On the transience of stability of subthreshold psychopathology

Symptoms of psychopathology lie on a continuum ranging from mental health to psychiatric disorders. Although much research has focused on progression along this continuum, for most individuals, subthreshold symptoms do not escalate into full-blown disorders. This study investigated how the stability of psychopathological symptoms (attractor strength) varies across severity levels (homebase). Data were retrieved from the TRAILS TRANS-ID study, where 122 at-risk young adults (mean age 23.6 years old, 57% males) monitored their mental states daily for a period of six months (± 183 observations per participant). We estimated each individual’s homebase and attractor strength using generalized additive mixed models. Regression analyses showed no association between homebases and attractor strengths (linear model: B = 0.02, p = 0.47, R(2) < 0.01; polynomial model: B < 0.01, p = 0.61, R(2) < 0.01). Sensitivity analyses where we (1) weighed estimates according to their uncertainty and (2) removed individuals with a DSM-5 diagnosis from the analyses did not change this finding. This suggests that stability is similar across severity levels, implying that subthreshold psychopathology may resemble a stable state rather than a transient intermediate between mental health and psychiatric disorder. Our study thus provides additional support for a dimensional view on psychopathology, which implies that symptoms differ in degree rather than kind

The Associations of Affection and Rejection During Adolescence with Interpersonal Functioning in Young Adulthood:A Macro- and Micro-Level Investigation Using the TRAILS TRANS-ID Study

Affection and rejection in close relationships during adolescence are thought to impact adult interpersonal functioning, but few studies focused on how the quality of adolescents' relationships with different people (e.g. parents, peers, and teachers) impacts the daily, micro-level social experiences as well as general, macro-level interpersonal functioning in young adulthood. The present study investigated the associations between: (i) parental, teacher and peer affection and rejection during adolescence and macro-level (over several months) interpersonal functioning as well as different patterns (i.e. mean, variability and inertia) of micro-level (daily social experiences) during young adulthood; (ii) macro-level interpersonal functioning and the patterns of micro-level social experiences during young adulthood. The sample consisted of N = 122 (43% female) youth. At 11.2 +/- 0.4 and 16.0 +/- 0.6 years old, self- and other-reported parental, peer and teacher affection and rejection were assessed. At 23.7 +/- 0.6 years old, participants reported daily social experiences and interpersonal functioning across six months. The results suggested that: (i) higher teacher-reported peer rejection was associated with lower macro-level interpersonal functioning, higher means and higher variability in negative social experiences during adulthood; (ii) higher macro-level interpersonal functioning during young adulthood was associated with higher means and lower inertia in positive and lower variability in negative daily social experiences. These findings indicate that the affection and rejection during adolescence impact interpersonal functioning at macro- and micro-level during adulthood. The present study also shows distinct associations between macro-level interpersonal functioning and dynamics in daily social experiences

Anticipating Transitions in Mental Health in At-Risk Youths:A 6-Month Daily Diary Study Into Early-Warning Signals

If psychopathology behaves like a complex dynamic system, sudden onset or worsening of symptoms may be preceded by early-warning signals (EWSs). EWSs could thus reflect personalized warning signals for impending psychopathology. We empirically investigated this hypothesis in at-risk youths (N = 122, mean age = 23.6 ± 0.7 years, 57% males) from the clinical cohort of Tracking Adolescents’ Individual Lives Survey (TRAILS-CC), who provided daily emotion assessments for 6 months. We analyzed whether EWSs (rising autocorrelations and standard deviations in emotions) preceded transitions toward psychopathology. Across indicators and a range of analytical options, EWSs had low sensitivity (M = 26%, SD = 11%) and moderate specificity (M = 75%, SD = 14%). Thus, in the present sample, the proposed generic nature and clinical utility of EWSs could not be substantiated. Given this finding, we call for a more nuanced view on the application of complex-dynamic-systems principles to psychopathology and lay out key questions to be addressed in the future

Systematic investigation of the elastic proton-deuteron differential cross section at intermediate energies

To investigate the importance of three-nucleon forces (3NF) systematically over a broad range of intermediate energies, the differential cross sections of elastic proton-deuteron scattering have been measured at proton bombarding energies of 108, 120, 135, 150, 170 and 190 MeV at center-of-mass angles between $30^\circ$ and $170^\circ$. Comparisons with Faddeev calculations show unambiguously the shortcomings of calculations employing only two-body forces and the necessity of including 3NF. They also show the limitations of the latest few-nucleon calculations at backward angles, especially at higher beam energies. Some of these discrepancies could be partially due to relativistic effects. Data at lowest energy are also compared with a recent calculation based on \chipt

The effects of molar activity on [F-18]FDOPA uptake in patients with neuroendocrine tumors

BACKGROUND: 6-[(18)F]fluoro-l-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [(18)F]FDOPA is decarboxylated to [(18)F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [(18)F]FDOPA has been developed, [(18)F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([(18)F]FDOPA-L). AIMS: This study aimed to investigate whether the difference in molar activity affects the [(18)F]FDOPA uptake at physiological sites and in tumor lesions, in patients with NET. It was anticipated that the specific uptake of [(18)F]FDOPA-H would be equal to or higher than [(18)F]FDOPA-L. METHODS: We retrospectively analyzed 49 patients with pathologically confirmed NETs and stable disease who underwent PET scanning using both [(18)F]FDOPA-H and [(18)F]FDOPA-L within a time span of 5 years. A total of 98 [(18)F]FDOPA scans (49 [(18)F]FDOPA-L and 49 [(18)F]FDOPA-H with average molar activities of 8 and 107 GBq/mmol) were analyzed. The SUVmean was calculated for physiological organ uptake and SUVmax for tumor lesions in both groups for comparison, and separately in subjects with low tumor load (1–2 lesions) and higher tumor load (3–10 lesions). RESULTS: Comparable or slightly higher uptake was demonstrated in various physiological uptake sites in subjects scanned with [(18)F]FDOPA-H compared to [(18)F]FDOPA-L, with large overlap being present in the interquartile ranges. Tumor uptake was slightly higher in the [(18)F]FDOPA-H group with 3–10 lesion (SUVmax 6.83 vs. 5.19, p < 0.001). In the other groups, no significant differences were seen between H and L. CONCLUSION: [18F]FDOPA-H provides a higher activity yield, offering the possibility to scan more patients with one single production. Minor differences were observed in SUV’s, with slight increases in uptake of [(18)F]FDOPA-H in comparison to [(18)F]FDOPA-L. This finding is not a concern for clinical practice, but could be of importance when quantifying follow-up scans while introducing new production methods with a higher molar activity of [(18)F]FDOPA

Effects of training and motivation on auditory P300 brain–computer interface performance

Objectives Brain–computer interface (BCI) technology aims at helping end-users with severe motor paralysis to communicate with their environment without using the natural output pathways of the brain. For end-users in complete paralysis, loss of gaze control may necessitate non-visual BCI systems. The present study investigated the effect of training on performance with an auditory P300 multi-class speller paradigm. For half of the participants, spatial cues were added to the auditory stimuli to see whether performance can be further optimized. The influence of motivation, mood and workload on performance and P300 component was also examined. Methods In five sessions, 16 healthy participants were instructed to spell several words by attending to animal sounds representing the rows and columns of a 5 × 5 letter matrix. Results 81% of the participants achieved an average online accuracy of ≥70%. From the first to the fifth session information transfer rates increased from 3.72 bits/min to 5.63 bits/min. Motivation significantly influenced P300 amplitude and online ITR. No significant facilitative effect of spatial cues on performance was observed. Conclusions Training improves performance in an auditory BCI paradigm. Motivation influences performance and P300 amplitude. Significance The described auditory BCI system may help end-users to communicate independently of gaze control with their environment

The Substrate-Bound Crystal Structure of a Baeyer–Villiger Monooxygenase Exhibits a Criegee-like Conformation

The Baeyer\u2013Villiger monooxygenases (BVMOs) are a family of bacterial flavoproteins that catalyze the synthetically useful Baeyer\u2013Villiger oxidation reaction. This involves the conversion of ketones into esters or cyclic ketones into lactones by introducing an oxygen atom adjacent to the carbonyl group. The BVMOs offer exquisite regio- and enantiospecificity while acting on a wide range of substrates. They use only NADPH and oxygen as cosubstrates, and produce only NADP+ and water as byproducts, making them environmentally attractive for industrial purposes. Here, we report the first crystal structure of a BVMO, cyclohexanone monooxygenase (CHMO) from Rhodococcus sp. HI-31 in complex with its substrate, cyclohexanone, as well as NADP+ and FAD, to 2.4 \uc5 resolution. This structure shows a drastic rotation of the NADP+ cofactor in comparison to previously reported NADP+-bound structures, as the nicotinamide moiety is no longer positioned above the flavin ring. Instead, the substrate, cyclohexanone, is found at this location, in an appropriate position for the formation of the Criegee intermediate. The rotation of NADP+ permits the substrate to gain access to the reactive flavin peroxyanion intermediate while preventing it from diffusing out of the active site. The structure thus reveals the conformation of the enzyme during the key catalytic step. CHMO is proposed to undergo a series of conformational changes to gradually move the substrate from the solvent, via binding in a solvent excluded pocket that dictates the enzyme\u2019s chemospecificity, to a location above the flavin\u2013peroxide adduct where catalysis occurs.Peer reviewed: YesNRC publication: Ye

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study

International audienceBACKGROUND:Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH.METHODS:In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation.RESULTS:We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23–100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15–80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2–2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6–3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4–1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1–0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7–50 months), with a cumulative hazard of 47% at 10 years.CONCLUSIONS:The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted

The ATLAS Level-1 muon topological trigger information for run 2 of the LHC

For run 2 of the LHC, the ATLAS Level-1 trigger system will include topological information on trigger objects in order to cope with the increased trigger rates. The existing Muon-to-Central-Trigger- Processor interface (MUCTPI) has been modified in order to provide coarse-grained topological information on muon candidates. A MUCTPI- to-Level-1-Topological-Processor interface (MuCTPiToTopo) has been developed to receive the electrical information and to send it optically to the Level-1 Topological Processor (L1TOPO). This poster will describe the different modules mentioned above and present results of functionality and connection tests performed