Determinants of the international performance of services: a conceptual model

Countless determinants of export success that are supposed to help managers reduce the failure rates of export ventures have been identified. Despite this abundance of studies, however, little is known about the determinants of the internationalization success of services. In this paper, based on prior studies focusing primarily on manufactured goods and the key characteristics distinguishing services from goods, a comprehensive conceptual model for the successful internationalization of services is developed. --Services,export performance,internationalization,success factors

Determinants of the international performance of services a conceptual model

Countless determinants of export success that are supposed to help managers reduce the failure rates of export ventures have been identified. Despite this abundance of studies, however, little is known about the determinants of the internationalization success of services. In this paper, based on prior studies focusing primarily on manufactured goods and the key characteristics distinguishing services from goods, a comprehensive conceptual model for the successful internationalization of services is developed

The role of endosomal Toll-like receptors in the tumor microenvironment

Tumore bestehen aus malignen Zellen und dem Tumorstroma. Letzteres setzt sich aus nicht-hämatopoetischen Zellen und dem Immunzellinfiltrat zusammen und macht häufig einen Großteil der Tumormasse aus. Wechselwirkungen zwischen den Tumorzellen und dem Stroma beeinflussen die Biologie der beteiligten Zellen und die Pathophysiologie der Erkrankung. Toll-like Rezeptoren (TLRs) haben eine Schlüsselfunktion in der Aktivierung des Immunsystems. Die Aktivierung von TLRs kann anti-tumorale Effekte induzieren, die vor allem durch den Einsatz therapeutischer exogener Liganden hervorgerufen werden, während eine pro-tumorale Wirkung vorrangig für endogene Liganden beschrieben wurde. Um diese gegensätzlichen Befunde besser verstehen zu können, wurden in dieser Arbeit die Rolle endosomaler TLRs auf den verschiedenen Kompartimenten der Tumormikroumgebung analysiert. Initiale Untersuchungen der vorliegenden Arbeit sollten in TLR3/7/9-/- Mäusen Aufschluss darüber geben, welche TLRs und nachfolgende Signalwege an der Tumorabstoßung beteiligt sind. Die Untersuchung von Einzel- und Doppel-TLR-Knockoutmäusen zeigte, dass nur durch das Fehlen aller drei endosomaler Rezeptoren eine effiziente Abstoßung eintrat. Die Beteiligung mehrere TLR-Signalwege wurde durch die Tumorabstoßung in den MyD88/Trif-/- Mäusen bestätigt. Interessanterweise entwickelten jedoch die meisten der TLR2/3/4/7/9-Knockoutmäuse einen soliden Tumor, was für einen entgegengesetzten Effekt der endosomalen TLRs (3, 7, 9) und der Oberflächenrezeptoren TLR2 und TLR4 spricht. Um den relativen Beitrag des nicht-hämatopoetischen Stromas und des Immunzellinfiltrats an der Tumorregression zu untersuchen, wurden Knochenmarkchimären eingesetzt. Deren Untersuchung zeigte, dass beide Kompartimente an der Abstoßungsreaktion beteiligt waren. Dies wurde durch den adoptiven Transfer markierter Milzzellen bestätigt, da es nur zur Immunzellrekrutierung in den Tumor kam, wenn auf beiden Kompartimenten endosomale TLRs fehlten. Anschließende Untersuchungen des nicht-hämatopoetischen Stromas zeigten deutliche Unterschiede in der Ausbildung von Tumorgefäßen. Während die Tumore der WT Mäuse von einem feinen Kapillarsystem durchzogen wurden, bildeten sich in den Tumoren der TLR3/7/9-/- Mäuse eine geringere Anzahl heterogener Gefäße, die einen deutlich größeren Durchmesser aufwiesen, von Perizyten ummantelt waren und nicht alle Bereiche des Tumors versorgten. Im Kompartiment des hämatopoetischen Stromas konnte gezeigt werden, dass eine lokale anti-tumorale Immunreaktion für die Tumorabstoßung verantwortlich war. Während systemisch keine Unterschiede in der Aktivierung von dendritischen Zellen und T-Zellen festgestellt werden konnten, waren die Tumore der TLR3/7/9-/- Mäuse sehr stark mit Zellen des angeborenen und des adaptiven Immunsystems infiltriert. Durch Depletionsversuche konnte demonstriert werden, dass sowohl CD4+ als auch CD8+ T-Zellen für die Abstoßung verantwortlich waren. Dies wurde durch den Befund bestätigt, dass TLR3/7/9-/- Mäuse nach einmaliger Injektion der Tumorzellen eine Immunität gegen diese Zellen ausbildeten, sodass es zu keiner erneuten Ausbildung eines Tumors kommen konnte. Zusammenfassend konnte in der vorliegenden Arbeit zum ersten Mal gezeigt werden, dass durch das Fehlen der endosomalen Toll-like Rezeptoren TLR3, TLR7 und TLR9 Veränderungen in der Tumormikroumgebung auftreten, die zu eine T-Zell-abhängigen Tumorabstoßung führten. Daraus lässt sich ein pro-tumoraler Effekt dieser Rezeptoren in der WT-Situation bzw. die Ermöglichung einer anti-tumoralen Immunreaktion in den TLR3/7/9-/- Mäusen ableiten. Dieser Befund ist von besonderer Bedeutung, da endosomale TLRs bislang vorwiegend mit exogener therapeutischer Stimulation in Verbindung gebracht wurden und die Stimulation durch endogene Liganden kaum untersucht ist. In dieser Arbeit konnte nun gezeigt werden, dass, unabhängig von therapeutischer Intervention, die endosomale TLR-Expression auf den hämatopoetischen und nicht-hämatopoetischen Zellen das Tumorwachstum beeinflussen kann. Die TLR-Aktivierung durch bislang nicht identifizierte endogene Liganden könnte zu einer pro-tumoralen Stimulation der Tumorzellen führen. Daher könnte die Inhibierung endosomaler TLRs eine neue Möglichkeit der therapeutischen Intervention bei bestimmten Tumorerkrankungen darstellen.Tumors consist of malignant cells and the tumor stroma, which is composed of non-hematopoietic cells and the infiltrating immune cells. Often the stroma represents the major fraction of the whole tumor mass. The interaction between tumor and stromal cells influences the biology of the involved cells and the pathophysiology of the disease. Toll-like receptors (TLRs) are known as key players in immune activation. The activation of TLRs can induce anti-tumor effects, which are mostly generated by the use of therapeutic exogenous ligands, while pro-tumor effects are primarily described for endogenous ligands. To better understand these contrary indications, the impact of endosomal TLR expression on different compartments of the tumor microenvironment was analyzed in this thesis. Firstly the aim was to investigate which TLRs and subsequent pathways are involved in the tumor regression in the TLR3/7/9-/- mice. Tumor growth analysis in single and double TLR knockout mice showed that depletion of all three TLRs is necessary to induce tumor rejection. The involvement of several TLR pathways was confirmed by tumor rejection in MyD88/Trif-/- mice. Surprisingly, the majority of TLR2/3/4/7/9-/- mice developed a solid tumor, revealing a converse function of endosomal TLRs (3, 7, 9) and TLR2/4 located on the cell surface. To identify the relative contribution of the non-hematopoietic stromal cells and the infiltrating immune cells to tumor regression, bone marrow chimeras were generated. The investigation of these chimeras demonstrated the involvement of both compartments in the process of tumor rejection. This was confirmed by the adaptive transfer of labeled splenocytes and it was found that only if both compartments were deficient for endosomal TLRs then immune cells would be recruited to the tumor. Further investigation of the non-hematopoietic compartment revealed clear differences in the blood vessel development. While in WT mice, tumors were supplied by a fine capillary network, TLR3/7/9-/- mice developed a reduced number of tumor vessels which were characterized by a heterogeneous structure. TLR-deficient vessels showed an increased diameter and coverage by pericytes compared to tumor vessels of WT mice. Investigation of the hematopoietic compartment indicates a local anti-tumor response of the immune system. While no systemic activation of dendritic cells or T cells could be determined, tumors of TLR mice were highly infiltrated by innate and adaptive immune cells. Depletion of CD4+ or CD8+ T cells in vivo demonstrated that both cell types are necessary for tumor rejection. This was verified by the observation, that TLR3/7/9-/- tumor regressor mice were protected against a secondary challenge by the same tumor cell line. In summary, the experiments of this thesis showed for the first time that depletion of endosomal TLR3, TLR7 and TLR9 induces modification of the tumor microenvironment resulting in a T cell dependent tumor rejection. The data suggest a tumor promoting effect in the WT situation or alternatively the enabling of previously inactive anti-tumor mechanisms in TLR3/7/9-/- mice. These findings are of relevance as previously endosomal TLRs were mainly associated with exogenous therapeutic TLR stimulation while the relevance of endogenous signaling via these TLRs is largely unknown. This study now shows an effect of endosomal TLR expression by non-hematopoietic and hematopoietic stroma cells on tumor growth in the absence of therapeutic intervention. TLR activation, by still elusive ligands, in different compartments of the tumor/stroma entity by endogenous ligands could promote tumor growth. Thus inhibition of endosomal TLRs could lead to new therapeutic options in solid tumors

Spatio-temporal patterns and dynamics of net primary productivity for Kazakhstan

Monitoring of net primary productivity (NPP) is especially important for the fragile ecosystems in arid and semi-arid regions. Great interest exists in observing large-scale vegetation dynamics and understanding spatial and temporal patterns of NPP in these areas. In this study we present results of NPP obtained with the model BETHY/DLR for Kazakhstan for 2003-2011 and its spatial and temporal dynamics. The spatial distribution of vegetation productivity shows a gradient from North to South and clear differences between individual vegetation classes. The monthly NPP values show the highest productivity in June. Differences between rain-fed and irrigated areas indicate the dependency on water availability. Annual NPP variability was high for agricultural areas, but showed low values for natural vegetation. The analysis of different patterns in vegetation productivity provides valuable information for the identification of regions that are vulnerable to a possible climate change. This information may thus substantially support a sustainable land management

Risk Factors and Prognosis in T-Cell Posttransplantation Lymphoproliferative Diseases: Reevaluation of 163 Cases

Background. Posttransplantation lymphoproliferative diseases (PTLD) are mainly Epstein-Barr virus (EBV)-associated disorders of B-cell origin. Due to the rarity of monomorphic T-cell PTLD (T-PTLD), knowledge about pathogenesis, risk factors, therapy, and prognosis relies predominantly on case reports and small series. Therefore, we aimed to provide an overview and a retrospective analysis of this rare PTLD subtype. Methods. We analyzed all available articles on T-PTLD in the PubMed database as well as in our own databases (Institute of Pathology/Department of Paediatric Haematology and Oncology, Hannover Medical School) from 1988 to 2010. Reevaluated parameters were gender, age, transplanted organ, immunosuppressant regimen, time between transplantation and T-PTLD manifestation, T-PTLD subtype, virus positivity, localization, therapy, and follow-up. Results. A total of 163 cases were evaluated. We found that hematopoietic stem cell transplantation was associated with early-onset T-PTLD, whereas late onset occurred after immunosuppression with steroids and azathioprine without administration of calcineurin inhibitors. The major independent favorable prognostic factors were T-PTLD of the large granular lymphocytic leukemia subtype, young age, and a combination of radiotherapy/radiochemotherapy and reduced immunosuppression, whereas the hepatosplenic T-cell lymphoma subtype and cases with involvement of bone marrow, the central nervous system, or graft had an adverse prognosis. Conclusion. T-PTLD is a heterogeneous group of different aberrant T-cell proliferations and represents a significant complication following transplantation, showing a uniformly poor prognosis

Utilization and spending trends for antiretroviral medications in the U.S. Medicaid program from 1991 to 2005

<p>Abstract</p> <p>Background</p> <p>HIV/AIDS incidence and mortality rates have decreased in the U.S. since 1996. Accompanying the longer life spans of those diagnosed with the disease, however, is a tremendous rise in expenditures on medication. The objective of this study is to describe the trends in utilization of, spending on, and market shares of antiretroviral medications in the U.S. Medicaid Program. Antiretroviral drugs include nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and fusion inhibitors (FIs).</p> <p>Methods</p> <p>Utilization and payment data from 1991 to 2005 are provided by the Centers for Medicare & Medicaid Services. Descriptive summary analyses were used to assess quarterly prescription numbers and amounts of payment.</p> <p>Results</p> <p>The total number of prescriptions for antiretrovirals increased from 168,914 in 1991 to 2.0 million in 1998, and 3.0 million in 2005, a 16.7-fold increase over 15 years. The number of prescriptions for NRTIs reached 1.6 million in 2005. Prescriptions for PIs increased from 114 in 1995 to 932,176 in 2005, while the number of prescriptions for NNRTIs increased from 1,339 in 1996 to 401,272 in 2005. The total payment for antiretroviral drugs in the U.S. Medicaid Program increased from US$30.6 million in 1991 to US$ 1.6 billion in 2005, a 49.8-fold increase. In 2005, NRTIs as a class had the highest payment market share. These drugs alone accounted for US$787.9 million in Medicaid spending (50.8 percent of spending on antiretrovirals). Payment per prescription for each drug, with the exception of Agenerase^®, increased, at least somewhat, over time. The relatively expensive drugs in 2005 included Trizivir^®($1040) and Combivir^®($640), as well as Reyataz^®($750), Lexiva^®($700), Sustiva^®($420), Viramune^®($370), and Fuzeon^®($1914).</p> <p>Conclusion</p> <p>The tremendous growth in antiretroviral spending is due primarily to rising utilization, secondarily to the entry of newer, more expensive antiretrovirals, and, finally, in part to rising per-prescription cost of existing medications.</p

Weight-based vs. BSA-based Fluid Resuscitation Predictions in Pediatric Burn Patients

Fluid resuscitation for pediatric burns uses formulas that estimate fluid requirements based on weight, and/or body surface area (BSA) along with percent total burn surface area (TBSA). Adult studies have shown that these formulas can cause fluid overload in obese patients and increase risk of complications. These findings have not been validated in pediatric patients. This study provides a retrospective review conducted with 110 children (≤ 18 years old) admitted to an ABA-verified urban pediatric burn center from October 2008 to May 2020. Patients were resuscitated with the weight-based Parkland formula, and had fluids titrated to urine output every two hours. BSA-based Galveston and BSA-incorporated Cincinnati formula resuscitation predictions were also calculated. Complications were collected throughout the hospital stay. Patients were classified into CDC-defined weight groups based on percentile ranges. We found that predicted resuscitation volumes increased as CDC percentile increased for all three formulas (p=0.033, 0.092, 0.038), however there were no significant differences between overweight and obese children. Total fluid administered was higher as CDC percentile increased (p=0.023). However, overweight children received more total fluid than obese children. The difference between total fluids given and Galveston predicted resuscitation volumes were significant across all groups (p=0.042); however, the difference using the Parkland and Cincinnati formulas were not statistically significant. There were more children in the normal weight group who developed complications compared to other groups, but these findings were not significant. Overall, the Parkland formula tended to underpredict fluid needs in the underweight, normal, and overweight children, and it overpredicted fluid needs for the obese. Further research is needed to determine the value of weight-based vs BSA-based or incorporated formulas in terms of their risk of complications

Entwicklung und Integration einer Benutzeroberfläche zur Darstellung von Flugzustandsdaten im Flugversuch

Zur Erhöhung der Effizienz und Sicherheit im Flugversuch soll in dieser Arbeit ein OnboardMessdatenvisualisierungswerkzeug entwickelt werden. Diese Arbeit setzt bei den Messanlagen der Dornier 228-101 D-CODE und dem Helikopter Bo105 D-HDDP des Deutschen Zentrums für Luft- und Raumfahrt (DLR) an mit dem Ziel, die im Flugversuch ermittelten Messdaten zu entschlüsseln und in Echtzeit darzustellen, um Flugversuchsingenieure in ihrer Arbeit zu unterstützen und eventuelle Sensorfehler durch fehlerhafte Messanlageneingänge rechtzeitig zu erkennen. Diese Arbeit beginnt bei den Grundlagen der Netzwerktechnik und stellt die proprietären binären Formate vor, in denen die Daten verschlüsselt sind, um den Datentransfer nachvollziehen zu können. Darauf aufbauend werden die Grundlagen der Mensch-Maschine Schnittstelle benutzt, um, basierend auf Anforderungen der Flugversuchsingenieure, einen Entwurf für die letztliche Nutzeroberfläche zu entwerfen. Zuletzt werden der Entwicklungsprozess und die entstandenen Funktionen um dieses Ziel zu erreichen dargestellt. Auf Basis der in dieser Arbeit entwickelten Schnittstellen und Benutzeroberflächen werden zukünftig die Messdaten aus den Messdatenerfassungssystemen der D-CODE und der D-HDDP sowohl offline dekodiert als auch im Flug dem Flugversuchsingenieur dargestellt

FAIR Sensor Health Monitoring of Flight Test Data

The DLR’s ISTAR research aircraft is equipped with extensive permanent sensor instrumentation for the scientific investigation of aerophysical phenomena. The measurement data as well as a large part of the parameters on the aircraft’s own data bus are continuously recorded by an additional Data Acquisitioning System (DAQ). To evaluate measurement data in order to gain knowledge, the form of data storage and the linkage of fault detections is vital to avoid erroneous conclusions. By honoring FAIR (Findable, Accessible, Interoperable, Reusable) principles, the detected faults andaAnomalies shall aptly be linked to the measurement data. In this work, a python application is developed to solve this problem by detecting faults, sensibly linking them to the measurement data and then visualizing the results to the user. To solve this task, data modeling techniques developed at the WZL are employed. In addition, data is checked for completeness, plausibility and correctness by using statistical methods as well as approaches from the field of Fault Mode and Effect Analysis (FMEA). Finally, the performance and trueness of the application-toolchain is tested against known errors and validated on a dataset of ISTAR Flight Test data

Comparison of Veterinary Nutrition Exam Results After Classroom or Virtual Teaching During the COVID-19 Pandemic at a German University

Due to the COVID-19 pandemic, university teaching had to be kept up in spite of severe contact restrictions. Virtual teaching of animal nutrition was implemented at the Veterinary Faculty of the Ludwig-Maximilians-Universität (LMU) München, Germany, for both lectures and practical courses. Live online classes were held via Zoom®, and recordings were accessible afterwards. Animal nutrition is taught in the 5th and 6th term of the veterinary studies, followed by an oral state exam about subjects from both terms. In this study, the success of classroom vs. virtual teaching in veterinary animal nutrition was evaluated by comparison of exam results. Two exam cohorts (2019, before the pandemic; 2020, with one term of virtual teaching during the pandemic) were evaluated. The results indicated no significant difference of teaching method on the grades. However, there was a significantly higher probability of students not taking or failing the exam in the 2020 exam cohort, suggesting a general effect of the pandemic on the students. Additionally, two surveys were distributed among the students during summer term 2020 and winter term 2020/21, when virtual teaching due to the pandemic had been implemented for the first time. The survey results provide insights into the students' view of benefits and problems of virtual teaching in animal nutrition at the LMU. The majority was in favor of the live online format for lectures and courses in computed-based ration calculation, whilst feedstuff demonstrations were preferred in classroom setting