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Using [18F]altanserin, a serotonin 2A receptor (5-HT2AR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT2AR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT2AR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT2AR and neuroticism are both modulated by HPA axis function.
Aims
In this study, we examined whether the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT2AR agonist tracer [11C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT2AR and reduce neuroticism.
Method
Eighty healthy volunteers underwent [11C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT2AR binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.
Results
The study confirms the positive association between 5-HT2AR binding and the inward facets of neuroticism (β = 0.01, 95% CI = [0.0005: 0.02], P = 0.04), and this association is independent of CAR (P = 0.33).
Conclusions
The findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT2AR and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.
Objectives: We estimated the change to health-service costs and health benefits resulting from a decision to adopt temporary isolation rooms, which are effective at isolating the patient within a general ward environment. We assessed the cost-effectiveness of the decision to adopt temporary isolation rooms in a Singapore hospital. Methods: Existing data were used to update a model of the impact of adopting temporary isolation rooms on healthcare-associated infections. We predicted the expected change to health service costs and health benefits, measured in life years gained. Uncertainty was addressed using probabilistic sensitivity analysis, and the findings were tested with plausible scenarios to determine the effectiveness of the intervention. Results: We predicted 478 fewer HAIs per 100,000 occupied bed days resulting from a decision to adopt temporary isolation rooms. This decreased would result in cost savings of SGD$329,432 (US $247,302) and 1,754 life years gained. When the effectiveness of the intervention was set at 1% of cases of HAI prevented, the incremental cost per life year saved was SGD$16,519 (US $12,400), indicating that this would be a cost-effective measure in Singapore. Conclusions: We have provided evidence that adoption of a temporary isolation room would be cost-effective for Singapore acute-care hospitals. Using temporary isolation rooms may be a positive decision for other countries in the region with fewer resources for infection prevention and control.
Science forms a vital part of animal welfare assessment. However, many animal welfare issues are more influenced by public perception and political pressure than they are by science. The discipline of epidemiology has had an important role to play in examining the effects that management, environment and infrastructure have on animal-based measures of welfare. Standard multifactorial analyses have been used to investigate the effects of these various inputs on outcomes such as lameness. Such research has thereby established estimates of the probability of occurrence of these adverse welfare outcomes (AWOs) and given exposure to particular management inputs (welfare challenges). Welfare science has established various measures of the consequences of challenges to welfare. In this paper, a method is proposed for comparing the likely impact of different welfare challenges, incorporating both the probability of AWOs resulting from that welfare challenge, and their impacts or consequences if they do, using risk assessment principles. The rationale of this framework is explained. Its scope lies within a science-based risk assessment framework. This method does not provide objective measures or score of welfare without some context of comparison and does not provide new welfare measures but only provides a framework enabling objective comparison. Possible applications of this method include comparing the effects of specific management inputs, assigning priority to welfare challenges in order to inform allocation of resources for addressing those challenges, and comparisons of the lifetime welfare effects of management inputs or systems. The use of risk assessment methods in the animal welfare field can facilitate objective comparisons of situations that are currently assessed with some level of subjectivity. This methodology will require significant validation to determine its most productive use. The risk assessment approach could have a productive role in advancing quantitative assessment in animal welfare science.
In Australia, flystrike can severely compromise sheep welfare. Traditionally, the surgical practice of mulesing was performed to alter wool distribution and breech conformation and thereby reduce flystrike risk. The aim of this study was to use published data to evaluate the effectiveness of an epidemiologically based risk assessment model in comparing welfare outcomes in sheep undergoing mulesing, mulesing with pain relief, plastic skin-fold clips, and no mulesing. We used four measures, based on cortisol, haptoglobin, bodyweight and behavioural change, across three farming regions in Australia. All data were normalised to a common scale, based on the range between the highest and lowest responses for each variable (‘welfare impact’; I). Lifetime severity of welfare challenge (SWC) was estimated by summing annual SWCs (SWC = I × P, where P = probability of that impact occurring). The severity of welfare challenge during the first year of life was higher for mulesed animals compared to unmulesed. However, over five years of life, the highest severity of welfare challenge was for unmulesed animals, and the lowest was for the plastic skin-fold clips. The model produced estimates of SWC that are in broad agreement with expert consensus that, although mulesing historically represented a welfare benefit for sheep under Australian conditions, the replacement of mulesing with less invasive procedures, and ultimately genetic selection combined with anti-fly treatments, will provide a sustainable welfare benefit. However, the primary objective of this work was to evaluate the use of the risk assessment framework; not to compare welfare outcomes from mulesing and its alternatives.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.
Technical summary
A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.
Social media summary
How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
This study examined the impact of a school readiness intervention on external response monitoring in children in foster care. Behavioral and event-related potential (ERP) data were collected during a flanker task from children who received the Kids In Transition to School (KITS) Program (n = 26) and children who received services as usual (n = 19) before and after the intervention. While there were no significant group differences on the behavioral data, the ERP data for the two groups of children significantly differed. Specifically, in contrast to the children who received services as usual, the children who received the KITS Program displayed greater amplitude differences between positive and negative performance feedback over time for the N1, which reflects early attention processes, and feedback-related negativity, which reflects evaluation processes. In addition, although the two groups did not differ on amplitude differences between positive and negative performance feedback for these ERP components before the intervention, the children who received the KITS Program displayed greater amplitude differences than the children who received services as usual after the intervention. These results suggest that the KITS Program had an effect on responsivity to external performance feedback, which may be beneficial during the transition into kindergarten.
Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7–73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
A preliminary investigation of the synthesis and characterization of simulant ‘lava-like’ fuel containing materials (LFCM), as low activity analogues of LFCM produced by the melt down of Chernobyl Unit 4. Simulant materials were synthesized by melting batched reagents in a tube furnace at 1500 °C, under reducing atmosphere with controlled cooling to room temperature, to simulate conditions of lava formation. Characterization using XRD and SEM-EDX identified several crystalline phases including ZrO2, UOx and solid solutions with spherical metal particles encapsulated by a glassy matrix. The UOX and ZrO2 phase morphology was very diverse comprising of fused crystals to dendritic crystallites from the crystallization of uranium initially dissolved in the glass phase. This project aims to develop simulant LFCM to assess the durability of Chernobyl lavas and to determine the rate of dissolution, behavior and evolution of these materials under shelter conditions.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.