Background Understanding the impact of the tumor immune microenvironment and BRCA-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer (mTNBC). In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA alterations were evaluated for association with clinical benefit with atezolizumab (A) + nab-paclitaxel (nP) vs placebo + nP in unresectable locally advanced or mTNBC. Methods Patients were randomized 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) + atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival (PFS) and overall survival (OS) were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells (TC), intratumoral CD8, stromal tumor-infiltrating lymphocytes (sTILs), and BRCA1/2 mutations. Results PD-L1 IC+ in either primary or metastatic tumor tissue was linked to PFS and OS benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and sTILs positivity were associated with PD-L1 IC+ status; A+nP vs P+nP improved outcomes were observed only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status. Conclusions Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.S

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Context] Software startups have long been a significant driver in economic growth and innovation. The on-going failure of the major number of startups calls for a better understanding of state-of-the-practice of startup activities.[Objective] With a focus on engineering perspective, this study aims at identifying the change in focus of research area and thematic concepts operating startup research. [Method] A systematic mapping study on 74 primary papers (in which 27 papers are newly selected) from 1994 to 2017 was conducted with a comparison with findings from previous mapping studies. A classification schema was developed, and the primary studies were ranked according to their rigour. [Results] We discovered that most research has been conducted within the SWEBOK knowledge areas software engineering process, management, construction, design, and requirements, with the shift of focus towards process and management areas. We also provide an alternative classification for future startup research. We find that the rigour of the primary papers was assessed to be higher between 2013-2017 than that of 1994-2013. We also find an inconsistency of characterizing startups. [Conclusions] Future work can focus on certain research themes, such as startup evolution models and human aspects, and consolidate the thematic concepts describing software startups.

Cheating in e-exams and paper exams: the perceptions of engineering students and teachers in Norway. Assessment & Evaluation in Higher Education.

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