Efficient deployment of satellite navigation systems in Finland : Action plan 2017–2020

Along with digitalisation, satellite navigation has become an important part of our everyday life. For example, the operation of power and communication networks and transport services requires satellite positioning and accurate timing. The satellite navigation sector is indeed growing and, in 2017, the European Commission estimated the value of the satellite navigation sector at over EUR 70 billion. With the growth of automated transport and the development of 5G and IoT, the market value is estimated to rise to about EUR 195 billion by 2025. Europe is undergoing an important phase in the development of satellite navigation as the Initial Services of Galileo, the European Global Navigation Satellite System (GNSS), have recently been introduced and the system is expected to be in full operation in 2020. Over the past few decades, Finnish experts and Finnish expertise have been part of several space and satellite projects. In addition, the first satellites of our own have been developed over the past few years and Finland is indeed becoming a new operator in the satellite markets. This Action plan describes the current state of satellite navigation systems and how they are deployed in the different sectors of our society, especially in automated transport. At the same time, it describes the current model of Finnish space administration and the pressure to reform it. At the end of the Action plan, 17 concrete measures are proposed to promote the deployment of satellite navigation especially at a national level. The Action plan is part of one of the key projects in Juha Sipilä’s Government Programme: A growth environment will be created for digital business operations. The work has been carried out by listening to a wide range of actors in the sector. The Action plan aims to ensure that satellite navigation systems are deployed in all sectors of society in all of Finland. Its key goals in terms of the future are the following: making Finland one of the leading countries in the deployment of satellite systems and enhancing the preconditions for the current high quality of space research in Finland, enhancing the deployment of satellite data in business activities and service provision, ensuring the quality of positioning and the deployment of satellite navigation systems in all Arctic regions, promoting the deployment of small satellites, and determining the need and possibilities to establish a space administration in Finland

Satelliittinavigointijärjestelmien tehokas hyödyntäminen Suomessa. Toimenpideohjelma 2017–2020

Digitalisaation myötä satelliittinavigoinnista on tullut merkittävä osa tavallista arkeamme. Esimerkiksi sähköverkkojen, tietoliikenneverkkojen sekä liikenteen palvelujen toiminta edellyttää satelliittipaikannusta ja tarkkaa aikatietoa. Satelliittinavigoinnin markkinat ovatkin kasvussa ja Euroopan komissio on arvioinut niiden arvoksi vuonna 2017 yli 70 miljardia euroa, jonka odotetaan kasvavan automaattiliikenteen, 5G:n ja IoT:n kehityksen vuoksi 195 miljardiin euroon vuoteen 2025 asti. Euroopassa eletään tärkeää vaihetta satelliittinavigoinninkehityksessä, sillä eurooppalainen globaali Galileo-satelliittinavigointijärjestelmään on juuri otettu käyttöön ensimmäiset palvelut ja sen on tarkoitus olla täysimääräisessä käytössä vuonna 2020. Suomalaiset ja suomalainen osaaminen ovat olleet mukana lukuisissa viime vuosikymmenten avaruus- ja satelliittihankkeissa. Lisäksi viime vuosien aikana Suomessa on kehitetty ensimmäistä kertaa omia satelliitteja ja valtiostamme onkin kehittymässä uusi toimija satelliittimarkkinoille. Tämä toimenpideohjelma kuvaa satelliittinavigointijärjestelmien nykytilaa sekä niiden hyödyntämistä yhteiskuntamme eri osa-alueilla, erityisesti automaattiliikenteessä. Samalla kuvataan Suomen avaruushallinnon nykymallia ja siihen kohdistuvia muutospaineita. Toimenpideohjelman lopuksi esitetään 17 konkreettista toimenpidettä, joilla pyritään edistämään satelliittinavigoinnin hyödyntämistä erityisesti kansallisella tasolla. Toimenpideohjelma on osa Juha Sipilän hallitusohjelman kärkihanketta: Rakennetaan digitaalisen liiketoiminnan kasvuympäristö. Työ on tehty laajasti alaa kuullen. Toimenpideohjelman tavoitteena on varmistaa satelliittinavigointijärjestelmien hyödyntäminen koko Suomessa yhteiskunnan kaikilla sektoreilla. Keskeisimmät tavoitteet tulevaisuutta ajatellen ovat: Suomen nostaminen kärkimaaksi satelliittijärjestelmien hyödyntämisessä ja nykyisen korkealaatuisen kotimaisen avaruustutkimustoiminnan edellytysten vahvistaminen, edistää satelliittitiedon hyödyntämistä liiketoiminnassa ja palvelujen tarjonnassa, varmistaa paikannuksen laatu ja satelliittinavigointijärjestelmien hyödyntäminen kaikkialla arktisilla alueilla, edistää piensatelliittien hyödyntämistä ja selvittää tarve ja mahdollisuus perustaa Suomeen avaruushallint

HE4 in the evaluation of tumor load and prognostic stratification of high grade serous ovarian carcinoma

Objective Human epididymis protein 4 (HE4) is a validated, complementary biomarker to cancer antigen 125 (CA125) for high grade serous ovarian carcinoma (HGSC). Currently, there are insufficient data on the utility of longitudinal HE4 measurement during HGSC treatment and follow up. We set to provide a comprehensive analysis on the kinetics and prognostic performance of HE4 with serial measurements during HGSC treatment and follow up. Methods This prospective study included 143 patients with advanced HGSC (ClinicalTrials.gov identifier: NCT01276574). Serum CA125 and HE4 were measured at baseline, before each cycle of chemotherapy and during follow up until first progression. Baseline biomarker values were compared to the tumor load assessed during surgery and to residual disease. Biomarker nadir values and concentrations at progression were correlated to survival. Results The baseline HE4 concentration distinguished patients with a high tumor load from patients with a low tumor load assessed during surgery (pPeer reviewe

Combined ASRGL1 and p53 immunohistochemistry as an independent predictor of survival in endometrioid endometrial carcinoma

Objective. In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods. A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results. A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (295%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P <0.001) of dying of EEC compared to the low-risk group. Conclusions. P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe

Open Source Infrastructure for Health Care Data Integration and Machine Learning Analyses

PURPOSE We have created a cloud-based machine learning system (CLOBNET) that is an open-source, lean infrastructure for electronic health record (EHR) data integration and is capable of extract, transform, and load (ETL) processing. CLOBNET enables comprehensive analysis and visualization of structured EHR data. We demonstrate the utility of CLOBNET by predicting primary therapy outcomes of patients with high-grade serous ovarian cancer (HGSOC) on the basis of EHR data. MATERIALS AND METHODS CLOBNET is built using open-source software to make data preprocessing, analysis, and model training user friendly. The source code of CLOBNET is available in GitHub. The HGSOC data set was based on a prospective cohort of 208 patients with HGSOC who were treated at Turku University Hospital, Finland, from 2009 to 2019 for whom comprehensive clinical and EHR data were available. RESULTS We trained machine learning (ML) models using clinical data, including a herein developed dissemination score that quantifies the disease burden at the time of diagnosis, to identify patients with progressive disease (PD) or a complete response (CR) on the basis of RECIST (version 1.1). The best performance was achieved with a logistic regression model, which resulted in an area under receiver operating characteristic curve (AUROC) of 0.86, with a specificity of 73% and a sensitivity of 89%, when it classified between patients who experienced PD and CR. CONCLUSION We have developed an open-source computational infrastructure, CLOBNET, that enables effective and rapid analysis of EHR and other clinical data. Our results demonstrate that CLOBNET allows predictions to be made on the basis of EHR data to address clinically relevant questions.Peer reviewe

HE4 in the evaluation of tumor load and prognostic stratification of high grade serous ovarian carcinoma

Objective Human epididymis protein 4 (HE4) is a validated, complementary biomarker to cancer antigen 125 (CA125) for high grade serous ovarian carcinoma (HGSC). Currently, there are insufficient data on the utility of longitudinal HE4 measurement during HGSC treatment and follow up. We set to provide a comprehensive analysis on the kinetics and prognostic performance of HE4 with serial measurements during HGSC treatment and follow up. Methods This prospective study included 143 patients with advanced HGSC (ClinicalTrials.gov identifier: NCT01276574). Serum CA125 and HE4 were measured at baseline, before each cycle of chemotherapy and during follow up until first progression. Baseline biomarker values were compared to the tumor load assessed during surgery and to residual disease. Biomarker nadir values and concentrations at progression were correlated to survival. Results The baseline HE4 concentration distinguished patients with a high tumor load from patients with a low tumor load assessed during surgery (p<.0001). The baseline CA125 level was not associated with tumor load to a similar extent (p=.067). At progression, the HE4 level was an independent predictor of worse survival in the multivariate analysis (p=.002). All patients that were alive 3 years post-progression had a serum HE4 concentration below 199.20 pmol/l at the 1st recurrence. Conclusion HE4 is a feasible biomarker in the treatment monitoring and prognostic stratification of patients with HGSC. Specifically, the serum level of HE4 at first relapse was associated with the survival of patients and it may be a useful complementary tool in the selection of second line treatments. This is to the best of our knowledge the first time this finding has been reported

Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality

Erythropoietin producing hepatocellular (Eph) receptors and their membrane-bound ligands ephrins are variably expressed in epithelial cancers, with context-dependent implications to both tumor-promoting and-suppressive processes in ways that remain incompletely understood. Using ovarian cancer tissue microarrays and longitudinally collected patient cells, we show here that ephrinA5/EFNA5 is specifically overexpressed in the most aggressive high-grade serous carcinoma (HGSC) subtype, and increased in the HGSC cells upon disease progression. Among all the eight ephrin genes, high EFNA5 expression was most strongly associated with poor overall survival in HGSC patients from multiple independent datasets. In contrast, high EFNA3 predicted improved overall and progression-free survival in The Cancer Genome Atlas HGSC dataset, as expected for a canonical inducer of tumor-suppressive Eph receptor tyrosine kinase signaling. While depletion of either EFNA5 or the more extensively studied, canonically acting EFNA1 in HGSC cells increased the oncogenic EphA2-S897 phosphorylation, EFNA5 depletion left unaltered, or even increased the ligand-dependent EphA2-Y588 phosphorylation. Moreover, treatment with recombinant ephrinA5 led to limited EphA2 tyrosine phosphorylation, internalization and degradation compared to ephrinA1. Altogether, our results suggest a unique function for ephrinA5 in Eph-ephrin signaling and highlight the clinical potential of ephrinA5 as a cell surface biomarker in the most aggressive HGSCs.Peer reviewe

Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status

ObjectiveA major challenge in the treatment of platinum-resistant high-grade serous ovarian cancer (HGSOC) is lack of effective therapies. Much of ongoing research on drug candidates relies on HGSOC cell lines that are poorly documented. The goal of this study was to screen for effective, state-of-the-art drug candidates using primary HGSOC cells. In addition, our aim was to dissect the inhibitory activities of Wee1 inhibitor adavosertib on primary and conventional HGSOC cell lines. MethodsA comprehensive drug sensitivity and resistance testing (DSRT) on 306 drug compounds was performed on three patient-derived genetically unique HGSOC cell lines and two commonly used ovarian cancer cell lines. The effect of adavosertib on the cell lines was tested in several assays, including cell-cycle analysis, apoptosis induction, proliferation, wound healing, DNA damage, and effect on nuclear integrity. ResultsSeveral compounds exerted cytotoxic activity toward all cell lines, when tested in both adherent and spheroid conditions. In further cytotoxicity tests, adavosertib exerted the most consistent cytotoxic activity. Adavosertib affected cell-cycle control in patient-derived and conventional HGSOC cells, inducing G2/M accumulation and reducing cyclin B1 levels. It induced apoptosis and inhibited proliferation and migration in all cell lines. Furthermore, the DNA damage marker gamma H2AX and the number of abnormal cell nuclei were clearly increased following adavosertib treatment. Based on the homologous recombination (HR) signature and functional HR assays of the cell lines, the effects of adavosertib were independent of the cells' HR status. ConclusionOur study indicates that Wee1 inhibitor adavosertib affects several critical functions related to proliferation, cell cycle and division, apoptosis, and invasion. Importantly, the effects are consistent in all tested cell lines, including primary HGSOC cells, and independent of the HR status of the cells. Wee1 inhibition may thus provide treatment opportunities especially for patients, whose cancer has acquired resistance to platinum-based chemotherapy or PARP inhibitors.Peer reviewe