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BACKGROUND Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin -- an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation -- to standard chemotherapy would prolong overall survival in this population. METHODS We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively). Allogeneic transplantation was allowed. The primary end point was overall survival. RESULTS A total of 717 patients underwent randomization; 360 were assigned to the midostaurin group, and 357 to the placebo group. The FLT3 subtype was ITD (high) in 214 patients, ITD (low) in 341 patients, and TKD in 162 patients. The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts but not with respect to sex (51.7% in the midostaurin group vs. 59.4% in the placebo group were women, P = 0.04). Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P = 0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P = 0.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of midostaurin was consistent across all FLT3 subtypes. The rate of severe adverse events was similar in the two groups. CONCLUSIONS The addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [ABSTRACT FROM AUTHOR]

Some lines of evidence have shown that sensory input, especially related to vestibular and somatosensory stimulation, may reduce the symptoms related to simulator sickness and increase the sense of presence in VR. The present study aims at understanding how mechanical vibration and auditory stimulation can be used to improve user experience in the context of VR mediated by head-mounted displays. Four different groups comprising a total of 80 participants were tested under different conditions of sensory input (visual and vibration, visual-auditory, combined visual-auditory and vibratory, and visual only), during a VR roller-coaster experience. No significant differences in simulator sickness were found between the groups exposed to seat vibration and/or audio. However, sense of presence showed to be increased when vibratory stimuli were included. Post-hoc analyses showed that female users but not male ones, experienced an increase of sense of presence when vibratory stimulation was used. Practitioner summary: The study showed that including sound or vibration stimulation during VR experience does not reduce simulator sickness. However, sense of presence is promoted by vibratory stimulation. Post-hoc analyses showed that female users experienced an increase of sense of presence by vibratory stimulation, but not male ones.

This research investigated the organizational challenges related to the development and implementation of virtual reality (VR) technology for operation in a conservative heavy machinery industry. The incorporation of a VR solution for heavy machinery equipment enhanced the safety and convenience of operation under dangerous work conditions. However, the development and implementation processes faced challenges. Furthermore, the adoption of the solution by users was perceived to be slower than anticipated. We aimed to explore the main challenges that the developer organization faced and how it also influenced user organizations. Due to the exploratory nature of the research, qualitative analysis was chosen, interviews were conducted, and thematic analysis was applied. The themes and subthemes were identified and discussed. The results showed the existence of challenges related to technology maturity, managerial challenges regarding communication and support coordination, workload, and multiple stakeholder management. The findings emphasize the importance of attending to the existing and potential organizational challenges before and throughout technological innovation. Theoretical and managerial implications are discussed, and a future research agenda is suggested., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saghafian, Laumann and Skogstad.)

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54-0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Sense of presence has been often explored in the context of virtual reality (VR) and immersive visual technologies; however, standardized and objective measures of the sense of presence have been difficult to find. Studies attempting to find physiological correlates of sense presence using electroencephalography (EEG) have reported mixed results. In the present study, we used brain event-related potentials (ERPs) elicited by auditory stimuli to identify an objective physiological index of sense of presence during VR, attempting to replicate the findings of previous studies and explain the heterogeneity of results reported in the literature. Participants in our experiment were asked to experience an immersive virtual environment using a modern head-mounted display while passively hearing task-irrelevant frequent standard and infrequent deviant tones as in a classic auditory oddball paradigm. Subsequently, they were asked to complete a battery of questionnaires aimed to estimate their sense of presence during the VR. EEG and questionnaire data from three-seventh participants were analyzed. ERP components evoked by the auditory stimuli were then analyzed. Late ERP components (after 450 ms from stimulus onset) registered over central brain areas were associated with the sense of presence as measured with questionnaires, while earlier components were not associated with presence. The use of different questionnaires and the content of the VR environment may both be a plausible explanation for heterogeneous results as reported in previous studies. The present study showed that late ERP components recorded over the central brain may represent good electrophysiological correlates of the subjective sense of presence., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

This paper provides a stagewise overview of the important issues that play a role in technology adoption and use in organizations. In the current literature, there is a lack of consistency and clarity about the different stages of the technology adoption process, the important issues at each stage, and the differentiation between antecedents, after-effects, enablers, and barriers to technology adoption. This paper collected the relevant issues in technology adoption and use, mentioned dispersedly and under various terminologies, in the recent literature. The qualitative literature review was followed by thematic analysis of the data. The resulting themes were organized into a thematic map depicting three stages of the technology adoption process: pre-change, change, and post-change. The relevant themes and subthemes at each stage were identified and their significance discussed. The themes at each stage are antecedents to the next stage. All the themes of the pre-change and change stages are neutral, but the way they are managed and executed makes them enablers or barriers in effect. The thematic map is a continuous cycle where every round of technology adoption provides input for the subsequent rounds. Based on how themes have been addressed and executed in practice, they can either enhance or impair the subsequent technology adoption. This thematic map can be used as a qualitative framework by academics and practitioners in the field to evaluate technological changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saghafian, Laumann and Skogstad.)

This study investigates how Human Factors (HF) is applied when designing and developing Immersive Visual Technologies (IVT), including Augmented Reality, Mixed Reality, and Virtual Reality. We interviewed fourteen people working at different organizations, that develop IVT applications in the Nordic region. We used thematic analysis to derive themes from the interviews. The results showed an insufficient knowledge and application of HF in IVT development, due to the lack of awareness of both scope and significance of HF, resource allocation strategy, market inertia, stakeholder's involvement, standardization of HF application and IVT uses, and technology maturity. This situation could be improved by allocating experts, adjusting organizational strategy to balance resource allocation, training developers and user organizations to raise awareness and to encourage co-creative design and knowledge sharing, create a sense of ownership amongst stakeholders, and ensure the usefulness of the technology to the user's work., Competing Interests: TAS was employed by company CrossControl AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saghafian, Sitompul, Laumann, Sundnes and Lindell.)

Adolescents and young adults (AYAs) with acute lymphoblastic leukemia have improved outcomes when treated with pediatric-inspired regimens. CALGB 10403 was the largest prospective study to evaluate the feasibility of using a pediatric regimen in AYAs with acute lymphoblastic leukemia up to 40 years of age. This article presents the toxicity events observed in the CALGB 10403 study and compares these toxicities vs those observed among AYAs treated on the same arm of the companion Children's Oncology Group (COG) AALL0232 study. Toxicities in CALGB 10403 were similar to those observed in COG AALL0232. Some grade 3 to 4 adverse events were more often reported in CALGB 10403 compared with COG AALL0232 (hyperglycemia, hyperbilirubinemia, transaminase elevation, and febrile neutropenia). Adverse events correlated with body mass index ≥30 kg/m2 and some with increasing age. The mortality rate in CALGB 10403 was low (4%) and similar to that in the COG AALL0232 trial. A caveat to this analysis is that only 39% of CALGB 10403 patients completed all planned protocol treatment. In COG AALL0232, although 74% of patients aged <18 years completed treatment, only 57% of patients aged ≥18 years completed treatment. This scenario suggests that issues associated with age and treating physician may be a factor. Due to its improved survival rates compared with historical controls, the CALGB 10403 regimen is now a standard of care. The hope is that the rate of protocol completion will increase as more familiarity is gained with this regimen. These trials were registered at www.clinicaltrials.gov as #NCT00558519 (CALGB 10403) and #NCT00075725 (COG AALL0232)., (© 2021 by The American Society of Hematology.)

The aim of this research was to explore trainees' perceptions and evaluation of Virtual Reality fire extinguisher training. Virtual Reality technology is being adopted by many industries for various purposes including safety training for safety critical industries. The future direction of Virtual Reality training requires an understanding of trainees' evaluation of it; this fact motivated this research. Data were collected from 85 participants using a questionnaire after the training. Observation notes were taken to provide a better understanding of the context. Qualitative research with a thematic analysis was used to analyze the data. The results of this analysis revealed that the most salient themes reflect on issues surrounding the realism of the Virtual Reality simulation, namely different emotional and bodily experiences during the training, while the benefits of the training (health, safety, environmental advantages, efficiency and convenience, repeatability and variety of scenarios) make it a good supplement. Nevertheless, improved realism is needed to make it more effective and enhance transfer and acceptance. This study encourages the consideration of important matters (such as realism and emotions) when using Virtual Reality for fire training. It also describes the positive perceptions of this type of training (repeatability of training, safety and environmental concerns)., (Copyright © 2020 Saghafian, Laumann, Akhtar and Skogstad.)