Discovering Business Area Effects to Process Mining Analysis Using Clustering and Influence Analysis

A common challenge for improving business processes in large organizations is that business people in charge of the operations are lacking a fact-based understanding of the execution details, process variants, and exceptions taking place in business operations. While existing process mining methodologies can discover these details based on event logs, it is challenging to communicate the process mining findings to business people. In this paper, we present a novel methodology for discovering business areas that have a significant effect on the process execution details. Our method uses clustering to group similar cases based on process flow characteristics and then influence analysis for detecting those business areas that correlate most with the discovered clusters. Our analysis serves as a bridge between BPM people and business, people facilitating the knowledge sharing between these groups. We also present an example analysis based on publicly available real-life purchase order process data.Comment: 12 pages. Paper accepted in 23rd International Conference on Business Information Systems (BIS 2020) to be published in a proceedings edition of the Lecture Notes in Business Information Processin

Efficacy and safety of rociletinib versus chemotherapy in patients with EGFR-mutated NSCLC: the results of TIGER-3, a phase 3 randomized study

Introduction: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR T790M and common EGFR-activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs. Methods: Patients with advanced or metastatic EGFR-mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). Results: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07, p = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively). Conclusions: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced EGFR-mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point

Experimental and numerical investigation of hydrogen gas auto-ignition

ABSTRACT This paper describes hydrogen self-ignition as a result of the formation of a shock wave in front of a high-pressure hydrogen gas propagating in the tube and the semi-confined space, for which the numerical and experimental investigation was done. An increase in the temperature behind the shock wave leads to the ignition on the contact surface of the mixture of combustible gas with air. The required condition of combustible self-ignition is to maintain the high temperature in the mixture for a time long enough for inflammation to take place. Experimental technique was based on a highpressure chamber inflating with hydrogen, burst disk failure and pressurized hydrogen discharge into tube of round or rectangular cross section filled with air. A physicochemical model involving the gasdynamic transport of a viscous gas, the detailed kinetics of hydrogen oxidation, k-ω differential turbulence model, and the heat exchange was used for calculations of the self-ignition of high-pressure hydrogen. The results of our experiments and model calculations show that self-ignition in the emitted jet takes place. The stable development of self-ignition naturally depends on the orifice size and the pressure in the vessel, a decrease in which leads to the collapse of the ignition process. The critical conditions are obtained

Modern agglutinated foraminifera from the Hovgård ridge, fram strait, west of Spitsbergen: Evidence for a deep bottom current

Deep-water agglutinated foraminifera on the crest of the Hovgârd Ridge, west of Spitsbergen, consist mostly of large tubular astrorhizids. At a boxcore station collected from the crest of Hovgârd Ridge at a water depth of 1169 m, the sediment surface was covered with patches of large (1 mm diameter) tubular forms, belonging mostly to the species Astrorhiza crassatina Brady, with smaller numbers of Saccorhiza, Hyperammina, and Psammosiphonella. Non-tubutar species consisted mainly of opportunistic forms, such as Psammosphaera and Reophax. The presence of large suspension-feeding tubular genera as well as opportunistic forms point to the presence of deep currents at this locality that are strong enough to disturb the benthic fauna. This is confirmed by data obtained from sediment echosounding, which exhibit lateral variation in relative sedimentation rates within the Pleistocene sedimentary drape covering the ridge, indicative of winnowing in a south-easterly direction

Neonates’ responses to repeated exposure to a still face

The main aims of the study were to examine whether human neonates' responses to communication disturbance modelled by the still-face paradigm were stable and whether their responses were affected by their previous experience with the still-face paradigm.The still face procedure, as a laboratory model of interpersonal stress, was administered repeatedly, twice, to 84 neonates (0 to 4 day olds), with a delay of an average of 1.25 day.Frame-by-frame analysis of the frequency and duration of gaze, distressed face, crying, sleeping and sucking behaviours showed that the procedure was stressful to them both times, that is, the still face effect was stable after repeated administration and newborns consistently responded to such nonverbal violation of communication. They averted their gaze, showed distress and cried more during the still-face phase in both the first and the second administration. They also showed a carry-over effect in that they continued to avert their gaze and displayed increased distress and crying in the first reunion period, but their gaze behaviour changed with experience, in the second administration. While in the first administration the babies continued averting their gaze even after the stressful still-face phase was over, this carry-over effect disappeared in the second administration, and the babies significantly increased their gaze following the still-face phase.After excluding explanations of fatigue, habituation and random effects, a self-other regulatory model is discussed as a possible explanation for this pattern

The impact of COVID-19 on the management of European protected areas and policy implications

The COVID-19 pandemic led to many European countries imposing lockdown measures and limiting people’s movement during spring 2020. During the summer 2020, these strict lockdown measures were gradually lifted while in autumn 2020, local restrictions started to be re-introduced as a second wave emerged. After initial restrictions on visitors accessing many Nature Protected Areas (PAs) in Europe, management authorities have had to introduce measures so that all users can safely visit these protected landscapes. In this paper, we examine the challenges that emerged due to COVID-19 for PAs and their deeper causes. By considering the impact on and response of 14 popular European National and Nature Parks, we propose tentative longer-term solutions going beyond the current short-term measures that have been implemented. The most important challenges identified in our study were overcrowding, a new profile of visitors, problematic behavior, and conflicts between different user groups. A number of new measures have been introduced to tackle these challenges including information campaigns, traffic management, and establishing one-way systems on trail paths. However, measures to safeguard public health are often in conflict with other PA management measures aiming to minimize disturbance of wildlife and ecosystems. We highlight three areas in which management of PAs can learn from the experience of this pandemic: managing visitor numbers in order to avoid overcrowding through careful spatial planning, introducing educational campaigns, particularly targeting a new profile of visitors, and promoting sustainable tourism models, which do not rely on large visitor numbers.European Research Council (ERC) under the European Union’s Horizon 2020 research programme (Project FIDELIO, grant agreement no. 802605)

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal\u2013epithelial transition factor (MET) amplification, epithelial\u2013mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation. Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC

РАСПРЕДЕЛЕНИЕ ГЕНОТИПОВ И ВСТРЕЧАЕМОСТЬ АЛЛЕЛЕЙ ГЕНА АЛЬДОСТЕРОН-СИНТАЗЫ У БОЛЬНЫХ АБДОМИНАЛЬНЫМ ОЖИРЕНИЕМ

We observed 140 patients with abdominal obesity (AO) (IDF, 2005), the residents of St. Petersburg (44.6 ± 0.6 years). Metabolic syndrome (MS) (IDF, 2005) was diagnosed in 49.2% of patients with AO. The most frequent component of MS in patients with AO was arterial hypertension (AH). The distribution of genotypes and -alleles of the aldosterone-synthase gene in patients with AO and in the comparison group (56 subjects without AO, 41.0 ± 1.1 years) didn't differ (p> 0.05). Levels of both systolic and diastolic blood pressure (BP) were higher in carriers of -344T allele of aldosterone-synthase gene. Plasma renin activity, plasma aldosterone and glucose levels, anthropometric parameters, serum blood lipids and carbohydrate metabolism indices in obese patients with different genotypes of aldosterone-synthase gene didn't differ. -344T allele of aldosterone-synthase gene in patients with AO is associated with the increased risk of AH.Обследованы 140 больных абдоминальным ожирением (АО) (IDF, 2005), жителей Санкт-Петербурга (44,6±0,6 года). У 49,2 % пациентов с АО был выявлен метаболический синдром (МС) (IDF, 2005). Самым частым компонентом МС у больных АО была артериальная гипертензия (АГ). Распределение генотипов и встречаемость аллелей гена альдостерон-синтазы у больных АО и в группе сравнения (56 обследованных без АО, 41,0±1,1 года) не различалось (р>0,05). Уровни артериального давления (АД), как систолического, так и диастолического, были выше у носителей -344Т-алле-ля гена альдостерон-синтазы. Активность ренина плазмы крови, уровень альдостерона плазмы крови, антропометрические параметры, показатели липидного спектра сыворотки крови и углеводного обмена у пациентов с АО, носителей различных генотипов гена альдостерон-синтазы, не различались. Носительство -344Т-аллеля гена альдостеронсинтазы у больных АО ассоциировано с увеличением риска развития артериальной гипертензии