Cohomogeneity one manifolds and homogeneous spaces of positive scalar curvature

We characterize cohomogeneity one manifolds and homogeneous spaces with a compact Lie group action admitting an invariant metric with positive scalar curvature

E-Requirements Negotiation: Elektronische Verhandlungen in der verteilten Softwareentwicklung

Der Beitrag zeigt Potenziale der elektronischen Unterstützung von Anforderungsverhandlungen im Kontext verteilter Softwareentwicklung anhand der Disziplin des Requirements Engineering (RE) auf. Dazu erfolgt die Vorstellung und Einordnung des Begriffs „Requirements Negotiation" in die Begriffswelt des e-Business und die Verzahnung mit e-Collaboration, als ein Bestandteil der 4C-Klassifikation bestehend aus Communication, Coordination, Cooperation sowie Collaboration. Anhand von Verhandlungsunterstützungssystemen werden drei wesentliche Aspekte der elektronischen Anforderungsverhandlung verdeutlicht, die Ansatzpunkte für die Weiterentwicklung des Tools im Kontext des RE liefern (Entscheidungs- und Kommunikationsunterstützung, Dokumentenmanagement)

Analysis of death in major trauma: value of prompt post mortem computed tomography (pmCT) in comparison to office hour autopsy

Background: To analyze diagnostic accuracy of prompt post mortem Computed Tomography (pmCT) in determining causes of death in patients who died during trauma room management and to compare the results to gold standard autopsy during office hours. Methods: Multiple injured patients who died during trauma room care were enrolled. PmCT was performed immediately followed by autopsy during office hours. PmCT and autopsy were analyzed primarily regarding pmCT ability to find causes of death and secondarily to define exact causes of death including accurate anatomic localizations. For the secondary analysis data was divided in group-I with equal results of pmCT and autopsy, group-II with autopsy providing superior results and group-III with pmCT providing superior information contributing to but not majorly causing death. Results: Seventeen multiple trauma patients were enrolled. Since multiple trauma patients were enrolled more injuries than patients are provided. Eight patients sustained deadly head injuries (47.1 %), 11 chest (64.7 %), 4 skeletal system (23.5 %) injuries and one patient drowned (5.8 %). Primary analysis revealed in 16/17 patients (94.1 %) causes of death in accordance with autopsy. Secondary analysis revealed in 9/17 cases (group-I) good agreement of autopsy and pmCT. In seven cases autopsy provided superior results (group-II) whereas in 1 case pmCT found more information (group-III). Discussion: The presented work studied the diagnostic value of pmCT in defining causes of death in comparison to standard autopsy. Primary analysis revealed that in 94.1% of cases pmCT was able to define causes of death even if only indirect signs were present. Secondary analysis showed that pmCT and autopsy showed equal results regarding causes of death in 52.9%. Conclusions: PmCT is useful in traumatic death allowing for an immediate identification of causes of death and providing detailed information on bony lesions, brain injuries and gas formations. It is advisable to conduct pmCT especially in cases without consent to autopsy to gain information about possible causes of death and to rule out possible clinical errors

Incidence of delayed and missed diagnoses in whole-body multidetector CT in patients with multiple injuries after trauma

Background: Whole-body CT (WBCT) is the imaging modality of choice during the initial diagnostic work-up of multiple injured patients in order to identify serious injuries and initiate adequate treatment immediately. However, delayed diagnosed or even missed injuries have been reported frequently ranging from 1.3% to 47%. Purpose: To highlight commonly missed lesions in WBCT of patients with multiple injuries. Material and Methods: A total of 375 patients (age 42.8 +/- 17.9 years, ISS 26.6 +/- 17.0) with a WBCT (head to symphysis) were included. The final CT report was compared with clinical and operation reports. Discrepant findings were recorded and grouped as relevant and non-relevant to further treatment. In both groups, an experienced trauma radiologist read the CT images retrospectively, whether these lesions were missed or truly not detectable. Results: In 336 patients (89.6%), all injuries in the regions examined were diagnosed correctly in the final reports of the initial CT. Forty-eight patients (12.8%) had injuries in regions of the body that were not included in the CT. Fourteen patients (3.7%) had injuries that did not require further treatment. Twenty-five patients (6.7%) had injuries that required further treatment. With secondary interpretation, 85.4% of all missed lesions could be diagnosed in retrospect from the primary CT data-set. Small pancreatic and bowel contusions were identified as truly non-detectable. Conclusion: In multiple traumas, only a few missed injuries in initial WBCT reading are clinically relevant. However, as the vast majority of these injuries are detectable, the radiologist has to be alert for commonly missed findings to avoid a delayed diagnosis

Effects of Silver Nanoparticles on Primary Mixed Neural Cell Cultures: Uptake, Oxidative Stress and Acute Calcium Responses

In the body, nanoparticles can be systemically distributed and then may affect secondary target organs, such as the central nervous system (CNS). Putative adverse effects on the CNS are rarely investigated to date. Here, we used a mixed primary cell model consisting mainly of neurons and astrocytes and a minor proportion of oligodendrocytes to analyze the effects of well-characterized 20 and 40 nm silver nanoparticles (SNP). Similar gold nanoparticles served as control and proved inert for all endpoints tested. SNP induced a strong size-dependent cytotoxicity. Additionally, in the low concentration range (up to 10 μg/ml of SNP), the further differentiated cultures were more sensitive to SNP treatment. For detailed studies, we used low/medium dose concentrations (up to 20 μg/ml) and found strong oxidative stress responses. Reactive oxygen species (ROS) were detected along with the formation of protein carbonyls and the induction of heme oxygenase-1. We observed an acute calcium response, which clearly preceded oxidative stress responses. ROS formation was reduced by antioxidants, whereas the calcium response could not be alleviated by antioxidants. Finally, we looked into the responses of neurons and astrocytes separately. Astrocytes were much more vulnerable to SNP treatment compared with neurons. Consistently, SNP were mainly taken up by astrocytes and not by neurons. Immunofluorescence studies of mixed cell cultures indicated stronger effects on astrocyte morphology. Altogether, we can demonstrate strong effects of SNP associated with calcium dysregulation and ROS formation in primary neural cells, which were detectable already at moderate dosage

Effects of Silver Nanoparticles on Primary Mixed Neural Cell Cultures: Uptake, Oxidative Stress and Acute Calcium Responses

In the body, nanoparticles can be systemically distributed and then may affect secondary target organs, such as the central nervous system (CNS). Putative adverse effects on the CNS are rarely investigated to date. Here, we used a mixed primary cell model consisting mainly of neurons and astrocytes and a minor proportion of oligodendrocytes to analyze the effects of well-characterized 20 and 40 nm silver nanoparticles (SNP). Similar gold nanoparticles served as control and proved inert for all endpoints tested. SNP induced a strong size-dependent cytotoxicity. Additionally, in the low concentration range (up to 10 μg/ml of SNP), the further differentiated cultures were more sensitive to SNP treatment. For detailed studies, we used low/medium dose concentrations (up to 20 μg/ml) and found strong oxidative stress responses. Reactive oxygen species (ROS) were detected along with the formation of protein carbonyls and the induction of heme oxygenase-1. We observed an acute calcium response, which clearly preceded oxidative stress responses. ROS formation was reduced by antioxidants, whereas the calcium response could not be alleviated by antioxidants. Finally, we looked into the responses of neurons and astrocytes separately. Astrocytes were much more vulnerable to SNP treatment compared with neurons. Consistently, SNP were mainly taken up by astrocytes and not by neurons. Immunofluorescence studies of mixed cell cultures indicated stronger effects on astrocyte morphology. Altogether, we can demonstrate strong effects of SNP associated with calcium dysregulation and ROS formation in primary neural cells, which were detectable already at moderate dosages

Recent progress in translational research on neurovascular and neurodegenerative disorders

The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient’s outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms. This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode- and -regeneration to late stage translational or early stage clinical investigations

18F–FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6 inhibitor combination therapy in a murine model of human melanoma

Background: The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by F-18-FDG-PET/CT and diffusionweighted MRI (DW-MRI). Methods: Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18F-FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12;dabrafenib, 20 mg/kg/d;ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq F-18-FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density -CD31;tumor cell proliferation -Ki-67). Results: Tumor glucose uptake was significantly suppressed under therapy (Delta TTLTherapy -1.00 +/- 0.53 vs.Delta TTLControl 0.85 +/- 1.21;p < 0.001). In addition, tumor diffusivity was significantly elevated following the BRAF and CDK 4/6 inhibitor combination therapy (Delta ADC(Therapy) 0.12 +/- 0.14 x 10(-3) mm(2)/s;Delta ADCControl -0.12 +/- 0.06 x 10(-3) mm(2)/s;p < 0.001). Immunohistochemistry revealed a significant suppression of microvascular density (CD31, 147 +/- 48 vs. 287 +/- 92;p = 0.001) and proliferation (Ki-67, 3718 +/- 998 vs. 5389 +/- 1332;p = 0.007) in the therapy compared to the control group. Conclusion: A novel BRAF and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic and anti-proliferative effects in experimental human melanomas, monitored by F-18-FDG-PET/CT and DW-MRI