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The novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative enzyme-linked immunosorbent assays (ELISAs) that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive coronavirus disease-2019 (COVID-19) cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients who had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.
The purpose of this article was to determine the impact of employing a telephone clinic for follow-up of patients with stable lateral skull-base tumours.
An analysis of 1515 patients in the national lateral skull-base service was performed, and 148 patients enrolled in the telephone clinic to date were identified. The length of time that patients waited for results of their follow-up scans and the travel distance saved by patients not having to attend the hospital for their results was determined.
The mean time from scan to receiving results was 30.5 ± 32 days, 14 days sooner than in the face-to-face group (p = 0.0016). The average round-trip distance travelled by patients to the hospital for results of their scans was 256 ± 131 km.
The telephone clinic led to a significant reduction in time until patients received their scan results and helped reduce travel distance and clinic numbers in traditional face-to-face clinics.
The Late Triassic fauna of the Lossiemouth Sandstone Formation (LSF) from the Elgin area, Scotland, has been pivotal in expanding our understanding of Triassic terrestrial tetrapods. Frustratingly, due to their odd preservation, interpretations of the Elgin Triassic specimens have relied on destructive moulding techniques, which only provide incomplete, and potentially distorted, information. Here, we show that micro-computed tomography (μCT) could revitalise the study of this important assemblage. We describe a long-neglected specimen that was originally identified as a pseudosuchian archosaur, Ornithosuchus woodwardi. μCT scans revealed dozens of bones belonging to at least two taxa: a small-bodied pseudosuchian and a specimen of the procolophonid Leptopleuron lacertinum. The pseudosuchian skeleton possesses a combination of characters that are unique to the clade Erpetosuchidae. As a basis for investigating the phylogenetic relationships of this new specimen, we reviewed the anatomy, taxonomy and systematics of other erpetosuchid specimens from the LSF (all previously referred to Erpetosuchus). Unfortunately, due to the differing representation of the skeleton in the available Erpetosuchus specimens, we cannot determine whether the erpetosuchid specimen we describe here belongs to Erpetosuchus granti (to which we show it is closely related) or if it represents a distinct new taxon. Nevertheless, our results shed light on rarely preserved details of erpetosuchid anatomy. Finally, the unanticipated new information extracted from both previously studied and neglected specimens suggests that fossil remains may be much more widely distributed in the Elgin quarries than previously recognised, and that the richness of the LSF might have been underestimated.
Recent technological advances have led to a novel class of microfluidic devices which can be rapidly fabricated by printing a fluid onto a solid substrate with flows generated passively via surface tension. The nonlinear dependence between flow and the heights of the conduits, however, prevent straightforward calculation of the resulting dynamics. In this paper we use matched asymptotic expansions to predict how flow through these devices can be tuned by changing their geometry. We begin with the simple ‘dumbbell’ configuration in which two fluid drops with different sizes are connected by a long, thin and narrow conduit. We calculate the time scale required for one drop to drain into the other and how this depends both on the geometry of the pinned contact line and volume of fluid deposited into the drops. Our model therefore provides the mechanistic basis to design conduits with a particular fluid flux and/or shear stress, which are often key experimental constraints. Our asymptotic predictions are shown to be in excellent agreement with numerical simulations even for moderate aspect ratios (the ratio of conduit width to length). Next, we show how our results for the simple dumbbell configuration can be extended to predict the flow through networks of conduits with multiple drops and nodes, and hence may assist in their design and implementation. This new mathematical framework has the potential to increase the use of surface tension driven microfluidics across a wide range of disciplines as it allows alternate designs to be rapidly assessed.
The development of the ileal pouch anal anastomosis (IPAA) has led to significant improvements in the quality of life for patients after proctocolectomy. The complex anatomy of the pouch requires a systematic examination of the different IPAA components at pouchoscopy and sampling of different histological zones, i.e. pre-pouch, pouch, rectal cuff, and anal mucosa. The main roles of the pathologist are to corroborate a clinical diagnosis of pouchitis, to identify secondary causes of inflammation when present, to be aware of the differential diagnosis, and to exclude histologically identifiable complications such as CMV infection, dysplasia and malignancy. Assessment can be difficult for several reasons, e.g. the anatomical location of a biopsy is not always obvious, adaptive changes may occur that lead to alterations in mucosal morphology, and Crohn’s-like changes may occur as a consequence of pouchitis and may cause diagnostic confusion.
Introduction: The opioid crisis has reached epidemic levels in Canada, driven in large part by prescription drug use. Emergency physicians are frequent prescribers of opioids; therefore, the emergency department (ED) represents an important setting for potential intervention to encourage rational and safe prescribing. The objective of this study was to systematically review the literature on interventions aimed to influence opioid prescribing in the ED. Methods: Electronic searches of Medline and Cochrane were conducted and reference lists were hand-searched. All quantitative studies published in English from 2009 to 2019 were eligible for inclusion. Two reviewers independently screened the search output to identify potentially eligible studies, the full texts of which were retrieved and assessed for inclusion. Outcomes of interest included opioid prescribing rate (proportion of ED visits resulting in an opioid prescription at discharge), morphine milligram equivalents per prescription and variability among prescribers. Results: The search strategy yielded 797 potentially relevant citations. After eliminating duplicate citations and studies that did not meet eligibility criteria, 34 potentially relevant studies were retrieved in full text. Of these, 28 studies were included in the review. The majority (26, 92.9%) of studies were based in the United States and two (7.1%) were from Australia. Four (14.3%) were randomized controlled trials. The interventions were classified into six categories: prescribing guidelines (n = 10), regulation/rescheduling of opioids (n = 6), prescribing data transparency (n = 4), education (n = 4), care coordination (n = 3), and electronic medical record changes (n = 1). The majority of interventions reduced the opioid prescribing rate from the ED (21/28, 75.0%), although regulation/rescheduling of opioids had mixed effectiveness, with 3/6 (50%) studies reporting a small increase in the opioid prescribing rate post-intervention. Education had small yet consistent effects on reducing the opioid prescribing rate. Conclusion: A variety of interventions have attempted to improve opioid prescribing from the ED. These interventions include prescribing guidelines, regulation/rescheduling, data transparency, education, care coordination, and electronic medical record changes. The majority of interventions reduced the opioid prescribing rate; however, regulation/rescheduling of opioids demonstrated mixed effectiveness.
We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia.
The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group.
OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings.
Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.
P300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.
Results of a co-morbid insomnia and depression study of eszopiclone and fluoxetine demonstrated that co-therapy produced greater improvements in sleep and depression than fluoxetine monotherapy. To determine if changes in the HAMD17 were due to sleep, individual HAMD17 items were evaluated.
Patients met DSM-IV criteria for MDD and insomnia, with screening HAMD17 >14. All patients received fluoxetine QAM for 10 weeks, and randomly received double-blind eszopiclone 3mg or placebo QHS for 8 weeks, followed by a single-blind placebo 2-week run-out. HAMD17 was completed at Weeks 4, 8, and 10. Individual items were compared with ANCOVA using an LOCF approach.
Mean baseline HAMD17 scores were 22 for each group. At Week 4, differences were noted between treatment groups in the total score, and the individual items of insight, the three insomnia items (p<0.02 vs monotherapy), with a trend for guilt (p=0.07). At Week 8, significant differences between groups were noted in total score (p=0.0005), in the clinician-administered Bech subscale (p<0.001), in the three insomnia items (p<0.001), guilt, work/activities, and anxiety psychic (p<0.05). At Week 10, the total score, guilt, the three insomnia items, work/activities, retardation, agitation, anxiety psychic, general somatic symptoms, and hypochondriasis demonstrated significant improvements (p<0.05 vs monotherapy) despite discontinuation of eszopiclone.
Eszopiclone/fluoxetine co-therapy resulted in significant improvements in the insomnia items of the HAMD17. In addition, several items related to core depressive symptoms were also improved with co-therapy compared with monotherapy.
The aim of the study was to assess the experiences of discrimination as reported by people with mental health problems and to explore the impact of hospitalisation.
306 people with mental health problems provided sociodemographic data and data on discrimination using the discrimination and stigma scale version 12 (DISC-12) with the domains negative experienced discrimination, anticipated discrimination, overcoming stigma and discrimination, and positive experienced discrimination. Logistic regression analysis was used to test the impact of hospitalisation on discrimination, controlled for age, gender, education, employment, diagnosis and having been prescribed medication.
Hospitalisation had a major impact on negative discrimination: People were more likely to be treated unfairly in making or keeping friends, in marriage or divorce, by people in their neighbourhood, in social life, by mental health staff and in terms of privacy, if they had been hospitalised. They were also more likely to be avoided or shunned by people who knew about the mental health problem. People with a history of hospitalisation also reported more anticipated discrimination: They had stopped themselves more often from having a close personal relationship and concealed their mental health problem from others more often than those without a history of hospitalisation. However, people who had been hospitalised also experienced more positive discrimination in terms of being treated more positively in getting welfare benefits or disability pensions and in housing.
Findings suggest that treatment in hospital contributed to a higher extent to experienced discrimination than treatment in the community.
Although genetic and environmental factors operating before or around the time of birth have been demonstrated to be relevant to the aetiology of the major psychoses, a seasonal variation in the rates of admission of such patients has long been recognised. Few studies have compared first and readmissions. This study examined for seasonal variation of admission in the major psychoses, and compared diagnostic categories by admission status. Patients admitted to Irish psychiatric inpatient facilities between 1989 and 1994 with an ICD-9/10 diagnosis of schizophrenia or affective disorder were identified from the National Psychiatric Inpatient Reporting System (NPIRS). The data were analysed using a hierarchical log linear model, the chi-square test, a Kolmogorov-Smirnov (KS) type statistic, and the method of Walter and Elwood. The hierarchical log linear model demonstrated significant interactions between the month of admission and admission order (change in scaled deviance 28.77, df = 11, P < 0.003). Both first admissions with mania, and readmissions with bipolar affective disorder exhibited significant seasonality. In contrast, only first admissions with schizophrenia showed significant seasonal effects. Although first admissions with mania and readmissions with bipolar disorder both show seasonality, seasonal influences appear to be more relevant to onset of schizophrenia than subsequent relapse.
Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.
Recent literature suggests that over 70% of cases of antibody-mediated encephalitis present to psychiatry services with features of psychosis predominantly.
To investigate the seroprevalence of N-Methyl-D-Aspartate receptor antibodies (NMDAr-Ab) in patients with first episode psychosis (FEP)
Following ethical approval, all cases meeting entry criteria were invited to participate. Participants were interviewed with SCID to obtain a DSM diagnosis. NMDAr-Ab were identified in serum by cell based assay using co-transfected Human Embryonic Kidney (HEK)cells. Positive cases were reviewed by clinical neurology. Decision to treat with immunotherapy was made on a case by case basis.
85/115 (72%) of patients with FEP entered the study. 49 (58%) participants were male, mean age (SD) 37 (15.7) years. 42 (52%) were outpatients at the time of assessment. Four cases (5%) were serum NMDAr-Ab positive. 3 of these cases were male, age 48 (16.3) years. All four were admitted as inpatients with normal brain MRI imaging. One case (female, 55) was confirmed as NMDAr-Ab encephalitis based on case presentation, EEG demonstrating bilateral cerebral dysfunction and NMDAr-Ab in CSF. Immunotherapy treatment lead to clinical improvement. In remaining cases, EEG was normal and CSF negative. All 3 of these cases showed clinical improvement following psychiatric treatment as usual.
Our findings support the current estimates as to NMDAr-Ab prevalence in FEP. Increased awareness has lead to rapid treatment of florid cases of NMDAr-Ab encephalitis in our service. Additional seropositive cases are being followed with neuro-cognitive testing for any evidence of decline.
Little is known about who would benefit from Internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an Internet-based PN intervention. Adults (n 1607) from seven European countries were recruited into a 6-month, randomised controlled trial (Food4Me) and randomised to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity (PA), blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5 % change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, PA, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants, women and participants with lower HEI scores at baseline. Benefit was greater for individuals reporting greater self-efficacy for ‘sticking to healthful foods’ and who ‘felt weird if [they] didn’t eat healthily’. Participants benefited more if they reported wanting to improve their health and well-being. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.