concept of saccades as inherently conjugate. Instead, they suggest a monocular mechanism in the sensorimotor transformation stage of saccade generation. This commentary will discuss the implications of these data for the saccade generation (...) model proposed in Findlay & Walker's target article. (shrink)

Evidence suggests divergent thinking is the cognitive basis of creative thoughts. Neuroimaging literature using resting-state functional connectivity has revealed network reorganizations during divergent thinking. Recent studies have revealed the changes of network organizations when performing creativity tasks, but such brain reconfigurations may be prolonged after task and be modulated by the trait of creativity. To investigate the dynamic reconfiguration, 40 young participants were recruited to perform consecutive Alternative Uses Tasks for divergent thinking and two resting-state scans were used for mapping (...) the brain reorganizations after AUT. We split participants into high- and low-creative groups based on creative achievement questionnaire and targeted on reconfigurations of the two brain networks: default-mode network and the network seeded at the left inferior frontal gyrus because the between-group difference of AUT-induced brain activation located at the left IFG. The changes of post-AUT RSFCs indicated the prolonged effect of divergent thinking. More specifically, the alterations of RSFCIFG−AG and RSFCIFG−IPL in the high-creative group had positive relationship with their AUT performances, but not found in the low-creative group. Furthermore, the RSFC changes of DMN did not present significant relationships with AUT performances. The findings not only confirmed the possibility of brain dynamic reconfiguration following divergent thinking, but also suggested the distinct IFGN reconfiguration between individuals with different creativity levels. (shrink)

Volume 20, Issue 5, June 2020, Page 38-40.

This paper draws on the economics of ethical compliance model to examine the association between ethical reasoning, perceived risk of detection, perceived levels of penalties and Chinese auditors'' ethical behavior in an audit conflict situation. Using 53 Chinese auditors from Shenzen as subjects, and a survey questionnaire, this study found that there is a significant negative association between ethical reasoning and the likelihood of unethical behavior and that this negative association is weaker for auditors who perceive higher risks of detection.

Executive control of attention refers to processes that detect and resolve conflict among competing thoughts and actions. Despite the high-level nature of this faculty, the role of awareness in executive control of attention is not well understood. In this study, we used interocular suppression to mask the flankers in an arrow flanker task, in which the flankers and the target arrow were presented simultaneously in order to elicit executive control of attention. Participants were unable to detect the flanker arrows or (...) to reliably identify their direction when masked. There was a typical conflict effect (prolonged reaction time and increased error rate under flanker-target incongruent condition compared to congruent condition) when the flanker arrows were unmasked, while the conflict effect was absent when the flanker arrows were masked with interocular suppression. These results suggest that blocking awareness of competing stimuli with interocular suppression prevents the involvement of executive control of attention. (shrink)