Simulation of expected future efficacy from HRAC group B herbicides against loose silky-bent grass, depending on cropping factors

Das hessische Windhalm-Resistenzmonitoring aus dem Jahr 2014 zeigte, dass Resistenzen gegenüber Herbiziden der HRAC-Klasse B landesweit verbreitet sind. Daten von am Monitoring beteiligten Schlägen wurden herangezogen, um Bewirtschaftungsparameter wie z. B. Saattermin, Anteil Pflug in der Fruchtfolge u.a. zu identifizieren, welche den Wirkungsgrad und damit die Bildung von Resistenzen beeinflussen können. Korrelationen zwischen Bewirtschaftungsparametern und dem jeweils im Biotest erzielten Wirkungsgrad gegen Windhalm wurden berechnet. Daraufhin folgte ein Modellbildungsprozess, um Wirkungsgrade in Abhängigkeit der o. g. Einflussfaktoren simulieren zu können. Die Modellergebnisse zeigen, dass beispielsweise eine Erhöhung des Anteils von Herbiziden der HRAC-Klasse B in der Fruchtfolge zu einem hohen Wirkungsverlust führt. Um diesen Effekt zu neutralisieren, müsste der Pfluganteil steigen und der Anteil an Winterungen in der Fruchtfolge sinken. Das Modell sollte auf weitere Datensätze angewendet und weiter trainiert werden, um Strategien zur Resistenzvermeidung voran zu treiben.Results from the resistance monitoring on loose silky-bent grass conducted in 2014 in Hessen showed that resistance against herbicides from HRAC group B is disseminated throughout the federal state. Cropping data like seeding date, ploughing intensity etc. where collected for fields involved in the monitoring in order to identify the impact of such cropping practices on herbicide efficacy and evolution of resistance. Correlations were calculated between field cropping data and corresponding efficacy rates against loose silky-bent grass, generated from bioassays conducted in 2014. A simulation model was developed and validated to forecast efficacy rates in dependence of the collected cropping data. The simulation results demonstrate high efficacy losses if the proportion of herbicide from the HRAC group B will increase in the crop rotation. To neutralize the effect, ploughing intensity would have to increase and proportion of winter cereals should decrease. The simulation model should be applied to further datasets and further trained, to forward anti-resistance strategies

Untersuchungen zur Resistenz von Apera spica-venti (L.) P. Beauv. (Gemeiner Windhalm) gegenüber Herbiziden unterschiedlicher HRAC-Klassen in Hessen

Im Sommer 2014 wurden Windhalmrispen von 109 hessischen Standorten gesammelt, um die Verbreitung der Resistenz des Gemeinen Windhalms gegenüber Herbiziden der HRAC-Klassen A, B und F1/K3 im Biotest zu überprüfen. Sowohl Windhalmrispen aus angelegten Spritzfenstern als auch Rispen, die vor der Ernte in „Windhalmnestern“ innerhalb hessischer Getreidefelder auffielen, wurden in das Monitoring einbezogen. Im Dezember 2014 wurden Windhalmsamen aller Biotypen in Töpfe ausgesät und im Gewächshaus des hessischen Pflanzenschutzdienstes in Wetzlar angezogen. Die jungen Windhalmpflanzen wurden mit Herbiziden der HRAC-Klassen A, B und F1/K3 zum für das jeweilige Herbizid optimalen BBCH-Stadium behandelt. Die Wirkungsgrade wurden im Biotest ermittelt. Jede Herkunft wurde molekulargenetisch auf Mutationen untersucht, die eine Veränderung der Aminosäuresequenz der Acetolactat-Synthase (ALS) bewirken. Herkünfte, die im Biotest eine Minderwirkung gegen das Herbizid der Wirkstoffklasse A zeigten, wurden molekulargenetisch auf Mutationen untersucht, die eine Veränderung der Aminosäuresequenz der Acetyl-Coenzym-A- Carboxylase (ACCase) bewirken. Nahezu alle Windhalmherkünfte konnten durch das Herbizid der Wirkstoffklasse F1/K3 bekämpft werden. Ebenso zeigte die Wirkstoffklasse A mit wenigen Ausnahmen eine hohe Wirkungssicherheit. Dagegen wurde mit Herbiziden der Wirkstoffklasse B nur in bis zu 12 Herkünften ein Wirkungsgrad von mehr als 90 % erzielt. In 45 Herkünften wurden Mutationen festgestellt, die eine Resistenz gegenüber der Wirkstoffklasse B bewirken. In einer Herkunft wurde eine Mutation gefunden, die zu einer Veränderung der Aminosäuresequenz der ACCase führt. Die Ergebnisse der Untersuchung sollen als Basis für eine Folgeuntersuchung dienen, um Unterschiede in der Bewirtschaftungsweise zwischen Resistenzstandorten und sensitiven Standorten aufzudecken. Daraus sollen Beratungsempfehlungen geschaffen werden, die helfen sollen, eine Ausbreitung von Resistenzen zu verlangsamen.Investigations on Apera spica-venti (L.) P. Beauv. (loose silky-bent grass) resistance against herbicides from different HRAC-classes in HessenIn the summer of 2014, panicles from loose silky-bent grass (Apera spica-venti) were collected at 109 sites across the federal state Hessen, to analyze the level of loose silky-bent grass resistance against herbicides from HRAC-class A, B and F1/K3. Panicles from established spraying windows as well as panicles from A. spica-venti patches, which were identified at time of harvest within cereal fields, were included into the monitoring. In December 2014 the loose silky-bent grass seeds were seeded into pots and placed in the greenhouse of plant protection service Hessen in Wetzlar. The young seedlings were sprayed (repeated) with herbicides from HRAC group A, B and F1/K3 at BBCH-stages which provided optimal efficacy for each individual herbicide. Efficacy was rated. Each biotype was tested for well-known mutations, which modify the amino acid sequence of acetolactate-synthase (ALS). Biotypes, in which the herbicide from HRAC group A reached low efficacy, were tested for well-known mutations in the acetyl coenzyme a carboxylase (ACCase) gene. The treatments with the herbicide from HRAC group F1/K3 reached very high efficacy up to 100% in nearly all biotypes. The herbicide treatment with an herbicide from HRAC group A reached high efficacy in most cases. However, all herbicides from HRAC group B showed very low efficacy. Only 12 biotypes could be controlled with an efficacy of more than 90%. 45 biotypes contained several mutations in the ALS gene, which cause ALS-resistance. Only one biotype contained a mutation, which can cause ACCase resistance. These results will be used to study reasons for development of resistance in order to develop guidance information to prevent further increase of resistance

The current understanding of precision medicine and personalised medicine in selected research disciplines:study protocol of a systematic concept analysis

INTRODUCTION: The terms ‘precision medicine’ and ‘personalised medicine’ have become key terms in health-related research and in science-related public communication. However, the application of these two concepts and their interpretation in various disciplines are heterogeneous, which also affects research translation and public awareness. This leads to confusion regarding the use and distinction of the two concepts. Our aim is to provide a snapshot of the current understanding of these concepts. METHODS AND ANALYSIS: Our study will use Rodgers’ evolutionary concept analysis to systematically examine the current understanding of the concepts ‘precision medicine’ and ‘personalised medicine’ in clinical medicine, biomedicine (incorporating genomics and bioinformatics), health services research, physics, chemistry, engineering, machine learning and artificial intelligence, and to identify their respective attributes (clusters of characteristics) and surrogate and related terms. A systematic search of the literature will be conducted for 2016–2022 using databases relevant to each of these disciplines: ACM Digital Library, CINAHL, Cochrane Library, F1000Research, IEEE Xplore, PubMed/Medline, Science Direct, Scopus and Web of Science. These are among the most representative databases for the included disciplines. We will examine similarities and differences in definitions of ‘precision medicine’ and ‘personalised medicine’ in the respective disciplines and across (sub)disciplines, including attributes of each term. This will enable us to determine how these two concepts are distinguished. ETHICS AND DISSEMINATION: Following ethical and research standards, we will comprehensively report the methodology for a systematic analysis following Rodgers’ concept analysis method. Our systematic concept analysis will contribute to the clarification of the two concepts and distinction in their application in given settings and circumstances. Such a broad concept analysis will contribute to non-systematic syntheses of the concepts, or occasional systematic reviews on one of the concepts that have been published in specific disciplines, in order to facilitate interdisciplinary communication, translational medical research and implementation science

Extra cardiac findings by 64-multidetector computed tomography in patients with symptomatic atrial fibrillation prior to pulmonal vein isolation

The aim of this study was to investigate the prevalence of extracardiac findings diagnosed by 64-multidetector computed tomography (MDCT) examinations prior to circumferential pulmonary vein (PV) ablation of atrial fibrillation (AF). A total of 158 patients (median age, 60.5 years; male 68%) underwent 64-MDCT of the chest and upper abdomen to characterize left atrial and PV anatomy prior to AF ablation. MDCT images were evaluated by a thoracic radiologist and a cardiologist. For additional scan interpretation, bone, lung, and soft tissue window settings were used. CT scans with extra-cardiac abnormalities categorized for the anatomic distribution and divided into two groups: Group 1—exhibiting clinically significant or potentially significant findings, and Group 2—patients with clinically non-significant findings. Extracardiac findings (n = 198) were observed in 113/158 (72%) patients. At least one significant finding was noted in 49/158 patients (31%). Group 1 abnormalities, such as malignancies or pneumonias, were found in 85/198 findings (43%). Group 2 findings, for example mild degenerative spine disease or pleural thickening, were observed in 113/198 findings (72%). 74/198 Extracardiac findings were located in the lung (37%), 35/198 in the mediastinum (18%), 8/198 into the liver (4%) and 81/198 were in other organs (41). There is an appreciable prevalence of prior undiagnosed extracardiac findings detected in patients with AF prior to PV-Isolation by MDCT. Clinically significant or potentially significant findings can be expected in ~40% of patients who undergo cardiac MDCT. Interdisciplinary trained personnel is required to identify and interpret both cardiac and extra cardiac findings

INDEED–Utilization and Cross-Sectoral Patterns of Care for Patients Admitted to Emergency Departments in Germany: Rationale and Study Design

Introduction: The crowding of emergency departments (ED) has been a growing problem for years, putting the care of critically ill patients increasingly at risk. The INDEED project's overall aim is to get a better understanding of ED utilization and to evaluate corresponding primary health care use patterns before and after an ED visit while driving forward processes and methods of cross-sectoral data merging. We aim to identify adequate utilization of EDs and potentially avoidable patient contacts as well as subgroups and clusters of patients with similar care profiles. Methods: INDEED is a joint endeavor bringing together research institutions and hospitals with EDs in Germany. It is headed by the Charite-Universitatsmedizin Berlin, collaborating with Otto von Guericke University Magdeburg, Technische Universitat Berlin, the Central Research Institute of Ambulatory/Outpatient Health Care in Germany (Zi), and the AOK Research Institute as part of the Federal Association of AOK, as well as experts in the technological, legal, and regulatory aspects of medical research (TMF). The Institute for Information Technology (OFFIS) was involved as the trusted third party of the project. INDEED is a retrospective study of approximately 400,000 adult patients with statutory health insurance who visited the ED of one of 16 participating hospitals in 2016. The routine hospital data contain information about treatment in the ED and, if applicable, about the subsequent hospital stay. After merging the patients' hospital data from 2016 with their outpatient billing data from 2 years before to 1 year after the ED visit (years 2014-2017), a harmonized dataset will be generated for data analyses. Due to the complex data protection challenges involved, first results will be available in 2021. Discussion: INDEED will provide knowledge on extracting and harmonizing large scale data from varying routine ED and hospital information systems in Germany. Merging these data with the corresponding outpatient care data of patients offers the opportunity to characterize the patient's treatment in outpatient care before and after ED use. With this knowledge, appropriate interventions may be developed to ensure adequate patient care and to avoid adverse events such as ED crowding

Macrophage-Mediated Antibody Dependent Effector Function in Aggressive B-Cell Lymphoma Treatment is Enhanced by Ibrutinib via Inhibition of JAK2

Targeted inhibition of Bruton's Tyrosine Kinase (BTK) with ibrutinib and other agents has become important treatment options in chronic lymphocytic leukemia, Waldenstrom's Macroglobulinemia, Mantle cell lymphoma, and non-GCB DLBCL. Clinical trials combining small molecule inhibitors with monoclonal antibodies have been initiated at rapid pace, with the biological understanding between their synergistic interactions lagging behind. Here, we have evaluated the synergy between BTK inhibitors and monoclonal antibody therapy via macrophage mediated antibody dependent cellular phagocytosis (ADCP). Initially, we observed increased ADCP with ibrutinib, whilst second generation BTK inhibitors failed to synergistically interact with monoclonal antibody treatment. Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment. We validated this potential off-target effect via JAK inhibition in vitro as well as with CRISPR/Cas9 JAK2(-/-)experiments in vivo, showing increased ADCP and prolonged survival, respectively. This data supports inhibition of the JAK-STAT (Signal Transducers and Activators of Transcription) signaling pathway in B-cell malignancies in combination with monoclonal antibody therapy to increase macrophage-mediated immune responses

Personalizing medicine and technologies to address the experiences and needs of people with multiple sclerosis

There is enormous variation in the manifestations of disease experienced by people with multiple sclerosis (PwMS). While this variation makes personalized medicine an attractive goal, there are many challenges to be overcome before this opportunity can be realized. Personalized medicine often focuses on targeted therapies and detailed monitoring, but we also need to recognize that there will be variation in acceptance of these approaches by different PwMS. In other words, deep personalization of medicine will encompass targeted therapy, precision monitoring, tailored to variation in personal attitudes to these transformations in health care. In order to meet the promise of personalized medicine for MS, understanding the experiences of PwMS is necessary both to aid in the uptake of personalized medicine, and to ensure that personalized approaches to monitoring disease and treatment provide a net benefit to PwMS rather than placing additional burdens and stressors on them. Here, we describe recent research that identified five experiential themes for PwMS, and then interpret these themes according to the foundations of personalized medicine to provide a road map for implementation of personalized medicine solutions for PwM

Lung Cancer and SARS-CoV-2 infection: Identifying important knowledge gaps for investigation

[EN] Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the develop-ment/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge.Work in the Krammer laboratory on severe acute respiratory syndrome coronavirus 2. is supported by the National Institute of Allergy and Infectious Dis-eases Collaborative Influenza Vaccine Innovation Cen-ters contract 75N93019C00051, the Centers of Excellence for Influenza Research and Surveillance (contract #HHSN272201400008C) , the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 [5384]) , and anonymous donors. In addition, serology efforts in the Krammer laboratory are sup-ported by the National Cancer Institute SeroNet grant U54CA260560 and by the SeroNet in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number 75N91019D00024, task order number 75N91021F00001. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Rolfo, C.; Meshulami, N.; Russo, A.; Krammer, F.; Garcia-Sastre, A.; Mack, PC.; Gomez, JE.... (2022). Lung Cancer and SARS-CoV-2 infection: Identifying important knowledge gaps for investigation. Journal of Thoracic Oncology. 17(2):214-227. https://doi.org/10.1016/j.jtho.2021.11.00121422717