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)

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)

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)

“Looking for Asian America shows real people engaged in the full range of human activity. This is no small accomplishment for the photographer or his subjects. For Asian Americans it is extraordinary to be merely ordinary. To others, even if not to themselves, Asian Americans appear to be contradictions of identity—a Chinese-Yankee is a knockoff.” —Frank H. Wu, from the Foreword In search of contemporary Asian America, celebrated photographer Wing Young Huie—the only member of his family not born in China—traveled (...) with his wife Tara through nearly forty states to explore and document the funny, touching, and sometimes strange intersection of Asian American and American cultures. Looking for Asian America illustrates their rich and surprising journey across the United States. Through Huie’s eyes, keenly aware of his own Midwestern roots and perspective, we witness such images as a Vietnamese Elvis, Miss Congeniality on her cell phone in San Francisco’s Chinatown, a Hmong street sign in rural North Carolina, a meditating Falun Gong protestor in Washington, D.C., a bubble tea Valley Girl, and a Chinese theme park in Orlando. Huie’s camera captures ABCs, FOAs, and a self-described “redneck” Chinese restaurant owner near the Okefenokee Swamp. Taken together the photographs reveal a complex portrait of the U.S. cultural landscape, and their dignified elegance invites a closer, deeper look. Accompanied by the personal reflections of both Wing and Tara Huie, the nearly one hundred spectacular photos tell a story that both mirrors and contradicts stereotypes of Asian Americans, ultimately questioning what it means to be ethnic and American in the twenty-first century. Wing Young Huie has received widespread acclaim for his works, including Lake Street USA, documenting the cultural landscape of his native Minnesota. He is a recipient of a Bush Artist Fellowship and two-time recipient of the McKnight Photography Fellowship. He lives in Minneapolis. Frank H. Wu is dean of Wayne State University Law School and the author of Yellow: Race in America Beyond Black and White. Anita Gonzalez teaches in the Master of Liberal Studies Program at the University of Minnesota. (shrink)

Complex, multigenic biological traits are shaped by the emergent interaction of proteins being the main functional units at the molecular scale. Based on a phenomenological approach, algorithms for quantifying two different aspects of emergence were introduced (Wegner and Hao in Progr Biophys Mol Biol 161:54–61, 2021) describing: (i) pairwise reciprocal interactions of proteins mutually modifying their contribution to a complex trait (denoted as weak emergence), and (ii) formation of a new, complex trait by a set of n ‘constitutive’ proteins at (...) concentrations exceeding individual threshold values (strong emergence). The latter algorithm is modified here to take account of protein redundancy with respect to a complex trait (‘full redundancy’). Irreducibility is considered a necessary and sufficient criterion for strong biological emergence; if one constitutive protein is missing, or its concentration drops below the threshold the trait is lost. A definition based on ‘unpredictability’ is dismissed, because this criterion is irrelevant for the evolution of a complex trait, and apparent unpredictability may rather reflect our basic deficits in understanding unless we can provide an unequivocal proof for it. The phenomenological approach advocated here allows to identify hidden rules according to which strongly emergent traits may be organized. This is of high value for understanding the evolution of complex traits which seems to require the saltational advent of all constitutive proteins ‘in one turn’ to arrive at a functional trait providing for an improved fitness of the organism. Rather than being a purely random process, it may be guided by fundamental structural principles. (shrink)

IPCC SPECIAL REPORT ON CLIMATE CHANGE AND LAND (SRCCL) -/- Chapter 3: Climate Change and Land: An IPCC special report on climate change, desertification, land degradation, sustainable land management, food security, and greenhouse gas fluxes in terrestrial ecosystems.

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)

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)

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)

Neurosurgery for psychiatric disorders, also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to (...) set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law, what types of regulations are required, and how to approach international harmonization given the potential migration of researchers and patients. (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)