Genetische Aufarbeitung des Marburger Video-EEG-Monitoring-Patientenkollektivs

Angehörige von Patienten mit Epilepsie haben ein erhöhtes Risiko, ebenfalls eine Epilepsie zu entwickeln. Das Risiko für Angehörige von Patienten mit genetisch (idiopathisch) generalisierten Epilepsien (GGE) ist höher als für Angehörige von Patienten mit fokalen Epilepsien mit struktureller oder unbekannter Ursache, wie die die Werte in der Literatur zeigen. Bei Forschung zur Genetik von Epilepsien ist die Erhebung der Familienanamnese ein wichtiger Bestandteil. Die Hauptfragestellung dieser Studie waren die Erhebung der Häufigkeit der positiven Familienanamnese in dem Studienkollektiv und ob die Befragung eines älteren, weiblichen Familienmitglieds die Familienanamnese verbessern könnte. Dabei wurden die Patienten im VEM (Video-EEG-Monitoring) des „Epilepsiezent-rums der Universitätsklinik Marburg“ der Jahre 2014 und 2015 untersucht. Die Ein-schlusskriterien dieser Studie erfüllten 73 Patienten. Patienten mit strukturellen Epilepsien, außer Dysplasien und Hippocampussklerosen, waren ausgeschlossen. Die Altersspanne der Patienten reichte von 11-66 Jahren. Hatten diese Patienten der Teilnahme an der „Biobank für paroxysmale neurologische Störungen“ zugestimmt, wurde versucht ein erneutes Telefongespräch mit der Erhebung der Familienanamnese durchzuführen und mit einem weiteren Familienmitglied, meist der Mutter, ebenfalls die Familienanamnese zu erheben. Die Ergebnisse dieser Studie zeigen, dass auch Patientenkollektive mit einem hohen Anteil an medikamentenrefraktären Patienten, wie im VEM, nicht selten eine positi-ve Familienanamnese aufweisen. In 37 % der Familien wurden weitere betroffene Familienmitglieder mit Epilepsien, Fieberkrämpfen oder einmaligen Anfällen be-nannt. Sicher diagnostizierte Epilepsien fanden sich bei weiteren Angehörigen bei 23 % der Familien. Die Häufigkeit von betroffenen erstgradigen Angehörigen (1,8 %) war jedoch geringer als in populationsbasierten Studien. Auch die Werte für generalisierte (2,6 %) und für fokale Epilepsien (0,8 %) lagen niedriger als ver-gleichbare Werte in der Literatur. Es ist also sehr wahrscheinlich, dass dies mit dem hohen Teil der medikamentenrefraktären Patienten in der untersuchten Kohorte zu-sammenhängt. Auch wenn die Werte im Vergleich relativ gering sind, ist es unerlässlich eine genaue Erhebung der Familienanamnese in der ärztlichen Anamnese, auch bei der Durchführung eines VEM, durchzuführen. Auswertungen der Angehörigengespräche zeigten, dass die Befragung eines älteren Angehörigen deutlich die Sensitivität für eine positive Familienanamnese erhöht, vor allem bei Patienten im Alter zwischen 10 - 40 Jahren. Daher ist die Durchführung einer Angehörigenbefragung zur Familienanamnese, wenn möglich auch im Kliniksalltag, auf Grundlage der Ergebnisse dieser Studie zu empfehlen. Hier sind vor allem Zusatzgewinne in Bezug auf Verwandte außerhalb der Kernfamilie (erstgradige Verwandte) zu erwarten. Dies kann unter anderem Hinweise auf eine genetische Komponente in der Ätiologie der Epilepsie oder auf mögliche Syndrome in der Familie geben. In Bezug auf erstgradige Angehörige gab es in dieser Studie fast keinen Zusatznutzen, da bei diesem Verwandtschaftsgrad der Austausch oft ausreichend zu sein scheint

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies

ERC DarkMix : Large Eddy Observatory, Voitsumra Experiment 2019 (LOVE19)

The weak-wind Stable Boundary Layer (wwSBL) is poorly described by theory and breaks basic assumptions necessary for observations of turbulence. Understanding the wwSBL requires distributed observations capable of separating between submeso and turbulent scales. To this end, we present the Large Eddy Observatory, Voitsumra Experiment 2019 (LOVE19) which featured 1350m of fiber optic distributed sensing of air temperature and wind speed, as well as an experimental wind direction method, at scales as fine as 1s and 0.127m, in addition to a suite of point observations of turbulence and ground-based remote sensing. Additionally, flights with a fiber optic cable attached to a tethered balloon provide an unprecedented detailed view of the boundary layer structure with a resolution of 0.254m and 10s between 1-200m height. We anticipate that these data will be of interest to boundary layer researchers, but also may be applicable to other communities that study the exchange between the atmosphere and the surface. The novelty of the DTS data, supported by additional observations, hopefully allows the investigation of research questions that could not be adequately addressed before. A pdf detailing the experiment documentation (LOVE19_AE-Documentation.pdf) is provided to give an overview of the experiment and data in addition to a submitted (and hopefully future) Earth System Science Data (ESSD) manuscript. The AE-Documentation is volume 65 of the Arbeitsergebnisse, Universität Bayreuth, Mikrometeorologie publication series. All data are provided as self-describing netcdfs. Two example scripts (as python-based Jupyter Notebooks) are provided, reconstructing the example figures from the ESSD paper. The examples demonstrate the unique capabilities of the LOVE19 data for examining boundary layer processes: 1) FODS observations between 1m and ~200m height during a period of gravity waves propagating across the entire boundary layer and 2) tracking a near-surface, transient submeso structure that causes an intermittent burst of turbulence

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. Objectives: The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Design: Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Methods: Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Results: Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5–20% for half of the patients if the treatment considered superior by the MS-TDS is used. Conclusion: Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established

Swabian MOSES 2021: An interdisciplinary field campaign for investigating convective storms and their event chains

The Neckar Valley and the Swabian Jura in southwest Germany comprise a hotspot for severe convective storms, causing tens of millions of euros in damage each year. Possible reasons for the high frequency of thunderstorms and the associated event chain across compartments were investigated in detail during the hydro-meteorological field campaign Swabian MOSES carried out between May and September 2021. Researchers from various disciplines established more than 25 temporary ground-based stations equipped with state-of-the-art in situ and remote sensing observation systems, such as lidars, dual-polarization X- and C-band Doppler weather radars, radiosondes including stratospheric balloons, an aerosol cloud chamber, masts to measure vertical fluxes, autosamplers for water probes in rivers, and networks of disdrometers, soil moisture, and hail sensors. These fixed-site observations were supplemented by mobile observation systems, such as a research aircraft with scanning Doppler lidar, a cosmic ray neutron sensing rover, and a storm chasing team launching swarmsondes in the vicinity of hailstorms. Seven Intensive Observation Periods (IOPs) were conducted on a total of 21 operating days. An exceptionally high number of convective events, including both unorganized and organized thunderstorms such as multicells or supercells, occurred during the study period. This paper gives an overview of the Swabian MOSES (Modular Observation Solutions for Earth Systems) field campaign, briefly describes the observation strategy, and presents observational highlights for two IOPs

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders

Background: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. Objective: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Methods: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. Results: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%;p40years. Conclusion: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD

Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Vascularized composite allotransplantation (VCA) is an evolving field of reconstructive surgery that has revolutionized the treatment of patients with devastating injuries, including those with limb losses or facial disfigurement. The transplanted units are typically comprised of different tissue types, including skin, mucosa, blood and lymphatic vasculature, muscle, and bone. It is widely accepted that the antigenicity of some VCA components, such as skin, is particularly potent in eliciting a strong recipient rejection response following transplantation. The fine line between tolerance and rejection of the graft is orchestrated by different cell types, including both donor and recipient-derived lymphocytes, macrophages, and other immune and donor-derived tissue cells (e.g., endothelium). Here, we delineate the role of different cell and tissue types during VCA rejection. Rejection of VCA grafts and the necessity of life-long multidrug immunosuppression remains one of the major challenges in this field. This review sheds light on recent developments in decoding the cellular signature of graft rejection in VCA and how these may, ultimately, influence the clinical management of VCA patients by way of novel therapies that target specific cellular processes

LSHTM and Colonialism: A report on the Colonial History of the London School of Hygiene & Tropical Medicine (1899– c.1960)

This report was commissioned in 2019 by the LSHTM Senior Leadership Team (now Executive Team) to conduct a time-limited piece of research on the School’s colonial history (1899-1960). LSHTM was set up as a colonial institution and benefitted from and contributed to British colonialism in a variety of ways between 1899 and 1960. It is largely to its role in British colonialism that the LSHTM owes its current power and position as a leader in health research and teaching