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Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
The common brushtail possum (Trichosurus vulpecula), introduced from Australia about 150 years ago, has become a major pest threatening the native biota of New Zealand. It is also an important disease vector, acting as a wildlife reservoir of infection. Conventional methods of control have had little effect on reducing the national population, so there is a quest to find more effective and humane methods. This has led to an upsurge in research aimed at increasing our knowledge of the biology of this marsupial, with an attendant increase in requirements for access to colony-housed animals.
Possums kept for research purposes have often been housed in individual cages, and several colonies have experienced high mortality rates. After capture, possums have shown inappetence, weight loss and a predisposition to infection, suggesting that this species is susceptible to post-capture stress. For our reproductive studies, research animals are only useful if maintained under conditions that ensure behavioural and physiological processes remain normal. We have adopted an ‘animal husbandry’ approach for our possum colony, where social interaction and the ability to exhibit instinctive behaviour patterns are considered as important as adequate nutrition and housing.
In this colony, group-housed possums show no signs of post-capture stress, and mortality rate has been less than one per cent (of > 600 animals housed to date). Virtually all possums gain weight over the first month of captivity. Procedures for monitoring, handling and the collection of data from these animals, are carried out with little apparent stress to either animals or staff.
Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.
To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.
Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance.
The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months.
We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%–72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%–77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%–16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).
In March 2020, New York City became the epicenter of the coronavirus disease 2019 (COVID-19) pandemic in the United States. Because healthcare facilities were overwhelmed with patients, the Jacob K. Javits Convention Center was transformed into the nation’s largest alternate care site: Javits New York Medical Station (hereafter termed Javits). Protecting healthcare workers (HCWs) during a global shortage of personal protective equipment (PPE) in a nontraditional healthcare setting posed unique challenges. We describe components of the HCW safety program implemented at Javits.
Javits, a large convention center transformed into a field hospital, with clinical staff from the US Public Health Service Commissioned Corps and the US Department of Defense.
Key strategies to ensure HCW safety included ensuring 1-way flow of traffic on and off the patient floor, developing a matrix detailing PPE required for each work activity and location, PPE extended use and reuse protocols, personnel training, and monitoring adherence to PPE donning/doffing protocols when entering or exiting the patient floor. Javits staff who reported COVID-19 symptoms were immediately isolated, monitored, and offered a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) test.
A well-designed and implemented HCW safety plan can minimize the risk of SARS-CoV-2 infection for HCWs. The lessons learned from operating the nation’s largest COVID-19 alternate care site can be adapted to other environments during public health emergencies.
There has been increased interest in the adoption of an intracapsular tonsillectomy technique in the UK in recent years. The adoption of any newer surgical technique inevitably is accompanied by an educational need.
This paper aims to outline the equipment preparation and surgical steps for intracapsular coblation tonsillectomy, including recognition of the tonsillar capsule. The paper also discusses how to avoid and deal with common complications and technical difficulties.
To quantify patient eligibility for cochlear implantation following National Institute for Health and Care Excellence 2019 guidelines (TA566) over five years at our institution, and identify factors influencing patients’ decisions surrounding cochlear implantation referral.
A multi-perspective service evaluation was conducted at a district general hospital, comprising cochlear implantation eligible patients. The main outcome measures were: eligibility numbers for 2014–2019, comparing application of TA566 versus 2009 (TA166) guidelines; and patient interview transcripts and questionnaires.
There was a 259 per cent average increase in cochlear implantation eligibility from 2014 to 2019. Most patients’ thresholds were 80 dB HL or more at 3 kHz and 4 kHz. There are several cochlear implantation barriers, including patient-centred issues (e.g. health-related anxieties, implantation misperceptions) and external barriers (difficulty getting to regional implant centres). Motivating factors for cochlear implantation include improved quality of life and access to local cochlear implantation services.
The TA566 guidelines have increased cochlear implantation eligibility, putting pressure on cochlear implantation centres and referring hospitals. Current referral systems have external and patient-centred implantation barriers. British cochlear implantation delivery may need rethinking to meet increasing populational demands and improve accessibility for those most vulnerable to these barriers.
Two introduced carnivores, the European red fox Vulpes vulpes and domestic cat Felis catus, have had extensive impacts on Australian biodiversity. In this study, we collate information on consumption of Australian birds by the fox, paralleling a recent study reporting on birds consumed by cats. We found records of consumption by foxes on 128 native bird species (18% of the non-vagrant bird fauna and 25% of those species within the fox’s range), a smaller tally than for cats (343 species, including 297 within the fox’s Australian range, a subset of that of the cat). Most (81%) bird species eaten by foxes are also eaten by cats, suggesting that predation impacts are compounded. As with consumption by cats, birds that nest or forage on the ground are most likely to be consumed by foxes. However, there is also some partitioning, with records of consumption by foxes but not cats for 25 bird species, indicating that impacts of the two predators may also be complementary. Bird species ≥3.4 kg were more likely to be eaten by foxes, and those <3.4 kg by cats. Our compilation provides an inventory and describes characteristics of Australian bird species known to be consumed by foxes, but we acknowledge that records of predation do not imply population-level impacts. Nonetheless, there is sufficient information from other studies to demonstrate that fox predation has significant impacts on the population viability of some Australian birds, especially larger birds, and those that nest or forage on the ground.
Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.
MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.
VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.
Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.
COVID-19 altered research in Clinical and Translational Science Award (CTSA) hubs in an unprecedented manner, leading to adjustments for COVID-19 research.
CTSA members volunteered to conduct a review on the impact of CTSA network on COVID-19 pandemic with the assistance from NIH survey team in October 2020. The survey questions included the involvement of CTSAs in decision-making concerning the prioritization of COVID-19 studies. Descriptive and statistical analyses were conducted to analyze the survey data.
60 of the 64 CTSAs completed the survey. Most CTSAs lacked preparedness but promptly responded to the pandemic. Early disruption of research triggered, enhanced CTSA engagement, creation of dedicated research areas and triage for prioritization of COVID-19 studies. CTSAs involvement in decision-making were 16.75 times more likely to create dedicated diagnostic laboratories (95% confidence interval [CI] = 2.17–129.39; P < 0.01). Likewise, institutions with internal funding were 3.88 times more likely to establish COVID-19 dedicated research (95% CI = 1.12–13.40; P < 0.05). CTSAs were instrumental in securing funds and facilitating establishment of laboratory/clinical spaces for COVID-19 research. Workflow was modified to support contracting and IRB review at most institutions with CTSAs. To mitigate chaos generated by competing clinical trials, central feasibility committees were often formed for orderly review/prioritization.
The lessons learned from the COVID-19 pandemic emphasize the pivotal role of CTSAs in prioritizing studies and establishing the necessary research infrastructure, and the importance of prompt and flexible research leadership with decision-making capacity to manage future pandemics.
The peoples of southern Mesoamerica, including the Classic period Maya, are often claimed to exhibit a distinct type of spatial organization relative to contemporary urban systems. Here, we use the settlement scaling framework and properties of settlements recorded in systematic, full-coverage surveys to examine ways in which southern Mesoamerican settlement systems were both similar to and different from contemporary systems. We find that the population-area relationship in these settlements differs greatly from that reported for other agrarian settlement systems, but that more typical patterns emerge when one considers a site epicenter as the relevant social interaction area, and the population administered from a given center as the relevant interacting population. Our results imply that southern Mesoamerican populations mixed socially at a slower temporal rhythm than is typical of contemporary systems. Residential locations reflected the need to balance energetic and transport costs of farming with lower-frequency costs of commuting to central places. Nevertheless, increasing returns in activities such as civic construction were still realized through lower-frequency social mixing. These findings suggest that the primary difference between low-density urbanism and contemporary urban systems lies in the spatial and temporal rhythms of social mixing.
Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the ‘first wave’ of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57–82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57–2.27), hypertension (OR 1.72, 95% CI 1.10–2.70), cancer (OR 2.20, 95% CI 1.27–3.81), platelets <150 × 103/μl (OR 1.93, 95% CI 1.13–3.30), C-reactive protein ≥100 μg/ml (OR 1.68, 95% CI 1.05–2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16–3.77) and AKI (OR 2.60, 95% CI 1.64–4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.
Introduction: eCTAS is a real time electronic triage decision-support tool designed to improve patient safety and quality of care by standardizing the application of the Canadian Triage and Acuity Scale (CTAS). The tool dynamically calculates a recommended CTAS score based on the presenting complaint, vital signs and selected clinical modifiers. The primary objective was to assess consistency of CTAS score distributions across 35 emergency departments (EDs) by 16 presenting complaints pre and post eCTAS implementation. Methods: This retrospective cohort study used population-based administrative data from January 2016 to December 2018 from all hospital EDs in Ontario that had implemented eCTAS with at least 9 months of data. Following a 3-month stabilization period, we compared data for 6 months post-eCTAS implementation to the same 6-month period the previous year (pre-implementation) to account for potential seasonal variation, patient volume and case-mix. We included triage encounters of adult (≥18 years) patients if they had one of 16 pre-specified high-volume, presenting complaints. A paired-samples t-test was used to determine consistency by estimating the absolute difference in CTAS distribution for each presenting complaint, by each hospital, pre and post eCTAS implementation, compared to the overall average of the 35 EDs. Results: There were 183,231 triage encounters in the pre-eCTAS cohort and 179,983 in the post-eCTAS cohort from 35 EDs across the province. Triage scores were more consistent with the overall average after eCTAS implementation in 6 (37.5%) presenting complaints: chest pain (cardiac features) (p < 0.001), extremity weakness/symptoms of cerebrovascular accident (p < 0.001), fever (p < 0.001), shortness of breath (p < 0.001), syncope (p = 0.02), and hyperglycemia (p = 0.03). Triage consistency was similar pre and post eCTAS implementation for the presenting complaints of altered level of consciousness, anxiety/situational crisis, confusion, depression/suicidal/deliberate self-harm, general weakness, head injury, palpitations, seizure, substance misuse/intoxication or vertigo. Conclusion: A standardized, electronic approach to performing triage assessments increased consistency in CTAS scores across many, but not all, high-volume CEDIS complaints. This does not reflect triage accuracy, as there are no known benchmarks for triage accuracy. Improvements in consistency were greatest for sentinel presenting complaints with a minimum allowable CTAS score.
There has been considerable interest internationally in the assessment and treatment of individuals who have a severe personality disorder and who might pose a high-risk of future recidivism. In the United Kingdom, the ‘Dangerous and Severe Personality Disorder’ (DSPD) programme was initiated to deal with just this group. It is important, however, that the DSPD service is filling a treatment void and not competing with already well-established and effective services for (non-DPSD) personality disordered patients. Objective: To establish whether those admitted to innovative DSPD services are different from those admitted to conventional personality disorder (PD) services.
To compare patients admitted to DSPD services with those admitted to personality disordered (non-DPSD) services.
Sixty patients admitted to DSPD services, under DSPD criteria, were compared with 44 patients admitted to personality disordered (non-DSPD) services within the same high secure psychiatric hospital, on risk measures, including
(1) an index of predicted future violence
(2) previous offending behaviour and
(3) pre-treatment levels of institutional risk-related behaviour.
DSPD patients do pose a greater clinical and management risk, have a higher number of pre-treatment risk-related behaviour, and have a greater number of convictions and imprisonments after age 18, relative to PD patients.
The findings broadly confirm the hypotheses as to the higher risk in DSPD patients and thus offer support for the main purpose of DSPD services: to provide treatment for those who represent the highest priority in terms of treatment need and risk to public protection. Implications are discussed.
The utility of questionnaire based self-report measures for non-clinical psychotic symptoms is unclear and there are few reliable data about the nature and prevalence of these phenomena in children. The study aimed to investigate psychosis-like symptoms (PLIKS) in children utilizing both self-report measures and semi-structured observer rated assessments.
The study was cross-sectional; the setting being an assessment clinic for members of the ALSPAC birth cohort in Bristol, UK. 6455 respondents were assessed over 21 months, mean age 12.9 years. The main outcome measure was: 12 self-report screening questions for psychotic symptoms followed by semi-structured observer rated assessments by trained psychology graduates. The assessment instrument utilised stem questions, glossary definitions, and rating rules adapted from DISC-IV and SCAN items.
The 6-month period prevalence for one or more PLIKS rated by self-report questions was 38.9 % (95% CI = 37.7-40.1). Prevalence using observer rated assessments was 13.7% (95% CI = 12.8-14.5). Positive Predictive Values for the screen questions versus observer rated scores were low, except for auditory hallucinations (PPV=70%; 95% CI = 67.1-74.2). The most frequent observer rated symptom was auditory hallucinations (7.3%); in 18.8% of these cases symptoms occurred weekly or more. The prevalence of DSM-IV ‘core’ schizophrenia symptoms was 3.62%. Rates were significantly higher in children with low socio-economic status.
With the exception of auditory hallucinations, self-rated questionnaires are likely to substantially over-estimate the frequency of PLIKS in 12-year-old children. However, more reliable observer rated assessments reveal that PLIKS occur in a significant proportion of children.
Abnormal brain connectivity has recently been reported in obsessive compulsive disorder (OCD). However, structural differences in the corpus callosum (CC), the primary structure connecting the two hemispheres, have not been extensively studied. In this case-control study, we recruited 30 patients with OCD and 30 healthy control subjects carefully matched for age, sex and handedness. Combining surface-based mesh-modeling and voxel-based morphometry (VBM), we compared callosal thickness and white matter (WM) density in patients and controls. We investigated associations between callosal structure and cortical gray matter (GM) density, and we related CC measures to neuropsychological performance in OCD. OCD patients showed small anterior and posterior callosal regions compared to healthy control subjects. In the OCD group, anterior callosal thickness was positively correlated with GM density of the right mid-dorso-lateral prefrontal (BA 9/46) area, while posterior callosal thickness was positively correlated with GM density in the left supramarginal gyrus (BA 40). Moreover, posterior callosal WM density was positively correlated with verbal memory, visuo-spatial memory, verbal fluency, and visuo-spatial reasoning performances. Callosal attributes were related to GM density in cortical areas innervated by the CC, and were also related to performance in cognitive domains impaired in the disorder. The CC may therefore be integrally involved in OCD.
Borderline personality disorder (BPD) is a chronic condition with a strong impact on patients’ affective, cognitive and social functioning. Neuroimaging techniques offer invaluable tools to understand the biological substrate of the disease. We aimed to investigate gray matter alterations over the whole cortex in a group of Borderline Personality Disorder (BPD) patients compared to healthy controls (HC).
Magnetic resonance-based cortical pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD patients and in their age- and sex-matched HC (age: 38 ± 11; females: 16, 61%).
BPD patients showed widespread lower cortical GMD compared to HC (4% difference) with peaks of lower density located in the dorsal frontal cortex, in the orbitofrontal cortex, the anterior and posterior cingulate, the right parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and in the visual cortex (P < 0.005). Our BPD subjects displayed a symmetric distribution of anomalies in the dorsal aspect of the cortical mantle, but a wider involvement of the left hemisphere in the mesial aspect in terms of lower density. A few restricted regions of higher density were detected in the right hemisphere. All regions remained significant after correction for multiple comparisons via permutation testing.
BPD patients feature specific morphology of the cerebral structures involved in cognitive and emotional processing and social cognition/mentalization, consistent with clinical and functional data.