Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

We examine metonymy at psycho- and neurolinguistic levels, seeking to adjudicate between two possible processing implementations. We compare highly conventionalized systematic metonymy to lesser-conventionalized circumstantial metonymy. Whereas these two metonymy types differ in terms of contextual demands, they each reveal a similar dependency between the named and intended conceptual entities. We reason that if each metonymy yields a distinct processing time course and substantially non-overlapping preferential localization pattern, it would not only support a two-mechanism view but would suggest that conventionalization (...) acts as a linguistic categorizer. By contrast, a similar behavior in time course and localization would support a one-mechanism view and the inference that conventionalization acts instead as a modulator of contextual felicitousness, and that differences in interpretation introduced by conventionalization are of degree, not of kind. Results from three paradigms: self-paced reading, event-related potentials, and functional magnetic resonance imaging, reveal the following: no main effect by condition for either metonymy type immediately after the metonymy trigger, and a main effect for only the Circumstantial metonymy one word post-trigger ; a N400 effect across metonymy types and a late positivity for Circumstantial metonymy ; and a highly overlapping activation connecting the left ventrolateral prefrontal cortex and the left dorsolateral prefrontal cortex. Altogether, the pattern observed does not reach the threshold required to justify a two-mechanism system. Instead, the pattern is more naturally understood as resulting from the implementation of a generalized referential dependency mechanism, modulated by degree of context dependence/conventionalization, thus supporting architectures of language whereby “lexical” and “pragmatic” meaning relations are encoded along a cline of contextual underspecification. (shrink)

Advances in intracranial electroencephalography and neurophysiology have enabled the study of previously inaccessible brain regions with high fidelity temporal and spatial resolution. Studies of iEEG have revealed a rich neural code subserving healthy brain function and which fails in disease states. Machine learning, a form of artificial intelligence, is a modern tool that may be able to better decode complex neural signals and enhance interpretation of these data. To date, a number of publications have applied ML to iEEG, but clinician (...) awareness of these techniques and their relevance to neurosurgery, has been limited. The present work presents a review of existing applications of ML techniques in iEEG data, discusses the relative merits and limitations of the various approaches, and examines potential avenues for clinical translation in neurosurgery. One-hundred-seven articles examining artificial intelligence applications to iEEG were identified from 3 databases. Clinical applications of ML from these articles were categorized into 4 domains: i) seizure analysis, ii) motor tasks, iii) cognitive assessment, and iv) sleep staging. The review revealed that supervised algorithms were most commonly used across studies and often leveraged publicly available timeseries datasets. We conclude with recommendations for future work and potential clinical applications. (shrink)

While N6‐methyladenosine (m6A) is a well‐known epigenetic modification in bacterial DNA, it remained largely unstudied in eukaryotes. Recent studies have brought to fore its potential epigenetic role across diverse eukaryotes with biological consequences, which are distinct and possibly even opposite to the well‐studied 5‐methylcytosine mark. Adenine methyltransferases appear to have been independently acquired by eukaryotes on at least 13 occasions from prokaryotic restriction‐modification and counter‐restriction systems. On at least four to five instances, these methyltransferases were recruited as RNA methylases. Thus, (...) m6A marks in eukaryotic DNA and RNA might be more widespread and diversified than previously believed. Several m6A‐binding protein domains from prokaryotes were also acquired by eukaryotes, facilitating prediction of potential readers for these marks. Further, multiple lineages of the AlkB family of dioxygenases have been recruited as m6A demethylases. Although members of the TET/JBP family of dioxygenases have also been suggested to be m6A demethylases, this proposal needs more careful evaluation. (shrink)

Success in online and blended courses requires engaging in self-regulated learning, especially for challenging STEM disciplines, such as physics. This involves students planning how they will navigate course assignments and activities, setting goals for completion, monitoring their progress and content understanding, and reflecting on how they completed each assignment. Based on Winne & Hadwin’s COPES model, SRL is a series of events that temporally unfold during learning, impacted by changing internal and external factors, such as goal orientation and content difficulty. (...) Thus, as goal orientation and content difficulty change throughout a course, so might students’ use of SRL processes. This paper studies how students’ SRL behavior and achievement goal orientation change over time in a large college introductory level physics course taught online. Students’ achievement goal orientation was measured by repeated administration of the achievement goals questionnaire-revised. Students’ SRL behavior was measured by analyzing their clickstream event traces interacting with online learning modules via a combination of trace clustering and process mining. Event traces were first divided into groups similar in nature using agglomerative clustering, with similarity between traces determined based on a set of derived characteristics most reflective of students’ SRL processes. We then generated causal nets for each cluster of traces via process mining and interpreted the underlying behavior and strategy of each causal net according to the COPES SRL framework. We then measured the frequency at which students adopted each causal net and assessed whether the adoption of different causal nets was associated with responses to the AGQ-R. By repeating the analysis for three sets of online learning modules assigned at the beginning, middle, and end of the semester, we examined how the frequency of each causal net changed over time, and how the change correlated with changes to the AGQ-R responses. Results have implications for measuring the temporal nature of SRL during online learning, as well as the factors impacting the use of SRL processes in an online physics course. Results also provide guidance for developing online instructional materials that foster effective SRL for students with different motivational profiles. (shrink)

PURPOSE:To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS:Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS:The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS:In a family with autosomal dominant (...) drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration. (shrink)

As the capabilities of Artificial Intelligence (AI) have increased over recent years, so have the challenges of how to govern its usage. Consequently, prominent stakeholders across academia, government, industry, and civil society have called for states to devise and deploy principles, innovative policies, and best practices to regulate and oversee these increasingly powerful AI tools. Developing a robust AI governance system requires extensive collective efforts throughout the world. It also raises old questions of politics, democracy, and administration, but with the (...) new challenges posed by AI's growing influence on markets, governing structures, international relations, healthcare, science, and political activism. The Oxford Handbook of AI Governance delineates the scope of these issues and addresses the key questions of AI governance. Across forty-nine chapters, organized in nine major sections, the Handbook covers the theoretical and ethical foundations of AI governance, different frameworks for developing a governance structure for AI, practical perspectives on AI governance in different policy domains, economic analyses of AI governance, and concrete lessons about the impact of AI governance domestically and internationally. Chapter authors come from a wide set of disciplines, areas of study, and cultural backgrounds, providing a global perspective on AI governance. (shrink)

ObjectiveDespite its prevalence, insomnia disorder remains poorly understood. In this study, we used machine learning to analyze the functional connectivity disturbances underlying ID, and identify potential predictors of treatment response through recurrent transcranial magnetic stimulation and pharmacotherapy.Materials and methods51 adult patients with chronic insomnia and 42 healthy age and education matched controls underwent baseline anatomical T1 magnetic resonance imaging, resting-stage functional MRI, and diffusion weighted imaging. Imaging was repeated for 24 ID patients following four weeks of treatment with pharmacotherapy, with (...) or without rTMS. A recently developed machine learning technique, Hollow Tree Super was used to classify subjects into ID and control groups based on their FC, and derive network and parcel-based FC features contributing to each model. The number of FC anomalies within each network was also compared between responders and non-responders using median absolute deviation at baseline and follow-up.ResultsSubjects were classified into ID and control with an area under the receiver operating characteristic curve of 0.828. Baseline FC anomaly counts were higher in responders than non-responders. Response as measured by the Insomnia Severity Index was associated with a decrease in anomaly counts across all networks, while all networks showed an increase in anomaly counts when response was measured using the Pittsburgh Sleep Quality Index. Overall, responders also showed greater change in all networks, with the Default Mode Network demonstrating the greatest change.ConclusionMachine learning analysis into the functional connectome in ID may provide useful insight into diagnostic and therapeutic targets. (shrink)

There are differences in caregivers’ literacy and health literacy levels that may affect their ability to consent to children participating in clinical research trials. This study aimed to explore the effectiveness, and caregivers’ understandings, of the process of informed consent that accompanied their child’s participation in a dental randomized control trial (RCT). Telephone interviews were conducted with a convenience sample of ten caregivers who each had a child participating in the RCT. Pre-tested closed and open-ended questions were used, and the (...) findings were produced from an inductive analysis of the latter and a descriptive analysis of the former. Participants had limited understanding of the purpose of the RCT and rated the readability of the consent form more highly than they rated their understanding of the research. All felt that informed consent was vital, but some caregivers had not read the consent documents. Some caregivers enrolled their child in the RCT because they trusted the researchers, and the majority wanted to improve dental care for children. The informed consent process was not always effective despite high readability of the informed consent documents. Researchers must consider the health literacy of the study group, and actively engaging with caregivers to achieve meaningful informed consent may be challenging. Future research could explore participants’ perspectives of informed consent in populations with low health literacy and assess whether an underlying expectation not to comprehend health-related information may be a barrier to informed consent. (shrink)

Coronavirus disease 2019 can lead to respiratory failure. Some patients require extracorporeal membrane oxygenation support. During the current pandemic, health care resources in some cities have been overwhelmed, and doctors have faced complex decisions about resource allocation. We present a case in which a pediatric hospital caring for both children and adults seeks to establish guidelines for the use of extracorporeal membrane oxygenation if there are not enough resources to treat every patient. Experts in critical care, end-of-life care, bioethics, and (...) health policy discuss if age should guide rationing decisions. (shrink)

Children bring intuitive arithmetic knowledge to the classroom before formal instruction in mathematics begins. For example, children can use their number sense to add, subtract, compare ratios, and even perform scaling operations that increase or decrease a set of dots by a factor of 2 or 4. However, it is currently unknown whether children can engage in a true division operation before formal mathematical instruction. Here we examined the ability of 6- to 9-year-old children and college students to perform symbolic (...) and non-symbolic approximate division. Subjects were presented with non-symbolic or symbolic dividends ranging from 32 to 185, and non-symbolic divisors ranging from 2 to 8. Subjects compared their imagined quotient to a visible target quantity. Both children and adults were successful at the approximate division tasks in both dots and numeral formats. This was true even among the subset of children that could not recognize the division symbol or solve simple division equations, suggesting intuitive division ability precedes formal division instruction. For both children and adults, the ability to divide non-symbolically mediated the relation between Approximate Number System acuity and symbolic math performance, suggesting that the ability to calculate non-symbolically may be a mechanism of the relation between ANS acuity and symbolic math. Our findings highlight the intuitive arithmetic abilities children possess before formal math instruction. (shrink)

The examination of the complex cell biology of the human malaria parasite Plasmodium falciparum usually relies on the time‐consuming generation of transgenic parasites. Here, metabolic labeling and click chemistry are employed as a fast transfection‐independent method for the microscopic examination of protein S‐palmitoylation, an important post‐translational modification during the asexual intraerythrocytic replication of P. falciparum. Applying various microscopy approaches such as confocal, single‐molecule switching, and electron microscopy, differences in the extent of labeling within the different asexual developmental stages of P. (...) falciparum and the host erythrocytes over time are observed. (shrink)

Since male CEOs dominate corporate leadership, the literature on top management decision making suffers from an implicit masculine bias. Although research indicates that males and females are biologically and psychologically different, the leadership characteristics of female CEOs are largely unexplored. Two of these characteristics, risk aversion and ethical sensitivity, are tied to key accounting issues, such as conservatism in financial reporting and steadfast opposition to fraud. In this study, we examine the relationship between CEO gender and accounting conservatism, and find (...) a positive association between the two. Consistent with conventional wisdom, this association appears to be stronger in firms with high rather than low litigation and takeover risks. This study contributes to the ethics literature by highlighting the benefits of gender diversity in upholding the integrity of financial reporting. (shrink)

Evidence from our research on young children's temporal understanding supports Hoerl & McCormack's view that young children rely on a temporal updating system to change representations over time. We propose that the shift from temporal updating to temporal reasoning is enabled by children's expanding representations of event sequences, along with developments in language, memory, and other cognitive competencies.

The teacher self is a composite psychological construct which encompasses the cognitive, affective, emotional, and social dimensions of teaching. This qualitative study draws on Bakhtin’s concepts of dialogism, answerability, and addressivity to discuss how English language teachers negotiated the shifting and conflictive context to construct selves in relation to the promoted communicative language teaching approach. Based on narrative interviews and classroom observations with five tertiary English teachers in China, we found that these teachers were actively engaged in the dialog with (...) their prior learning experiences and active, responsive in answering their contexts while authoring selves in everyday teaching practice. The multiple-case study data support a Bakhtinian understanding that teachers are active users and producers of theory in their own right, highlighting teachers’ agency, creativity, and autonomy. Based on Bakhtin’s dialogism and the case study findings, we bring cognition, identity and practice together and conceptualize the teacher self as having multiple facets and layers: the autobiographical self, the discursive self, and the pedagogical self. The three selves are constitutive of the consummated whole of the teacher self instead of being separate entities functioning individually. The study is concluded with implications for language teacher education and teacher development. (shrink)

The hematopoietic system consists of more than ten differentiated cell types, all of which are derived from a single type of hematopoietic stem cell. The accessibility and interest of this system have made it a model for understanding normal and abnormal differentiation of mammalian cells. Newer techniques have generated a mass of data that requires integrative approaches for analysis and interpretation. The traditional view of the differentiation program holds that a small number of regulators are involved in each stage of (...) cell specification. However, this may not be the case. Recent analyses have shown that almost all substantial subsets of genes, including the set of broadly expressed transcription factors, are expressed in patterns that are unique for each lineage. Further, much of this difference between lineages can be captured in two‐dimensional graphs. Understanding the biologic significance, mechanisms and constraints underlying these differences is a challenge for experimentalists and computational biologists alike. BioEssays 26:1276–1287, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Megastable chaotic systems are somehow the newest in the family of special chaotic systems. In this paper, a new megastable two-dimensional system is proposed. In this system, coexisting attractors are in some islands, interestingly covered by megalimit cycles. The introduced two-dimensional system has no defined equilibrium point. However, it seems that the origin plays the role of an unstable equilibrium point. Therefore, the attractors are determined as hidden attractors. Adding a forcing term to the system, we can obtain chaotic solutions (...) and coexisting strange attractors. Moreover, the effect of three different values of the forcing term’s amplitude is studied. The dynamical properties of the designed system are investigated using attractor plots, bifurcation diagrams, and Lyapunov Exponents diagram. Phase portraits of the novel megastable oscillator are presented by FPGA design. Xilinx system generator block diagrams of the proposed system and trigonometric functions are also presented. (shrink)

Producing content-related gestures has been found to impact students’ learning, whether such gestures are spontaneously generated by the learner in the course of problem-solving, or participants are instructed to pose based on experimenter instructions during problem-solving and word learning. Few studies, however, have investigated the effect of (a) performing instructed gestures while learning concepts or (b) producing gestures without there being an implied connection between the gestures and the concepts being learned. The two studies reported here investigate the impact of (...) instructed hand movements on students’ subsequent understanding of a concept. Students were asked to watch an instructional video—focused on the concept of statistical model—three times. Two experimental groups were given a secondary task to perform while watching the video, which involved moving their hands to mimic the placement and orientation of red rectangular bars overlaid on the video. Students were told that the focus of the study was multitasking, and that the instructed hand movements were unrelated to the material being learned. In the content-match group the placement of the hands reinforced the concept being explained, and in the content-mismatch group it did not. A control group was not asked to perform a secondary task. In both studies, findings indicate that students in the content-match group performed better on the posttest, and showed less variation in performance, than did students in the content-mismatch group, with control students falling in between. Instructed hand movement—even when presented as an unrelated, secondary task—can affect students’ learning of a complex concept. (shrink)

The article describes an approach of systematic, rule guided qualitative text analysis, which tries to preserve some methodological strengths of quantitative content analysis and widen them to a concept of qualitative procedure. First the development of content analysis is delineated and the basic principles are explained (units of analysis, step models, working with categories, validity and reliability). Then the central procedures of qualitative content analysis, inductive development of categories and deductive application of categories, are worked out. The possibilities of computer (...) programs in supporting those qualitative steps of analysis are shown and the possibilities and limits of the approach are discussed. (shrink)

BackgroundDepressive disorders are a common form of psychiatric illness and cause significant disability. Regulation authorities, the medical profession and the public require high safety standards for antidepressants to protect vulnerable psychiatric patients. Ketamine is a dissociative anaesthetic and a derivative of a hallucinogen. Its abuse is a major worldwide public health problem. Ketamine is a scheduled drug and its usage is restricted due to its abuse liability. Recent clinical trials have reported that ketamine use led to rapid antidepressant effects in (...) patients suffering from treatment-resistant depression. However, various flaws in study designs, and possible biased reporting of results, may have influenced those findings. Further analyses of ketamine use are needed to ensure patient safety.DiscussionThe use of ketamine in research and treatment of depressive disorders is controversial. Recently, mental health professionals raised ethical concerns about an ongoing ketamine trial in the UK. Also, a Canadian agency reviewed the existing evidence and did not recommend prescribing ketamine to treat depressive disorders. Findings obtained from tightly controlled research settings cannot be easily translated to clinical practice as substance abuse is commonly comorbid with depressive disorders. An effective antidepressant should reduce severity of depressive symptoms without liability problems. Although the US FDA has not approved the use of ketamine to treat depressive disorders, some psychiatrists offer off-label repeat prescription of ketamine. Prescribing ketamine for treating depressive disorders requires substantial empirical evidence. Clinicians should also consider research findings on ketamine abuse. Depressive disorders can be chronic conditions and the current evidence does not rule out the risk of substance abuse after repeat prescription of ketamine. Off-label ketamine use in treating depressive disorders may breach ethical and moral standards, especially in countries seriously affected by ketamine abuse. This article presents two real-world clinical vignettes which highlight ethical principles and theories, including autonomy, nonmaleficience, fidelity and consequentialism, as related to off-label ketamine use.ConclusionWe urge clinicians to minimise the risk of harming patients by considering the empirical evidence on ketamine properties and attempting all standard antidepressant therapies before considering the off-label use of ketamine. (shrink)

Nowadays, the development of big data is getting faster and faster, and the related research on motion sensing recognition and complex systems under the background of big data is gradually being valued. At present, there are relatively few related researches on vertical Baduanjin in the academic circles; research in this direction can make further breakthroughs in motion sensor recognition. In order to carry out related action recognition research on the lifting action of vertical Baduanjin, this paper uses sensor technology to (...) collect the motion video image of vertical Baduanjin based on the background of big data and uses action recognition technology and related algorithms to obtain the action. Recognize the video image to obtain the data, get the acceleration, angular velocity, and EMG data, and count the end time and duration according to the change of the action. According to the data table and graph change trend compiled at the end of the experiment, we can see the following: after the data is preprocessed, the acceleration signal change range is limited to [−1, 1], and the acceleration change has a clear directionality; and, after 15 lifts of the detected object, its angular velocity in X-axis direction is basically negative. However, when the ninth lift is performed, the angular velocity of the movement in X-axis direction is 36.09, the largest of all angular velocities. When performing the 15th lifting action, the angular velocity of this action in Z-axis direction is −26.05, which is the smallest of all angular velocities. The longest duration of the left muscle discharge during the lifting action of the subject is 15.24 for the tibial anterior muscle and 8.91 for the external oblique muscle with the shortest duration. The longest discharge duration of the right muscle is also the tibial anterior muscle with 12.15, and the shortest duration is the erector spinae with 8.79. (shrink)

With the growing need to nurture students’ independent learning, English language teaching practices should reflect student-centered assessment approaches, such as self-assessment, an ultimate goal of higher education. It has been pointed out that to conduct effective self-assessment, students need to be taught systematically, and that is where teachers are expected to step in. Prior to implementing such a change in ELT, it is important to conduct research on English as a foreign language teachers’ attitudes toward, and self-efficacy beliefs about, implementing (...) self-assessment to cultivate capable student self-assessors. Although the strong global endorsement of self-assessment over the past two decades has witnessed its classroom implementation in different disciplines, such studies are scant in relation to EFL writing classrooms. To address this gap, the present qualitative research examined five Chinese tertiary EFL writing teachers’ attitudes toward and self-efficacy beliefs about student self-assessment of writing, as well as possible reasons that discourage them from engaging students in self-assessment practices. Data collected from in-depth, semi-structured interviews indicated that self-assessment, a critical element of self-regulated learning, is surprisingly missing from the teachers’ knowledge base and previous practices. Additionally, the findings offer insights into the striking differences in teachers’ understanding of, attitudes toward, and low self-efficacy beliefs about self-assessment of writing. Reasons why teachers choose not to implement self-assessment of writing are also discussed. Findings from this study contribute to a deeper understanding of how EFL teachers’ attitudes and self-efficacy beliefs are enacted in relation to their classroom assessment practices in order to move forward discussions on the feasibility of implementing self-assessment of writing in tertiary EFL classrooms. (shrink)