Futterqualität, Vorfruchtleistung und Nitratauswaschung von über Winter beweideten Kleegrasbeständen

In comparison to harvesting, grazing is less cost intensive. For economical reasons an extended duration of grazing period is recommended. Grazing during winter can cause pasture damages, which is of minor relevance for older grass clover grown on arable land, which will be ploughed in the following spring. Against this background yield and forage quality of 3 different legume species, i.e. white clover, red clover and alfalfa, grown in binary mixtures with two grass species, perennial ryegrass and tall fescue, respectively, were examined before grazing the third growth in autumn or winter. Nitrate leaching losses during winter and yield of the following spring wheat were recorded. Yield and forage quality of the total sward was not significantly influenced by grass species while the interaction of legume species and grazing date had a high impact on yield and quality of the swards. Before grazing in October, swards with white clover showed lower yields and through lower legume contents also lower crude protein concentrations compared to swards with alfalfa or red clover. Losses of leave material led to losses of crude protein concentration in swards with alfalfa or red clover as well as high losses of energy content in swards with alfalfa, which at the latest grazing date were significantly lower than in sward with white clover. Mulching the last growth and autumn grazing led to higher nitrate losses than late winter grazing. After ploughing, no effect of clover grass management on spring wheat yields was observed. Grazing in January led to higher grain crude protein contents in spring wheat than autumn gazing or cutting of the last growth for silage

Sensor guiado por robot para determinar regiones tumorales en la superficie cerebral: optimización de puntos de contacto

La habilidad del neurocirujano puede suponer la diferencia entre el éxito o el fracaso de una operación de neurocirugía. Para facilitar su labor se han desarrollado a lo largo de la historia complejas técnicas de diagnóstico clínico y quirúrgicas. Actualmente las técnicas de diagnóstico más comunes son la tomografía axial computerizada (TAC), la tomografía por emisión de positrones (PET), la resonancia magnética nuclear (RMN) y la magnetoencefalografía (MEG). La microcirugía, la cirugía endoscópica o la cirugía estereotáxica representan algunos de los recientes avances más importantes en técnicas de quirófano. La neurocirugía es una especialidad médica que se encuentra en constante y rápida evolución. El uso de robots en las operaciones en general y en neurocirugía en particular cada vez tiene un mayor interés e importancia porque permiten sobrepasar la precisión y las habilidades humanas. La distinción entre tejido sano y tumoral es un problema añadido durante las operaciones de extirpación de tumores cerebrales. Es vital eliminar totalmente el tumor para evitar su reaparición, a la vez que conservar el mayor volumen posible de tejido sano circundante ayuda a reducir las secuelas y mejora la recuperación. En este documento se describe un método asistido por robot, con la ayuda de un sensor de fuerza y un sensor tumoral desarrollado en la Universidad Leibniz de Hanóver, para construir un mapa del tejido tumoral de la superficie del cerebro. A diferencia de otras tecnologías actuales, el proceso se puede efectuar de forma automatizada bajo supervisión humana. El objetivo de este proyecto es lograr movimientos seguros y precisos del brazo robótico mientras se construye el mapa, permitiendo incluso desplazar el sensor sobre la superficie en movimiento sin dañarla. Completar correctamente la tarea requiere un contacto perpendicular y constante del sensor con la superficie cerebral en cada punto a medir. Para ello se han desarrollado algoritmos, métodos, un controlador PID por software y las pruebas que se detallan en este documento. Aproximar el sensor tumoral de forma suave es uno de los requisitos más importantes, siendo otro compensar los movimientos de la superficie del cerebro debidos al pulso cardiaco mientras se mantiene el contacto con una fuerza constante. Si los movimientos del robot no se realizan con extrema precisión se pueden ocasionar daños graves al paciente o incluso su muerte. Las principales dificultades que se han enfrentado durante el proyecto son compensar la variación del peso medido por el sensor de fuerza al cambiar la orientación de la mano del robot, e identificar y reducir las fuentes de error como por ejemplo la precisión del sensor de fuerza o la alineación de las articulaciones del robot. Este proyecto también representa un punto de partida y de referencia para la investigación de nuevas aplicaciónes roboticas en cirugía de tejidos blandos

Towards Runtime Monitoring of Complex System Requirements for Autonomous Driving Functions

Autonomous driving functions (ADFs) in public traffic have to comply with complex system requirements that are based on knowledge of experts from different disciplines, e.g., lawyers, safety experts, psychologists. In this paper, we present a research preview regarding the validation of ADFs with respect to such requirements. We investigate the suitability of Traffic Sequence Charts (TSCs) for the formalization of such requirements and present a concept for monitoring system compliance during validation runs. We find TSCs, with their intuitive visual syntax over symbols from the traffic domain, to be a promising choice for the collaborative formalization of such requirements. For an example TSC, we describe the construction of a runtime monitor according to our novel concept that exploits the separation of spatial and temporal aspects in TSCs, and successfully apply the monitor on exemplary runs. The monitor continuously provides verdicts at runtime, which is particularly beneficial in ADF validation, where validation runs are expensive. The next open research questions concern the generalization of our monitor construction, the identification of the limits of TSC monitorability, and the investigation of the monitor's performance in practical applications. Perspectively, TSC runtime monitoring could provide a useful technique in other emerging application areas such as AI training, safeguarding ADFs during operation, and gathering meaningful traffic data in the field

First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 ± 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments

A short-term plastic adherence incubation of the stromal vascular fraction leads to a predictable GMP-compliant cell-product

Introduction: Mesenchymal stromal/stem cells (MSCs) derived from fat tissue are an encouraging tool for regenerative medicine. They share properties similar to the bone marrow-derived MSCs, but the amount of MSCs per gram of fat tissue is 500x higher. The fat tissue can easily be digested by collagenase, releasing a heterogeneous cell fraction called stromal vascular fraction (SVF) which contains a variable amount of stromal/stem cells. In Europe, cell products like the SVF derived from fat tissue are considered advanced therapy medicinal product (ATMPs). As a consequence, the manufacturing process has to be approved via GMP-compliant process validation. The problem of the process validation for SVF is the heterogeneity of this fraction. Methods: Here, we modified existing purification strategies by adding an additional plastic adherence incubation of maximal 20 hours after SVF isolation. The resulting cell fraction was characterized and compared to SVF as well as cultivated adipose-derived stromal/stem cells (ASCs) with respect to viability and cell yield, the expression of surface markers, differentiation potential and cytokine expression. Results: Short-term incubation significantly reduced the heterogeneity of the resulting cell fraction compared to SVF. The cells were able to differentiate into adipocytes, chondrocytes, and osteoblasts. More importantly, they expressed trophic proteins which have been previously associated with the beneficial effects of MSCs. Furthermore, GMP compliance of the production process described herein was acknowledged by the national regulatory agencies (DE_BB_01_GMP_2017_1018). Conclusion: Addition of a short purification-step after the SVF isolation is a cheap and fast strategy to isolate a homogeneous uncultivated GMP-compliant cell fraction of ASCs