A central principle of bioethics is “subject autonomy,” the acknowledgement of the primacy of the informed consent of the subject of research. Autonomy requires informed consent — the assurance that the research participant is informed about the possible risks and benefits of the research. In fact, informed consent is difficult when a single drug is being tested, although subjects have a baseline understanding of the testing of a pharmacological agent and the understanding that they can stop taking the drug if (...) there were an adverse event. However, informed consent is even less easily achieved in the modern arena of complex new molecular and cellular therapies. In this article, we argue that as science confronts new issues such as transplantation of stem cell products, which may live within the participant for the rest of their lives, researchers must carefully consider and constantly re-examine how they properly inform subjects considering participation trials of these novel therapeutic strategies.For example, the manufacture of a vial of a cell product that consists of a collection of growing cells is very different than the production of a vial of identical pills, which can be presumed to be identical. The scientific concepts on which these cellular approaches are based may seem alien and incomprehensible to a research subject, who thinks of a clinical trial as simply the selection and testing of the most efficacious pharmaceutical agent already proven to work in preclinical animal studies. The research subject would be wrong. (shrink)

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. (...) S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage. (shrink)

Multiteam systems are complex organizational forms comprising interdependent teams that work towards their own proximal goals within and across teams to also accomplish a shared superordinate goal. MTSs operate within high-stakes, dangerous contexts with high consequences for suboptimal performance. We answer calls for nuanced exploration and cross-context comparison of MTSs “in the wild” by leveraging the MTS action sub-phase behavioral taxonomy to determine where and how MTS failures occur. To our knowledge, this is the first study to also examine how (...) key MTS attributes influence MTS processes and performance. We conducted historiometric analysis on 40 cases of failed MTS performance across various contexts to uncover patterns of within- and between-team behaviors of failing MTSs, resulting in four themes. First, component teams of failing MTSs over-engaged in within-team alignment behaviors by enacting acting, monitoring, and recalibrating behaviors more often within than between teams. Second, failing MTSs over-focused on acting behaviors and tended to not fully enact the action sub-phase cycle. Third and fourth, boundary status and goal type exacerbated these behavioral patterns, as external and physical MTSs were less likely to enact sufficient between-team behaviors or fully enact the action sub-phase cycle compared to internal and intellectual MTSs. We propose entrainment as a mechanism for facilitating MTS performance wherein specific, cyclical behavioral patterns enacted by teams align to facilitate goal achievement via three multilevel behavioral cycles. We argue that the degree to which these cycles are aligned both between teams and with the overarching MTS goal determines whether and how an MTS fails. Our findings add nuance beyond single-context MTS studies by showing that the identified behavioral patterns hold both across contexts and almost all types of MTS action-phase behaviors. We show that these patterns vary by MTS boundary status and goal type. Our findings inform MTS training best practices, which should be structured to integrate all component teams and tailored to both MTS attributes and situation type. (shrink)

Corporate social responsibility involvement and disclosure has been becoming increasingly popular among US public firms, including those that qualify as real estate investment trusts. This paper aims to discover the relationship between CSR involvement and potential determinants such as growth opportunities, profitability, visibility, and agency costs. Types of CSR involvement are assessed in terms of environmental, community, and governance disclosures and are quantified using word count from the company’s voluntary disclosure. Our results support the hypothesis that CSR has a strategic (...) element and that REITs have greater CSR involvement when they have greater growth and investment opportunities. When the type of disclosure is broken into subcategories, the results show that not all dimensions of CSR are alike: environmental, community, and governance CSR disclosures appear to be motivated by different sets of incentives and reasons. (shrink)

Importance Informed consent is essential to ethical, rigorous research and is important to recruitment and retention in cancer trials.Objective To examine cancer clinical trial (CCT) participants’ perceptions of informed consent processes and variations in perceptions by cancer type.Design and Setting and Participants Cross-sectional survey from mixed-methods study at National Cancer Institute–designated Northeast comprehensive cancer center. Open-ended and forced-choice items addressed: (1) enrollment and informed consent experiences and (2) decision-making processes, including risk-benefit assessment. Eligibility: CCT participant with gastro-intestinal or genitourinary, hematologic-lymphatic (...) malignancies, lung cancer, and breast or gynecological cancer (N = 334).Main Outcome Measures Percentages satisfied with consent process and information provided; and assessing participation’s perceptions of risks/benefits. Multivariable logistic or ordinal regression examined differences by cancer type.Results Most patient-participants felt well informed by the consent process (more than 90% overall and by cancer type) and. most (87.4%) reported that the consent form provided all the information they wanted, although nearly half (44.8%) reported that they read the form somewhat carefully or less. More than half (57.9%) said that talking to research staff (i.e., the consent process) had a greater impact on participation decisions than reading the consent form (2.1%). A third (31.1%) were very sure of joining in research studies before the informed consent process (almost half of lung cancer patients did—47.1%). Most patients personally assessed the risks and benefits before consenting. However, trust in physicians played an important role in the decision to enroll in CCT.Conclusions and Relevance Cancer patients rely less on written features of the informed consent process than on information obtained from the research staff and their own physicians. Research should focus on information and communication strategies that support informed consent from referring physicians, researchers, and others to improve patient risk-benefit assessment and decision-making. (shrink)

We study an application of gaggle theory to unary negative modal operators. First we treat negation as impossibility and get a minimal logic system Ki that has a perp semantics. Dunn 's kite of different negations can be dealt with in the extensions of this basic logic Ki. Next we treat negation as “unnecessity” and use a characteristic semantics for different negations in a kite which is dual to Dunn 's original one. Ku is the minimal logic that has a (...) characteristic semantics. We also show that Shramko's falsification logic FL can be incorporated into some extension of this basic logic Ku. Finally, we unite the two basic logics Ki and Ku together to get a negative modal logic K-, which is dual to the positive modal logic K+ in [7]. Shramko has suggested an extension of Dunn 's kite and also a dual version in [12]. He also suggested combining them into a “united” kite. We give a united semantics for this united kite of negations. (shrink)

The microstructures of cryogenically ball-milled Cu were investigated by high-resolution electron microscopy. It was found that the grain-size reduction is a dislocation-controlled continuous process which consists of the formation of small-angle grain boundaries , a gradual increase in misorientations as a result of accumulation of more dislocations and, finally, the formation of large-angle GBs. The GBs were generally curved, wavy or faceted, and heavily strained, which are typical characteristics of nanostructured materials. In addition, extrinsic dislocations were found in many GBs, (...) indicating that most are in a high-energy non-equilibrium configuration, which is consistent with observations in equal-channel angular pressing processed Cu, Ni, and Al-Mg, repetitive corrugation and straightening processed Cu and room-temperature ball-milled Cu. These results support a still-disputed concept that GBs in nanostructured metals processed by severe plastic deformation are mostly in non-equilibrium states. (shrink)

Family carers of individual’s living with Huntington’s Disease (HD) manage a distinct and unique series of difficulties arising from the complex nature of HD. This paper presents the validation of the definitive measure of quality of life for this group. The Huntington’s Disease Quality of Life Battery for carers (HDQoL-C) was expanded and then administered to an international sample of 1716 partners and family carers from 13 countries. In terms of the psychometric properties of the tool, exploratory analysis of half (...) of the sample, demonstrated good internal consistency and reliability. Some items on the full version did not meet psychometric thresholds and a short version (HDQoL-Cs) was developed based on more stringent criteria. Confirmatory Factor Analysis of the model structure showed a good fit for all Factors and, indicated that the HDQoL-C and HDQoL-Cs are psychometrically robust measures of quality of life. We found that carers who lived with and looked after their spouse/partner had reduced sense of coping, hope for the future and overall quality of life. Carers with children who were at risk, carried the gene or were symptomatic also had poorer quality of life outcomes. Findings indicated the HDQoL-C and HDQoL-Cs are valid in multiple languages and across varied cultures as measures of self-reported quality of life in family carers of individual’s living with HD. These psychometrically validated tools can aid and guide the implementation of therapeutic interventions to improve life quality in this population. (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)

As a well-established service offered at many hospitals internationally, clinical ethics consultation (CEC) is increasingly recognized as a tool to improve patient care quality (Fox et al. 2022; Ta...

Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work: Hyperosmolar nonketotic hyperglycemic coma is a serious, rare complication induced by methylprednisolone pulse therapy for acute rejection after orthotopic liver transplantation. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in (...) MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment. (shrink)

Language is central to the interactional nature of the social life within which it is situated. To react or respond in a particular situation, we must be able to recognize the social situation. Growing evidence has demonstrated the negative impact of perceived loneliness on late-life executive functions. Yet little is known about how social factors impact language processing for older people. The current study aims to fill this gap, first by assessing age-related changes in lexical processing during Chinese word reading, (...) second, by examining whether older adults’ individual differences, such as processing speed and verbal abilities, modulate meaning retrieval and, third, by investigating whether perceived loneliness can hinder word reading. The use of compound words in Chinese enables significant sublexical ambiguity, requiring varying executive load during word recognition: when a word’s constituent characters carry multiple meanings, readers must consider the meaning contributions of both constituent characters and use top-down word information to determine the most accurate meaning of the ambiguous character, a process termed “sublexical ambiguity resolution.” In this study, adults read real Chinese words and pseudowords, and they were asked to make lexical decisions. Older adults exhibited greater lexicality effects and similar sublexical ambiguity effects compared with young adults. Among older participants, processing speed could account for their ability to differentiate between words and pseudowords. In contrast, the level of perceived loneliness modulated the efficacy of sublexical ambiguity resolution: the participants with higher perceived loneliness displayed a greater sublexical ambiguity disadvantage effect. These results indicate that perceived loneliness may affect the use of contextual information in meaning retrieval during reading. The findings provide an important link between social connections and language processing. (shrink)

Abstract:Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury (...) in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation. (shrink)

Online data collection methods are expanding the ease and access of developmental research for researchers and participants alike. While its popularity among developmental scientists has soared during the COVID-19 pandemic, its potential goes beyond just a means for safe, socially distanced data collection. In particular, advances in video conferencing software has enabled researchers to engage in face-to-face interactions with participants from nearly any location at any time. Due to the novelty of these methods, however, many researchers still remain uncertain about (...) the differences in available approaches as well as the validity of online methods more broadly. In this article, we aim to address both issues with a focus on moderated data collected using video-conferencing software. First, we review existing approaches for designing and executing moderated online studies with young children. We also present concrete examples of studies that implemented choice and verbal measures and looking time across both in-person and online moderated data collection methods. Direct comparison of the two methods within each study as well as a meta-analysis of all studies suggest that the results from the two methods are comparable, providing empirical support for the validity of moderated online data collection. Finally, we discuss current limitations of online data collection and possible solutions, as well as its potential to increase the accessibility, diversity, and replicability of developmental science. (shrink)

Drug Safety Communications are used by the Food and Drug Administration to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone (...) between July 1, 2012 and June 30, 2013. Among the 594 respondents, two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited. Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep and seek out more information about the safety of their specific sleeping pill. Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications. (shrink)

In many countries consumers have shown an increasing interest to the way in which food products are being produced. This study investigates Chinese consumers’ attitudes towards different pig production systems by means of a conjoint analysis. While there has been a range of studies on Western consumers’ attitudes to various forms of food production, little is known about the level of Chinese consumers’ attitudes. A cross-sectional survey was carried out with 472 participants in 6 Chinese cities. Results indicate that Chinese (...) consumers prefer industrial pig production systems, where traditional pig breeds are raised, over large-scale and small family farms. Farms with maximum attention to food safety, which furthermore can provide lean meat with consistent quality, are also preferred. Imported pig breeds and tasty but variable meat were rejected. A 3-cluster solution found that consumers from cluster 1 focus almost exclusively on the food safety aspect (food safety focused). Consumers from cluster 2 (indifferent) show weak overall attitudes to pig production systems in general. Cluster 3 (industrial production oriented) stands out by being very positive about industrial, large-size farms and consistent quality. From a Chinese consumer’s perspective, the industrial approach seems to represent values such as achievement and evolution, as well as quality and safety, since pig production is moving away from low-cost, low-quality, and low-safety family-scale systems. A complex set of rural and environmental development, quality aspects, and food safety measures are challenges that must be met by the stakeholders of pig production systems in China. (shrink)

While cochlear implantation has benefitted many patients with single-sided deafness (SSD), there is great variability in cochlear implant (CI) outcomes and binaural performance remains poorer than that of normal-hearing (NH) listeners. Differences in sound quality across ears – temporal fine structure (TFS) information with acoustic hearing versus coarse spectro-temporal envelope information with electric hearing – may limit integration of acoustic and electric patterns. Binaural performance may also be limited by inter-aural mismatch between the acoustic input frequency and the place of (...) stimulation in the cochlea. SSD CI patients must learn to accommodate these differences between acoustic and electric stimulation to maximize binaural performance. It is possible that training may increase and/or accelerate accommodation and further improve binaural performance. In this study, we evaluated lateralization training in NH subjects listening to broad simulations of SSD CI signal processing. A 16-channel vocoder was used to simulate the coarse spectro-temporal cues available with electric hearing; the degree of inter-aural mismatch was varied by adjusting the simulated insertion depth (SID) to be 25 mm (SID25), 22 mm (SID22), and 19 mm (SID19) from the base of the cochlea. Lateralization was measured using headphones and head-related transfer functions (HRTFs). Baseline lateralization was measured for unprocessed speech (UN) delivered to the left ear to simulate SSD and for binaural performance with the acoustic ear combined with the 16-channel vocoders (UN+SID25, UN+SID22, and UN+SID19). After completing baseline measurements, subjects completed 6 lateralization training exercises with the UN+SID22 condition, after which performance was re-measured for all baseline conditions. Post-training performance was significantly better than baseline for all conditions (p<0.05 in all cases), with no significant difference in training benefits among conditions. Given that there was no significant difference between the SSD and the SSD CI conditions before or after training, the results suggest that NH listeners were unable to integrate TFS and coarse spectro-temporal cues across ears for lateralization, and that inter-aural mismatch played a secondary role at best. While lateralization training may benefit SSD CI patients, the training may largely improve spectral analysis with the acoustic ear alone, rather than improve integration of acoustic and electric hearing. (shrink)

The rise of global civil society as a new discourse in the last century, in the new century has been of concern. Western academic circles around the concept of global civil society, global civil society and the emergence and development of global civil society influence on the political realities and trends and other issues had extensive discussions and the formation of a different theoretical framework and research camp. While the Western world made ​​a series of civil society, research results, but (...) still insufficient to demonstrate the normative study, mainly confined to the liberal democratic framework of the inadequacies of the middle. China scholars have been from international relations, political science and political philosophy point of view about global civil society, but in general, the power of research in this area is still relatively weak, insufficient results, further research needs to be made. As a word rising from the late of last century, Global Civil Society is very attractable in the early new century. Western academy has initiated abroad discussion on the concept of GCS, the process of its formation and development, its impact on political realities and its future. In the discussion, theory analysis frames and theory camps have already come into being. Though a great achievements have been gotten, there are still some deficiencies lie in the Western studies, such as lacking of normative studies and main studies are limited in the frames of liberal democracy. In China some scholars have studied about GCS from the views of international relationship, political science and political philosophy. But as a whole, research force in the realm is still weak and the fruits are insufficient, deep discussion is needed. (shrink)