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Zwirtz, Kevin ; Hardt, Juliane ; Acker, Güliz ; Bauer, Alexander D. J. ; Pavel, Marianne ; Huang, Kai ; Brenner, Winfried ; Prasad, Vikas
Aim:
The most suitable method for assessment of response to peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET) is still under debate. In this study we aimed to compare size (RECIST 1.1), density (Choi), Standardized Uptake Value (SUV) and a newly defined ZP combined parameter derived from Somatostatin Receptor (SSR) PET/CT for prediction of both response to PRRT and overall survival (OS).
Material and Methods:
Thirty-four NET patients with progressive disease (F:M 23:11; mean age 61.2 y; SD ± 12) treated with PRRT using either Lu-177 DOTATOC or Lu-177 DOTATATE and imaged with Ga-68 SSR PET/CT approximately 10–12 weeks prior to and after each treatment cycle were retrospectively analyzed. Median duration of follow-up after the first cycle was 63.9 months (range 6.2–86.2). A total of 77 lesions (2–8 per patient) were analyzed. Response assessment was performed according to RECIST 1.1, Choi and modified EORTC (MORE) criteria. In addition, a new parameter named ZP, the product of Hounsfield unit (HU) and SUVmean (Standard Uptake Value) of a tumor lesion, was tested. Further, SUV values (max and mean) of the tumor were normalized to SUV of normal liver parenchyma. Tumor response was defined as CR, PR, or SD. Gold standard for comparison of baseline parameters for prediction of response of individual target lesions to PRRT was change in size of lesions according to RECIST 1.1. For prediction of overall survival, the response after the first and second PRRT were tested.
Results:
Based on RECIST 1.1, Choi, MORE, and ZP, 85.3%, 64.7%, 61.8%, and 70.6% achieved a response whereas 14.7%, 35.3%, 38.2%, and 29.4% demonstrated PD (progressive disease), respectively. Baseline ZP and ZPnormalized were found to be the only parameters predictive of lesion progression after three PRRT cycles (AUC ZP 0.753; 95% CI 0.6–0.9, p 0.037; AUC ZPnormalized 0.766; 95% CI 0.6–0.9; p 0.029). Based on a cut-off-value of 1201, ZP achieved a sensitivity of 86% and a specificity of 67%, while ZPnormalized reached a sensitivity of 86% and a specificity of 76% at a cut-off-value of 198. Median OS in the total cohort was not reached. In univariate analysis amongst all parameters, only patients having progressive disease according to MORE after the second cycle of PRRT were found to have significantly shorter overall survival (median OS in objective responders not reached, in PD 29.2 months; p 0.015). Patients progressive after two cycles of PRRT according to ZP had shorter OS compared to those responding (median OS for responders not reached, for PD 47.2 months, p 0.066).
Conclusions:
In this explorative study, we showed that Choi, RECIST 1.1, and SUVmax-based response evaluation varied significantly from each other. Only patients showing progressive disease after two PRRT cycles according to MORE criteria had a worse prognosis while baseline ZP and
ZPnormalized performed best in predicting lesion progression after three cycles of PRRT.
Die empfindliche Verteuerung des Rohöls im Laufe der letzten Jahre und die in ihrem Sog erfolgten Preissteigerungen auch für die anderen Energieträger haben Energie zu einem besonders kostbaren Wirtschaftsgut werden lassen. Es ist ganz deutlich geworden, dass Energie in allen Lebens- und Produktionsbereichen äußerst sparsam verwendet und optimal genutzt werden muss. Mittel- und langfristig gesehen sind daher gezielt Anstrengungen zu unternehmen, nicht einen Brennstoff durch einen anderen zu ersetzen, sondern - wo immer auch möglich - die natürlcihen Energiequellen zu nutzem.
Fenster versorgen die Innenräume mit Tageslicht, dienen der Lufterneuerung in den Räumen und schützen vor Umwelteinflüssen wie Kälte, Wärme, Lärm, Wind und Niederschlägen. Entsprechend weitgefächert ist das Spektrum deer planungsrelevanten Aspekte. Sowohl licht-, lüftungs-, wärme-, schall und wohntechnische als auch hygienische, psychologische und nicht zuletzt wirtschaftliche Gesichtspunkte sind bei edr täglichen Arbeit zu beachten.
Die Funktion eines Gebäudes, seine flächenmäßige Ausdehnung und seine Gliederung sowie seine Einbettung in die Umgebung bestimmen letztendlich die Dachkonstruktion. Der Planer steht hierbei vor der Aufgabe, unter Beachtung aller bauphysikalischen wie bautechnischen Gegebenheiten ein Optimum an gestalterischer Qualität bei Respektierung wirtschaftlicher und baupraktischer Belange zu realisieren, wobei zu beachten ist, dass gerade das Dach von den die Gebäudehülle bildenden Bauteilen der größten und unmittelbarsten Beanspruchung unterliegt.
Zapf, Antonia ; Albert, Christian ; Frömke, Cornelia ; Haase, Michael ; Hoyer, Annika ; Jones, Hayley E. ; Rücker, Gerta
Methods for standard meta-analysis of diagnostic test accuracy studies are well established and understood. For the more complex case in which studies report test accuracy across multiple thresholds, several approaches have recently been proposed. These are based on similar ideas, but make different assumptions. In this article, we apply four different approaches to data from a recent systematic review in the area of nephrology and compare the results. The four approaches use: a linear mixed effects model, a Bayesian multinomial random effects model, a time-to-event model and a nonparametric model, respectively. In the case study data, the accuracy of neutrophil gelatinase-associated lipocalin for the diagnosis of acute kidney injury was assessed in different scenarios, with sensitivity and specificity estimates available for three thresholds in each primary study. All approaches led to plausible and mostly similar summary results. However, we found considerable differences in results for some scenarios, for example, differences in the area under the receiver operating characteristic curve (AUC) of up to 0.13. The Bayesian approach tended to lead to the highest values of the AUC, and the nonparametric approach tended to produce the lowest values across the different scenarios. Though we recommend using these approaches, our findings motivate the need for a simulation study to explore optimal choice of method in various scenarios.
In this study, we calculated the energetics of hydrogen atoms adsorbing on and diffusing into the first few layers of γ-Fe for the (100), (110) and (111) surfaces and for the non-magnetic (NM), ferromagnetic (FM), and antiferromagnetic single (AFM1) and double layer (AFMD) structures. These studies are relevant as they atomistically simulate the early stages of hydrogen embrittlement in steels. We employed density functional theory to establish adsorption sites and energies for each plane and the minimum energy pathways for diffusion through the first few layers with associated activation barriers. Adsorption energies for all cases vary between ∼3.7 and 4.4 eV, and the energy barriers to diffusion in the bulk region vary between ∼0.2 and 1.2 eV for the twelve cases, with the highest and lowest bulk diffusion barriers occurring in the NM(111) and the FM(100) case, respectively. We conclude that the texturing of steels in order to expose certain cleavage planes or magnetic structures can decrease the likelihood of hydrogen embrittlement.
Bei der Integration technischer Energiemanagementsysteme (tEnMS) in Automatisierungsanlagen fällt ein hoher Engineering-Aufwand an, besonders für die Steuerungsprogrammierung. Dieser Engineering-Aufwand ist für industrielle Anwender der Hauptgrund, integrierte tEnMS nicht einzusetzen. Im Rahmen des Forschungsprojektes „Integriertes Anlagenengineering zur Erhöhung der Energieeffizienz (IAE4)“ (Förderkennzeichen: ZN2948; Forschungsprofessur des Landes Niedersachsen/Volkswagenstiftung) wurde untersucht, wie sich dieser Engineering-Aufwand reduzieren lässt. Hierzu wurde ein Software-Werkzeug entwickelt, das die benötigten Steuerungsprogramme automatisch aus Engineering-Daten und Gerätebeschreibungsdateien generiert. Dieser Beitrag stellt die Ergebnisse des IAE4-Projektes vor.
Woudstra, Svenja ; Wente, Nicole ; Zhang, Yanchao ; Leimbach, Stefanie ; Kirkeby, Carsten ; Gussmann, Maya Katrin ; Krömker, Volker
To design cost-effective prevention strategies against mastitis in dairy cow farms, knowledge about infection pathways of causative pathogens is necessary. Therefore, we investigated the reservoirs of bacterial strains causing intramammary infections in one dairy cow herd. Quarter foremilk samples (n = 8056) and milking- and housing-related samples (n = 251; from drinking troughs, bedding material, walking areas, cow brushes, fly traps, milking liners, and milker gloves), were collected and examined using culture-based methods. Species were identified with MALDI-TOF MS, and selected Staphylococcus and Streptococcus spp. typed with randomly amplified polymorphic DNA-PCR. Staphylococci were isolated from all and streptococci from most investigated locations. However, only for Staphylococcus aureus, matching strain types (n = 2) were isolated from milk and milking-related samples (milking liners and milker gloves). Staphylococcus epidermidis and Staphylococcus haemolyticus showed a large genetic diversity without any matches of strain types from milk and other samples. Streptococcus uberis was the only Streptococcus spp. isolated from milk and milking- or housing-related samples. However, no matching strains were found. This study underlines the importance of measures preventing the spread of Staphylococcus aureus between quarters during milking.
Woudstra, Svenja ; Wente, Nicole ; Zhang, Yanchao ; Leimbach, Stefanie ; Gussmann, Maya ; Kirkeby, Carsten ; Krömker, Volker
To effectively prevent and control bovine mastitis, farmers and their advisors need to take infection pathways and durations into account. Still, studies exploring both aspects through molecular epidemiology with sampling of entire dairy cow herds over longer periods are scarce. Therefore, quarter foremilk samples were collected at 14-d intervals from all lactating dairy cows (n = 263) over 18 wk in one commercial dairy herd. Quarters were considered infected with Staphylococcus aureus, Streptococcus uberis, or Streptococcus dysgalactiae when ≥100 cfu/mL of the respective pathogen was detected, or with Staphylococcus epidermidis or Staphylococcus haemolyticus when ≥500 cfu/mL of the respective pathogen was detected. All isolates of the mentioned species underwent randomly amplified polymorphic DNA (RAPD)-PCR to explore strain diversity and to distinguish ongoing from new infections. Survival analysis was used to estimate infection durations. Five different strains of Staph. aureus were isolated, and the most prevalent strain caused more than 80% of all Staph. aureus infections (n = 46). In contrast, 46 Staph. epidermidis and 69 Staph. haemolyticus strains were isolated, and none of these caused infections in more than 2 different quarters. The 3 most dominant strains of Strep. dysgalactiae (7 strains) and Strep. uberis (18 strains) caused 81% of 33 and 49% of 37 infections in total, respectively. The estimated median infection duration for Staph. aureus was 80 d, and that for Staph. epidermidis and Staph. haemolyticus was 28 and 22 d, respectively. The probability of remaining infected with Strep. dysgalactiae or Strep. uberis for more than 84 and 70 d was 58.7 and 53.5%, respectively. Staphylococcus epidermidis and Staph. haemolyticus were not transmitted contagiously and the average infection durations were short, which brings into question whether antimicrobial treatment of intramammary infections with these organisms is justified. In contrast, infections with the other 3 pathogens lasted longer and largely originated from contagious transmission.