Competition between reverse water gas shift reaction and methanol synthesis from CO 2 : influence of copper particle size

Converting CO2 into value-added chemicals and fuels, such as methanol, is a promising approach to limit the environmental impact of human activities. Conventional methanol synthesis catalysts have shown limited efficiency and poor stability in a CO2/H2 mixture. To design improved catalysts, crucial for the effective utilization of CO2, an in-depth understanding of the active sites and reaction mechanism is desired. The catalytic performance of a series of carbon-supported Cu catalysts, with Cu particle sizes in the range of 5 to 20 nm, was evaluated under industrially relevant temperature and pressure, i.e. 260 °C and 40 bar(g). The CO2 hydrogenation reaction exhibited clear particle size effects up to 13 nm particles, with small nanoparticles having the lower activity, but higher methanol selectivity. MeOH and CO formation showed a different size-dependence. The TOFCO increased from 1.9 × 10−3 s−1 to 9.4 × 10−3 s−1 with Cu size increasing from 5 nm to 20 nm, while the TOFMeOH was size-independent (8.4 × 10−4 s−1 on average). The apparent activation energies for MeOH and CO formation were size-independent with values of 63 ± 7 kJ mol−1 and 118 ± 6 kJ mol−1, respectively. Hence the size dependence was ascribed to a decrease in the fraction of active sites suitable for CO formation with decreasing particle size. Theoretical models and DFT calculations showed that the origin of the particle size effect is most likely related to the differences in formate coverage for different Cu facets whose abundancy depends on particle size. Hence, the CO2 hydrogenation reaction is intrinsically sensitive to the Cu particle size

Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor

AbstractBACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts. METHODS: Included were MBC patients with a HER2-negative primary tumor, with ≥1 detectable CTC, starting a new line of treatment. CTCs were enumerated using the CellSearch system, characterized for HER2 with the CellSearch anti-HER2 phenotyping reagent, and characterized for ER mRNA expression. Primary end point was progression-free rate after 6 months (PFR6months) of endocrine treatment in HER2-positive versus HER2-negative CTC patients. RESULTS: HER2-positive CTCs were present in 29% of all patients. In the endocrine cohort (n=72), the PFR6months was 53% for HER2-positive versus 68% for HER2-negative CTC patients (P=.23). In the chemotherapy cohort (n=82), no prognostic value of HER2-positive CTCs on PFR6months was observed either. Discordances in ER status between the primary tumor and CTCs occurred in 25% of all patients but had no prognostic value in exploratory survival analyses. CONCLUSION: Discordances regarding HER2 status and ER status between CTCs and the primary tumor occurred frequently but had no prognostic impact in our MBC patient cohorts

Competition between reverse water gas shift reaction and methanol synthesis from CO2: influence of copper particle size

Converting CO2 into value-added chemicals and fuels, such as methanol, is a promising approach to limit the environmental impact of human activities. Conventional methanol synthesis catalysts have shown limited efficiency and poor stability in a CO2/H2 mixture. To design improved catalysts, crucial for the effective utilization of CO2, an in-depth understanding of the active sites and reaction mechanism is desired. The catalytic performance of a series of carbon-supported Cu catalysts, with Cu particle sizes in the range of 5 to 20 nm, was evaluated under industrially relevant temperature and pressure, i.e. 260 °C and 40 bar(g). The CO2 hydrogenation reaction exhibited clear particle size effects up to 13 nm particles, with small nanoparticles having the lower activity, but higher methanol selectivity. MeOH and CO formation showed a different size-dependence. The TOFCO increased from 1.9 × 10−3 s−1 to 9.4 × 10−3 s−1 with Cu size increasing from 5 nm to 20 nm, while the TOFMeOH was size-independent (8.4 × 10−4 s−1 on average). The apparent activation energies for MeOH and CO formation were size-independent with values of 63 ± 7 kJ mol−1 and 118 ± 6 kJ mol−1, respectively. Hence the size dependence was ascribed to a decrease in the fraction of active sites suitable for CO formation with decreasing particle size. Theoretical models and DFT calculations showed that the origin of the particle size effect is most likely related to the differences in formate coverage for different Cu facets whose abundancy depends on particle size. Hence, the CO2 hydrogenation reaction is intrinsically sensitive to the Cu particle size

Neutrophil-guided dosing of anthracycline–cyclophosphamide-containing chemotherapy in patients with breast cancer: a feasibility study

The aim of this study was to investigate whether neutrophil-guided dose escalation of anthracycline–cyclophosphamide-containing chemotherapy (ACC) for breast cancer is feasible, in order to optimize outcome. Breast cancer patients planned for 3-weekly ACC were enrolled in this study. The first treatment cycle was administered in a standard BSA-adjusted dose. The absolute neutrophil count was measured at baseline and at day 8, 11 and 15 after administration of ACC. For patients with none or mild (CTC grade 0–2) neutropenia and no other dose-limiting toxicity, we performed a 10–25 % dose escalation of the second cycle with the opportunity to a further 10–25 % dose escalation of the third cycle. Thirty patients were treated in the adjuvant setting with either FE100C (n = 23) or AC (n = 4), or in the palliative setting with FAC (n = 3). Two out of 23 patients (9 %) treated with FEC did not develop grade 3–4 neutropenia after the first treatment cycle. Dose escalation was performed in these two patients (30 % in one and 15 % in the other patient). During dose escalation, there were no complications like febrile neutropenia. No patients treated with FAC or AC could be escalated, since all of them developed grade 3–4 neutropenia. We conclude that asymptomatic grade 3–4 neutropenia is likely to be achieved in the majority of patients with breast cancer treated with ACC according to presently advocated BSA-based dose levels. Escalation of currently advocated ACC doses without G-CSF, with a target of grade 3–4 neutropenia, is feasible, but only possible in a small proportion of patients. EudraCT 2010-020309-33

Particle Size Effects of Carbon Supported Nickel Nanoparticles for High Pressure CO2 Methanation

Supported nickel nanoparticles are promising catalysts for the methanation of CO2. The role of nickel particle size on activity and selectivity in this reaction is a matter of debate. We present a study of metal particle size effects on catalytic stability, activity and selectivity, using nickel on graphitic carbon catalysts. Increasing the Ni particle size from 4 to 8 nm led to a higher catalytic activity, both per gram of nickel and normalized surface area. However, the apparent activation energy remained the same (∼105 kJ mol−1). Comparing experiments at atmospheric to 30 bar pressure demonstrates the importance of testing under industrially relevant pressures; the highest selectivity is obtained at high CO2 conversions and pressures. Finally, the selectivity was particle size-dependent. The largest particles were not only most active but also most selective to methane. With this work we contribute to the ongoing debate about Ni particle size effects in CO2 methanation

Unlocking Synergy in Bimetallic Catalysts by Core-Shell Design

Extending the toolbox from mono- to bimetallic catalysts is key in realizing efficient chemical processes. Traditionally, the performance of bimetallic catalysts featuring one active and one selective metal is optimized by varying the metal composition, often resulting in a compromise between the catalytic properties of the two metals. Here we show that by designing the atomic distribution of bimetallic Au-Pd nanocatalysts, we obtain a synergistic catalytic performance in the industrially relevant selective hydrogenation of butadiene. Our single crystalline Au-core Pd-shell nanorods were up to 50 times more active than their alloyed and monometallic counterparts, while retaining high selectivity. We find a shell thickness dependent catalytic activity, indicating that not only the nature of the surface but also several sub-surface layers play a crucial role in the catalytic performance, and rationalize this finding using density-functional-theory calculations. Our results open up a novel avenue for the structural design of bimetallic catalysts.</div

A cost-consequence model of using the 21-gene assay to identify patients with early-stage node-positive breast cancer who benefit from adjuvant chemotherapy in the Netherlands

Patients with early-stage hormone receptor positive, human epidermal growth factor receptor-2 (HER2) negative invasive breast cancer with 1–3 positive lymph nodes (N1) often undergo surgical excisions followed by adjuvant chemotherapy (ACT). Many patients have no benefit from ACT and receive unnecessary, costly treatment often associated with short- and long-term adverse events (AEs). Gene expression profiling (GEP) assays, such as the 21-gene assay (i.e. the Oncotype DX assay), can identify patients at higher risk for recurrence who may benefit from ACT. However, the budgetary consequence of using the Oncotype DX assay versus no GEP testing in the Netherlands is unknown. Our study therefore assessed it using a cost-consequence model. A validated model was used to create the N1 model. The model compared the costs and consequences of using the Oncotype DX assay versus no GEP testing and MammaPrint, and subsequent ACT use with corresponding costs for chemotherapy, treatment of AEs, productivity losses, GEP testing, and treatment of recurrences, according to the Oncotype DX results. The model time horizon was 5 years. Costs for the total population amounted to €8.0 million (M), €16.2 M, and €9.5 M, and cost per patient amounted to €13,540, €27,455, and €16,154 for using the Oncotype DX assay, no GEP testing, and MammaPrint, respectively. Total cost savings of using the Oncotype DX assay amounted to €8.2 M versus no GEP testing and €1.5 M versus MammaPrint. Using the Oncotype DX assay would result in fewer patients receiving ACT and thus fewer AEs, sick days, and hospitalizations, leading to overall cost savings compared with no GEP testing and MammaPrint. Implementing Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system. Early-stage invasive breast cancer patients often undergo surgery followed by adjuvant chemotherapy. However, many of these patients have no benefit from adjuvant chemotherapy and thus receive unnecessary and costly treatment often associated with side-effects. Patients who may benefit from adjuvant chemotherapy can be identified by analyzing the genomic profile of the patients’ tumors using a molecular diagnostic test called the 21-gene assay (also known as Oncotype DX assay). However, the budgetary consequences of using Oncotype DX for this purpose in the Netherlands are currently unknown and, therefore, assessed using a health-economic model. The model compared the costs and consequences of using the Oncotype DX assay versus no molecular diagnostic testing and an alternative molecular diagnostic test called MammaPrint. The three diagnostic testing strategies resulted in different costs in terms of several different costing categories and were compared with one another. The total costs were lowest for the diagnostic strategy using the Oncotype DX assay, as it would result in fewer patients receiving adjuvant chemotherapy compared with no molecular diagnostic testing and MammaPrint. Implementing the Oncotype DX assay as a molecular diagnostic test can identify the right patient who benefits from chemotherapy (prevent over- and undertreatment) and lead to cost-savings, reducing the clinical and economic burden on the patient and Dutch healthcare system.</p

Unlocking synergy in bimetallic catalysts by core–shell design

Extending the toolbox from mono- to bimetallic catalysts is key in realizing efficient chemical processes1. Traditionally, the performance of bimetallic catalysts featuring one active and one selective metal is optimized by varying the metal composition1–3, often resulting in a compromise between the catalytic properties of the two metals4–6. Here we show that by designing the atomic distribution of bimetallic Au–Pd nanocatalysts, we obtain a synergistic catalytic performance in the industrially relevant selective hydrogenation of butadiene. Our single-crystalline Au-core Pd-shell nanorods were up to 50 times more active than their alloyed and monometallic counterparts, while retaining high selectivity. We find a shell-thickness-dependent catalytic activity, indicating that not only the nature of the surface but also several subsurface layers play a crucial role in the catalytic performance, and rationalize this finding using density functional theory calculations. Our results open up an alternative avenue for the structural design of bimetallic catalysts

Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment

Purpose: Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics. Methods: In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated. Results: A strong and highly significant correlation (r=-0.72; P < .001) was found between the exposures of dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration-time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = -0.70; P < .001). In a single patient using the potent CYP2D6 inhibitor paroxetine, the low endoxifen concentration was accurately predicted by dextromethorphan exposure. Conclusion: Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies