17,595 research outputs found
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor
Trusted teammates: Commercial digital games can be effective trust-building tools
Trust is a key component of high functioning virtual work teams. This study investigates the effectiveness of a commercial digital game in developing trust in virtual teams compared to a typical virtual team icebreaker. To achieve this, we outline important trust-building aspects that a game must have and identify the commercial digital game Spaceteam as a suitable candidate. Our results show that Spaceteam is more effective at developing trust in virtual teams compared to social icebreaker, indicated by differences in trusting behaviour. We did not find differences in perception of team trust or moderating effects of dispositional trust. Our findings suggest that digital games with trust-building aspects enable the verification of early trusting beliefs through gameplay, which in turn develops trust among team members. As these games are robust against individual differences in dispositional trust, it is applicable across any team composition. Our findings support the use of digital games as viable trust-building tools for virtual work teams
Synthesis of thiourea chitosan and thiourea chitosan metal complexes and antibactarial activity
Chitosan and its derivatives are becoming increasingly important natural polymers because of their unique combination of properties like biodegradability, biocompatibility and bioactivity, in addition to attractive physical and mechanical properties. Here we wish to report the synthesis and characterization of thiourea chitosan and its metal-complex. Thiourea chitosan was prepared by the reaction of chitosan with ammonium thiocyanate in ethanol. Its metal complex was prepared by dissolving thiourea chitosan in 1% CH3COOH solution follow by adding metal salt solution. Antimicrobial activities of the complexs were evaluated against three species of bacteria. These complexs had an effect on study bacteria, which minimum inhibition concentrate (MIC) values against bacteria were 2 times lower than those of Thiourea-chitosan; the complex had higher antibacterial activity on Staphylococcus aureus than E. coli and Pseudomonas aeruginosa
A TRNSYS Simulation Case Study on Utilization of Heat Pump
This paper presents a TRNSYS simulation case study on the integration of a heat pump into a hot water and cold water storage systems for the purpose of providing heating and cooling to a residential home or office building in a tropical climate. The motivation is to utilize waste heat rejected by the heat pump.The heat pump is integrated with two water storage tanks. One is the cold water tank where heat is extracted by the heat pump and the other is the hot water which stores the heat rejected by the heat pump. The cold water tank provides cooling water for air conditioning to the building. The hot water tank is used for daily usage like bathing and washing. The sizing of the two storage tanks and the balancing of the heat transfer between the two tanks are important design factors to maintain suitable temperatures in the storage tanks. The paper discusses the performance of the integrated system under different operational modes and the effects of each storage tank size on the performance.Key words: Heat pump; Heating; Cooling; TRNSYS; Simulation; Air conditionin
Plain language summary of the TOPAZ-1 study: Durvalumab and chemotherapy for advanced biliary tract cancer
WHAT IS THIS SUMMARY ABOUT?: This is a summary describing the results of a Phase III study called TOPAZ-1. The study looked at treatment with durvalumab (a type of immunotherapy) and chemotherapy to treat participants with advanced biliary tract cancer (BTC). Advanced BTC is usually diagnosed at late stages of disease, when it cannot be cured by surgery. This study included participants with advanced BTC who had not received previous treatment, or had their cancer come back at least 6 months after receiving treatment or surgery that aimed to cure their disease. Participants received treatment with durvalumab and chemotherapy or placebo and chemotherapy. The aim of this study was to find out if treatment with durvalumab and chemotherapy could increase the length of time that participants with advanced BTC lived, compared with placebo and chemotherapy.
WHAT WERE THE RESULTS OF THE STUDY?: Participants who took durvalumab and chemotherapy had a 20% lower chance of experiencing death at any point in the study compared with participants who received placebo and chemotherapy. The side effects experienced by participants were similar across treatment groups, and less than 12% of participants in either treatment group had to stop treatment due to treatment-related side effects.
WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, these results support durvalumab and chemotherapy as a new treatment option for people with advanced BTCs. Based on the results of this study, durvalumab is now approved for the treatment of adults with advanced BTCs in combination with chemotherapy by government organizations in Europe, the United States and several other countries
The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer
BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology.
PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes.
RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%).
CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC
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