Diagnose und Graduierung zervikaler intraepithelialer Neoplasien

Zusammenfassung: Diagnose und Graduierung von zervikalen intraepithelialen Neoplasien (CIN) gehören zu den häufigen Fragestellungen in der histopathologischen Diagnostik. Trotzdem kann die Unterscheidung zwischen reaktiven Veränderungen und CIN1 bzw. die Graduierung einer CIN Schwierigkeiten bereiten. In dieser Studie wurde untersucht, ob die Bestimmung der Proliferationsmarker Ki-67 und Mcm2 sowie von p16 zur Beantwortung dieser Fragestellungen beitragen. Untersucht wurden die immunhistochemischen Expressionsprofile dieser Marker an 297Proben aus dysplasiefreiem Portioepithel, CIN1, CIN2 und CIN3 mittels Gewebemikroarrays. Die mittels Ki-67 bzw. Mcm2 ermittelte Proliferationsrate zeigte eine Zunahme von dysplasiefreiem Epithel über CIN1, CIN2 zu CIN3 (p<0.001 bei beiden Markern). Mittels Ki-67 ließ sich am besten zwischen dysplasiefreiem Epithel und CIN1 unterscheiden. Zur Abgrenzung von CIN1 zu CIN2 bot sich eine Kombination von Ki-67 und p16 an. Bei einer Ki-67-Expression von<25% handelte es sich um eine CIN1 mit einer Sensitivität von 91,7% und einer Spezifität von 54,3%. Die zusätzliche Untersuchung der Expression von p16 konnte einen weiteren Teil der Fälle mit einer Ki-67-Expression von<25% stratifizieren. Die Anzahl p16-positiver Fälle betrug bei normalen Epithelien 0%, bei CIN1 7%, bei CIN2 46% und bei CIN3 86%. Somit war mittels p16 eine Abgrenzung der CIN2 zur CIN3 nur zum Teil möglich. Die histopathologische Evaluation am HE-Schnitt bleibt Grundlage der Beurteilung von zervikalen intraepithelialen Neoplasien, jedoch kann die Analyse von Ki-67 und p16 zur Diagnose und Graduierung beitrage

Klonale Verwandtschaft von Hodgkin-Lymphomen und deren Rezidiven

Zusammenfassung: In dieser Studie untersuchten wir, ob es sich bei Rezidiven von klassischen Hodgkin-Lymphomen (HL) um Rezidive im engeren Sinn oder aber um klonal unverwandte Sekundärtumoren handelt. Die Untersuchungen erfolgten an formalinfixierten, paraffineingebetteten Gewebeproben von 11Patienten. Hodgkin- bzw. Sternberg-Reed-Riesenzellen wurden nach immunhistochemischer Markierung mit CD30 mittels Laser mikrodisseziert und die Fragmentlängen des Schwerkettenimmunglobulin-Gens (IgH) unter Verwendung von FR3- und J-Konsensusprimern analysiert. Zwei Frührezidive nach einer HL-Erstdiagnose zeigten klonale Verwandschaft zu den Primärtumoren, während 3 von 4Frührezidiven nach einem Erst- oder Zweitrezidiv nicht mit dem vorangegangenen HL verwandt waren. Drei Spätrezidive waren mit dem ursprünglichen HL klonal unverwandt. Wir schließen daraus, dass es sich bei so genannten "Rezidiven" von HL z.T. um klonal unverwandte Zweitneoplasien handeln kann, was möglicherweise von therapeutischer Relevanz sein könnt

Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: The trigeminal neuralgia experience

Background: This study aimed to describe recruitment challenges encountered during a phase IIa study of vixotrigine, a state and use-dependent Nav1.7 channel blocker, in individuals with trigeminal neuralgia. Methods: This was an international, multicenter, placebo-controlled, randomized withdrawal study that included a 7-day run-in period, a 21-day open-label phase, and a 28-day double-blind phase in which patients (planned n = 30) were randomized to vixotrigine or placebo. Before recruitment, all antiepileptic drugs had to be stopped, except for gabapentin or pregabalin. After the trial, patients returned to their original medications. Patient recruitment was expanded beyond the original five planned (core) centers in order to meet target enrollment (total recruiting sites N = 25). Core sites contributed data related to patient identification for study participation (prescreening data). Data related to screening failures and study withdrawal were also analyzed using descriptive statistics. Results: Approximately half (322/636; 50.6%) of the patients who were prescreened at core sites were considered eligible for the study and 56/322 (17.4%) were screened. Of those considered eligible, 26/322 (8.1%) enrolled in the study and 6/322 (1.9%) completed the study. In total, 125 patients were screened across all study sites and 67/125 (53.6%) were enrolled. At prescreening, reasons for noneligibility varied by site and were most commonly diagnosis change (78/314; 24.8%), age &gt; 80 years (75/314; 23.9%), language/distance/mobility (61/314; 19.4%), and noncardiac medical problems (53/314; 16.9%). At screening, frequently cited reasons for noneligibility included failure based on electrocardiogram, insufficient pain, and diagnosis change. Conclusions: Factors contributing to recruitment challenges encountered in this study included diagnosis changes, anxiety over treatment changes, and issues relating to distance, language, and mobility. Wherever possible, future studies should be designed to address these challenges. Trial registration: ClinicalTrials.gov, NCT01540630. EudraCT, 2010-023963-16. 07 Aug 2015

Toward Citizen Centricity: Leveraging the Citizens Academy to Foster Inclusive, Sustainable, and Generative Civic Engagement in Midland, MI

This service learning project aims to utilize positive psychology research to foster inclusive, sustainable, and generative civic engagement among residents of Midland, Michigan. We conceptualize civic engagement as an outgrowth of social capital, and we leverage the constructs of mattering, fairness, belonging, and bridging to offer positive interventions aimed at increasing Midland’s social capital. Specifically, we propose several changes to evolve the city government’s existing educational civic leadership program called the Citizens Academy. First, we suggest adjusting the academy’s recruitment process to expand access and inclusion by increasing the number and diversity of participants. Second, we introduce a more participatory and citizen-centered approach to the program content that builds on Midland’s four strategic pillars as a guiding framework. We offer four positive psychology-based exercises to be interwoven into the Citizens Academy curriculum: Strengths and Values, Community Exploration Guide, Citizen-to-Citizen Coaching, and Storytelling. Third, we recommend a Civic Engagement Scale as a simple tool to measure initial outcomes. It is our hope that this service learning project will serve not only as an initial catalyst for Midland’s goal of increasing civic engagement, but as a model for other cities and communities looking to utilize the science of positive psychology to effect large-scale change

On-surface synthesis of super-heptazethrene

Zethrenes are model diradicaloids with potential applications in spintronics and optoelectronics. Despite a rich chemistry in solution, on-surface synthesis of zethrenes has never been demonstrated. We report the on-surface synthesis of super-heptazethrene on Au(111). Scanning tunneling spectroscopy investigations reveal that super-heptazethrene exhibits an exceedingly low HOMO–LUMO gap of 230 meV and, in contrast to its open-shell singlet ground state in the solution phase and in the solid-state, likely adopts a closed-shell ground state on Au(111)

HV/HR-CMOS sensors for the ATLAS upgrade—concepts and test chip results

In order to extend its discovery potential, the Large Hadron Collider (LHC) will have a major upgrade (Phase II Upgrade) scheduled for 2022. The LHC after the upgrade, called High-Luminosity LHC (HL-LHC), will operate at a nominal leveled instantaneous luminosity of 5× 1034 cm−2 s−1, more than twice the expected Phase I . The new Inner Tracker needs to cope with this extremely high luminosity. Therefore it requires higher granularity, reduced material budget and increased radiation hardness of all components. A new pixel detector based on High Voltage CMOS (HVCMOS) technology targeting the upgraded ATLAS pixel detector is under study. The main advantages of the HVCMOS technology are its potential for low material budget, use of possible cheaper interconnection technologies, reduced pixel size and lower cost with respect to traditional hybrid pixel detector. Several first prototypes were produced and characterized within ATLAS upgrade R&#38;D effort, to explore the performance and radiation hardness of this technology. In this paper, an overview of the HVCMOS sensor concepts is given. Laboratory tests and irradiation tests of two technologies, HVCMOS AMS and HVCMOS GF, are also given