Decoding Complex Imagery Hand Gestures

Brain computer interfaces (BCIs) offer individuals suffering from major disabilities an alternative method to interact with their environment. Sensorimotor rhythm (SMRs) based BCIs can successfully perform control tasks; however, the traditional SMR paradigms intuitively disconnect the control and real task, making them non-ideal for complex control scenarios. In this study, we design a new, intuitively connected motor imagery (MI) paradigm using hierarchical common spatial patterns (HCSP) and context information to effectively predict intended hand grasps from electroencephalogram (EEG) data. Experiments with 5 participants yielded an aggregate classification accuracy--intended grasp prediction probability--of 64.5\% for 8 different hand gestures, more than 5 times the chance level.Comment: This work has been submitted to EMBC 201

The role of formyl peptide receptors within the hypothalamic pituitary adrenal axis

Annexin 1 (ANXA1) is an important mediator of the regulatory effects of glucocorticoids (GCs) within the neuroendocrine and host defence systems. Recent data suggest that it acts via a formyl peptide receptor (FPR) as a mediator of the negative feedback effects of GCs on adrenocorticotrophic hormone (ACTH) release. In the present study, in vitro and in vivo methods were used to detect and explore further the function of these receptors within the hypothalamo-pituitary-adrenocortical (HPA) axis. Lipopolysaccharide (LPS), given intra-peritoneally (i.p.) or centrally (i.c.v.), increased expression of mRNAs for ANXA1 and Fpr1, Fpr2 and Fpr3 in the spleen, pituitary and adrenal gland, but not in the brain. Given i.p., it also caused inflammatory cell infiltration in the adrenal gland, but not the pituitary, together with decreased vacuolation in the steroidogenic cells, increases in serum pro-inflammatory cytokines and corticosterone (CORT) and a subsequent loss of sensitivity to ACTH. The increases in ANXA1, Fpr1 and Fpr3 expression were dependent on inflammatory cell infiltration (predominantly eosinophils) but those of Fpr2 were not. The decrease in vacuolation was also independent of the inflammatory cell infiltration but was severely compromised by deletion of the genes encoding ANXA1 and Fpr2. Pharmacological studies on isolated adrenal cells in vitro suggest that ANXA1 may act via Fpr2 to inhibit ACTH-stimulated CORT release but that Fpr1 effects a tonic stimulatory effect on ACTH-driven steroidogenesis. These data suggest that ANXA1 and the FPRs play an important role within the adrenal in mediating the HPA responses to endotoxin and provide new evidence to suggest that infiltrating leukocytes are are also important in this regard

Fluoreszenzspektroskopie und -mikroskopie von Nanopartikeln und Biomolekülen in Entzündung und Schmerz

The focus of this thesis is on the application of time-resolved fluorescence methods, fluorescence anisotropy and state-of-the-art fluorescence microscopy, such as single-molecule microscopy and fluorescence lifetime imaging microscopy (FLIM), to gain new insights into the molecular properties of nanoparticles and their interaction with tissue in the context of inflammation and pain. Single-molecule microscopy was applied to determine the morphology and the internal structure of nanostructured lipid carriers (NLC). To visualize the morphology an affinity labeling procedure was developed, employing principals of localized stochastic reconstruction microscopy to generate super-resolution images of NLC structures below the Abbe diffraction limit. Visualization of the internal structure of NLCs was achieved by single particle tracking of fluorescent drug mimetics. It could be shown for the first time that the analyzed NLCs consist of a fluid core in a solid lipid shell. Thus, the single-molecule microscopy methodology established here allows the direct visualization of NLC structures, enabling the correlation between NLC composition and the NLC structure required to generate tailor-made NLCs. Knowledge of the physicochemical properties of nanoparticles is of paramount importance for their nanomedical application. In this work, fluorescence lifetime and time-resolved fluorescence anisotropy were used to investigate the influence of the environment and temperature on the structure and dynamics of two polymer particles (dendritic polyglycerol sulfate (dPGS) and core-multishell (CMS) nanoparticles). Structural changes within the physiological temperature range were detected, which influence either particle size or the internal distribution of drug mimetics, both of which can directly affect therapeutic efficacy. Imaging techniques allow for the localization of nanoparticles in tissue. Confocal raster scanning microscopy in combination with FLIM measures the fluorescence lifetime decay curve of excited fluorescent molecules in every image pixel. Therefore FLIM has an increased contrast compared to conventional fluorescence microscopy. A major challenge in FLIM data analysis is the poor signal-to-noise ratio of the fluorescence lifetime curves recorded in each pixel which complicate the determination of fluorescence lifetimes, particularly if a specific fluorescence lifetime signature, e.g. of a fluorescently labeled nanoparticle, is to be detected against the autofluorescent background of tissue samples. Ratiometric FLIM analysis, which uses the specific amplitude ratio of the fluorescence lifetimes, enabled the detection of the specific binding of an opioid to its membrane receptor as well as the localization of dPGS in liver tissue. Since the ratiometric method reaches its limits at low photon count rates and when the fluorescence lifetime decay curves contains more than two decay components, a multivariate analysis method was developed in the group of Prof. Alexiev, and applied in this thesis to study the skin penetration and localization of CMS and silica nanoparticles as well as fluorescently labeled biomolecules.Der Schwerpunkt dieser Doktorarbeit lag auf der Anwendung und Etablierung neuer analytische und bildgebende Verfahren um Informationen über molekulare Eigenschaften von Nanopartikeln und ihrer Interaktion mit Gewebe im Kontext von Schmerz- und Entzündungsprozessen zu erhalten. Insbesondere wurden Techniken der zeitaufgelösten Fluoreszenz, Fluoreszenzdepolarisation und state-of-the-art Fluoreszenzmikroskopiemethoden, wie Einzelmolekül- Totalreflexionsfluoreszenzmikroskopie und Fluoreszenzlebensdauerimagingmikroskopie (FLIM) angewandt. Basierend auf Methoden der Einzelmolekülmikroskopie konnten die Morphologie und die innere Struktur von NLC bestimmt werden. Zur Visualisierung der Morphologie wurde eine Affinitätslabeling-Strategie entwickelt, die mittels stochastischer Bildrekonstruktion Superresolution-Images der NLC-Strukturen unterhalb des Abbe'schen Beugungslimits ermöglichte. Die internen Strukturen von NLCs wurden mittels Einzel-Partikel-Verfolgung von fluoreszierenden Wirkstoff-Mimetika sichtbar gemacht. Es konnte so zum ersten Mal gezeigt werden, dass die untersuchten NLCs einen fluiden Kern in einer festen Lipidschale haben. Die hier etablierte Methodik der Einzelmolekülmikroskopie erlaubt es somit, direkt die NLC Strukturen sichtbar zu machen. Damit ist eine Korrelation der Struktur und der Zusammensetzung der NLC Komponenten möglich, die für ein zielgerichtetes NLC Design unerlässlich ist. Die Kenntniss der physikochemischen Eigenschaften von Nanopartikeln ist für ihre Anwendung in der Nanomedizin von großer Bedeutung. In dieser Arbeit wurde anhand der Fluoreszenzlebensdauer und der zeitaufgelösten Fluoreszenzanisotropie der Einfluss der Umgebung und der Temperatur auf die Struktur und Dynamik von zwei Polymerpartikeln (dendritisches Polyglycerolsulfat (dPGS) und Core-Multishell (CMS) Nanopartikel) untersucht. Es konnten Änderungen im physiologischen Temperaturbereich festgestellt werden, die entweder Auswirkungen auf die Größe der Partikel oder auf die Verteilung von Wirkstoff-Mimetika im Inneren des Partikel hatten. Beides kann direkt die therapeutische Wirksamkeit beeinflussen. Bildgebende Verfahren erlauben die Lokalisation von Nanopartikeln im Gewebe. Konfokale Rastermikroskopie in Kombination mit FLIM basiert auf der Messung der Fluoreszenzlebensdauer von angeregten fluoreszierenden Molekülen in jedem Bildpixel. Damit hat FLIM gegenüber der konventionellen Fluoreszenzmikroskopie einen erhöhten Kontrast. Eine Herausforderung für die Datenanalyse ist jedoch das schlechte Signal-Rausch- Verhältnis der pixelbasierten Fluoreszenzlebensdauerkurven, die eine Bestimmung der Fluoreszenzlebensdauern komplizieren, speziell wenn eine spezifische Fluoreszenzlebensdauer-Signatur, z.B. eines fluoreszenzmarkierten Nanopartikels, im autofluoreszierenden Gewebe detektiert werden soll. Mit Hilfe einer ratiometrischen FLIM Analyse, die das spezifische Amplitudenverhältnis der Fluoreszenzlebensdauern nutzt, konnte sowohl die spezifische Bindung eines Opioids an seinen Membranrezeptor als auch die Lokalisation von dPGS im Lebergewebe gezeigt werden

Preface to measurement, specification and forecasting of the Solar Energetic Particle (SEP) environment and Ground Level Enhancements (GLEs)

The Sun emits energetic particles following eruptive events such as solar flares and Coronal Mass Ejections (CMEs). Solar Energetic Particles (SEPs) arrive in bursts known as Solar Particle Events (SPEs), which penetrate into the Earth’s magnetosphere. SEPs with large enough energy induce a complicated atmospheric cascade, which secondary particles lead to an enhancement of count rate of ground-based detectors e.g. Neutron Monitors (NMs). This class of SEPs is therefore referred as Ground Level Enhancements (GLEs). The characterisation of the high-energy SEPs environment with corresponding space weather effects is important for space flights, aviation, and satellite industry. In this topical issue recent developments, addressing important user needs in the space radiation environment domain are published. Some articles are relevant to the specification of the SEP environment whilst others focus on space weather prediction of SEP fluxes. Catalogues based on measurement and processing of SEPs including ground-based data, and modelling of aircrew radiation exposure during major events are also presented

Axitinib in patients with advanced/metastatic soft tissue sarcoma (Axi-STS): an open-label, multicentre, phase II trial in four histological strata

Background: Axitinib is an oral vascular endothelial growth factor receptor inhibitor with anti-tumour activity in renal, thyroid, and pancreatic cancer. // Methods: Axi-STS was a pathologically-stratified, non-randomised, open-label, multi-centre, phase II trial of continuous axitinib treatment in patients ≥16 years, performance status ≤2, with pathologically-confirmed advanced/metastatic soft tissue sarcoma (STS). Patients were recruited within four tumour strata, each analysed separately: angiosarcoma, leiomyosarcoma, synovial sarcoma, or other eligible STSs. The primary outcome was progression-free survival at 12 weeks (PFS12). A Simon’s two-stage design with activity defined as PFS12 rate of 40% determined a sample size of 33 patients per strata. // Results: Between 31-August-2010 and 29-January-2016, 145 patients were recruited: 38 angiosarcoma, 37 leiomyosarcoma, 36 synovial sarcoma, and 34 other subtypes. PFS12 rate for each stratum analysed was 42% (95% lower confidence interval (LCI); 29), 45% (95% LCI; 32), 57% (95% LCI; 42), and 33% (95% LCI; 21), respectively. There were 74 serious adverse events including two treatment-related deaths of pulmonary haemorrhage and gastrointestinal bleeding. Fatigue and hypertension were the most common grade 3 adverse events. // Conclusions: Axitinib showed clinical activity in all STS strata investigated. The adverse event profile was acceptable, supporting further investigation in phase III trials. // Clinical Trial Registration: ISRCTN 6079133

Outcomes of ICU patients with and without perceptions of excessive care:a comparison between cancer and non-cancer patients

BACKGROUND: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer.METHODS: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer.RESULTS: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p &lt; 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60-1.72 and HR 0.87, 95% CI 0.49-1.54) and TLDs (HR 0.81, 95% CI 0.33-1.99 and HR 0.70, 95% CI 0.27-1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58-3.15 and 1.66, 95% CI 1.28-2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups.CONCLUSIONS: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU.</p

Outcomes of ICU patients with and without perceptions of excessive care:a comparison between cancer and non-cancer patients

BACKGROUND: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer.METHODS: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer.RESULTS: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p &lt; 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60-1.72 and HR 0.87, 95% CI 0.49-1.54) and TLDs (HR 0.81, 95% CI 0.33-1.99 and HR 0.70, 95% CI 0.27-1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58-3.15 and 1.66, 95% CI 1.28-2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups.CONCLUSIONS: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU.</p