About the authors

BACKGROUND: Although it is generally agreed that personality disorders are an important topic in old-age psychiatry, DSM-5 has paid relatively little attention to older persons affected with this severe mental disorder. AIM: To look closely and carefully at several aspects of the way in which DSM-5 defines personality disorders relating to older persons. METHOD: We make a critical evaluation of the description of personality disorders given in DSM-5. RESULTS: First of all, we question whether the phrase 'personality change due to another medical condition' should really be included in the dsm-5 chapter of personality disorders because a personality change actually has the features of a persistent conduct disorder. Secondly, we argue that in a future revised version of dsm-5 personality disorders affecting older persons should be referred to specifically as 'late-onset' personality disorders. Thirdly, we stress that the research programme relating to the dimensional dsm-5 model of personality disorders should involve a larger number of older persons. In addition, more research is needed with regard to the use, wording and validity of the phrase 'personality change due to a medical condition'. Those responsible for the revision of the DSM-5 should ensure that the concept 'late-onset personality disorders' is incorporated in the text. CONCLUSION: The description of personality disorders in DSM-5 is confusing. This is probably due to the transitional period between the old categorical (dsm-iv) system and the newly proposed dimensional approach to personality disorders in DSM-5, an approach that needs further investigation. However, this intervening period could be a good opportunity for doing further research into personality disorders in older adults

Radiolabeled humanized anti-CD3 monoclonal antibody visilizumab for imaging human T-lymphocytes

Visilizumab is an IgG2 humanized monoclonal antibody (mAb) characterized by non-FcγR binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a radiolabeled anti-CD3 antibody might serve as a diagnostic tool for imaging T-cell traffic and lymphocytic infiltration of tissues and organs affected by autoimmune diseases. Here we describe the results of in vitro and animal experiments with 99mTc-succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH)-visilizumab. Methods: For mAb labeling, we used a 2-step method with a heterobifunctional linker SHNH. Several titrations were performed to obtain the best labeling efficiency. In vitro quality controls included stability assay, cysteine challenge, sodium dodecyl sulfate polyacrylamide gel electrophoresis, binding assay, and immunoreactivity assay. In vivo studies by high-resolution images were performed at 6 and 24 h after the injection of 99mTc-SHNH-visilizumab. These included cell-targeting experiments in BALB/c mice xenografted subcutaneously with an increasing number of HuT78 cells in the leg and displaced with an excess of cold antibody. We also studied irradiated severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells (hPBMCs) and injected with 99mTclabeled visilizumab or control mAb. After dynamic imaging for 3 h, major organs were removed, counted, and processed for immunohistologic examination. Results: Visilizumab was labeled with HYNIC with high labeling efficiency (>90%) and high specific activity (SA; 10,360-11,100 MBq/mg), with retained biochemical integrity and in vitro binding activity to CD3-positive cells. The in vivo targeting experiment showed a proportional increase of specific uptake with the number of injected cells, both at 6 and at 24 h, and the in vivo competition study demonstrated more than 60% decreased uptake after an excess of unlabeled antibody. In SCID mice, hPBMCs in different tissues were detected by 99mTc-labeled visilizumab and confirmed by histology. Conclusion: Visilizumab can be efficiently labeled with 99mTc with high efficiency and SA and could be a valuable tool for the study of human T-lymphocyte trafficking and lymphocytic infiltration of tissues and organs. Copyright © 2009 by the Society of Nuclear Medicine, Inc

A retrospective analysis of the diagnostic performance of 11C-choline PET/CT for detection of hyperfunctioning parathyroid glands after prior negative or discordant imaging in primary hyperparathyroidism

BACKGROUND: Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine the diagnostic performance of 11C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging. METHODS: This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing 11C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the 11C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard. RESULTS: In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on 11C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of 11C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions. CONCLUSIONS: In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by 11C-choline PET/CT with high sensitivity and accuracy

A Fashi lymphoproliferative phenotype reveals non-apoptotic Fas signalling in HTLV-1-associated neuroinflammation.

Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely Adult T-cell Leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fashi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC) and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fashi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signalling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e. blocking vs. triggering Fas receptor in vitro with antagonist and agonist- anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating biased but not defective Fas signalling in HAM/TSP. In silico analysis revealed biased Fas signalling towards proliferation and inflammation, driven by RelA/NF-kB. Correlation of Fas transcript levels with proliferation (but not apoptosis) was confirmed in HAM/TSP ex vivo transcriptomes. In conclusion, we demonstrated a two-step increase in Fas expression, revealing a unique Fashi lymphocyte phenotype in HAM/TSP, distinguishable from multiple sclerosis. Non-apoptotic Fas signalling might fuel HAM/TSP pathogenesis, through increased lymphoproliferation, inflammation and early age of onset

Light-Element Abundance Variations at Low Metallicity: the Globular Cluster NGC 5466

We present low-resolution (R~850) spectra for 67 asymptotic giant branch (AGB), horizontal branch and red giant branch (RGB) stars in the low-metallicity globular cluster NGC 5466, taken with the VIRUS-P integral-field spectrograph at the 2.7-m Harlan J. Smith telescope at McDonald Observatory. Sixty-six stars are confirmed, and one rejected, as cluster members based on radial velocity, which we measure to an accuracy of 16 km s-1 via template-matching techniques. CN and CH band strengths have been measured for 29 RGB and AGB stars in NGC 5466, and the band strength indices measured from VIRUS-P data show close agreement with those measured from Keck/LRIS spectra previously taken of five of our target stars. We also determine carbon abundances from comparisons with synthetic spectra. The RGB stars in our data set cover a range in absolute V magnitude from +2 to -3, which permits us to study the rate of carbon depletion on the giant branch as well as the point of its onset. The data show a clear decline in carbon abundance with rising luminosity above the luminosity function "bump" on the giant branch, and also a subdued range in CN band strength, suggesting ongoing internal mixing in individual stars but minor or no primordial star-to-star variation in light-element abundances.Comment: 10 pages, emulateapj format, AJ accepte

Other Radiopharmaceuticals for Imaging GEP‐NET

In GEP‐NETs, especially the catecholamine and serotonin biosynthetic pathways are upregulated. Therefore, increased biosynthesis of these specific amines in GEP‐NETs enables imaging with specific amine precursors. For the catecholamine pathway, 6‐18F ‐l‐3,4‐dihydroxyphenylalanine (18F‐DOPA) is available, while for the serotonin pathway, carbon‐11‐labeled 5‐hydroxy‐l‐tryptophan ([11C]‐5‐HTP) is available as tracer. 11C‐5‐HTP PET and 18F‐DOPA PET are excellent functional imaging techniques for evaluating patients with proven pancreatic islet cell tumors and carcinoids. For both tracers, the combination with CT further improves the detection rate of NET, which shows that performing PET scans with these tracers in PET/CT scanners is beneficial for patients.Since well‐differentiated GEP‐NETs generally have a low glucose metabolism, 18F‐fluorodexyglucose (18F‐FDG) PET scanning has limited value for the primary staging of patients with well‐differentiated GEP‐NETs. However, in patients with rapidly progressive disease, dedifferentiation of GEP‐NET tumors can lead to a higher glucose metabolism in tumor cells. In these patients, 18F‐FDG PET can be of benefit for tumor staging. Also, 18F‐FDG PET can be of value when other malignancies are suspected in patients with GEP‐NETs, since these patients experience a higher incidence of these malignancies compared to the general population.Nowadays, (GEP)‐NETs can also be imaged with 68Ga‐labeled analogues of somatostatin, which are also PET tracers. Advantages of 68Ga‐labeled somatostatin analogues are the relatively easy generator‐based synthesis and the possibility to evaluate whether peptide (somatostatin) receptor radionuclide therapy (PRRT) for NETs can be considered

A Photocleavable Contrast Agent for Light-Responsive MRI

Thanks to its innocuousness and high spatiotemporal resolution, light is used in several established and emerging applications in biomedicine. Among them is the modulation of magnetic resonance imaging (MRI) contrast agents' relaxivity with the aim to increase the sensitivity, selectivity and amount of functional information obtained from this outstanding whole-body medical imaging technique. This approach requires the development of molecular contrast agents that show high relaxivity and strongly pronounced photo-responsiveness. To this end, we report here the design and synthesis of a light-activated MRI contrast agent, together with its evaluation using UV-vis spectroscopy, Fast Field Cycling (FFC) relaxometry and relaxometric measurements on clinical MRI scanners. The high relaxivity of the reported agent changes substantially upon irradiation with light, showing a 17% decrease in relaxivity at 0.23T upon irradiation with lambda = 400 nm (violet) light for 60 min. On clinical MRI scanners (1.5T and 3.0T), irradiation leads to a decrease in relaxivity of 9% and 19% after 3 and 60 min, respectively. The molecular design presents an important blueprint for the development of light-activatable MRI contrast agents

Shopping centre siting and modal choice in Belgium: a destination based analysis

Although modal split is only one of the elements considered in decision-making on new shopping malls, it remarkably often arises in arguments of both proponents and opponents. Today, this is also the case in the debate on the planned development of three major shopping malls in Belgium. Inspired by such debates, the present study focuses on the impact of the location of shopping centres on the travel mode choice of the customers. Our hypothesis is that destination-based variables such as embeddedness in the urban fabric, accessibility and mall size influence the travel mode choice of the visitors. Based on modal split data and location characteristics of seventeen existing shopping centres in Belgium, we develop a model for a more sustainable siting policy. The results show a major influence of the location of the shopping centre in relation to the urban form, and of the size of the mall. Shopping centres that are part of a dense urban fabric, measured through population density, are less car dependent. Smaller sites will attract more cyclists and pedestrians. Interestingly, our results deviate significantly from the figures that have been put forward in public debates on the shopping mall issue in Belgium

Mitigation of noise-induced bias of PET radiomic features

INTRODUCTION: One major challenge in PET radiomics is its sensitivity to noise. Low signal-to-noise ratio (SNR) affects not only the precision but also the accuracy of quantitative metrics extracted from the images resulting in noise-induced bias. This phantom study aims to identify the radiomic features that are robust to noise in terms of precision and accuracy and to explore some methods that might help to correct noise-induced bias. METHODS: A phantom containing three 18F-FDG filled 3D printed inserts, reflecting heterogeneous tracer uptake and realistic tumor shapes, was used in the study. The three different phantom inserts were filled and scanned with three different tumor-to-background ratios, simulating a total of nine different tumors. From the 40-minute list-mode data, ten frames each for 5 s, 10 s, 30 s, and 120 s frame duration were reconstructed to generate images with different noise levels. Under these noise conditions, the precision and accuracy of the radiomic features were analyzed using intraclass correlation coefficient (ICC) and similarity distance metric (SDM) respectively. Based on the ICC and SDM values, the radiomic features were categorized into four groups: poor, moderate, good, and excellent precision and accuracy. A "difference image" created by subtracting two statistically equivalent replicate images was used to develop a model to correct the noise-induced bias. Several regression methods (e.g., linear, exponential, sigmoid, and power-law) were tested. The best fitting model was chosen based on Akaike information criteria. RESULTS: Several radiomic features derived from low SNR images have high repeatability, with 68% of radiomic features having ICC ≥ 0.9 for images with a frame duration of 5 s. However, most features show a systematic bias that correlates with the increase in noise level. Out of 143 features with noise-induced bias, the SDM values were improved based on a regression model (53 features to excellent and 67 to good) indicating that the noise-induced bias of these features can be, at least partially, corrected. CONCLUSION: To have a predictive value, radiomic features should reflect tumor characteristics and be minimally affected by noise. The present study has shown that it is possible to correct for noise-induced bias, at least in a subset of the features, using a regression model based on the local image noise estimates

Non-adherence to consensus guidelines on preoperative imaging in surgery for primary hyperparathyroidism

Objective: The aim of this study was to determine the adherence to consensus guidelines on preoperative imaging of patients with primary hyperparathyroidism (pHPT) in real local practice. Methods: This was a retrospective multicenter cohort study of 411 patients undergoing parathyroidectomy for pHPT from 2007 to 2017 in three referral centers. Results: In 286/411 patients (69%) the preoperative imaging workup adhered to guidelines (utilizing ultrasound and parathyroid scintigraphy). In patients in whom guidelines were followed 63% were discharged within one day versus 37% in whom guidelines were not followed (P< .0005). The use of a bimodality imaging workup, starting with ultrasound and parathyroid scintigraphy followed by imaging upscaling aiming for anatomical and functional concordance, was a predictor for the performance of a minimally invasive parathyroidectomy (OR 4.098, 95% CI 2.296-7.315,P< .0005). Conclusion: The level of compliance to preoperative imaging guidelines is suboptimal in this population. Patients in whom adherence was achieved showed a shorter length of stay. More education of physicians is required regarding the appropriate preoperative imaging workup in pHPT