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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.
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.
The acoustic pulse emitted from the Bragg peak of a laser-accelerated proton bunch focused into water has recently enabled the reconstruction of the bunch energy distribution. By adding three ultrasonic transducers and implementing a fast data analysis of the filtered raw signals, I-BEAT (Ion-Bunch Energy Acoustic Tracing) 3D now provides the mean bunch energy and absolute lateral bunch position in real-time and for individual bunches. Relative changes in energy spread and lateral bunch size can also be monitored. Our experiments at DRACO with proton bunch energies between 10 and 30 MeV reveal sub-MeV and sub-mm resolution. In addition to this 3D bunch information, the signal strength correlates also with the absolute bunch particle number.
Background: Eating disorders (EDs) are severe psychiatric disorders which, when left untreated, can lead to psychosocial impairment, physical disability and death. In the United Kingdom, many specialist ED services collect routine outcome measures (ROMs) which serve to assess illness severity, patients’ quality of life and function. The repeated collection of ROMs over the course of treatment allows for the objective evaluation of patient progress towards recovery. Recent National Health Service (NHS) guidance on adult ED care in England suggests that all services should use ROMs, not just to track progress, but also to support the achievement of collaboratively identified, person-specific recovery goals, to empower patients and inform individualised treatment. To achieve this objective, clinicians need access to psychometrically sound ROMs which can be utilised in a collaborative and person-centred manner. Traditionally, ROMs have been collected using standardised patient-reported outcome measures (PROMs), but increasingly individualised PROMs (i-PROMs) are also being developed. Methods & Findings: In this talk I will review the ‘why, what and how’ of ROMs, PROMs, I-PROMS and of associated normative and ipsative feedback on these measures in the eating disorders context. Conclusions: Use of PROMs has much to be commended both in regard to treating individual patients, at service level and also the wider health care system.
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.
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.
The structure of the anticancer drug carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, C5H9Cl2N3O2) was successfully determined from laboratory X-ray powder diffraction data recorded at 278 K and at 153 K. Carmustine crystallizes in the orthorhombic space group P212121 with Z = 4. The lattice parameters are a = 19.6935(2) Å, b = 9.8338(14) Å, c = 4.63542(6) Å, V = 897.71(2) ų at 153 K, and a = 19.8522(2) Å, b = 9.8843(15) Å, c = 4.69793(6) Å, V = 921.85(2) ų at 278 K. The Rietveld fits are very good, with low R-values and smooth difference curves of calculated and experimental powder data. The molecules form a one-dimensional hydrogen bond pattern. At room temperature, the investigated commercial sample of carmustine was amorphous.
Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29 142 women and 26 029 men aged 50–64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.
People with eating disorders (ED) are at high risk for suicidal behavior. Among different ED, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of completed suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an ED.
Method
Case-control study in cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity.
Results
AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4–7.9), with a higher expectation of dying (OR = 3.7, 95% CI 1.1–13.5), and an increased risk of lethality (OR = 3.4, 95% CI 1.2–9.6). BN patients did not differ from the control group.
Conclusion
There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Deaths from suicide in AN may not be the result simply of their greater physical frailty.
The concept of endophenotypes has attracted considerable interest in psychiatry. It is thought that endophenotypes might be more closely related to the underlying biological processes and the genetic basis that give rise to a particular disorder than the relatively crude diagnostic categories defined in our conventional classificatory systems. In order to qualify as an endophenotype a characteristic has to be measurable and heritable, cosegregates with the illness, is state independent, is observed in unaffected family members and is a biologically plausible causal mechanism. In the field of eating disorders the study of endophenotypes is still in its infancy. The aims of this paper are to:
a. give an introduction to the concept of endophenotypes and its criticism,
b. review what is known about endophenotypes in eating disorders, and
c. present recent data from our own recent work on putative social cognitive endophenotypes.
Methods and results:
Based on a review of the literature and our own research findings a handful of different temperamental and personality traits, neurocognitive and social characteristics can be identified that fulfill all the criteria to qualify as an endophenotypes. Other candidate endophenotypes need further study to ascertain whether they qualify.
Conclusions:
The implications of this research for the classification of eating disorders are potentially far reaching.
Data about quality of life (QoL) are important to estimate the impact of diseases on functioning and well-being. The present study was designed to assess the association of different aspects of panic disorder (PD) with QoL and to examine the relationship between QoL and symptomatic outcome following brief cognitive-behavioral group therapy (CBGT).
Methods
The sample consisted of 55 consecutively recruited outpatients suffering from PD who underwent CBGT. QoL was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at baseline, post-treatment and six months follow-up. SF-36 baseline scores were compared with normative data obtained from a large German population sample.
Results
Agoraphobia, disability, and worries about health were significantly associated with decreased QoL, whereas frequency, severity and duration of panic attacks were not. Treatment responders showed significantly better QoL than non-responders. PD symptom reduction following CBGT was associated with considerable improvement in emotional and physical aspects of QoL. However, the vitality subscale of the SF-36 remained largely unchanged over time.
Conclusions
Our results are encouraging for cognitive-behavior therapists who treat patients suffering from PD in groups, since decrease of PD symptoms appears to be associated with considerable improvements in QoL. Nevertheless, additional interventions designed to target specific aspects of QoL, in particular vitality, may be useful to enhance patients’ well-being.
Psychotic and psychotic-like experiences (PLEs) are frequently found in the general population when assessed with self-report questionnaires. It is not clear how these assessments can help to predict the future development of mental disorders. The degree of certainty in appraisal or the experience-related distress may add prognostic power of clinical PLE assessments. This study was designed to provide baseline data of PLEs in a representative sample, which will be monitored for the future development.
Methods
We studied the frequency of PLEs in a representative sample of 4483 participants of the German population recruited through the Mental Health Module of the German Health Interview and Examination Survey for Adults (DEGS1-MH). Participants were asked if they had had psychotic or psychosis-like experiences over their lifetime. We used the psychosis section of the Composite International Diagnostic Interview (CIDI), the Launay-Slade Hallucination Scale (LSHS) and the Peter's Delusion Inventory (PDI).
Preliminary Results
33.3% of the participants endorsed at least one item of the CIDI psychosis scale, 68.8% of the PDI and 49.0% of the LSHS. In the PDI assessments, conspiracy-related delusional experiences were most often experienced as distressing, while religious beliefs were experienced less distressing, but with high levels of conviction.
Discussion
Our findings show frequent endorsement of lifetime psychotic or psychotic-like experiences in the general population in self-report questionnaires with varying degrees of distress and conviction. This provides the needed baseline assessment for follow-up studies observing the development of mental disorders with a view to determine the predictive values of these tests.
Repetitive Transcranial Magnetic Stimulation (rTMS) research in psychiatry mostly excludes left-handed participants. We recruited left-handed people with a bulimic disorder and found that stimulation of the left prefrontal cortex may result in different effects in left- and right-handed people. This highlights the importance of handedness and cortex lateralisation for rTMS.
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.
Attachment and companionship are fundamental basic needs of human beings and contribute the feeling of security and social affiliation. It is assumed that dysfunctional attachment behaviour in people with Borderline Personality Disorder leads to difficulties in the interpersonal contact. Unsecure and especially disorganized manners of attachment seem to be frequently represented by mentally ill people. In this study the release of oxytocin according to attachment relevant situations was investigated and attachment representations of people with BPD have been analysed.
Methods
In order to determine attachment representations of healthy people and of people with BPD we used the validated ‘Adult Attachment Projective’/ ‘AAP’ by George, West and Pettem (1999). The projective contains eight contour drawings of attachment relevant situations. The participant should make up a story of each picture, which was evaluated by its coherence, its content and the used defence mechanisms. Attachment representations of 30 patients with BPD were surveyed. Furthermore we measured the release of oxytocin evoked by an activation of the attachment system via the ‘AAP’ in 10 healthy people. Therefor blood drawings were performed at four different points of time.
Discussion
Here, we present pilot data on oxytocin measures induced via the ‘AAP’. We could detect a decrease of oxytocin in healthy people caused by an activation of the attachment system. Moreover attachment representations of patients with BPD will be presented and discussed. These preliminary data could lead to further studies on a possible dysregulation of the attachment- and the oxytocin system of people with BPD.