We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Background: Blood loss quantification and management are important facets of cranial surgery, having been linked with adverse outcomes if management is inadequate. While many studies report estimated blood loss (EBL) as an outcome measure, inconsistencies exist in EBL quantification and management strategies Methods: A systematic review of cranial surgery literature on blood loss measurement and management was conducted according to PRISMA guidelines utilizing a novel software platform, Nested Knowledge Results: Initial search yielded 1029 non-duplicated. 107 full-text studies were included. 70% of studies were retrospective. Most common treatment conditions were 41% craniosynostosis (44/107) and 36% tumor (39/107). Most common EBL measurement methods were comparison of pre-operative and post-operative hemoglobin/hematocrit in 46.7% (50/107), anesthesia record in 26.2% (28/107), and surgeon estimation in 9.3% (10/107). 53.3% of studies did not specify a quantification methodology. Blood loss management strategies also varied, with transfusion being the most common method in 64.5% (69/107) of studies Conclusions: EBL quantification and blood loss management remain important clinical and research metrics. Despite this, significant heterogeneity exists in blood loss quantification and management strategies, with most studies providing no data on EBL quantification. Standardization of EBL quantification/reporting should be undertaken to improve comparability and consistency across studies.
Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.
Volume reductions in brain structures of patients with schizophrenia spectrum disorder (SSD) have repeatedly been found in voxel-based morphometry MRI studies. Hence, an underlying neurodegenerative etiological component of SSD is currently being discussed. In recent years, the imaging method of optical coherence tomography (OCT) has shown its potential in evaluating structural changes in the retina in patients with confirmed neurodegenerative disorders, providing a window into the brain.
Objectives
To evaluate potential differences in measurements of retinal layers between patients with schizophrenia spectrum disorder and healthy controls with OCT.
Methods
Twenty-six patients with schizophrenia or schizoaffective disorder and 23 age- and sex-matched healthy controls were examined with the Heidelberg Spectralis OCT system to derive a single-layer analysis of both retinas. The segmentation of retinal layers was manually corrected to minimize artifacts and software imprecisions.
Results
Compared to the control group, SSD patients showed reduced thickness and volume measurements for nearly all retinal layers, and these differences reached significance for macular volume, macular thickness, retinal nerve fiber layer (RNFL) and inner nucleiform layer (INL). Furthermore, a significant correlation between the duration of illness and the total volume of the RNFL was found.
Conclusions
Our OCT measurements demonstrate reduced single retinal layer thickness in patients with SSD. In the context of the MRI volume changes, our results provide further evidence that structural changes seen in the brain of patients are also observable in the retina, potentially allowing further insights into the different components of the nervous system that are altered in this highly etiologically complex disorder.
We will present experience developing a system for monitoring training placements in psychiatry and community paediatrics, and how this was expanded to provide an automated anonymised MSF for trainers for annual appraisal and will identify trainers in need of additional support and other post/training programme issues. The session will be of interest to educators and medical education leads with practical tips and lessons learnt over the last 8 years since the system was first developed.
Objectives
The system was also used to identify trainers in need of additional support and other post/training programme issues.
Methods
We used an electronic system to gain the infromation as stated in the introduction.
Results
Over the last 8 years we have collected data using this system. the results for our trust will be displayed annoymously but the system is the ficus of this presenation.
Conclusions
The advantages of the system are that it runs throughout the year (so covers each post and placement), has high trainee response rates, has no selection bias (compared with some other MSF systems) and the results are embedded within local quality systems and individual consultant appraisals. The data that the system collects can help provide robust evidence when investigating concerns that might only arise periodically (for example through the annual GMC trainee survey in the UK). We believe that this system will be applicable for doctors providing training in other countries and empowers the improvement of psychiatric training for the profession.
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.
Method
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.
Results
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.
Conclusions
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.
Evidence on the impact of the pandemic on healthcare presentations for self-harm has accumulated rapidly. However, existing reviews do not include studies published beyond 2020.
Aims
To systematically review evidence on presentations to health services following self-harm during the COVID-19 pandemic.
Method
A comprehensive search of databases (WHO COVID-19 database; Medline; medRxiv; Scopus; PsyRxiv; SocArXiv; bioRxiv; COVID-19 Open Research Dataset, PubMed) was conducted. Studies published from 1 January 2020 to 7 September 2021 were included. Study quality was assessed with a critical appraisal tool.
Results
Fifty-one studies were included: 57% (29/51) were rated as ‘low’ quality, 31% (16/51) as ‘moderate’ and 12% (6/51) as ‘high-moderate’. Most evidence (84%, 43/51) was from high-income countries. A total of 47% (24/51) of studies reported reductions in presentation frequency, including all six rated as high-moderate quality, which reported reductions of 17–56%. Settings treating higher lethality self-harm were overrepresented among studies reporting increased demand. Two of the three higher-quality studies including study observation months from 2021 reported reductions in self-harm presentations. Evidence from 2021 suggests increased numbers of presentations among adolescents, particularly girls.
Conclusions
Sustained reductions in numbers of self-harm presentations were seen into the first half of 2021, although this evidence is based on a relatively small number of higher-quality studies. Evidence from low- and middle-income countries is lacking. Increased numbers of presentations among adolescents, particularly girls, into 2021 is concerning. Findings may reflect changes in thresholds for help-seeking, use of alternative sources of support and variable effects of the pandemic across groups.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.
Aims
We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection.
Method
Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data.
Results
We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10−5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies.
Conclusions
We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The mechanics of extreme intensity events in the buffer and logarithmic layers of a turbulent channel at $Re_\tau =2000$ is investigated. The 99.9th percentile of the most intense events in the dissipation of turbulent kinetic energy is analysed by means of conditional space–time proper orthogonal decomposition. The computed spatio-temporal modes are coherent in space and over the considered time frame, and optimally capture the energy of the ensemble. The most energetic mode with transverse symmetric structure describes a turbulent burst event. The underlying mechanism is a varicose instability which generates localized extrema in the dissipation and production of turbulent kinetic energy and drives the formation of a hairpin vortex. The most energetic anti-symmetric mode is related to a sinuous-type instability that is situated in the shear layer between two very-large-scale streaks. Statistical results show the energy in the symmetric mode to exceed that in the anti-symmetric mode by a near constant factor for the considered wall distances. Both mechanisms occur throughout the range of wall distances in an effectively self-similar manner that is consistent with the attached-eddy hypothesis. By analogy with transitional flows, the results suggest that the events are induced by an exponential growth mechanism.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
Method
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Results
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Conclusions
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.
Frowning expresses negative emotions like anger, fear, and sadness. According to the facial feedback hypothesis, suppression of frowning will also diminish the corresponding negative emotions. Hence, mood improvement has been observed in patients who underwent treatment of glabellar frown lines with botulinum neurotoxin. This observation suggests the possibility that the intervention may be employed for the management of psychiatric disorders associated with negative emotions. Preliminary data from an open case series indicate that the intervention might improve the symptoms of depression.
Aims & objectives
To test whether an onabotulinumtoxinA injection into the glabellar region is benefical as an adjunctive treatment of major depression within a clinical trial.
Methods
We used a randomized, double-blinded, placebo-controlled study design (n = 30; ClinicalTrials.gov, number, NCT00934687).
Results
We show that a single onabotulinumtoxinA treatment shortly leads to a strong and sustained improvement in partly chronic major depression that did not respond sufficiently to previous treatment. As for the primary end-point, Hamilton Depression Rating Scale (HAM-D17) six weeks after treatment compared to baseline, scores of onabotulinumtoxinA recipients showed 37.9% (8.34 points) more improvement than those of placebo-treated participants (F = 12.30, p = 0.002, η2 = 0.31, d = 1.28).
Conclusion
Our findings support the concept that the facial musculature not only expresses, but also regulates, mood states. As it stands, treatment of glabellar frown lines with botulinum neurotoxin can be considered for depressed patients with the objective of inducing mood-lifting effects.
Psychiatric comorbidity is an important aspect of neurological disorders. It affects about 30-50% of neurologic patients but is frequently underrecognized.
Objectives
Our objective was to determine the prevalence and severity of the symptoms of mental disorders in neurologic in-patients.
Methods
Between May and September 2014, all neurologic in-patients of a university neurologic center were asked to complete two self report questionnaires for assessing symptoms of mental disorders, namely the Beck Depression Inventory (BDI) and the Brief Symptom Inventory (BSI), which allow to assess a range of nine different psychiatric domains. We performed a multivariate covariance analysis in order to relate the type and frequency of symptoms of mental disorders with the neurological discharge diagnosis, while age, gender, and duration of in-patient treatment served as putative covariates.
Results
Of all responders (n = 157), 51% stated to have suffered from psychological distress within the past seven days, and 43% indicated depressive symptoms (21% mild, 17% moderate, 5% severe). The mean global severity index GSI (M = 0.64, SD = 0.52) exceeded the 1 SD range of healthy persons but was lower than that of psychiatric in-patients known from the literature. Furthermore, our subanalysis revealed different patterns of symptoms of mental disorders between neurologic patients with degenerative, vascular, demyelinating or epileptic disoders.
Conclusion
Psychometric measurement is useful to characterize the burden of the symptoms of mental disorders and will be used to further develop the psychiatric liaison services.
Mental trauma may precede persistent changes in a person's mental health in the form of psychosis and dissociation. Presently, there are no subtypes to the diagnosis of PTSD. A psychotic subtype of PTSD has been proposed, and studies show that these patients differ as well in symptoms as biologically from patients with non-psychotic PTSD. Dissociation and psychosis are generally viewed as different phenomena. Where dissociation is understood as a disintegration of the mind, psychosis is viewed as a neurodegenerative disorder on a mainly biological/genetic basis. The delineation of psychotic and dissociative symptoms is not clear however.
Objectives
Our objective is to clarify, whether psychologists and psychiatrists describe trauma-related changes of consciousness (TCC) differently as dissociative or psychotic. Furthermore, we wish to compare scientific journals, and look for differences in how psychiatrists’ and psychologists’ make use of the terms dissociation and psychosis in relation to TCC.
Aims
We aim to investigate whether TCC are interpreted differently among psychiatrists and psychologists.
Methods
This study is a systematic critical review of the literature. The databases PubMed, Embase and PsychInfo will be used. Articles involving PTSD with TCC will be included. Studies will be classified as viewing TCC's as either psychotic or dissociative, based on the terms the authors use to describe the observed phenomena.
Results
The results will be presented at the EPA in March 2016 in Madrid.
Conclusion
The study will reveal differences in how psychiatrists and psychologists classify TCC's in PTSD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
We present a conditional space–time proper orthogonal decomposition (POD) formulation that is tailored to the eduction of the average, rare or intermittent events from an ensemble of realizations of a fluid process. By construction, the resulting spatio-temporal modes are coherent in space and over a predefined finite time horizon, and optimally capture the variance, or energy of the ensemble. For the example of intermittent acoustic radiation from a turbulent jet, we introduce a conditional expectation operator that focuses on the loudest events, as measured by a pressure probe in the far field and contained in the tail of the pressure signal’s probability distribution. Applied to high-fidelity simulation data, the method identifies a statistically significant ‘prototype’, or average acoustic burst event that is tracked over time. Most notably, the burst event can be traced back to its precursor, which opens up the possibility of prediction of an imminent burst. We furthermore investigate the mechanism underlying the prototypical burst event using linear stability theory and find that its structure and evolution are accurately predicted by optimal transient growth theory. The jet-noise problem demonstrates that the conditional space–time POD formulation applies even for systems with probability distributions that are not heavy-tailed, i.e. for systems in which events overlap and occur in rapid succession.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.