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Negative symptoms in schizophrenia, particularly motivational deficits, pose significant challenges to treatment and recovery. Despite their profound impact on functional outcomes, these symptoms remain poorly understood and inadequately addressed by current interventions.
Aims
The CHANSS (Characterising Negative Symptoms in Schizophrenia) study aims to dissect the cognitive mechanisms underlying motivational impairments by focusing on three interconnected domains: executive cognition, motivational cognition and meta-cognition.
Method
This large, international, cross-sectional study recruits a heterogeneous sample of patients across illness stages – from first-episode psychosis to treatment-resistant schizophrenia – and uses a comprehensive cognitive battery, clinical scales, self-report measures and computerised cognitive tasks. Four novel tasks assess key processes in motivated behaviour: option generation, reward-based decision-making, risk sensitivity and performance self-evaluation. By incorporating control for secondary influences like depression, psychosis, sedation and illness chronicity, the study seeks to identify distinct cognitive and behavioural subtypes within motivational dysfunction.
Results
CHANSS tests the hypothesis that specific patient profiles exhibit predominant impairments in one or more cognitive domains, which may differentially affect goal-directed behaviour. The study’s design allows exploration of hierarchical relationships between cognitive processes, such as how neurocognitive deficits may cascade to impair motivation and self-evaluation.
Conclusions
Ultimately, CHANSS aims to advance mechanistic understanding of motivational deficits in schizophrenia and pave the way for personalised, targeted interventions. Its findings may inform future clinical trials and contribute to a shift away from one-size-fits-all approaches towards more effective, stratified treatment strategies in schizophrenia.
Giant cell arteritis (GCA), a form of large vessel vasculitis, carries the risk of irreversible loss of vision due to involvement of arteries supplying optic nerve, retina and choroid. As such, timely diagnosis of GCA is crucial. The study examines the presenting symptoms among suspected GCA patients with both positive and negative biopsy results and the association of computed tomography angiography (CTA) findings of the suspected GCA patients with superficial temporal artery (STA) biopsy results.
Materials and Methods:
A retrospective study involving 22 patients who underwent STA biopsy and CTA at Kingston Health Science Center. The CTA images of the patients were analyzed for the following imaging signs: blurred STA wall, perivascular enhancement, presence of stenosis or occlusion of STA and calcification. The association between imaging signs and STA biopsy results was assessed using odds ratios (ORs). Additionally, the final alternative diagnosis for the patients with negative biopsy results was also investigated.
Results:
There was a strong association between the presence of two CTA imaging findings : blurred STA wall and perivascular enhancement, and positive STA biopsy results (OR: 29, p: 0.001). Suspected GCA patients with negative STA biopsy results had no single unifying alternative diagnosis.
Conclusion:
This study provides evidence for the potential role of CTA in the initial assessment of suspected GCA patients.
Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.
Attention-deficit/hyperactivity disorder (ADHD) is more commonly missed or diagnosed later in females than in males. One explanation is that diagnostic criteria have been informed by research primarily based on male samples and may not adequately capture the female presentation of ADHD.
Aims
This study used a qualitative approach to better understand female ADHD in childhood, from the perspective of young women and non-binary adults with ADHD.
Method
Twelve young adults (10 women and 2 non-binary individuals assigned female at birth, aged 18–25 years) with ADHD were interviewed to describe their lived experiences of ADHD throughout childhood. Interviews were transcribed verbatim and qualitatively analysed using the framework method, a codebook approach to thematic analysis.
Results
Participants reported experiencing a range of ADHD symptoms, some of which are not included in current diagnostic criteria. Four core themes were identified: (a) socially oriented and internalised symptoms, (b) social impacts, (c) masking and compensation and (d) the importance of context. Theme one describes how girls with ADHD may experience symptoms as more socially oriented (e.g. losing track of thoughts in a conversation), non-disruptive (e.g. doodling) and internalised (e.g. feeling frustrated) than those described by current diagnostic criteria. Theme two highlights the importance of social impacts of ADHD on friends, home and school. Theme three describes the desire to ‘fit in’ socially, behaviours and strategies used to mask symptoms and associated unfavourable consequences. Theme four highlights variability in symptoms across different environmental contexts.
Conclusions
This study suggests that the presentation of ADHD symptoms in girls may be socially oriented, internalised and especially influenced by the social context. Also, female ADHD symptoms may be less visible due to scaffolding, masking and context. Future research should consider whether current ADHD diagnostic criteria require adjustment, to aid earlier recognition and diagnosis of ADHD in children and young people, especially in females.
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
Archaeogenetics, the study of ancient DNA, can reveal powerful insights into kinship and the movement of individuals in (pre)history. Here, the authors report on the identification of two individuals with genetic profiles consistent with recent sub-Saharan African ancestry, both of whom were buried in early-medieval cemeteries in southern Britain. Focusing primarily on a sub-adult female from Updown in Kent, the authors explore the societal and cultural contexts in which these individuals lived and died, and the widening geographic links indicated by their presence, pointing back to the Byzantine reconquest of North Africa in AD 533–534.
Sít’ Tlein (Malaspina Glacier), located in Southeast Alaska, has a complex flow history. This piedmont glacier, the largest in the world, is fed by three main tributaries that all exhibit similar flow patterns, yet with varying surge cycles. The piedmont lobe is dramatically reshaped by surges that occur at approximately decadal timescales. By combining historical accounts with modern remote sensing data, we derive a surge history over the past century. We leverage the Stochastic Matrix Factorization, a novel data analysis and interpolation technique, to process and interpret large datasets of glacier surface velocities. A variant of the Principal Component Analysis allows us to uncover spatial and temporal patterns in ice dynamics. We show that Sít’ Tlein displays a wide range of behaviors, spanning quiescence to surge with seasonal to decadal variations of ice flow direction and magnitude. We find that in the lobe, surges dominate the velocity dataset’s variance (spanning 1984–2021), while seasonal variations represent a much smaller part of the variance. However, despite the regular surge pulses, the glacier lobe is far from equilibrium, and widespread retreat of the glacier is inevitable, even without further climate warming.
The glacial history of northeast Siberia is poorly understood compared with other high-latitude regions. Using 10Be and 26Al exposure dating together with remote sensing, we have investigated the glacial history of a remote, formerly glaciated valley in the Tas-Kystabyt Range of the Chersky Mountains in central northeast Siberia. Based on measurements from moraine boulders and bedrock samples, we find evidence for deglaciation of the valley 45.6 ± 3.4 ka ago, that is during the peak of Marine Isotope Stage 3. Satellite imagery of the range reveals at least two generations of moraines in other nearby valleys, indicating that multiple stages of glaciation took place across the Tas-Kystabyt Range. Based on calculated equilibrium-line altitudes, we speculate that the outer set of moraines is linked to the 45.6 ± 3.4 ka deglaciation event identified by our dating, while the inner generation of moraines is associated with a younger glaciation event, possibly the last glacial maximum (LGM). Thus, our results reaffirm current impressions that the maximum ice extent during the last glacial cycle was reached before the global LGM in northeast Siberia.
There has been debate about the frequency and severity of antidepressant withdrawal effects.
Methods
We set out to appraise and reanalyze an influential systematic review by Henssler and colleagues that concluded that withdrawal effects are not particularly common and rarely severe. We repeated the meta-analysis, including only studies where data were derived from systematic measures of withdrawal symptoms.
Results
Most data in the Henssler review are derived from pharmaceutical industry–sponsored efficacy studies in which withdrawal was a minor consideration. Shortcomings of the review include the use of spontaneously reported adverse events to estimate withdrawal symptoms, potential misclassification of withdrawal symptoms as relapse, inclusion of data from retrospective case-note studies, short duration of prior antidepressant use, short observation periods, the overlooking of differences between placebo and drug withdrawal effects, and the use of questionable proxies for severe withdrawal. There were also discrepancies and uncertainties in some figures used. In our reanalysis, we included only the five studies that used a systematic and relevant method to assess the incidence of any withdrawal symptom. Prior treatment was short-term (12 weeks or less) in all but one of these. The pooled percentage was 55% (95% confidence interval, CI, 31% to 81%; N = 601) without subtracting nocebo effects, with high heterogeneity.
Conclusions
Henssler’s review is based on unreliable data and does not provide an adequate basis for the evaluation of antidepressant withdrawal effects. Further good-quality research on antidepressant withdrawal is required.
This chapter describes the application of VBP principles in radically redesigning health services for the elderly. Extensive consultation revealed similar priorities for the public and third sector and professional stakeholders in that they preferred less fragmented services and to be cared for at home if possible. Patients wanted services to work as one team. Community services including district nursing, occupational therapy, physiotherapy, old age psychiatry, geriatrics, inpatient rehabilitation, psychiatric inpatient services, minor injury units, and a variety of specialist teams came under one organization, presenting a unique opportunity to integrate physical and mental healthcare. Feedback has been collected and reviewed by management so that the patients’ voices can continue to inform the evolution of these services, leading to excellent satisfaction rates.
Understanding the mechanisms of major depressive disorder (MDD) improvement is a key challenge to determining effective personalized treatments.
Methods
To identify a data-driven pattern of clinical improvement in MDD and to quantify neural-to-symptom relationships according to antidepressant treatment, we performed a secondary analysis of the publicly available dataset EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care). In EMBARC, participants with MDD were treated either by sertraline or placebo for 8 weeks (Stage 1), and then switched to bupropion according to clinical response (Stage 2). We computed a univariate measure of clinical improvement through a principal component (PC) analysis on the variations of individual items of four clinical scales measuring depression, anxiety, suicidal ideas, and manic-like symptoms. We then investigated how initial clinical and neural factors predicted this measure during Stage 1 by running a linear model for each brain parcel’s resting-state global brain connectivity (GBC) with individual improvement scores during Stage 1.
Results
The first PC (PC1) was similar across treatment groups at stages 1 and 2, suggesting a shared pattern of symptom improvement. PC1 patients’ scores significantly differed according to treatment, whereas no difference in response was evidenced between groups with the Clinical Global Impressions Scale. Baseline GBC correlated with Stage 1 PC1 scores in the sertraline but not in the placebo group.
Using data-driven reduction of symptom scales, we identified a common profile of symptom improvement with distinct intensity between sertraline and placebo.
Conclusions
Mapping from data-driven symptom improvement onto neural circuits revealed treatment-responsive neural profiles that may aid in optimal patient selection for future trials.
Coughing is essential for survival as it clears secretions and foreign bodies from the central airways. Insufficient cough flows and aspiration of saliva are frequent problems in neurological illness and lead to tracheobronchial retention of secretions. Comorbidities like chronic obstructive pulmonary disease, certain medications and failure to adequately humidify the lower airways can lead to hypersecretion, thick and tenacious secretions and ciliary dysfunction, respectively. This can further aggravate any bronchopulmonary retention of secretions, finally leading to atelectasis, pneumonia, respiratory failure as well as death. Noninvasive ventilatory support is effective only if accompanied by adequate management of secretions. This chapter provides a comprehensive overview of the neuronal control, physiology and pathophysiology of coughing and bronchopulmonary retention of secretions as well as effective techniques to reduce secretions and to eliminate them from the airways.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
Transthoracic intracardiac lines provide a unique access point for postoperative monitoring and management in paediatric cardiothoracic surgeries, particularly within the single ventricle population where preserving vasculature is crucial for future interventions. This retrospective review examined paediatric single ventricle patients undergoing cardiothoracic surgeries at a tertiary children’s hospital between 2011 and 2018, focusing on the use of and factors associated with transthoracic line complications (infection, thrombosis, malfunction, and migration). A total of 338 lines were placed during the study period, with the majority occurring during palliative surgeries (86.5%). Lines remained in place for a median of 14 days postoperatively. Complications occurred in 21 lines (6.2%), comprising 8 migrations (2.4%), 7 thrombosis (2.1%), 4 malfunctions (1.2%), and 2 infections (0.6%). The presence of a surgical shunt was significantly associated with line complications (odds ratio 2.58, confidence interval 1.05 – 6.31; P 0.03). The use of transthoracic intracardiac lines seems to be safe and should be considered as a primary alternative to other central lines in the single ventricle population. A prospective assessment of transthoracic line complications, along with delineation of unit protocols, may further enhance outcomes in this complex population.
Objectives/Goals: Here, we utilize deep learning to automate the analysis of dual X-ray absorptiometry (DEXA) scans in the UK Biobank (UKB) imaging dataset to enable a large-scale assessment of lumbar spine disc degeneration, low back pain, and socioeconomic status. Methods/Study Population: Study Population: The UKB is a biomedical database that includes lateral spine DEXA imaging for 50,000 participants. Deep Learning Model Development: A computer vision model was developed that receives a DEXA scan as input and outputs a quadrilateral that corresponds to the corners of 5 lumbar vertebral bodies. The model is a deep, fully convolutional, encoder–decoder network using DeepLabV3. Statistical Analysis: To determine our preliminary model accuracy, we used the intersection over union (IoU) metric.We analyzed data using an ordinal regression model to determine the relationship between income/ neighborhood level multiple deprivation index (MDI) and low back pain (LBP), as well as a mixed effects model to estimate the relationship between income/MDI and disc height index (DHI). Results/Anticipated Results: Our model predicted vertebral body quadrilaterals in training and unseen test data (train IoU = 0.96, test IoU = .91) and was used to infer data for 10,440 participants. Confirming previous studies, there were significant relationships (p0.05) between income or MDI and DHI (Figure 2). Discussion/Significance of Impact: Low back pain is the world’s leading cause of disability, and socioeconomic factors play an important role. We found no relationship between disc height index and socioeconomic status. Thus, disc degeneration may not be a factor in this low back pain phenotype.
Domestic cats have lived alongside human communities for thousands of years, hunting rats, mice, and other pests and serving as pets and a source of pelts and meat. Cats have received limited archaeological attention because their independence limits direct insight into human societies. An adult and juvenile cat recovered from the Emanuel Point wreck 2 (EP2) reflect what are, most likely, the earliest cats in what is now the United States. Zooarchaeological analyses of these and other archaeological cats in the Americas demonstrate that cats ranged substantially in size: some were comparable to modern house cats, and others were much smaller. Isotopic analyses of the adult cat from EP2 provides insight into early shipboard cat behavior and their diet, which appears to have focused on consumption of fish and possibly domestic meat. Cats accompanied sailors on ships where they were relied on to hunt rats and mice that were infesting ships’ holds. Interestingly, based on these isotopic results, the adult cat from EP2 does not seem to have relied heavily on rats as a source of food. These pests were unintentionally introduced to the New World, and cats would have followed, hunting both native and invasive pests.
Maladaptive daydreaming is a distinct syndrome in which the main symptom is excessive vivid fantasising that causes clinically significant distress and functional impairment in academic, vocational and social domains. Unlike normal daydreaming, maladaptive daydreaming is persistent, compulsive and detrimental to one’s life. It involves detachment from reality in favour of intense emotional engagement with alternative realities and often includes specific features such as psychomotor stereotypies (e.g. pacing in circles, jumping or shaking one’s hands), mouthing dialogues, facial gestures or enacting fantasy events. Comorbidity is common, but existing disorders do not account for the phenomenology of the symptoms. Whereas non-specific therapy is ineffective, targeted treatment seems promising. Thus, we propose that maladaptive daydreaming be considered a formal syndrome in psychiatric taxonomies, positioned within the dissociative disorders category. Maladaptive daydreaming satisfactorily meets criteria for conceptualisation as a psychiatric syndrome, including reliable discrimination from other disorders and solid interrater agreement. It involves significant dissociative aspects, such as disconnection from perception, behaviour and sense of self, and has some commonalities with but is not subsumed under existing dissociative disorders. Formal recognition of maladaptive daydreaming as a dissociative disorder will encourage awareness of a growing problem and spur theoretical, research and clinical developments.
This study is the first to attempt to isolate a relationship between cognitive activity and equilibration to a Nash Equilibrium. Subjects, while undergoing fMRI scans of brain activity, participated in second price auctions against a single competitor following predetermined strategy that was unknown to the subject. For this auction there is a unique strategy that will maximize the subjects’ earnings, which is also a Nash equilibrium of the associated game theoretic model of the auction. As is the case with all games, the bidding strategies of subjects participating in second price auctions most often do not reflect the equilibrium bidding strategy at first but with experience, typically exhibit a process of equilibration, or convergence toward the equilibrium. This research is focused on the process of convergence.
In the data reported here subjects participated in sixteen auctions, after which all subjects were told the strategy that will maximize their revenues, the theoretical equilibrium. Following that announcement, sixteen more auctions were performed. The question posed by the research concerns the mental activity that might accompany equilibration as it is observed in the bidding behavior. Does brain activation differ between being equilibrated and non-equilibrated in the sense of a bidding strategy? If so, are their differences in the location of activation during and after equilibration? We found significant activation in the frontal pole especially in Brodmann's area 10, the anterior cingulate cortex, the amygdala and the basal forebrain. There was significantly more activation in the basal forebrain and the anterior cingulate cortex during the first sixteen auctions than in the second sixteen. The activity in the amygdala shifted from the right side to the left after the solution was given.
The weaning process negatively affects the haematological parameters and innate immune response of dairy calves, even when managed under an intensive milk program. Here we describe haematological and innate immunity changes in 47 Holstein calves aged 69-85 days subjected to a gradual weaning process. Blood samples were collected at six (D-6), four (D-4), and two (D-2) days before and on the weaning day (D0) for the phagocytosis assay and to measure the production of reactive oxygen species (ROS) after stimulation with Staphylococcus aureus, Escherichia coli, and Mannhemia haemolytica, in addition to total protein (TP), haptoglobin (Hp), and iron concentration. The highest mean neutrophil number was recorded at D-2. The absolute number of monocytes was initially high on D-6 and D-4 but declined as the calf progressed to weaning. The number of basophils decreased rapidly, reaching a low value on D-4, and remained low for the remainder of the study period. The TP, Hp, and Fe concentrations decreased. Overall, polymorphonuclear leukocyte phagocytosis activity induced by S. aureus and E. coli decreased from D-6 to D-2, indicating persistence of the low phagocytosis rate for S. aureus. ROS production was constant for all bacterial stimulations from D-6 to D-2, followed by an increase on D0. Phagocytosis and ROS production indicate that the weaning process dampens the innate immune response relative to exposure to these common pathogenic bacteria in dairy calves. Phagocytosis and the corresponding indicators of intracellular killing activities (ROS production and myeloperoxidase index) represent the most accepted core mechanisms for the early elimination of pathogenic microorganisms in calves. Despite a slow gradual weaning management system, the study concluded that intensive milk production programs contribute to innate immune response suppression during weaning.