Selective intra-carotid blood cooling in acute ischemic stroke : a safety and feasibility study in an ovine stroke model

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy

Encouraging brand loyalty among young Millennials for the luxury appliance brand Gaggenau

Despite the growth the luxury industry has experienced in recent years, marketers are increasingly facing the emergence of a younger luxury consumer that has different values, priorities, and attitudes. Since these consumers are soon to replace the current luxury clientele as the primary luxury consumer due to their size and purchasing power, successful luxury brands have changed their strategies in order to stay relevant. Being faced with a considerable decrease in brand loyalty, a deeper understanding of the drivers of brand loyalty among this clientele is of utmost importance. Whereas loyalty has often simply been defined as repeat behavior of purchasing one single brand, the literature suggests a more complex definition, which emphasizes the importance of a favorable attitude toward the brand in order for a consumer to be considered truly loyal. Since this attitudinal part of brand loyalty does not necessarily presuppose actual brand usage, Gaggenau as a luxury appliance brand needs to find ways to attract and establish a pre-purchase bond with these consumers even before they have reached their peak buying power, which will create the basis for enduring brand loyalty. This thesis was set out to explore the complex process of loyalty creation in view of a different luxury consumer, which is increasingly gaining strategic importance. Focus of this thesis was to provide the luxury appliance brand Gaggenau with advice on how to create the basis for enduring brand loyalty among young Generation Y consumers. As a basis for the analysis, the term “luxury” including its different facets and the role aspirations play in the consumption motives for luxury goods has been investigated. This was followed by an examination of the important role of a new type of luxury consumer, characterized by different traits and attitudes. These consumers are likely members of the Generation Y cohort. Due to decreasing loyalty levels, particular emphasis has been put on understanding how to establish an enduring customer-brand relationship. For this, the formation of loyalty, including different degrees and types of loyalty, has been thoroughly investigated. The importance of truly knowing the consumer’s values, desires, and preferences in the creation of brand commitment or in other words the attitudinal part of loyalty as an ultimate milestone to creating enduring brand loyalty, has also been pointed out. Therefore, the next step was to understand Generation Y consumers. The investigation has mainly focused on the opportunities for creating aspiration or an emotional bond with the consumer at the early stage of the consumer journey. Then, the specific challenges Gaggenau is facing with regard to this new luxury consumer and due to the difficulty of reconciling its status as luxury and appliance brand have been presented. The insights gained throughout this dissertation have then been summarized in a recommended course of action. Finally, based on the development of a Weighted Average Scoring Model for potential Gaggenau consumers, a selection of specific touch points has been evaluated on their effectiveness of creating the basis for enduring brand loyalty at the early stages of the consumer journey

Proteomic Characterization of Prostate Cancer to Distinguish Nonmetastasizing and Metastasizing Primary Tumors and Lymph Node Metastases

Patients with metastatic prostate cancer (PCa) have a poorer prognosis than patients with organ-confined tumors. We strove to uncover the proteome signature of primary PCa and associated lymph node metastases (LNMs) in order to identify proteins that may indicate or potentially promote metastases formation. We performed a proteomic comparative profiling of PCa tissue from radical prostatectomy (RPE) of patients without nodal metastases or relapse at the time of surgical resection (n = 5) to PCa tissue from RPE of patients who suffered from nodal relapse (n = 5). For the latter group, we also included patient-matched tissue of the nodal metastases. All samples were formalin fixed and paraffin embedded. We identified and quantified more than 1200 proteins by liquid chromatography tandem mass spectrometry with subsequent label-free quantification. An increase of ribosomal or proteasomal proteins in LNM (compared to corresponding PCa) became apparent, while extracellular matrix components rather decreased. Immunohistochemistry (IHC) corroborated accumulation of poly-(ADP-ribose)-polymerase 1 and N-myc-downstream-regulated-gene 3, alpha/beta hydrolase domain-containing protein 11, and protein phosphatase slingshot homolog 3 in LNM. These findings strengthen the present interest in examining PARP inhibitors for the treatment of aggressive PCa. IHC also corroborated increased abundance of retinol dehydrogenase 11 in metastasized primary PCa compared to organ-confined PCa. Generally, metastasizing primary tumors were characterized by an enrichment of proteins involved in cellular lipid metabolic processes with concomitant decrease of cell adhesion proteins. This study highlights the usefulness of a combined proteomic-IHC approach to explore novel aspects in tumor biology. Our initial results open novel opportunities for follow-up studies

Alteration of Tissue Marking Dyes Depends on Used Chromogen during Immunohistochemistry

Pathological biopsy protocols require tissue marking dye (TMD) for orientation. In some cases (e.g., close margin), additional immunohistochemical analyses can be necessary. Therefore, the correlation between the applied TMD during macroscopy and the examined TMD during microscopy is crucial for the correct orientation, the residual tumour status and the subsequent therapeutic regime. In this context, our group observed colour changes during routine immunohistochemistry. Tissue specimens were marked with various TMD and processed by two different methods. TMD (blue, red, black, yellow and green) obtained from three different providers (A, B and C, and Whiteout/Tipp-Ex®) were used. Immunohistochemistry was performed manually via stepwise omission of reagents to identify the colour changing mechanism. Blue colour from provider A changed during immunohistochemistry into black, when 3,3′-Diaminobenzidine-tetrahydrochloride-dihydrate (DAB) and H2O2 was applied as an immunoperoxidase-based terminal colour signal. No other applied reagents, nor tissue texture or processing showed any influence on the colour. The remaining colours from provider A and the other colours did not show any changes during immunohistochemistry. Our results demonstrate an interesting and important pitfall in routine immunohistochemistry-based diagnostics that pathologists should be aware of. Furthermore, the chemical rationale behind the observed misleading colour change is discussed

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n ¼ 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n ¼ 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 C/3.1 C after 10/60 minutes in the TH group and 0.3 C/0.4 C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p ¼ 0.74) and neurological outcome (p ¼ 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy