123I-Methyljodbenzylguanidin- (MIBG-) Szintigraphie: Paradoxe Nuklidspeicherung eines onkozytären Nebennierenrindenkarzinoms

Zusammenfassung: Das mit Radiojod markierte Katecholaminanalogon Methyljodbenzylguanidin (MIBG) eignet sich aufgrund seiner selektiven Aufnahme in chromaffine Gewebe in hervorragender Weise für die bildgebende Diagnostik des Phäochromozytoms und besitzt hier nach Literaturangaben eine Sensitivität von etwa 90% und eine Spezifität von annähernd 100%. Die falsch-positive oder paradoxe MIBG-Speicherung einer adrenokortikalen Neoplasie stellt demgegenüber eine Rarität dar. Wir berichten über diese Situation am Beispiel eines metastasierten onkozytären Nebennierenrindenkarzinoms mit teilweise therapeutisch genutzter MIBG-Speicherung in verschiedenen Tumormanifestatione

Reluplex: An Efficient SMT Solver for Verifying Deep Neural Networks

Deep neural networks have emerged as a widely used and effective means for tackling complex, real-world problems. However, a major obstacle in applying them to safety-critical systems is the great difficulty in providing formal guarantees about their behavior. We present a novel, scalable, and efficient technique for verifying properties of deep neural networks (or providing counter-examples). The technique is based on the simplex method, extended to handle the non-convex Rectified Linear Unit (ReLU) activation function, which is a crucial ingredient in many modern neural networks. The verification procedure tackles neural networks as a whole, without making any simplifying assumptions. We evaluated our technique on a prototype deep neural network implementation of the next-generation airborne collision avoidance system for unmanned aircraft (ACAS Xu). Results show that our technique can successfully prove properties of networks that are an order of magnitude larger than the largest networks verified using existing methods.Comment: This is the extended version of a paper with the same title that appeared at CAV 201

Minimizing the stabbing number of matchings, trees, and triangulations

The (axis-parallel) stabbing number of a given set of line segments is the maximum number of segments that can be intersected by any one (axis-parallel) line. This paper deals with finding perfect matchings, spanning trees, or triangulations of minimum stabbing number for a given set of points. The complexity of these problems has been a long-standing open question; in fact, it is one of the original 30 outstanding open problems in computational geometry on the list by Demaine, Mitchell, and O'Rourke. The answer we provide is negative for a number of minimum stabbing problems by showing them NP-hard by means of a general proof technique. It implies non-trivial lower bounds on the approximability. On the positive side we propose a cut-based integer programming formulation for minimizing the stabbing number of matchings and spanning trees. We obtain lower bounds (in polynomial time) from the corresponding linear programming relaxations, and show that an optimal fractional solution always contains an edge of at least constant weight. This result constitutes a crucial step towards a constant-factor approximation via an iterated rounding scheme. In computational experiments we demonstrate that our approach allows for actually solving problems with up to several hundred points optimally or near-optimally.Comment: 25 pages, 12 figures, Latex. To appear in "Discrete and Computational Geometry". Previous version (extended abstract) appears in SODA 2004, pp. 430-43

Loneliness, Social Isolation and Their Difference: A Cross-Diagnostic Study in Persistent Depressive Disorder and Borderline Personality Disorder

Background: Interpersonal difficulties are a key feature of persistent depressive disorder (PDD) and borderline personality disorder (BPD). Caught in a vicious circle of dysfunctional interpersonal transaction, PDD and BPD patients are at great risk of experiencing prolonged loneliness. Loneliness, in turn, has been associated with the development of mental disorders and chronic illness trajectories. Besides, several factors may contribute to the experience of loneliness across the lifespan, such as social network characteristics, a history of childhood maltreatment (CM), and cognitive-affective biases such as rejection sensitivity (RS). This cross-diagnostic study approached the topic of perceived loneliness by comparing PDD and BPD patients with healthy controls (HC) in its interplay with symptom burden, social network characteristics, RS as well as CM. Method: Thirty-four PDD patients (DSM-5; 15 female, Mage = 38.2, SD = 12.3), 36 BPD patients (DSM-5; 19 female, Mage = 28.8, SD = 9.2), and 70 age- and gender-matched HC were assessed cross-sectionally using the following self-report measures: UCLA Loneliness Scale, Social Network Index (SNI; size, diversity, and embeddedness), Beck Depression Inventory (BDI-II), Borderline Symptom List (BSL-23), Childhood Trauma Questionnaire (CTQ), and Rejection Sensitivity Questionnaire (RSQ). Results: Both patient groups reported significantly higher levels of perceived loneliness, symptom severity, and smaller social network characteristics compared to HC. Loneliness was significantly correlated with severity of self-reported clinical symptoms in PDD and at trend level in BPD. Besides, loneliness tended to be related to social network characteristics for all groups except PDD patients. Both PDD and BPD patients showed higher RS as well as CTQ scores than HC. A history of emotional abuse and emotional neglect was associated with loneliness, and this association was mediated by RS as demonstrated by an exploratory mediation analysis. Discussion: Loneliness is highly prevalent in PDD and BPD patients and contributes to the overall symptom burden. Interestingly, loneliness showed an association with prior experiences of CM as well as current RS. We therefore propose a comprehensive model on how intra- und interpersonal aspects may interplay in the dynamics of loneliness in light of CM. Finally, this model may have further implications for psychotherapeutic interventions

How to read a next-generation sequencing report-what oncologists need to know.

Next-generation sequencing (NGS) of tumor cell-derived DNA/RNA to screen for targetable genomic alterations is now widely available and has become part of routine practice in oncology. NGS testing strategies depend on cancer type, disease stage and the impact of results on treatment selection. The European Society for Medical Oncology (ESMO) has recently published recommendations for the use of NGS in patients with advanced cancer. We complement the ESMO recommendations with a practical review of how oncologists should read and interpret NGS reports. A concise and straightforward NGS report contains details of the tumor sample, the technology used and highlights not only the most important and potentially actionable results, but also other pathogenic alterations detected. Variants of unknown significance should also be listed. Interpretation of NGS reports should be a joint effort between molecular pathologists, tumor biologists and clinicians. Rather than relying and acting on the information provided by the NGS report, oncologists need to obtain a basic level of understanding to read and interpret NGS results. Comprehensive annotated databases are available for clinicians to review the information detailed in the NGS report. Molecular tumor boards do not only stimulate debate and exchange, but may also help to interpret challenging reports and to ensure continuing medical education

Unbiased Global Optimization of Lennard-Jones Clusters for N <= 201 by Conformational Space Annealing Method

We apply the conformational space annealing (CSA) method to the Lennard-Jones clusters and find all known lowest energy configurations up to 201 atoms, without using extra information of the problem such as the structures of the known global energy minima. In addition, the robustness of the algorithm with respect to the randomness of initial conditions of the problem is demonstrated by ten successful independent runs up to 183 atoms. Our results indicate that the CSA method is a general and yet efficient global optimization algorithm applicable to many systems.Comment: revtex, 4 pages, 2 figures. Physical Review Letters, in pres

Multinucleated Giant Cells’ Incidence, Immune Markers, and Significance: A Study of 172 Cases of Papillary Thyroid Carcinoma

Multinucleated giant cells (MGCs) are often detected in cases of papillary thyroid carcinoma (PTC). Their origin and significance, however, has not been established. One possibility is that they form in response to injury induced by fine needle aspiration biopsy (FNAB). Other hypotheses are that the chemically-altered colloid produced by PTC induces MGCs to act as colloidophages, or else MGCs are a non-specific immune response ingesting neoplastic follicle cells. We assigned 172 cases of PTC a semi-quantitative score for MGCs. Cases with “many” MGCs were immunohistochemically stained for AEI/AEIII, CD68, and CD163 to assess for epithelial vs histiocytic differentiation, and for thyroglobulin and TTF-1 to assess for MGC ingestion of colloid or thyroid follicle cells respectively. Overall, we identified MGCs in 100/172 (58.1%) PTC specimens; in 45 (26.2%), “many” MGCs were found, while in 55 (31.9%) MGCs were “few.” The mean sizes of PTC in cases with many as opposed to rare/no MGCs was 2.50 cm vs 1.8 [P = 0.003]. The cases of PTC with many MGCs had higher multifocality (26/45 vs 51/127 [P = 0.06]), extrathyroidal extension (21/45 vs 36/127 [P = 0.03]), and recurrence (8/45 vs 9/127 [P = 0.08]), than did cases with rare or no MGCs. The majority of patients both with and without numerous MGCs had previous histories of FNA or hemilobectomy: 40/45 and 99/127 respectively (P = 0.062). The majority of MGCs were positive for CD68 (45/45), CD163 (44/45), thyroglobulin (34/45) and negative for AEI/AEIII (44/45) and TTF-1 (44/45). These results indicate that MGCs in PTC are of histiocytic origin. Cases of PTC with many MGCs have a significantly greater likelihood of extrathyroidal extension and greater tumor size than cases with few/no MGCs. MGCs appear to be functioning largely as colloidophages

Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel