Silicon crystallized in the usual cubic (diamond) lattice structure has dominated the electronics industry for more than half a century. However, cubic silicon (Si), germanium (Ge) and SiGe alloys ...are all indirect-bandgap semiconductors that cannot emit light efficiently. The goal
of achieving efficient light emission from group-IV materials in silicon technology has been elusive for decades
. Here we demonstrate efficient light emission from direct-bandgap hexagonal Ge and SiGe alloys. We measure a sub-nanosecond, temperature-insensitive radiative recombination lifetime and observe an emission yield similar to that of direct-bandgap group-III-V semiconductors. Moreover, we demonstrate that, by controlling the composition of the hexagonal SiGe alloy, the emission wavelength can be continuously tuned over a broad range, while preserving the direct bandgap. Our experimental findings are in excellent quantitative agreement with ab initio theory. Hexagonal SiGe embodies an ideal material system in which to combine electronic and optoelectronic functionalities on a single chip, opening the way towards integrated device concepts and information-processing technologies.
Neutron diffraction data with hydrogen isotope substitution on aqueous solutions of NaCl and KCl at concentrations ranging from high dilution to near-saturation are analyzed using the Empirical ...Potential Structure Refinement technique. Information on both the ion hydration shells and the microscopic structure of the solvent is extracted. Apart from obvious effects due to the different radii of the three ions investigated, it is found that water molecules in the hydration shell of K+ are orientationally more disordered than those hydrating a Na+ ion and are inclined to orient their dipole moments tangentially to the hydration sphere. Cl- ions form instead hydrogen-bonded bridges with water molecules and are readily accommodated into the H-bond network of water. The results are used to show that concepts such as structure maker/breaker, largely based on thermodynamic data, are not helpful in understanding how these ions interact with water at the molecular level.
Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the ...perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.
We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures.
We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0–6 h, 6–24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality.
As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.
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.
The ion induced modification to the tetrahedral structure of water is a topic of much current interest. We address this question by interpreting neutron diffraction data from monovalent ionic ...solutions of NaCl and KCl using a computer assisted structural modeling technique. We investigate the effect that these ions have on the water-water O-O, O-H and H-H radial distribution functions as a function of ionic concentration. It is found that the O-H and H-H functions are only marginally affected by ionic composition, signaling that hydrogen bonding between water molecules remains largely intact, even at the highest concentrations. On the other hand the O-O functions are strongly modified by the ions. In particular the position of the second peak in g(OO)(r), is found to move inwards with increasing salt concentration, in a manner closely analogous to what happens in pure water under pressure. Furthermore by recalculating g(OO)(r) after excluding all the water molecules in the first hydration shell of each ion, we show that this structural perturbation exists outside the first hydration shell of the ions.
There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for ...postoperative pulmonary complications research.
A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials.
From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition.
A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.
The underground muon detector of the Pierre Auger Observatory is aimed at attaining direct measurements of the muonic component of extensive air showers produced by cosmic rays with energy from ...1016.5 eV up to the region of the ankle (around 1018.7 eV). It consists of two nested triangular grids of underground scintillators with 433 m and 750 m spacings, and a total of 71 positions, each with 192 scintillator strips (30 m2) deployed 2.3 m underground. The light produced by impinging muons in the scintillators is propagated with optical fibers towards an array of silicon photomultipliers. In this work, we present the development, validation, and performance of an end-to-end tool for simulating the response of the underground muon detector to single-muon signals, which constitutes the basis for further simulations of the whole array. Laboratory data and simulation outcomes are found consistent, showing that with the underground muon detector we can measure single muons, with an efficiency of 99%, up to about 1050 particles arriving at exactly the same time in 30 m2 of scintillator.
Abstract Silicon is indisputably the most advanced material for scalable electronics, but it is a poor choice as a light source for photonic applications, due to its indirect band gap. The recently ...developed hexagonal Si 1− x Ge x semiconductor features a direct bandgap at least for x > 0.65, and the realization of quantum heterostructures would unlock new opportunities for advanced optoelectronic devices based on the SiGe system. Here, we demonstrate the synthesis and characterization of direct bandgap quantum wells realized in the hexagonal Si 1− x Ge x system. Photoluminescence experiments on hex-Ge/Si 0.2 Ge 0.8 quantum wells demonstrate quantum confinement in the hex-Ge segment with type-I band alignment, showing light emission up to room temperature. Moreover, the tuning range of the quantum well emission energy can be extended using hexagonal Si 1− x Ge x /Si 1− y Ge y quantum wells with additional Si in the well. These experimental findings are supported with ab initio bandstructure calculations. A direct bandgap with type-I band alignment is pivotal for the development of novel low-dimensional light emitting devices based on hexagonal Si 1− x Ge x alloys, which have been out of reach for this material system until now.
Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and ...PIK3CA mutations, in order to assess potential clinical implications.
Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculated by multiplying by 2 the frequency of mutant alleles in neoplastic cells. Therefore, HS virtually corresponds to the fraction of neoplastic cells carrying a specific mutation.
The KRAS HS ranged between 12 and 260 with mean value of 87.1 and median value of 84.4, suggesting that in most CRC, the majority of neoplastic cells carry mutant KRAS. Similar findings were observed for NRAS (HS range 35.5–146.7; mean 102.8; median 117.1). In contrast, in BRAF (HS range 17.1–120; mean 54.8; median 54.3) and PIK3CA (HS range 14.3–120; mean 59.5; median 47.3) mutant cases, only a fraction of neoplastic cells seem to carry the mutant allele. The response rate was 70% in KRAS mutant patients with an HS <33 (low KRAS; n = 10) and 45.7% in KRAS HS >33 patients (high KRAS; n = 35); median progression-free survival were 7.97 and 8.37 months, respectively. Low-KRAS tumors had a higher frequency of additional mutations in PIK3CA when compared with high-KRAS (6/10 versus 8/35).
KRAS and NRAS mutations are usually present in the majority of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might be driven by the complex mutational profile rather than KRAS mutation load.
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