Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre [C-11]PBR28 HRRT PET study

Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies

EXPERIMENTAL AND THEORETICAL WORK OF DOUBLY CHARGED MOLECULAR IONS: N22+N^{2+}_{2} AND CO2+CO^{2+}

$^{1}$ B.J. Olsson, G. Kindvall and M. Larsson, J. Chem. Phys. (in press).Author Institution: Research Institute of Physics, Frescativagen 24Only a few doubly charged molecular ions are known to possess emission spectra. The $^{1}\Sigma^{+}_{u}-x^{1}\Sigma^{+}_{g}$ transition of $N^{2+}_{2}$ was rotationally analyzed by Carroll already 1958 and more recently by Cossart and coworkers. We have used the high frequency deflection technique to perform the first direct vibrationally resolved measurement of a fluorescence lifetime of a doubly charged molecular $ion^{1}$. Furthermore, we have used the complete active space SCF (CASSCF) method to calculate the electronic transition moment function of the D-X transition. The contracted CI (CCI) method was used to improve the potential curves obtained at the CASSCF level and the radiative lifetime was obtained with help of these potential curves and the electronic transition moment function. The experimental and theoretical lifetimes, 6.010.5 and 8.0 ns respectively, are in good agrecement. No emission from the $CO^{2+}$ ion has yet been observed. The CASSCF and CCI methods have been used to obtain potential curves of low lying triplet states of $CO^{2+}$.With these curves as guidance, emission from $CO^{2+}$ following electron impact on jet cooled CO have been searched for. We also plan to search for a laser induced predissociation spectnm of $CO^{2+}$ with the fast ion beam laser technique

Modelling of ships as a source of underwater noise

In this paper, a methodology is presented for modelling underwater noise emissions from ships based on realistic vessel activity in the Baltic Sea region. This paper combines the Wittekind noise source model with the Ship Traffic Emission Assessment Model (STEAM) in order to produce regular updates for underwater noise from ships. This approach allows the construction of noise source maps, but requires parameters which are not commonly available from commercial ship technical databases. For this reason, alternative methods were necessary to fill in the required information. Most of the parameters needed contain information that is available during the STEAM model runs, but features describing propeller cavitation are not easily recovered for the world fleet. Baltic Sea ship activity data were used to generate noise source maps for commercial shipping. Container ships were recognized as the most significant source of underwater noise, and the significant potential for an increase in their contribution to future noise emissions was identified

Positron emission tomography studies of the Glial cell marker translocator protein in patients with psychosis: a meta-analysis using individual participant data

BACKGROUND: Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects. METHODS: PubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (VT), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients' TSPO levels compared with healthy control subjects. RESULTS: Five studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower VT in patients relative to no difference (all BFs > 32), or relative to higher VT (all BFs > 422), in all brain regions. From the posterior distributions, mean patient-control differences in standardized VT values were -0.48 for frontal cortex (95% credible interval [CredInt] = -0.88 to 0.09), -0.47 for temporal cortex (CredInt = -0.87 to -0.07), and -0.63 for hippocampus (CredInt = -1.00 to -0.25). CONCLUSIONS: The lower levels of TSPO observed in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment

Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data

Background: Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects. Methods: PubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (V T ), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients’ TSPO levels compared with healthy control subjects. Results: Five studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower V T in patients relative to no difference (all BFs > 32), or relative to higher V T (all BFs > 422), in all brain regions. From the posterior distributions, mean patient–control differences in standardized V T values were −0.48 for frontal cortex (95% credible interval [CredInt] = −0.88 to 0.09), −0.47 for temporal cortex (CredInt = −0.87 to −0.07), and −0.63 for hippocampus (CredInt = −1.00 to −0.25). Conclusions: The lower levels of TSPO observed in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment