Geometric Times, Linguistic Spaces

If the loop is the trademark of our times and truthiness the reversal of the uncanny, what is the correlation between logic and information? This writing investigates the role of repetition and motifs in the production of meaning, how kitsch and neutrality function as modes of signifiers and how authenticity relates to the banal

Teres Ligament Patch Reduces Relevant Morbidity After Distal Pancreatectomy (the DISCOVER Randomized Controlled Trial)

Objective:The aim of this study was to analyze the impact of teres ligament covering on pancreatic fistula rate after distal pancreatectomy (DP).Background:Postoperative pancreatic fistula (POPF) represents the most significant complication after DP. Retrospective studies suggested a benefit of covering the resection margin by a teres ligament patch.Methods:This prospective randomized controlled study (DISCOVER trial) included 152 patients undergoing DP, between October 2010 and July 2014. Patients were randomized to undergo closure of the pancreatic cut margin without (control, n = 76) or with teres ligament coverage (teres, n = 76). The primary endpoint was the rate of POPF, and the secondary endpoints included postoperative morbidity and mortality, length of hospital stay, and readmission rate.Results:Both groups were comparable regarding epidemiology (age, sex, body mass index), operative parameters (operation time [OP] time, blood loss, method of pancreas transection, additional operative procedures), and histopathological findings. Overall inhospital mortality was 0.6% (1/152 patients). In the group of patients with teres ligament patch, the rate of reoperations (1.3% vs 13.0%;P = 0.009), and also the rate of readmission (13.1 vs 31.5%;P = 0.011) were significantly lower. Clinically relevant POPF rate (grade B/C) was 32.9% (control) versus 22.4% (teres, P = 0.20). Multivariable analysis showed teres ligament coverage to be a protective factor for clinically relevant POPF (P = 0.0146).Conclusions:Coverage of the pancreatic remnant after DP is associated with less reinterventions, reoperations, and need for readmission. Although the overall fistula rate is not reduced by the coverage procedure, it should be considered as a valid measure for complication prevention due to its clinical benefit

BTK isoforms p80 and p65 are expressed in head and neck squamous cell carcinoma (HNSCC) and involved in tumor progression

Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer : An International Multicenter Cohort Study

Background. Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS.Methods. This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression.Results. The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS.Conclusions. This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.Peer reviewe

Einfluss einer Vitamin-D-Therapie auf die Insulinresistenz und Stoffwechseleinstellung bei Patienten mit Typ-2-Diabetes-mellitus

Die Effekte von Vitamin D (VD) auf den Stoffwechsel wurden bisher meist bei Nichtdiabetikern untersucht und erbrachten sehr kontroverse Ergebnisse. Das Ziel unserer Studie war es, den Einfluss einer sechsmonatigen VD-Gabe von 1904 IU/d auf den Metabolismus bei Patienten mit nichtinsulinpflichtigem Diabetes mellitus Typ 2 (DM Typ2) zu untersuchen. Dazu schlossen wir 86 Patienten mit DM Typ 2 in eine randomisierte, doppelblinde, placebokontrollierte Studie ein. Während der ersten sechs Monate nahmen die Patienten 20 Tropfen (1904 IE/d) Vigantol-Öl bzw. Placebo-Öl (mittelkettige Triglyceride) einmal pro Woche zu sich. Dem folgten 6 Monate der Nachbeobachtung. Zu Beginn und in dreimonatigen Abständen wurden 25- OHD, 1α, 25(OH)2-OHD, PTH, Calcium, Phosphat, Körpergewicht, Body mass index (BMI), Blutdruck, Nüchternglucose, HbA1c, Insulin, Homeostasis Model Assessment-Index (Homa-Index) und C-Peptid bestimmt. Zu Studienbeginn wiesen alle Patienten (n=86) im Median ein 25-OHD von 13,60 ng/ml (34 nmol/l) und somit einen VD-Mangel auf. Nach 6 Monaten der Therapie stieg der 25-OHD-Spiegel der Verumgruppe (n=40) um den Faktor 2,14 auf einen Median von 28,4 ng/ml (71 nmol/l) an. Der mittlere Anstieg von 11,85 ng/ml in der Verumgruppe (p<0,001) war signifikant stärker als in der Placebogruppe. Während der Interventionszeit befand sich das 25-OHD der Verumgruppe im Normbereich, wohingegen die Placebogruppe stets einen VD-Mangel aufwies. In beiden Gruppen korrelierte der 25-OHD-Verlauf mit der jahreszeitlichen Zuordnung der Studienvisiten. Innerhalb der sechsmonatigen Interventionszeit nahm das PTH in beiden Gruppen ab, tendenziell jedoch stärker in der Verumgruppe (p=0,08). Es zeigte sich keinerlei Zusammenhang zwischen PTH und den anderen erfassten Parametern. Körpergewicht, systolischer Blutdruck und Nüchternblutzucker zeigten keine signifikanten Veränderungen. Zu Studienbeginn und in der Nachbeobachtungszeit war eine signifikante negative Korrelation zwischen 25-OHD und BMI bei allen Probanden festzustellen. Während der Interventionszeit zeigte sich dieser Zusammenhang allerdings nur bei Patienten der Placebogruppe. Der HbA1c aller Patienten mit 25-OHDSpiegeln >20 ng/ml (52,5nmol/l) war bei Studienbeginn (n=14) um 0,35% (p=0,06), nach VD-Therapie (n=39) um 0,43% (p=0,05) niedriger im Vergleich 80 zu Patienten mit 25-OHD >20 ng/ml. Eine signifikante negative Korrelation zwischen 25-OHD und HbA1c war bei Studienbeginn (r= -0,33, p=0,002), sowie nach sechsmonatiger VD-Therapie (r= -0,26, p=0,02) zu sehen. Des Weiteren zeigten nach VD-Therapie alle Patienten mit 25-OHD-Serumspiegeln >20 ng/ml (52,5 nmol/l) ein signifikant höheres C-Peptid (p=0,02), Insulin (p=0,03) und einen höheren Homa-Index (p=0,09). Nach sechs Monaten der VD-Therapie war eine signifikante positive Korrelation zwischen 25-OHD und C-Peptid (r=0.27; p=0.02), Insulin (r=0.34; p=0.01) sowie Homa-Index (r=0.25; p=0.06) zu sehen. Unsere Studie zeigt somit eine negative Korrelation zwischen 25-OHD und BMI bei Patienten mit VD-Mangel, sowie einen negativen Zusammenhang zwischen HbA1c und 25-OHD-Status. Ferner war bei Patienten mit einem 25- OHD >20 ng/ml nach sechs Monaten der VD-Therapie ein signifikanter Anstieg des C-Peptid, Insulin und Homa-Index festzustellen. Die VD-Therapie führte zu einer signifikanten Verbesserung der Insulinsekretion, während die Insulinresistenz weiterhin bestand. Interventionelle Studien mit größeren Studienpopulationen und höheren VD-Dosen sind nötig, um unsere Ergebnisse zu bestätigen.The effects of vitamin D (VD) on metabolism have been mainly studied in nondiabetics and yielded controversial results. The aim of our study was to investigate the influence of a six-month VD supplementation of 1904 IU/d on the metabolism in patients with non-insulin-requiring diabetes mellitus type 2 (DM type 2). Therefore we included 86 patients with DM type 2 in a randomized, double-blind, placebo-controlled study. During the first six months the patients received 20 drops (1904 IU/d) Vigantol oil or placebo oil (medium chain triglycerides) once a week. This was followed by six months of follow-up. At the beginning and at three month intervals 25-OHD, 1,α 25-OHD, PTH, calcium, phosphate, body weight, body mass index (BMI), blood pressure, fasting glucose, HbA1c, insulin, homeostasis model assessment-index (Homa-Index) and C-peptide were measured. At baseline all patients (n=86) showed VD deficiency with a mean 25-OHD level of 13.60 ng/ml (34 nmol/l). After 6 months of VD therapy the verum group’s (n=40) 25-OHD level had increased by a factor of 2.14 to a median of 28.40 ng/ml (71 nmol/l). The mean increase of 11.85 81 ng/ml (p<0.001) in the verum group was significantly higher than in the placebo group. During VD therapy the verum group showed 25-OHD levels in normal range, whereas the placebo group showed VD deficiency through whole study time. The 25-OHD progress correlated with the seasonal timing of study visits in both groups. The PTH tended (p=0.08) to decrease more in the verum group until the end of therapy. No association between PTH and any other parameter was seen. The changes in body weight, systolic blood pressure and fasting glucose were not significant in any group. In all patients there was a negative association between 25-OHD and BMI at baseline and during follow-up. Throughout intervention this correlation was only significant in the placebo group. The HbA1c of all patients with 25-OHD >20 ng/ml (52.5 nmol/l) was 0.35% (p=0.06) lower at baseline (n=14) and 0.43% (p=0.05) lower after therapy (n=39) than in patients with VD <20 ng/ml. A significant negative association between 25-OHD and HbA1c was seen at baseline (r= -0.33; p=0.002) and after six months of therapy (r= -0.26; p=0.02). All patients with 25- OHD levels >20 ng/ml showed higher C-peptide (p=0.02), higher insulin (p=0.03) and higher Homa-Index (p=0.09) after VD therapy. There was a significant positive association between 25-OHD and C-peptide (r=0.27; p=0.02), insulin (r=0.34; p=0.01) and Homa-Index (r=0.25; p=0.06) at the end of therapy. This study shows a negative association between 25-OHD and BMI in VD deficient patients and lower HbA1c as a function of the 25-OHD status. Furthermore C-peptide, insulin and Homa-Index increased significantly after six months of VD therapy in patients with 25-OHD >20 ng/ml. VD therapy improved insulin secretion significantly while the underlying insulin resistance persisted. Interventional studies with bigger study populations and higher VD doses are required to verify our findings

Presence of Antibodies against Bluetongue Virus (BTV) in Sheep 5 to 7.5 Years after Vaccination with Inactivated BTV-8 Vaccines

Thirty-six female sheep, previously vaccinated against Bluetongue virus serotype 8 (BTV-8) using inactivated vaccines, were included in this field study. In Germany, vaccination was compulsory in 2008 and 2009, voluntary in 2010 and early 2011, and later, was prohibited in 2011. Due to their age, eighteen sheep had been vaccinated for two or more consecutive years, while a further eighteen animals had only been vaccinated once or not at all. The sheep were blood sampled five (n = 31) to 7.5 years (n = 5) after their last vaccination. All serum samples (n = 36) were tested for BTV group-specific antibodies by an ELISA (IDScreen&reg; Bluetongue Competition assay, ID Vet). In five of the animals, the BTV-8 serotype-specific antibody titers were measured by serum neutralization (SN). The majority of sheep that were vaccinated annually for two or more years showed a positive ELISA (14/18 sheep) and a SN (two of two sheep) result 5 years after their last vaccination. Most of the sheep vaccinated fewer than twice showed a negative ELISA result 5 to 7.5 years after their last vaccination (13/18 animals). The three animals in this group tested by SN showed one negative and two positive results. This short communication is the first to describe the presence of BTV antibodies in sheep 5 to 7.5 years after vaccination with inactivated BTV-8 vaccines

Unlocking the collaborative potential of an open innovation ecosystem - the 6-factor-theory for network organizations in R&D: Paper presented at the 17th Interdisciplinary European Conference on Entrepreneurship Research (IECER), 16. - 17. October 2019, Utrecht, Netherlands

Assuming the most important innovations of the future will not be generated by new technologies but by the way in which work is organised and collaborated, network organisations become more and more important. However, the current literature reveals a gap in research on the practical design of networks. This study presents a theory that systematically describes the practical configuration possibilities for network organisations in the field of R&D. The developed theory is empirically examined by a quantitative survey at the network organisation ARENA2036, an R&D campus for the future production. The results indicate 6 factors to unlock the collaborative potential in Open Innovation Ecosystems which, from the participant's point of view, considerably promote shared innovation between different partners in network organisations