Evolution of point defects in pulsed-laser-melted Ge1-xSnxprobed by positron annihilation lifetime spectroscopy.

Direct-band-gap Germanium-Tin alloys (Ge1-xSnx) with high carrier mobilities are promising materials for nano- and optoelectronics. The concentration of open volume defects in the alloy, such as Sn and Ge vacancies, influences the final device performance. In this article, we present an evaluation of the point defects in molecular-beam-epitaxy grown Ge1-xSnxfilms treated by post-growth nanosecond-range pulsed laser melting (PLM). Doppler broadening - variable energy positron annihilation spectroscopy and variable energy positron annihilation lifetime spectroscopy are used to investigate the defect nanostructure in the Ge1-xSnxfilms exposed to increasing laser energy density. The experimental results, supported with ATomic SUPerposition calculations, evidence that after PLM, the average size of the open volume defects increases, which represents a raise in concentration of vacancy agglomerations, but the overall defect density is reduced as a function of the PLM fluence. At the same time, the positron annihilation spectroscopy analysis provides information about dislocations and Ge vacancies decorated by Sn atoms. Moreover, it is shown that the PLM reduces the strain in the layer, while dislocations are responsible for trapping of Sn and formation of small Sn-rich-clusters.

Band-gap and strain engineering in GeSn alloys using post-growth pulsed laser melting.

The pseudomorphic growth of Ge1-xSnxon Ge causes in-plane compressive strain, which degrades the superior properties of the Ge1-xSnxalloys. Therefore, efficient strain engineering is required. In this article, we present strain and band-gap engineering in Ge1-xSnxalloys grown on Ge a virtual substrate using post-growth nanosecond pulsed laser melting (PLM). Micro-Raman and x-ray diffraction (XRD) show that the initial in-plane compressive strain is removed. Moreover, for PLM energy densities higher than 0.5 J cm-2, the Ge0.89Sn0.11layer becomes tensile strained. Simultaneously, as revealed by Rutherford Backscattering spectrometry, cross-sectional transmission electron microscopy investigations and XRD the crystalline quality and Sn-distribution in PLM-treated Ge0.89Sn0.11layers are only slightly affected. Additionally, the change of the band structure after PLM is confirmed by low-temperature photoreflectance measurements. The presented results prove that post-growth ns-range PLM is an effective way for band-gap and strain engineering in highly-mismatched alloys.

Substitutional synthesis of sub-nanometer InGaN/GaN quantum wells with high indium content.

InGaN/GaN quantum wells (QWs) with sub-nanometer thickness can be employed in short-period superlattices for bandgap engineering of efficient optoelectronic devices, as well as for exploiting topological insulator behavior in III-nitride semiconductors. However, it had been argued that the highest indium content in such ultra-thin QWs is kinetically limited to a maximum of 33%, narrowing down the potential range of applications. Here, it is demonstrated that quasi two-dimensional (quasi-2D) QWs with thickness of one atomic monolayer can be deposited with indium contents far exceeding this limit, under certain growth conditions. Multi-QW heterostructures were grown by plasma-assisted molecular beam epitaxy, and their composition and strain were determined with monolayer-scale spatial resolution using quantitative scanning transmission electron microscopy in combination with atomistic calculations. Key findings such as the self-limited QW thickness and the non-monotonic dependence of the QW composition on the growth temperature under metal-rich growth conditions suggest the existence of a substitutional synthesis mechanism, involving the exchange between indium and gallium atoms at surface sites. The highest indium content in this work approached 50%, in agreement with photoluminescence measurements, surpassing by far the previously regarded compositional limit. The proposed synthesis mechanism can guide growth efforts towards binary InN/GaN quasi-2D QWs.

NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC).

INTRODUCTION: Poorly differentiated (PD), extrapulmonary (EP), neuroendocrine carcinomas (NECs) are rare but aggressive neuroendocrine neoplasms. First-line treatment for advanced disease is an etoposide and platinum-based chemotherapy combination. There is no established second-line treatment for patients with PD-EP-NEC, and this is an area of unmet need. METHODS AND ANALYSIS: NET-02 is a UK, multicentre, randomised (1:1), parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive PD-EP-NEC. One hundred and two eligible participants will be randomised to receive either nal-IRI/5-FU/folinic acid or docetaxel. The primary objective is to determine the 6-month progression-free survival (PFS) rate. The secondary objectives of this study are to determine PFS, overall survival, objective response rate, toxicity, quality of life and whether neuron-specific enolase is predictive of treatment response. If either treatment is found to have a 6-month PFS rate of at least 25%, that treatment will be considered for a phase III trial. If both treatments meet this target, prespecified selection criteria will be applied to establish which treatment to take forward. ETHICS AND DISSEMINATION: This study has ethical approval from the Greater Manchester Central Research Ethics Committee (reference no. 18/NW/0031) and clinical trial authorisation from the Medicine and Healthcare Products Regulatory Agency. Results will be published in peer-reviewed journals and uploaded to the European Union Clinical Trials Register. TRIAL REGISTRATION NUMBERS: ISRCTN10996604, NCT03837977, EudraCT Number: 2017-002453-11.

[Joint Statement of the German Respiratory Society and German Society of Thoracic Surgery in Cooperation with the German Radiological Society: Structural Prerequisites of Centers for Interventional Treatment of Emphysema]. / Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Thoraxchirurgie in Kooperation mit der Deutschen Röntgengesellschaft: Strukturvoraussetzungen von Zentren für die interventionelle Emphysemtherapie.

Interventional treatment of emphysema offers a wide range of surgical and endoscopic options for patientes with advanced disease. Multidsciplinary collaboration of pulmonology, thoracic surgery and imaging disciplines in patient selection, therapy and follow up ensures treatment quality. The present joint statement describes the required structural and quality prerequsites of treatment centres.

Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy.

Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan-Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89-11.08) and 10.10 months (95% CI 6.30-12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients.

[Imaging before and after endoscopic lung volume reduction]. / Bildgebung vor und nach endoskopischer Lungenvolumenreduktion.

The treatment of symptomatic lung emphysema by lung volume reduction has become established over the last 15 years. While surgical partial lung resection has profited from improved and less invasive surgical techniques, various endoscopic interventional procedures have been developed and are now available for use. All treatment approaches are dependent on individual anatomical variants and a regional distribution of the lung emphysema, which is why no procedure can be designated as the gold standard for all patients. High-resolution computed tomography can be qualitatively evaluated and provides decisive information for treatment, which is why radiologists play a particularly important role in treatment planning and aftercare of an intervention for reduction of the lung volume. This article presents the various endoscopic techniques, names the demands of the treating physician on the advising radiologist and finally describes how a treatment decision is derived from the results obtained.

Urgent need for consensus: international survey of clinical practice exploring use of platinum-etoposide chemotherapy for advanced extra-pulmonary high grade neuroendocrine carcinoma (EP-G3-NEC).

BACKGROUND: Platinum-etoposide (PE) chemotherapy (CH) is a globally established combination for extra-pulmonary high grade neuroendocrine carcinoma (EP-G3-NEC); the optimal schedule has not been established. METHODS: An international survey was designed, and completed by clinicians with an expertise in the field to assess consistency in clinical practice. RESULTS: Seventy-five replies were received (June-Nov'17). A minority of physicians (13; 17.6%) did not take Ki-67 or morphology (9; 12.0%) into consideration for selection of CH. Most (72; 96.0%) selected PE-CH as first-line treatment for EP-G3-NEC. CH schedules varied: cisplatin-based (37/71; 52.1%), carboplatin-based (34/71; 47.9%); intravenous etoposide (64/71; 90.1%), oral etoposide (7/71; 9.9%). Choice of second-line CH depended on time to progression on PE-based first-line: if > 6 months, re-challenge with PE was the preferred choice (34; 45.9%); if < 6 months, alternative combinations such as fluoropyrimidine/irinotecan (21; 29.2%) or temozolomide/capecitabine (22; 30.6%) were used. CONCLUSION: Significant variation in PE regimen employed exists. Standardising clinical practice would facilitate clinical trial development.

Free-carrier dynamics in Au2Pb probed by optical conductivity measurements.

We measured the optical reflectivity of the Dirac material Au2Pb in a broad frequency range (30-48 000 cm-1) for temperatures between 9 and 300 K. The optical conductivity, computed from the reflectivity, is dominated by free-carrier contributions from topologically trivial bulk bands at all temperatures. The temperature-independent total plasma frequency of these carriers is [Formula: see text] eV. Overall, optical response of Au2Pb is typically metallic with no signs of localization and bad-metal behavior.

Morphological and Functional Modifications of Optical Thin Films for Space Applications Irradiated with Low-Energy Helium Ions.

Future space missions will operate in increasingly hostile environments, such as those in low-perihelion solar orbits and Jovian magnetosphere. This exploration involves the selection of optical materials and components resistant to the environmental agents. The conditions in space are reproduced on ground through the use of ion accelerators. The effects of He particles coming from the solar wind impinging on a gold thin film have been systematically investigated, considering absorbed doses compatible with the duration of the European Space Agency Solar Orbiter mission. Structural and morphological changes have been proved to be dependent not only on the dose but also on the irradiation flux. A predictive model of the variation of thin film reflectance has been developed for the case of lower flux irradiation. The results are discussed regarding reliability and limitations of laboratory testing. The outcomes are important to address the procedures for the space qualification tests of optical coatings.

Formation of n- and p-type regions in individual Si/SiO2 core/shell nanowires by ion beam doping.

A method for cross-sectional doping of individual Si/SiO2 core/shell nanowires (NWs) is presented. P and B atoms are laterally implanted at different depths in the Si core. The healing of the implantation-related damage together with the electrical activation of the dopants takes place via solid phase epitaxy driven by millisecond-range flash lamp annealing. Electrical measurements through a bevel formed along the NW enabled us to demonstrate the concurrent formation of n- and p-type regions in individual Si/SiO2 core/shell NWs. These results might pave the way for ion beam doping of nanostructured semiconductors produced by using either top-down or bottom-up approaches.

Quantum spin liquids unveil the genuine Mott state.

The localization of charge carriers by electronic repulsion was suggested by Mott in the 1930s to explain the insulating state observed in supposedly metallic NiO. The Mott metal-insulator transition has been subject of intense investigations ever since1-3-not least for its relation to high-temperature superconductivity4. A detailed comparison to real materials, however, is lacking because the pristine Mott state is commonly obscured by antiferromagnetism and a complicated band structure. Here we study organic quantum spin liquids, prototype realizations of the single-band Hubbard model in the absence of magnetic order. Mapping the Hubbard bands by optical spectroscopy provides an absolute measure of the interaction strength and bandwidth-the crucial parameters that enter calculations. In this way, we advance beyond conventional temperature-pressure plots and quantitatively compose a generic phase diagram for all genuine Mott insulators based on the absolute strength of the electronic correlations. We also identify metallic quantum fluctuations as a precursor of the Mott insulator-metal transition, previously predicted but never observed. Our results suggest that all relevant phenomena in the phase diagram scale with the Coulomb repulsion U, which provides a direct link to unconventional superconductivity in cuprates and other strongly correlated materials.

Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.

Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. Results: A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials.gov (NCT 01287585).

Plasmonic nanoparticles embedded in single crystals synthesized by gold ion implantation for enhanced optical nonlinearity and efficient Q-switched lasing.

We report on the synthesis of embedded gold (Au) nanoparticles (NPs) in Nd:YAG single crystals using ion implantation and subsequent thermal annealing. Both linear and nonlinear absorption of the Nd:YAG crystals have been enhanced significantly due to the embedded Au NPs, which is induced by the surface plasmon resonance (SPR) effect in the visible light wavelength band. Particularly, through a typical Z-scan system excited by a femtosecond laser at 515 nm within the SPR band, the nonlinear absorption coefficients of crystals with Au NPs have been observed to be nearly 5 orders of magnitude larger than that without Au NPs. This giant enhancement of nonlinear absorption properties is correlated with the saturable absorption (SA) effect, which is the basis of passive Q-switching or mode-locking for pulsed laser generation. In addition, the linear and nonlinear absorption enhancement could be tailored by varying the fluence of implanted Au+ ions, corresponding to the NP size and concentration modulation. Finally, the Nd:YAG wafer with embedded Au NPs has been applied as a saturable absorber in a Pr:LuLiF4 crystal laser cavity, and efficient pulsed laser generation at 639 nm has been realized, which presents superior performance to the MoS2 saturable absorber based system. This work opens an avenue to enhance and modulate the nonlinearities of dielectrics by embedding plasmonic Au NPs for efficient pulsed laser operation.

Biotransformation and detoxification of selenite by microbial biogenesis of selenium-sulfur nanoparticles.

This study combines the interaction between the toxic oxyanions selenite and selenate and the plant growth promoting bacterium Azospirillum brasilense with a comprehensive characterization of the formed selenium particles. As selenium is an essential trace element, but also toxic in high concentrations, its state of occurrence in nature is of major concern. Growth of the bacterium was affected by selenite (1-5mM) only, observable as a prolonged growth lag-phase of 3days. Subsequently, selenite reduction occurred under aerobic conditions resulting in extracellularly formed insoluble Se0 particles. Complementary studies by microscopic and spectroscopic techniques revealed the particles to be homogeneous and stable Se8-nSn structured spheres with an average size of 400nm and highly negative surface charge of -18mV in the neutral pH range. As this is the first study showing Azospirillum brasilense being able to biotransform selenite to selenium particles containing a certain amount of sulfur, even if environmental waters supplemented with selenite were used, they may significantly contribute to the biogeochemical cycling of both elements in soil as well as to their soil-plant transfer. Therefore, microbial biotransformation of selenite under certain circumstances may be used for various bio-remediation and bio-technological applications.

Sorafenib for the Treatment of Advanced Hepatocellular Cancer - a UK Audit.

AIMS: Sorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials. MATERIALS AND METHODS: Sorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan-Meier method. RESULTS: Data were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17-89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin-bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590 mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n=109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients. CONCLUSION: For Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade > 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment.

Identification of clinical biomarkers for patients with advanced hepatocellular carcinoma receiving sorafenib.

BACKGROUND: Identification of patients with advanced HCC-deriving preferential benefit from sorafenib is desirable, and treatment-related adverse events are potential clinical biomarkers. METHODS: Survival and toxicity data for patients with HCC treated with sorafenib at the Christie NHS Foundation Trust from 11/09 to 02/15 were collected retrospectively. RESULTS: Eighty-five eligible patients were identified. The most common grade 3 or 4 treatment-related toxicities were hypertension (HTN, 45 %), fatigue (8 %), and hand-foot syndrome (HFS, 8 %). Any-grade HFS and/or worsening HTN (HFS/HTN) were experienced by 58 % of patients. Estimated median progression-free and overall survival (OS) were 4.6 (95 % CI 2.8-5.2) and 6.5 (95 % CI 4.9-8.01) months, respectively. Child-Pugh score (p value <0.001) and the development of HFS/HTN were independent prognostic factors impacting on OS on multivariable analysis. Patients who developed HFS/HTN had median OS of 8.2 months (95 % CI 6.5-12.4) compared with 4.1 (95 % CI 2.7-5.4) for those without this toxicity (Hazard Ratio (HR) 0.4, 95 % CI 0.2-0.7, p value 0.003). The prognostic impact of HFS/HTN was confirmed by landmark analyses limited to patients who lived a minimum of 2 months (p value 0.019) or who developed HFS/HTN in the first 3 months of treatment (p value 0.006). CONCLUSION(S): The development of toxicities specific to sorafenib is associated with prolonged survival in a UK-based HCC patient series; prospective assessment of their significance is required.