Background Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. https://www.selleckchem.com/products/sodium-2-1h-indol-3-ylacetate.html We compared efficacies of both regimens in this randomised phase II study. Patients and methods Patients with wild-type KRAS exon 2 mCRC previously treated with fluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (11) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety. Results From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44-0.94, P less then 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44-1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%). Conclusion Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.Background and purpose Renal Resistive Index (RRI) and Venous Impedance Index (VII) might be of additional value for diagnosing Acute Kidney Injury (AKI). The purpose of this study was to assess the diagnostic accuracy of RRI and VII for AKI. Materials and methods In the prospective Simple Intensive Care Studies-II (NCT03577405), we measured RRI and VII in acutely admitted adult intensive care patients within 24 h of admission. AKI was defined by the Kidney Disease Improving Global Outcome (KDIGO) criteria. The primary outcome was persistent AKI, defined as non-resolved AKI on day three. We tested specificity, sensitivity and diagnostic accuracy of both RRI and VII for persistent AKI. Results In total, 371 patients were included of whom 123 patients (33%) had persistent AKI. RRI and VII did not differ between patients with and those without persistent AKI (p = .08 and p = .59). RRI had a moderate specificity (72%, 95%CI 66-78%) and low sensitivity (32%, 95%CI 24-41%) and VII had high sensitivity (93%, 95%CI 85-98%) and low specificity (11%, 95%CI 6-16%) for persistent AKI. Overall diagnostic accuracy of RRI and VII was moderate. Conclusions In acutely admitted critically ill patients, measures of renal perfusion by renal ultrasound were not different between patients with and without AKI, and show limited diagnostic accuracy for AKI. RegisteredNCT03577405.More than 40% of the crystalline silicon has been wasted as silicon cutting waste (SCW) during the wafer production process. This waste not only leads to resource wastage but also causes environmental burden. In this paper, SCW produced by the diamond-wire sawing process was recycled by Al-Si alloying process. Cryolite was introduced to the reaction system to dissolve the SiO2 layer existed on the surface of the Si particles in SCW. Alloys with 12.02 wt% of Si were prepared and the mechanism of the alloying process was investigated in detail. The Si-Al-cryolite system and SiO2-Al-cryolite system were studied individually to analyze the reaction process and transferring behavior of Si and SiO2 in SCW. The SiO2 shell was firstly transformed into Si-O-F ions. Then the Si-O-F ions diffused to the reaction interface by the effect of the concentration gradient and were reduced to Si by the aluminothermic reduction reaction 4Al (l) + 3SiO2 (dissolved in the melt) = 3Si (Al)+ 2Al2O3 (dissolved in the melt). Then the internal Si particles were released into cryolite after the dissolution of SiO2 and transferred to the reaction interface by the effect of gravity. The influences of the mass ratio of Al/SCW and agitation modes on the Si content of the alloys and the Si recovery ratio in SCW were investigated. With the increase of the mass ratio of Al/SCW from 2.2 to 6.5, the Si recovery ratio in SCW increased from 44.08% to 69.05%, but the silicon content of the alloys decreased from 16.06 wt% to 8.83 wt%. Agitation can effectively improve the smelting effect during smelting by which the silicon content of the alloys and the Si recovery ratio in SCW increased from 12.02 wt% and 64.25% to 13.17 wt% and 69.46%, respectively.Background Neuromelanin-pigmented neurons, which are highly susceptible to neurodegeneration in the Parkinson's disease substantia nigra, harbour elevated iron levels in the diseased state. Whilst it is widely believed that neuronal iron is stored in an inert, ferric form, perturbations to normal metal homeostasis could potentially generate more reactive forms of iron capable of stimulating toxicity and cell death. However, non-disruptive analysis of brain metals is inherently challenging, since use of stains or chemical fixatives, for example, can significantly influence metal ion distributions and/or concentrations in tissues. Aims The aim of this study was to apply synchrotron soft x-ray spectromicroscopy to the characterisation of iron deposits and their local environment within neuromelanin-containing neurons of Parkinson's disease substantia nigra. Methods Soft x-ray spectromicroscopy was applied in the form of Scanning Transmission X-ray Microscopy (STXM) to analyse resin-embedded tissue, without requirement for chemically disruptive processing or staining. Measurements were performed at the oxygen and iron K-edges in order to characterise both organic and inorganic components of anatomical tissue using a single label-free method. Results STXM revealed evidence for mixed oxidation states of neuronal iron deposits associated with neuromelanin clusters in Parkinson's disease substantia nigra. The excellent sensitivity, specificity and spatial resolution of these STXM measurements showed that the iron oxidation state varies across sub-micron length scales. Conclusions The label-free STXM approach is highly suited to characterising the distributions of both inorganic and organic components of anatomical tissue, and provides a proof-of-concept for investigating trace metal speciation within Parkinson's disease neuromelanin-containing neurons.
Background Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. https://www.selleckchem.com/products/sodium-2-1h-indol-3-ylacetate.html We compared efficacies of both regimens in this randomised phase II study. Patients and methods Patients with wild-type KRAS exon 2 mCRC previously treated with fluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (11) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety. Results From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44-0.94, P less then 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44-1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%). Conclusion Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.Background and purpose Renal Resistive Index (RRI) and Venous Impedance Index (VII) might be of additional value for diagnosing Acute Kidney Injury (AKI). The purpose of this study was to assess the diagnostic accuracy of RRI and VII for AKI. Materials and methods In the prospective Simple Intensive Care Studies-II (NCT03577405), we measured RRI and VII in acutely admitted adult intensive care patients within 24 h of admission. AKI was defined by the Kidney Disease Improving Global Outcome (KDIGO) criteria. The primary outcome was persistent AKI, defined as non-resolved AKI on day three. We tested specificity, sensitivity and diagnostic accuracy of both RRI and VII for persistent AKI. Results In total, 371 patients were included of whom 123 patients (33%) had persistent AKI. RRI and VII did not differ between patients with and those without persistent AKI (p = .08 and p = .59). RRI had a moderate specificity (72%, 95%CI 66-78%) and low sensitivity (32%, 95%CI 24-41%) and VII had high sensitivity (93%, 95%CI 85-98%) and low specificity (11%, 95%CI 6-16%) for persistent AKI. Overall diagnostic accuracy of RRI and VII was moderate. Conclusions In acutely admitted critically ill patients, measures of renal perfusion by renal ultrasound were not different between patients with and without AKI, and show limited diagnostic accuracy for AKI. RegisteredNCT03577405.More than 40% of the crystalline silicon has been wasted as silicon cutting waste (SCW) during the wafer production process. This waste not only leads to resource wastage but also causes environmental burden. In this paper, SCW produced by the diamond-wire sawing process was recycled by Al-Si alloying process. Cryolite was introduced to the reaction system to dissolve the SiO2 layer existed on the surface of the Si particles in SCW. Alloys with 12.02 wt% of Si were prepared and the mechanism of the alloying process was investigated in detail. The Si-Al-cryolite system and SiO2-Al-cryolite system were studied individually to analyze the reaction process and transferring behavior of Si and SiO2 in SCW. The SiO2 shell was firstly transformed into Si-O-F ions. Then the Si-O-F ions diffused to the reaction interface by the effect of the concentration gradient and were reduced to Si by the aluminothermic reduction reaction 4Al (l) + 3SiO2 (dissolved in the melt) = 3Si (Al)+ 2Al2O3 (dissolved in the melt). Then the internal Si particles were released into cryolite after the dissolution of SiO2 and transferred to the reaction interface by the effect of gravity. The influences of the mass ratio of Al/SCW and agitation modes on the Si content of the alloys and the Si recovery ratio in SCW were investigated. With the increase of the mass ratio of Al/SCW from 2.2 to 6.5, the Si recovery ratio in SCW increased from 44.08% to 69.05%, but the silicon content of the alloys decreased from 16.06 wt% to 8.83 wt%. Agitation can effectively improve the smelting effect during smelting by which the silicon content of the alloys and the Si recovery ratio in SCW increased from 12.02 wt% and 64.25% to 13.17 wt% and 69.46%, respectively.Background Neuromelanin-pigmented neurons, which are highly susceptible to neurodegeneration in the Parkinson's disease substantia nigra, harbour elevated iron levels in the diseased state. Whilst it is widely believed that neuronal iron is stored in an inert, ferric form, perturbations to normal metal homeostasis could potentially generate more reactive forms of iron capable of stimulating toxicity and cell death. However, non-disruptive analysis of brain metals is inherently challenging, since use of stains or chemical fixatives, for example, can significantly influence metal ion distributions and/or concentrations in tissues. Aims The aim of this study was to apply synchrotron soft x-ray spectromicroscopy to the characterisation of iron deposits and their local environment within neuromelanin-containing neurons of Parkinson's disease substantia nigra. Methods Soft x-ray spectromicroscopy was applied in the form of Scanning Transmission X-ray Microscopy (STXM) to analyse resin-embedded tissue, without requirement for chemically disruptive processing or staining. Measurements were performed at the oxygen and iron K-edges in order to characterise both organic and inorganic components of anatomical tissue using a single label-free method. Results STXM revealed evidence for mixed oxidation states of neuronal iron deposits associated with neuromelanin clusters in Parkinson's disease substantia nigra. The excellent sensitivity, specificity and spatial resolution of these STXM measurements showed that the iron oxidation state varies across sub-micron length scales. Conclusions The label-free STXM approach is highly suited to characterising the distributions of both inorganic and organic components of anatomical tissue, and provides a proof-of-concept for investigating trace metal speciation within Parkinson's disease neuromelanin-containing neurons.
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