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"Griffiths, R."
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China and the West : McMaster and Pillsbury vs. Mahbubani and Wang
\"Increasingly in the West, China is being characterized as a threat to the liberal international order, one that must be overcome through economic, political, technological, and even military means. For those who believe that the policies of the Chinese Communist Party pose a threat to free and open societies, the U.S. and like-minded nations must band together to preserve a rules-based international order. For others, this approach spells disaster; it ignores the history and dynamics propelling China's rise to superpower status. Rather than threatening the post-war order, China is its best, and maybe only, guarantor in an era of declining U.S. leadership, increased regional instability, and slowing global growth. The twenty-fourth semi-annual Munk Debate, held on May 9, 2019, pits former Assistant to the President for National Security Affairs H.R. McMaster and Director for Chinese Strategy at the D.C.-based Hudson Institute think tank Michael Pillsbury against former President of the United Nations Security Council Kishore Mahbubani and president of one of China's top independent think tanks, the Center for China Globalization, Huiyao Wang to debate the threat of China to the liberal international order.\"-- Provided by publisher.
Book
Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention
Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum is a subcortical nucleus that highly expresses 5-HT2A receptors and provides glutamatergic inputs to arguably all areas of the cerebral cortex. We therefore tested the hypothesis that psilocybin modulates claustrum function in humans. Fifteen healthy participants (10M, 5F) completed this within-subjects study in which whole-brain resting-state blood-oxygenation level-dependent (BOLD) signal was measured 100 min after blinded oral administration of placebo and 10 mg/70 kg psilocybin. Left and right claustrum signal was isolated using small region confound correction. Psilocybin significantly decreased both the amplitude of low frequency fluctuations as well as the variance of BOLD signal in the left and right claustrum. Psilocybin also significantly decreased functional connectivity of the right claustrum with auditory and default mode networks (DMN), increased right claustrum connectivity with the fronto-parietal task control network (FPTC), and decreased left claustrum connectivity with the FPTC. DMN integrity was associated with right-claustrum connectivity with the DMN, while FPTC integrity and modularity were associated with right claustrum and left claustrum connectivity with the FPTC, respectively. Subjective effects of psilocybin predicted changes in the amplitude of low frequency fluctuations and the variance of BOLD signal in the left and right claustrum. Observed effects were specific to claustrum, compared to flanking regions of interest (the left and right insula and putamen). This study used a pharmacological intervention to provide the first empirical evidence in any species for a significant role of 5-HT2A receptor signaling in claustrum functioning, and supports a possible role of the claustrum in the subjective and therapeutic effects of psilocybin.
Journal Article
Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects
Rationale
This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.
Objectives
This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions.
Methods
Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up.
Results
Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects.
Conclusions
Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.
Journal Article
Survey of subjective \God encounter experiences\: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT
Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose \"God\" as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose \"Ultimate Reality.\" Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
Journal Article
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance
Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects.
This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions.
The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior.
Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers.
When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
Journal Article
Additive Friction Stir-Enabled Solid-State Additive Manufacturing for the Repair of 7075 Aluminum Alloy
The repair of high strength, high performance 7075 aluminum alloy is essential for a broad range of aerospace and defense applications. However, it is challenging to implement it using traditional fusion welding-based approaches, owing to hot cracking and void formation during solidification. Here, the use of an emerging solid-state additive manufacturing technology, additive friction stir deposition, is explored for the repair of volume damages such as through -holes and grooves in 7075 aluminum alloy. Three repair experiments have been conducted: double through-hole filling, single through-hole filling, and long, wide-groove filling. In all experiments, additive friction stir deposition proves to be effective at filling the entire volume. Additionally, sufficient mixing between the deposited material and the side wall of the feature is always observed in the upper portions of the repair. Poor mixing and inadequate repair quality have been observed in deeper portions of the filling in some scenarios. Based on these observations, the advantages and disadvantages of using additive friction stir deposition for repairing volume damages are discussed. High quality and highly flexible repairs are expected with systematic optimization work on process control and repair strategy development in the future.
Journal Article
Land management shapes drought responses of dominant soil microbial taxa across grasslands
Soil microbial communities are dominated by a relatively small number of taxa that may play outsized roles in ecosystem functioning, yet little is known about their capacities to resist and recover from climate extremes such as drought, or how environmental context mediates those responses. Here, we imposed an in situ experimental drought across 30 diverse UK grassland sites with contrasting management intensities and found that: (1) the majority of dominant bacterial (85%) and fungal (89%) taxa exhibit resistant or opportunistic drought strategies, possibly contributing to their ubiquity and dominance across sites; and (2) intensive grassland management decreases the proportion of drought-sensitive and non-resilient dominant bacteria—likely via alleviation of nutrient limitation and pH-related stress under fertilisation and liming—but has the opposite impact on dominant fungi. Our results suggest a potential mechanism by which intensive management promotes bacteria over fungi under drought with implications for soil functioning.
Soil microbial communities are affected by climate extremes. Here, the authors impose experimental drought across 30 UK grasslands showing that bacteria and fungi exhibit drought resistance but that intensive management has a negative impact on fungi drought resilience.
Journal Article
Emotions and brain function are altered up to one month after a single high dose of psilocybin
Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin.
Journal Article
Adipose tissue macrophages as potential targets for obesity and metabolic diseases
Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9 + macrophages, lipid-associated macrophages, DARC + macrophages, and MFe hi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases.
Journal Article