Gas hydrate drilling conducted on the European Margin

Since 1996, the Norwegian government has licensed hydrocarbon exploration in seven deep water areas on the continental slope north of the Norwegian Trough. Data acquired in this region, which is of interest to both scientists and the oil industry, provide an opportunity to improve understanding of the geology and development of the area through Quaternary times. Gas hydrates, slope stability, and geohazards are especially important topics for research near the Norwegian Trough

Untersuchung und Erarbeitung eines Leitfadens zum Dokumentenmanagement in KMU des Bauwesens

In der heutigen Informationsgesellschaft sind alle Geschäftsprozesse in einem Unternehmen geprägt durch die Verwendung der vorhandenen Informations- und Kommunikationstechnologien. Diese haben zur Folge, dass Unternehmen mit einer wahren Flut an Informationen konfrontiert werden, die von extern und intern in das Unternehmen eingetragen wurden. Die erfolgreiche Beherrschung dieser Informationsflut bildet die Basis für das effektive Arbeiten im Unternehmen. Grundvoraussetzung hierfür ist vor allem ein harmonisches Zusammenspiel zwischen Mensch ↔ Organisation ↔ Technik. Dokumentenmanagementsysteme haben sich zur Aufgabe gemacht, den Anwender bei der technologischen Bewältigung dieser Aufgabenstellung zu unterstützen. Der hier vorgestellte Artikel zeigt die Probleme auf, die während der Umsetzung eines Dokumentenmanagementsystems auftreten können und konzentriert sich dabei besonders auf Kleinen und Mittleren Unternehmen (KMU) im Bauwesen. Charakteristisch für diese ist die Schwäche die eigenen Unternehmensstrukturen betriebswirtschaftlich aufzubereiten, woraus später bei einer technologischen Umsetzung schwerwiegende Probleme resultieren. Genau an diesem Punkt setzt der vorgestellte Artikel an und versucht den Zusammenhang zwischen Organisation und Technik herauszuarbeiten, um darauf aufsetzend einen allgemeingültigen Ansatz für die Umsetzung eines Dokumentenmanagementsystems zu liefern

Olaparib monotherapy as primary treatment in unselected triple negative breast cancer

Background - The antitumor efficacy of PARP inhibitors (PARPi) for breast cancer patients harboring germline BRCA1/2 (gBRCA1/2) mutations is well established. While PARPi monotherapy was ineffective in patients with metastatic triple negative breast cancer (TNBC) wild type for BRCA1/2, we hypothesized that PARPi may be effective in primary TNBCs without previous chemotherapy exposure. Patients and methods - In the phase II PETREMAC trial, patients with primary TNBC >2 cm received olaparib for up to 10 weeks before chemotherapy. Tumor biopsies collected before and after olaparib underwent targeted DNA sequencing (360 genes) and BRCA1 methylation analyses. In addition, BRCAness (multiplex ligation-dependent probe amplification), PAM50 gene expression, RAD51 foci, tumor-infiltrating lymphocytes (TILs) and PD-L1 analyses were performed on pretreatment samples. Results - The median pretreatment tumor diameter was 60 mm (range 25-112 mm). Eighteen out of 32 patients obtained an objective response (OR) to olaparib (56.3%). Somatic or germline mutations affecting homologous recombination (HR) were observed in 10/18 responders [OR 55.6%, 95% confidence interval (CI) 33.7-75.4] contrasting 1/14 non-responders (OR 7.1%; CI 1.3-31.5, P = 0.008). Among tumors without HR mutations, 6/8 responders versus 3/13 non-responders revealed BRCA1 hypermethylation (P = 0.03). Thus, 16/18 responders (88.9%, CI 67.2-96.9), in contrast to 4/14 non-responders (28.6%, CI 11.7-54.7, P = 0.0008), carried HR mutations and/or BRCA1 methylation. Excluding one gPALB2 and four gBRCA1/2 mutation carriers, 12/14 responders (85.7%, CI 60.1-96.0) versus 3/13 non-responders (23.1%, CI 8.2-50.3, P = 0.002) carried somatic HR mutations and/or BRCA1 methylation. In contrast to BRCAness signature or basal-like subtype, low RAD51 scores, high TIL or high PD-L1 expression all correlated to olaparib response. Conclusion - Olaparib yielded a high clinical response rate in treatment-naïve TNBCs revealing HR deficiency, beyond germline HR mutations

Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer

Purpose - Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD in non-TNBC to assess the potential for PARPi in a wider group of patients with breast cancer. Methods - HRD status was established using targeted gene panel sequencing (360 genes) and BRCA1 methylation analysis of pretreatment biopsies from 201 patients with primary breast cancer in the phase II PETREMAC trial (ClinicalTrials.gov identifier: NCT02624973). HRD was defined as mutations in BRCA1, BRCA2, BRIP1, BARD1, or PALB2 and/or promoter methylation of BRCA1 (strict definition; HRD-S). In secondary analyses, a wider definition (HRD-W) was used, examining mutations in 20 additional genes. Furthermore, tumor BRCAness (multiplex ligation-dependent probe amplification), PAM50 subtyping, RAD51 nuclear foci to test functional HRD, tumor-infiltrating lymphocyte (TIL), and PD-L1 analyses were performed. Results - HRD-S was present in 5% of non-TNBC cases (n = 9 of 169), contrasting 47% of the TNBC tumors (n = 15 of 32). HRD-W was observed in 23% of non-TNBC (n = 39 of 169) and 59% of TNBC cases (n = 19 of 32). Of 58 non-TNBC and 30 TNBC biopsies examined for RAD51 foci, 4 of 4 (100%) non-TNBC and 13 of 14 (93%) TNBC cases classified as HRD-S had RAD51 low scores. In contrast, 4 of 17 (24%) non-TNBC and 15 of 19 (79%) TNBC biopsies classified as HRD-W exhibited RAD51 low scores. Of nine non-TNBC tumors with HRD-S status, only one had a basal-like PAM50 signature. There was a high concordance between HRD-S and either BRCAness, high TIL density, or high PD-L1 expression (each P Conclusion - The prevalence of HRD in non-TNBC suggests that therapy targeting HRD should be evaluated in a wider breast cancer patient population. Strict HRD criteria should be implemented to increase diagnostic precision with respect to functional HRD