Molecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference ...also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using
CMADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p < 0.001).
CMADAM binding in patients increased in the composite region after treatment (p = 0.01), while no change was observed in the median raphe (p = 0.51). No significant difference between patients at baseline and healthy controls were observed in the composite region (p = 0.97) or the median raphe (p = 0.95). Our main finding was that patients suffering from a depressive episode show an overall increase in cerebral serotonin transporter availability as symptoms are alleviated. Our results suggest that previously reported cross-sectional molecular imaging findings of the serotonin transporter in depression most likely reflect the depressive state, rather than a permanent trait. The finding adds new information on the pathophysiology of major depressive disorder.
We describe the open-source global fitting package GAMBIT: the Global And Modular Beyond-the-Standard-Model Inference Tool. GAMBIT combines extensive calculations of observables and likelihoods in ...particle and astroparticle physics with a hierarchical model database, advanced tools for automatically building analyses of essentially any model, a flexible and powerful system for interfacing to external codes, a suite of different statistical methods and parameter scanning algorithms, and a host of other utilities designed to make scans faster, safer and more easily-extendible than in the past. Here we give a detailed description of the framework, its design and motivation, and the current models and other specific components presently implemented in GAMBIT. Accompanying papers deal with individual modules and present first GAMBIT results. GAMBIT can be downloaded from
gambit.hepforge.org
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lundberg J. (2006) Spatial interaction model of spillovers from locally provided public services, Regional Studies
40, 631-644. This paper tests the hypotheses that recreational and cultural services ...provided at the local government level in Sweden are associated with spillovers between municipalities. A representative voter model is derived and the demand for recreational and cultural services is estimated using spatial SUR techniques. The result suggests a negative correlation between recreational and cultural services provided by neighbouring municipalities that indicate that these services are associated with spillovers. In terms of strategic behaviour, this result suggests that these services are strategic substitutes. Moreover, the results provide week evidence that recreational and cultural services provided by local governments are complements.
Lundberg J. (2006) Un modèle d'interaction géographique des retombées des services publics locaux, Regional Studies
40, 631-644. Cet article cherche à tester l'hypothèse suivant: les services de loisirs et culturels locaux en Suède s'expliquent par des retombées intervilles. On construit un modèle du voteur type et estime la demande des services de loisirs et culturels à partir des techniques SUR géographiques. Les résultats laissent supposer une corrélation faible entre les services de loisirs et culturels fournis par des villes limitrophes, ce qui indique que ces services-là s'expliquent par des retombées. En termes du comportement stratégique, ce résultat laisse supposer que ces services sont des substituts stratégiques. En outre, les résultats fournissent des preuves faibles quant à la complémentarité des services de loisirs et culturels fournis par l'administration locale.
Dépenses publiques locales Effets externes Econométrie géographique
Lundberg J. (2006) Ein Modell räumlicher Wechselwirkung der Nebeneffekte örtlicher Angebote öffentlicher Dienstleistungen, Regional Studies
40, 631-644. In diesem Aufsatz wird die These geprüft, daß Erholungs-und kulturelle Angebote der Ortsverwaltungen in Schweden in Verbindung mit Nebeneffekten von einer Gemeinde zur andern zu sehen sind. Es wird ein repräsentatives Wählermodell entwickelt, und die Nachfrage nach Erholungs-und kulturellen Angeboten mit Hilfe von räumlicher SUR Technik berechnet. Die Ergebnisse legen nahe, daß eine negative Korrelation zwischen Erholungs-und kulturellen Angeboten besteht, die von benachbarten Stadtverwaltungen zur Verfügung gestellt werden, ein Zeichen, daß diese Dienstleistungen Nebenwirkungen haben. In Hinsicht auf strategisches Vorgehen legt dieses Ergebnis nahe, daß solche Angebote Ausweichmöglichkeiten darstellen. Darüberhinaus stellen die Ergebnisse Beweise dar, daß Erholungs-und kulturelle Angebote, die von der Ortsverwaltung organisiert werden, sich komplimentär ergänzen.
Öffentliche Ausgaben der Ortsverwaltung Externalitäten räumliche Ökonometrik
Lundberg J. (2006) Modelo de interacción espacial de desbordamientos en servicios públicos, Regional Studies
40, 631-644. En este ensayo comprobamos si es cierta la hipótesis de que los servicios culturales y recreativos que el gobierno sueco ofrece a nivel local están relacionados con desbordamientos entre los municipios. Obtenemos un modelo representativo de votante y calculamos la demanda aproximada de servicios culturales y recreativos usando técnicas espaciales SUR. El resultado indica que existe una correlación negativa entre los servicios culturales y recreativos ofrecidos por los municipios vecinos lo que supone que estos servicios están relacionados con desbordamientos. En términos de conducta estratégica, este resultado señala que estos servicios son sustitutos estratégicos. Además, los resultados sólo ofrecen tenues pruebas de que los servicios culturales y recreativos proporcionados por gobiernos locales son complementarios.
Gasto público local Efectos externos Factores econométricos espaciales
11Craclopride is a well established PET tracer for the quantification of dopamine 2/3 receptors (D2/3R) in the striatum. Outside of the striatum the receptor density is up to two orders of magnitude ...lower. In contrast to striatal binding, the characteristics of extrastriatal 11Craclopride binding quantification has not been thoroughly described. Still, binding data for e.g., neocortex is frequently reported in the scientific literature. Here we evaluate the validity and reliability of extrastriatal 11Craclopride binding quantification. Two sets of healthy control subjects were examined with HRRT and 11Craclopride: (i) To assess the validity of extrastriatal 11Craclopride binding estimates, eleven subjects were examined at baseline and after dosing with quetiapine, a D2/3R antagonist. (ii) To assess test-retest repeatability, nine subjects were examined twice. Non displaceable binding potential (BPND) was quantified using the simplified reference tissue model with cerebellum as reference. Quetiapine dosing was associated with decrease in 11Craclopride BPND in temporal cortex (18 ± 17% occupancy) and thalamus (20 ± 17%), but not in frontal cortex. Extrastriatal occupancy was lower than in putamen (51 ± 4%). The mean absolute variation was 4–7% in the striatal regions, 17% in thalamus, and 13–59% in cortical regions. Our data indicate that 11Craclopride PET, quantified using cerebellum as reference, is not a suitable tool to measure D2/3R in extrastriatal regions.
•Extrastriatal 11Craclopride binding characteristics has not been well described.•D2-blocking agent gave little to no decrease in extrastriatal 11Craclopride binding.•Test-retest repeatability was generally poor in cortical regions.•11Craclopride PET is not an apt tool for extrastriatal D2/3R binding quantification.
Advanced psychiatric treatments remain uncertain in preventing suicide among adolescents. Across the 21 Swedish regions, using nationwide registers between 2016-2020, we found negative correlation ...between adolescent excess suicide mortality (AESM) and regional frequencies of clozapine, ECT, and lithium (CEL) usage among adolescents (β = -0.613, p = 0.0003, 95% CI: -0.338, -0.889) and males (β = -0.404, p = 0.009, 95% CI: -0.130, -0.678). No correlation was found among females (p = 0.197). Highest CEL usage among male adolescents was seen in regions with lowest quartile (Q1) AESM (W = 74, p = 0.012). Regional CEL treatment frequency in 15-19-year-olds was related to lower AESM in males, reflecting potential treatment efficacy, treatment compliance or better-quality mental health care. Suicide prevention may benefit from early recognition and CEL treatment for severe mental illness in male adolescents. The results indicate association but further research, using independent samples and both prospective and observational methodologies, is needed to confirm causality.
Since the onset of the COVID-19 pandemic, there have been concerns over the mental health impact of COVID-19. This is a review of the utilization of antidepressants, anxiolytics, and hypnotics since ...the COVID-19 pandemic was declared on March the 11th 2020. A number of reports so far have been based on large prescription databases for administrative use at the national or regional level, but mainly in high-income countries. We found studies reporting increased prescription rates of antidepressants, anxiolytics, and hypnotics during March 2020, which has been interpreted as hoarding of such medications. In the following months, most studies of antidepressant prescription rates did not display a clear pattern of change compared with prepandemic trends. In later phases of the pandemic small increases in utilization of antidepressants, with higher than predicted prescription rates, have been the most consistent finding, especially in youth. In most high-income countries, there were increasing trends in utilization of antidepressants also before 2020, which needs to be considered when estimating utilization during the pandemic, whereas for anxiolytics and hypnotics, the prepandemic patterns of prescriptions were more varying. Overall, after March 2020 we could not find any distinct changes in the utilization of anxiolytics and hypnotics during the COVID-19 pandemic. Most studies did not contain information about the prevalence of indicated psychiatric disorders in the studied populations. More studies are needed about the long-term effects of COVID-19, particularly regarding utilization of antidepressants. Research relating antidepressant utilization with the prevalence of major depression and anxiety disorders would promote a better understanding of how well antidepressant prescription rates reflect the needs of the population.
Rationale and objectives
The purpose of this study was to evaluate the feasibility of unconstrained three-material decomposition in a human tissue specimen containing iodinated contrast agent, using ...an experimental multi-bin photon-counting silicon detector. It was further to evaluate potential added clinical value compared to a 1st-generation state-of-the-art dual-energy computed tomography system.
Materials and methods
A prototype photon-counting silicon detector in a bench-top setup for x-ray tomographic imaging was calibrated using a multi-material calibration phantom. A heart with calcified plaque was obtained from a deceased patient, and the coronary arteries were injected with an iodinated contrast agent mixed with gelatin. The heart was imaged in the experimental setup and on a 1st-generation state-of-the-art dual-energy computed tomography system. Projection-based three-material decomposition without any constraints was performed with the photon-counting detector data, and the resulting images were compared with those obtained from the dual-energy system.
Results
The photon-counting detector images show better separation of iodine and calcium compared to the dual-energy images. Additional experiments confirmed that unbiased estimates of soft tissue, calcium, and iodine could be achieved without any constraints.
Conclusion
The proposed experimental system could provide added clinical value compared to current dual-energy systems for imaging tasks where mix-up of iodine and calcium is an issue, and the anatomy is sufficiently small to allow iodine to be differentiated from calcium. Considering its previously shown count rate capability, these results show promise for future integration of this detector in a clinical CT scanner.
Key Points
• Spectral photon-counting detectors can solve some of the fundamental problems with conventional single-energy CT.
• Dual-energy methods can be used to differentiate iodine and calcium, but to do so must rely on constraints, since solving for three unknowns with only two measurements is not possible. Photon-counting detectors can improve upon these methods by allowing unconstrained three-material decomposition.
• A prototype photon-counting silicon detector with high count rate capability allows performing unconstrained three-material decomposition and qualitatively shows better differentiation of iodine and calcium than dual-energy CT.
Background
Retrospective studies indicate that the choice of anesthetic can affect long‐term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for ...breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long‐term breast cancer survival.
Methods
We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis.
Results
The database analysis identified 6305 patients. The 5‐year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non‐significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10‐1.95).
Conclusions
It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.
Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and ...test–retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand 11CFLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centers. Instead, the medium affinity radioligand 11Craclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of 11Craclopride in extrastriatal regions in a pharmacological competition study with quetiapine. Here, we utilise a data set of 16 healthy control subjects examined with both 11Craclopride and 11CFLB 457 to assess the correlation in binding potential (BPND) in extrastriatal brain regions. BPND was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BPND values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between 11Craclopride and 11CFLB 457 BPND extrastriatally (Pearson's R: 0.30–0.56), in contrast to very strong correlations between repeated 11CFLB 457 measurements (Pearson's R: 0.82–0.98). In comparison, correlations between repeated 11Craclopride measurements were low to moderate (Pearson's R: 0.28–0.75). These results are likely related to low signal to noise ratio of 11Craclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with 11Craclopride should be interpreted with caution.
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