Chapter Continuous Anything for Distributed Research Projects

International research projects involve large, distributed teams made up from multiple institutions. These teams create research artefacts that need to work together in order to demonstrate and ship the project results. Yet, in these settings the project itself is almost never in the core interest of the partners in the consortium. This leads to a weak integration incentive and consequently to last minute efforts. This in turn results in Big Bang integration that imposes huge stress on the consortium and produces only non-sustainable results. In contrast, industry has been profiting from the introduction of agile development methods backed by Continuous Delivery, Continuous Integration, and Continuous Deployment. In this chapter, we identify shortcomings of this approach for research projects. We show how to overcome those in order to adopt all three methodologies regarding that scope. We also present a conceptual, as well as a tooling framework to realise the approach as Continuous Anything. As a result, integration becomes a core element of the project plan. It distributes and shares responsibility of integration work among all partners, while at the same time clearly holding individuals responsible for dedicated software components. Through a high degree of automation, it keeps the overall integration work low, but still provides immediate feedback on the quality of the software. Overall, we found this concept useful and beneficial in several EU-funded research projects, where it significantly lowered integration effort and improved quality of the software components while also enhancing collaboration as a whole

Continuous Anything for Distributed Research Projects

International research projects involve large, distributed teams made up from multiple institutions. These teams create research artefacts that need to work together in order to demonstrate and ship the project results. Yet, in these settings the project itself is almost never in the core interest of the partners in the consortium. This leads to a weak integration incentive and consequently to last minute efforts. This in turn results in Big Bang integration that imposes huge stress on the consortium and produces only non-sustainable results. In contrast, industry has been profiting from the introduction of agile development methods backed by Continuous Delivery, Continuous Integration, and Continuous Deployment. In this chapter, we identify shortcomings of this approach for research projects. We show how to overcome those in order to adopt all three methodologies regarding that scope. We also present a conceptual, as well as a tooling framework to realise the approach as Continuous Anything. As a result, integration becomes a core element of the project plan. It distributes and shares responsibility of integration work among all partners, while at the same time clearly holding individuals responsible for dedicated software components. Through a high degree of automation, it keeps the overall integration work low, but still provides immediate feedback on the quality of the software. Overall, we found this concept useful and beneficial in several EU-funded research projects, where it significantly lowered integration effort and improved quality of the software components while also enhancing collaboration as a whole

The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>The voltage-gated potassium channel hEag1 (K_V10.1) has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general.</p> <p>Results</p> <p>Here we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells <it>in vitro</it>.</p> <p>Conclusion</p> <p>Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.</p

Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer

Brigatinib; NSCLC; Inhibidor de la tirosina quinasaBrigatinib; NSCLC; Inhibidor de la tirosina quinasaBrigatinib; NSCLC; Tyrosine kinase inhibitorBackground The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice. Methods UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes. Results Data for 104 patients (male: 43 %; median age: 53 [29–80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1–6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1–5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6–12.9) months and median OS was 23.3 (95 % CI: 16.0–NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34). Conclusions These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.This study was funded by Takeda Pharmaceuticals International AG, Zurich, Switzerland