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

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

Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis

We evaluated the efficacy and acceptability of transcranial direct current stimulation (tDCS) for treating acute depressive episodes using individual patient data that provide more precise estimates than aggregate data meta-analysis. A systematic review of placebo-controlled trials on tDCS as only intervention was conducted until December-2018. Data from each study was collated to estimate odds ratio (OR) and number needed to treat (NNT) of response and remission, and depression improvement. Endpoints were pre-determined. Nine eligible studies (572 participants), presenting moderate/high certainty of evidence, were included. Active tDCS was significantly superior to sham for response (30.9% vs. 18.9% respectively; OR = 1.96, 95%CI [1.30–2.95], NNT = 9), remission (19.9% vs. 11.7%, OR = 1.94 [1.19–3.16], NNT = 13) and depression improvement (effect size of β = 0.31, [0.15–0.47]). Moreover, continuous clinical improvement was observed even after the end of acute tDCS treatment. There were no differences in all-cause discontinuation rates and no predictors of response were identified. To conclude, active tDCS was statistically superior to sham in all outcomes, although its clinical effects were moderate

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

The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum

The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE 1) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C2; GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration ≥500 ms, vein diameter ≥3.5 mm) located underneath healed or active ulcers (CEAP class C5-C6; GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B)

Editor's Choice \u2013 Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)

2017 Clinical Practice Guidelines of the European Society for Vascular Surgery