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Findings from contemporary clinical trials suggest that psychedelics are generally safe and may be effective in the treatment of various psychiatric disorders. However, less is known about the risks associated with psychedelic use outside of medically supervised contexts, particularly in populations that are typically excluded from participation in clinical trials.
Methods
Using a preregistered longitudinal observational research design with a purposive sample of US residents between 18 and 50 years old (N=21,990), we investigated associations between self-reported naturalistic psychedelic use and psychotic and manic symptoms, with emphasis on those with psychiatric histories of schizophrenia or bipolar I disorder.
Results
The follow-up survey was completed by 12,345 participants (56% retention), with 505 participants reporting psychedelic use during the 2-month study period. In covariate-adjusted regression models, psychedelic use during the study period was associated with increases in the severity of psychotic and manic symptoms. However, such increases were only observed for those who reported psychedelic use in an illegal context. While increases in the severity of psychotic symptoms appeared to depend on the frequency of use and the intensity of challenging psychedelic experiences, increases in the severity of manic symptoms appeared to be moderated by a personal history of schizophrenia or bipolar I disorder and the subjective experience of insight during a psychedelic experience.
Conclusions
The findings suggest that naturalistic psychedelic use specifically in illegal contexts may lead to increases in the severity of psychotic and manic symptoms. Such increases may depend on the frequency of use, the acute subjective psychedelic experience, and psychiatric history.
The discovery of more than 600 whole and fragmentary engraved stone plaques in the early third millennium BC infill from the ditches of a causewayed enclosure at Vasagård, on the Danish island of Bornholm, represents a unique find in Neolithic miniature art. Termed ‘sun stones’ in reference to the rayed images that characterise many of the plaques, the stones were deposited en masse over a short period. This article offers a fundamental classification of the rich imagery captured in the engravings and examines its potential function at a time of possible climatic crisis that impacted not just Bornholm but the wider northern hemisphere.
Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation.
Methods
Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity (N = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice.
Results
The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week (B = 0.40, p = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week (B = 0.42, p = 0.021; B = 0.38, p = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period (B = −0.29, p = 0.037).
Conclusions
Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.
We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.
Technical summary
We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.
Social media summary
Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.
The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.
The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
Kinetoplastid parasites are responsible for both human and animal diseases across the globe where they have a great impact on health and economic well-being. Many species and life cycle stages are difficult to study due to limitations in isolation and culture, as well as to their existence as heterogeneous populations in hosts and vectors. Single-cell transcriptomics (scRNA-seq) has the capacity to overcome many of these difficulties, and can be leveraged to disentangle heterogeneous populations, highlight genes crucial for propagation through the life cycle, and enable detailed analysis of host–parasite interactions. Here, we provide a review of studies that have applied scRNA-seq to protozoan parasites so far. In addition, we provide an overview of sample preparation and technology choice considerations when planning scRNA-seq experiments, as well as challenges faced when analysing the large amounts of data generated. Finally, we highlight areas of kinetoplastid research that could benefit from scRNA-seq technologies.
Decreased levels of polyunsaturated membrane fatty acids (PUFA) and increased activity of cytosolic phospholipase A2 (PLA2) enzymes (key regulating enzymes of membrane remodelling and PUFA availability) are supporting pillars of the “membrane phospholipids concept of schizophrenia”. Assuming that membrane PUFA profile and PLA2 activity are altered during the at risk phase of disorder and influenced by fatty acid supplementation, we investigated PUFA profiles and PLA2 activity simultaneously in ultra high-risk (UHR) subjects before and after (n-3) fatty acids supplementation.
Method
In 81 UHR patients (aged between 13 and 25 years) PUFA levels were assessed in erythrocyte membranes using gas chromatography, and cytosolic PLA2 activity was measured in blood serum using a fluorometric HPTLC-based assay. Measurements were performed before and after a 6 month interval of placebo-controlled supplementation with n-3 fatty acids.
Results
At baseline significant associations were found between (n-9) and (n-6)-PUFA levels and psychopathology (especially in negative symptoms) assessed by the PANSS according to PACE criteria. (n-3)-PUFA supplementation caused significant changes in (n-3)- and (n-6)-PUFA levels and a significant decrease of PLA2 activity.
Conclusion
Our results support associations between membrane biochemistry and psychopathology (especially negative symptoms) in people at risk to develop psychosis. Supplementation of n-3 PUFA increases PUFA availability at membrane level and modulates membrane repair and remodelling processes. Assuming that PLA2 activity reflects neuronal damage, PUFA supplementation might unfold neuroprotective effects.
Verbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms.
Method
Forty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed.
Results
The working memory span was significantly impaired in patients (F(1,90) = 4.6, P < 0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89) = 0.03, P = 0.86, and F(1,89) = 0.03, P = 0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r = –0.52, P < 0.0001) and thought disorganisation (r = –0.34, P < 0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (β = –0.12, P = 0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (β = –0.10, P = 0.26).
Conclusions
Decrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.
Impaired social functioning is a hallmark characteristic of several mental disorders including those characterized by paranoid ideation (P) and social anxiety (SA). Social deficits have been related to impaired social cognition.
Objectives
To investigate the neurofunctional basis of social cognition in people with subclinical P and SA.
Methods
13 healthy participants with high paranoid ideation; 12 healthy participants with high social anxiety. Procedures and Instruments: Paranoid Thoughts Scale, Liebowitz Social Anxiety Scale, Cardiff Anomalous Perceptions Scale. Brain response to social stimuli was investigated with two event-related fMRI experiments with implicit processing of facial. expressions of happiness and anger in two different intensities, and with faces expressing no emotion.
Results
People with P recruit differentially and positively the Left Lingual (p < 0,05 FWEcorr), and close to significant (p < 0,06 FWEcorr) the Right Caudate when processing neutral faces. People with SA only showed significant positive differences (p < 0,05 FWEcorr) in the Right Inferior frontal gyrus when processing anger stimuli at 100%. When comparing both groups, we did not find significant differences.
Conclusions
The preliminary results indicate a stronger recruitment of emotional and visual areas in P subjects when processing neutral faces and a stronger recruitment of cognitive processing areas in SA subjects when processing angry faces.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.
Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. Current guidelines recommend systematic evaluation and management of neurodevelopmental outcomes with referral for early intervention services. The Single Ventricle Reconstruction Trial represents the largest cohort of children with hypoplastic left heart syndrome ever assembled. Data on life events and resource utilisation have been collected annually. We sought to determine the type and prevalence of early intervention services used from age 1 to 4 years and factors associated with utilisation of services.
Methods
Data from 14-month neurodevelopmental assessment and annual medical history forms were used. We assessed the impact of social risk and geographic differences. Fisher exact tests and logistic regression were used to evaluate associations.
Results
Annual medical history forms were available for 302 of 314 children. Greater than half of the children (52–69%) were not receiving services at any age assessed, whereas 20–32% were receiving two or more therapies each year. Utilisation was significantly lower in year 4 (31%) compared with years 1–3 (with a range from 40 to 48%) (p<0.001). Social risk factors were not associated with the use of services at any age but there were significant geographic differences. Significant delay was reported by parents in 18–43% of children at ages 3 and 4.
Conclusion
Despite significant neurodevelopmental delays, early intervention service utilisation was low in this cohort. As survival has improved for children with hypoplastic left heart syndrome, attention must shift to strategies to optimise developmental outcomes, including enrolment in early intervention when merited.
Friedrich Schiller is not merely one of Germany's foremost poets. He is also one of the major German contributors to world literature. The undying words he gave to characters such as Marquis Posa in Don Carlos and Wilhelm Tell in the eponymous drama continue to underscore the need for human freedom. Schiller cultivated hope in the actualization of moral knowledge through aesthetic education and critical reflection, leading to his ideal of a more humane humanity. At the same time, he was fully cognizant of the problems that attend various forms of idealism. Yet for Schiller, ultimately, love remains the gravitational center of the universe and of human existence, and beyond life and death joy prevails. This collection of cutting-edge essays by some of the world's leading Schiller experts constitutes a milestone in scholarship. It includes in-depth discussions of the writer's major dramatic and poetic works, his essays on aesthetics, and his activities as historian, anthropologist, and physiologist, as well as of his relation to the ancients and of Schiller reception in 20th-century Germany.
Contributors: Steven D. Martinson, Walter Hinderer, David Pugh, Otto Dann, Werner von Stransky-Stranka-Greifenfels, J. M. van der Laan, Rolf-Peter Janz, Lesley Sharpe, Norbert Oellers, Dieter Borchmeyer, Karl S. Guthke, Wulf Koepke.
Steven D. Martinson is Professor of German at the University of Arizona.
Counter-propagating and suitably polarized light (laser) beams can provide conditions for pair production. Here, we consider in more detail the following two situations: (i) in the homogeneity regions of anti-nodes of linearly polarized ultra-high intensity laser beams, the Schwinger process is dynamically assisted by a second high-frequency field, e.g. by an XFEL beam; and (ii) a high-energy probe photon beam colliding with a superposition of co-propagating intense laser and XFEL beams gives rise to the laser-assisted Breit–Wheeler process. The prospects of such bi-frequent field constellations with respect to the feasibility of conversion of light into matter are discussed.
The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.
Method.
Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.
Results.
Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.
Conclusions.
Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.
Feed intake behavior was studied between 9 weeks of age and slaughter in a total of 36 gilts, 32 immunocastrates, 33 surgically castrated barrows and 33 boars from 36 litters. Consequences for the concentration of substances contributing to off odor of pork (skatole, indole) were evaluated. Animals were kept in groups of 12 pigs of the same sex and treatment and fed ad libitum (13.4 MJ ME, 17% CP, 1.1% lysine). Individual feed intake behavior was recorded continuously by an electronic feeder. Immunocastration was carried out with two injections of Improvac with at least 4 weeks between both injections (1st: 12 to 17 weeks of age, 2nd: 19 to 21 weeks of age). Feed intake/day increased from an average of 0.91 ± 0.02 kg/day up to 3.15 ± 0.04 kg/day before slaughter. This increase was associated with a 50% reduction in the number of meals/day (from 15.8 ± 0.44 to 7.2 ± 0.29 meals/day). The larger meal sizes resulted from an increase in both, the duration of feed intake/meal and the feed intake rate (g/min). In addition, sex and treatment differences were observed: Feed intake in boars was lower than in all other groups due to a reduction in the number of meals/day and in the time spent feeding/day. In females, time spent feeding/day was quite similar to boars, but resulted from a higher number of meals of shorter duration. Barrows had a significantly higher feed intake because of a higher number of meals/day resulting in more time spent feeding/day. The feed intake rate was similar in boars, gilts and barrows and showed an increasing trend during the study, starting from about 15 g/min up to four times the amount. Immunocastration affected feed intake behavior severely, especially the meal size increased dramatically because of higher feed intake rate, which exceeded that of all other groups by 25% at the end of the study. The number of meals/day was not influenced by immunocastration and was almost identical to that of boars. Highest skatole concentrations were measured in fat of boars, whereas indole concentrations were higher in immunocastrates than in all other groups. In gilts and barrows, skatole concentrations were related to growth rate. Additionally, the feeding rate was an important factor explaining the variability in skatole/indole concentrations in adipose tissue. The physiological mechanisms however need further clarification.
Predicting and evaluating response to therapy may become one of the most important indications for FDG-PET in oncology. The FDG-PET result could serve as a surrogate for actual patient outcomes in clinical practice and in drug development. The FDG-PET end result can be qualitative or, increasingly often, quantitative.
In this context, three methodological aspects of a totally different nature are of crucial importance: getting the right numbers out of the scan (standardization, validation of simplified quantitative measures), validating the biological relevance of the tracer signal (changes), and developing and validating the response criteria. In this chapter, examples of each of these domains (physics, biology, and epidemiology) will be discussed. To some extent, the cases have been modified from actual practice for didactical reasons.
A 62-year-old female with locally advanced cancer of the leftbreast was treated with experimental neoadjuvant chemotherapy.No data have been published on FDG-PET and this newtherapeutic agent. A secondary aim of the study is to explorethe use of FDG-PET to evaluate the response to this therapy.
Acquisition and processing parametersand findings
Dynamic FDG-PET scans were obtained at baseline and afterone cycle of therapy. The PET scanner (ECAT EXACT HR+;Siemens/CTI, Knoxville) used provides an axial field of view of15.5 cmand produces 63 transaxial slices with a slice thickness of2.5mm. The patient fasted for at least 6 hours prior to theimaging sessions. The patient was scanned in the supine positionwith arms at her sides. The patient was positioned in such a waythat the dominant lesions were in the center of the field of view.