There are a number of papers that calculate how the limits or positive results of current experiments would be if some specific twist is applied to the standard interpretation framework (e.g., SI ...interactions with fp = fn). These works are usually not performed by members of the experiments, and therefore make very simple assumptions on experimental details like efficiencies. Nevertheless, it is possible to retain this type of information without actually knowing it, by starting from the final exclusion plots and working backwards. This possibility is discussed and exemplified.
The common analysis of direct searches for spin-independent weakly interacting massive particles (WIMPs) assumes that a spin-independent WIMP couples with the same strength with both nucleons, i.e., ...that the spin-independent interaction is also fully isospin independent. Though in a fully isospin-dependent interaction scenario the spin-independent WIMP-nucleus cross section is strongly quenched, the leading experiments are still sensitive enough to set limits 1-2 orders of magnitude less stringent than those traditionally presented. In the isospin-dependent scenario the difference between the limits of CDMS-II and ZEPLIN-I is significantly reduced. Here, a model-independent framework is discussed and applied to obtain the current general model-independent limits.
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Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation ...sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information.
In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer.
Objective responses in the NGS cohort were observed in 104/182 patients overall response rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4% with a median progression-free survival (mPFS) of 9.8 (95% CI 8.7–11.5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons 9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of 62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2–12.8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI 39.9–57.5%) with mPFS of 8.9 (95% CI 7.4–9.6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect.
This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.
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Modern electronic devices and novel materials often derive their extraordinary properties from the intriguing, complex behavior of large numbers of electrons forming what is known as an electron ...liquid. This book provides an in-depth introduction to the physics of the interacting electron liquid in a broad variety of systems, including metals, semiconductors, artificial nano-structures, atoms and molecules. One, two and three dimensional systems are treated separately and in parallel. Different phases of the electron liquid, from the Landau Fermi liquid to the Wigner crystal, from the Luttinger liquid to the quantum Hall liquid are extensively discussed. Both static and time-dependent density functional theory are presented in detail. Although the emphasis is on the development of the basic physical ideas and on a critical discussion of the most useful approximations, the formal derivation of the results is highly detailed and based on the simplest, most direct methods.
Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal ...growth factor receptor (EGFR) therapy beyond progression.
We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis.
Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 95% confidence interval (CI) 4.7–8.0 versus 4.5 months (95% CI 3.3–5.7); hazard ratio (HR), 0.81; 95% CI 0.58–1.12; P = 0.19, respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm median 6.9 (95% CI 5.5–8.2) versus 5.3 months (95% CI 3.7–6.9); HR, 0.56 (95% CI 0.33–0.94); P = 0.025. There was a trend in better overall survival: median 23.7 (95% CI 19.4–28.0) versus 19.8 months (95% CI 14.9–24.7); HR, 0.57 (95% CI 0.32–1.02); P = 0.056.
Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
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A systematic study of the effect of cold work (CW) on chloride-induced stress corrosion cracking (SCC) in 304L stainless steel was performed. CW between 0% and 40% was applied prior to corrosion of ...specimens at 75°C and 70% relative humidity, for 500h, using MgCl2 (at atmospheric pressure). Samples cracked most readily between 0.5% and 5% CW; at 20% and above no cracks were present. Additionally, above 5% CW, some specific orientation relationships become evident, with cracks primarily aligned along parallel to the transverse direction. The results suggest that at levels of CW >20%, the synergistic effect of micro-mechanisms may hinder SCC in this system.
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•DAYKE-Italy is a project that investigated daylighting in 5 Italian universities.•A survey was distributed to students (N = 542) on perception of daylight in classrooms.•DIVA+ALFA ...simulations were run to calculate daylight, circadian and energy metrics.•Most metrics have significant statistical correlation with subjective responses.•Highest correlation was found for DFm, ALE, and circadian EML.
Results from the DAYKE-Italy project are presented. An investigation on daylighting in eight classrooms in five Italian universities was carried out through a combined approach: an ad-hoc survey administered to students to investigate how they perceive daylight in classroom, and numerical simulations (DIVA + ALFA) to calculate a set of objective metrics (daylight, circadian, and energy-related). A sample of 542 questionnaires was collected through two sessions and the subjective judgments were correlated to objective metrics. Results from descriptive and statistical analyses showed: (i) the correlation was significant for all daylight metrics: among them, average daylight factor and annual light exposure performed higher correlations compared to daylight autonomy, spatial daylight autonomy and useful daylight illuminance; (ii) rooms with a scarce or an optimal daylight provision (according to standards) were rated with comparable subjective score; (iii) the equivalent melanopic lux showed a higher correlation than daylight metrics based on the horizontal workplane; (iv) energy saving up to 50% can be achieved in the presence of high daylight provision and through daylight responsive controls; however, a relamping of fluorescent systems with LED system is recommended to optimize the consumption; furthermore, estimated saving correlated significantly with objective metrics.
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Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in ...patients treated with first-line anti-EGFR monoclonal antibody-based therapy.
In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing.
A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis.
This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.
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Warm mix asphalt (WMA) and crumb rubber modified asphalt in the field of asphalt paving have been demonstrated to be green technologies for producing environmentally friendly pavement. However, ...limited research has assessed the behaviours of mixtures including both technologies. This study performed research aligned with environmental considerations and sustainability to examine the design and manufacturing of dense asphalt mixtures incorporating a crumb-rubber modifier through a wet or dry process and a specific vegetable additive for WMA technologies. The results indicated that, when rubber is added through a wet process, and a WMA vegetable additive is incorporated, the mixture can be manufactured and compacted at temperatures approximately 25 °C below that of the control mixture, while keeping the mechanical properties within the specifications.
I evaluate the current results of spin-dependent weakly interacting massive particle searches within a model-independent framework, showing the most restrictive limits to date derive from the ...combination of xenon and sodium iodide experiments. The extension of this analysis to the case of positive signal experiments is elaborated.
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