73 research outputs found
Towards a Conceptualization of Capabilities for Innovating Business Models in the Industrial Internet of Things
The emergence of Internet of Things (IoT) technologies offers promising value potentials for industrial manufacturers based on the combination of smart products and data-driven services. At the same time, many incumbent firms experience a threat to their traditional value proposition and are challenged to innovate and reconfigure their existing business models. However, many of these traditional manufacturers lack or are unaware of the required capabilities for successfully reinventing their business model using IoT technologies. We therefore adopt the lens of dynamic and operational capabilities and conduct an empirical analysis of organizational capabilities required for successful IoT-enabled business model innovation (BMI). Through an exploratory, qualitative study based on interviews with decision makers in industrial manufacturing companies and experts in practice-oriented research institutions, we identify eleven distinct dynamic and operational capabilities. Our findings provide useful insights for research and practice and advance the understanding of enablers in IoT-enabled BMI
Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction
Background: This phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction.
Methods: Patients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary endpoint was the DLT and the MTD of the RCT regimen. Secondary endpoints included overall response rate (ORR) and progression-free survival (PFS).
Results: A total of 24 patients were included. Four patients were treated at DL 1, 13 patients at DL 2 and 7 patients at DL 3. The MTD of the RCT was considered DL 2 with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2. Objective response (CR/PR) was observed in 32% (7/22) of patients. Eighteen patients (75%) underwent surgery after RCT. The median PFS for all patients (n = 24) was 6.5 months. The median overall survival for all patients (n = 24) was 16.3 months. Patients treated at DL 2 had a median overall survival of 29.5 months.
Conclusion: Neoadjuvant RCT with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2 was effective and showed a good toxicity profile. Future studies should consider the addition of targeted therapies to current neoadjuvant therapy regimens to further improve the outcome of patients with advanced cancer of the oesophagogastric junction.
Trial Registration: NCT0037498
Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma
Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration.Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS).Results: Median age at diagnosis was 74 (range, 42–100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender (p = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p = 0.011) and combined CD8/PD-L1 expression (p = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (p = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (p = 0.010) and N-stage (p = 0.037). A high viral load (>median) was significantly associated with worse OS (p = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p = 0.045).Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches
Total Neoadjuvant Therapy for Rectal Cancer in the CAO/ARO/AIO-12 Randomized Phase 2 Trial: Early Surrogate Endpoints Revisited
Background: Early efficacy outcome measures in rectal cancer after total neoadjuvant
treatment are increasingly investigated. We examined the prognostic role of pathological complete
response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free
survival (DFS) in patients with rectal carcinoma treated within the CAO/ARO/AIO-12 randomized
phase 2 trial. Methods: Distribution of pCR, TRG and NAR score was analyzed using the Pearson’s
chi-squared test. Univariable analyses were performed using the log-rank test, stratified by treatment
arm. Discrimination ability of non-pCR for DFS was assessed by analyzing the ROC curve as a
function of time. Results: Of the 311 patients enrolled, 306 patients were evaluable (Arm A:156, ArmB:150). After a median follow-up of 43 months, the 3-year DFS was 73% in both groups (HR, 0.95,
95% CI, 0.63–1.45, p = 0.82). pCR tended to be higher in Arm B (17% vs. 25%, p = 0.086). In both
treatment arms, pCR, TRG and NAR were significant prognostic factors for DFS, whereas survival
in subgroups defined by pCR, TRG or NAR did not significantly differ between the treatment arms.
The discrimination ability of non-pCR for DFS remained constant over time (C-Index 0.58) but was
slightly better in Arm B (0.61 vs. 0.56). Conclusion: Although pCR, TRG and NAR were strong
prognostic factors for DFS in the CAO/ARO/AIO-12 trial, their value in selecting one TNT approach
over another could not be confirmed. Hence, the conclusion of a long-term survival benefit of one
treatment arm based on early surrogate endpoints should be stated with caution
Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets.
We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (∅ 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions
ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells
Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose–effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a contribution of reactive oxygen species (ROS) and anti-oxidative factors to a reduced leukocyte adhesion. Here, we evaluated the expression of anti-oxidative enzymes and the transcription factor Nrf2 (Nuclear factor-erythroid-2-related factor 2), intracellular ROS content, and leukocyte adhesion in primary human microvascular endothelial cells (HMVEC) upon low-dose irradiation under physiological laminar shear stress or static conditions after irradiation with X-ray or Carbon (C)-ions (0–2 Gy). Laminar conditions contributed to increased mRNA expression of anti-oxidative factors and reduced ROS in HMVEC following a 0.1 Gy X-ray and 0.5 Gy C-ion exposure, corresponding to reduced leukocyte adhesion and expression of adhesion molecules. By contrast, mRNA expression of anti-oxidative markers and adhesion molecules, ROS, and leukocyte adhesion were not altered by irradiation under static conditions. In conclusion, irradiation of endothelial cells with low doses under physiological laminar conditions modulates the mRNA expression of key factors of the anti-oxidative system, the intracellular ROS contents of which contribute at least in part to leucocyte adhesion, dependent on the radiation source
Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock
Large clinical trials testing hydrocortisone therapy in septic shock have produced
conflicting results. Subgroups may benefit of hydrocortisone treatment depending on
their individual immune response. We performed an exploratory analysis of the database
from the international randomized controlled clinical trial Corticosteroid Therapy of Septic
Shock (CORTICUS) employing machine learning to a panel of 137 variables collected
from the Berlin subcohort comprising 83 patients including demographic and clinical
measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The
identified theranostic marker was validated against data from a cohort of the Hellenic
Sepsis Study Group (HSSG) (n = 246), patients enrolled in the clinical trial of Sodium
Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, n
= 118), and another, smaller clinical trial (Crossover study, n = 20). In addition, in vitro
blood culture experiments and in vivo experiments in mouse models were performed to
assess biological plausibility. A low serum IFNg/IL10 ratio predicted increased survival in
the hydrocortisone group whereas a high ratio predicted better survival in the placebo
group. Using this marker for a decision rule, we applied it to three validation sets and
observed the same trend. Experimental studies in vitro revealed that IFNg/IL10 was
negatively associated with the load of (heat inactivated) pathogens in spiked human blood
and in septic mouse models. Accordingly, an in silico analysis of published IFNg and
IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory
Response Syndrome supported this association between the ratio and pathogen burden.
We propose IFNg/IL10 as a molecular marker supporting the decision to administer
hydrocortisone to patients in septic shock. Prospective clinical studies are necessary
and standard operating procedures need to be implemented, particularly to define a
generic threshold. If confirmed, IFNg/IL10 may become a suitable theranostic marker for
an urging clinical need
Resultado do Edital Nº 47 -CAPES - Programa de Doutorado SanduÃche no Exterior
Here we present measurements of surface tension and viscosity of the bulk glass-forming alloy Pd_(43)Cu_(27)Ni_(10)P_(20) performed during containerless processing under reduced gravity. We applied the oscillating drop method in an electromagnetic levitation facility on board of parabolic flights. The measured viscosity exhibits a pronounced temperature dependence following an Arrhenius law over a temperature range from 1100 K to 1450 K. Together with literature values of viscosity at lower temperatures, the viscosity of Pd_(43)Cu_(27)Ni_(10)P_(20) can be well described by a free volume model. X-ray diffraction analysis on the material retrieved after the parabolic flights confirm the glassy nature after vitrification of the bulk samples and thus the absence of crystallization during processing over a wide temperature range
The Fermi energy as common parameter to describe charge compensation mechanisms: A path to Fermi level engineering of oxide electroceramics
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Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets
We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (∅ 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions
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