[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.

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.

[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.

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).

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.

Routine measurement of plasma chromogranin B has limited clinical utility in the management of patients with neuroendocrine tumours.

OBJECTIVE: Chromogranin A (CgA) and B (CgB) are markers for monitoring disease status in patients with gastroenteropancreatic neuroendocrine tumours (NETs). These are specialized diagnostic tests often necessitating referral of specimens to a supraregional assay service (SAS) laboratory for analysis. The aim of this audit was to assess whether measurement of either plasma CgA or CgB alone provides sufficient clinical information in comparison with the current practice of measuring both markers together. DESIGN: A retrospective analysis was undertaken for all chromogranin tests requested for patients with a known NET diagnosis. Results were categorized based on whether plasma concentrations were elevated for one or both CgA and CgB. RESULTS: A total of 325 sequential patients with a NET diagnosis had plasma chromogranin levels measured during the period of review. Baseline CgA was elevated in 60·9% of patients. Isolated elevations in CgA (with normal CgB) were found in 44·9% of patients, whilst combined elevations in both CgA and CgB were found in 16% of patients. Combined CgA and CgB concentrations within the normal range were observed for 38·5% of patients. Only two patients (0·6%) had an isolated elevation in CgB at baseline. Both patients had a diagnosis of pancreatic NET and were radiologically stable. Plasma CgA and CgB corresponded with disease stage (localized vs metastatic). CgB in addition to CgA did not provide any significant improvement in diagnostic performance for identification of metastatic disease compared to CgA alone. CONCLUSIONS: Based on this NET population and specific assay performance characteristics, CgA alone provides sufficient information for the management of NET patients; the routine estimation of CgB in all patients is not informative in clinical practice.

Production of three-dimensional quantum dot lattice of Ge/Si core-shell quantum dots and Si/Ge layers in an alumina glass matrix.

We report on the formation of Ge/Si quantum dots with core/shell structure that are arranged in a three-dimensional body centered tetragonal quantum dot lattice in an amorphous alumina matrix. The material is prepared by magnetron sputtering deposition of Al2O3/Ge/Si multilayer. The inversion of Ge and Si in the deposition sequence results in the formation of thin Si/Ge layers instead of the dots. Both materials show an atomically sharp interface between the Ge and Si parts of the dots and layers. They have an amorphous internal structure that can be crystallized by an annealing treatment. The light absorption properties of these complex materials are significantly different compared to films that form quantum dot lattices of the pure Ge, Si or a solid solution of GeSi. They show a strong narrow absorption peak that characterizes a type II confinement in accordance with theoretical predictions. The prepared materials are promising for application in quantum dot solar cells.

Second-line chemotherapy in advanced biliary cancer: a systematic review.

The randomized NCRN phase III ABC-02 trial provided level-A evidence for first-line chemotherapy with cisplatin and gemcitabine combination in advanced biliary cancer (ABC). This systematic literature review aims to evaluate the level of evidence for the use of second-line chemotherapy for patients with ABC in terms of overall survival (OS), response, toxicity and quality of life. Eligible studies were identified using Medline, ASCO, ESMO and the World Gastrointestinal Congress databases. Searches were last updated on 15 December 2013. Eligible studies reported survival and/or response data for patients with ABC receiving second-line systemic chemotherapy. This systematic review was registered in the PROSPERO database (No. CRD42013004205). Five hundred and fifty-eight studies were identified from the searches in Medline (n = 342), ASCO (n = 160), ESMO (n = 27) and World Gastrointestinal Congress (n = 29). Twenty-five studies were eligible: 14 phase II clinical trials, 9 retrospective analyses and 2 case reports. In total, data from 761 patients were reported with median number of patients included in each study of 22 (range 9-96). The mean OS was 7.2 months [95% confidence interval (CI) 6.2-8.2] [phase II: 6.6 (95% CI 5.1-8.1); retrospective analysis: 7.7 (95% CI 6.5-8.9)]. The mean progression-free survival (PFS), response rate (RR) and disease control rate were 3.2 months (95% CI 2.7-3.7), 7.7% (95% CI 4.6-10.9) and 49.5% (95% CI 41.4-57.7), respectively. The best correlations were between OS and PFS for all studies (r = 0.54; P = 0.01) and between OS and PFS (r = 0.61; P = 0.04) and OS and RR (r = 0.62; P = 0.03) for phase II studies, respectively. Biliary tract cancer is known to be a chemo-responsive disease. There is insufficient evidence (level C) to recommend a second-line chemotherapy schedule in ABC, although the available data suggest that a cohort of patients may benefit. Further prospective and randomized studies are needed to clarify the relative value of second-line chemotherapy in this setting.

Laser induced sponge-like Si in Si-rich oxides for photovoltaics.

We show that a sponge-like structure of interconnected Si nanowires embedded in a dielectric matrix can be obtained by laser annealing of silicon rich oxides (SRO). Due to quantum confinement, the large bandgap displayed by these percolated nanostructures can be utilized as a tandem stage in 3rd generation thin-film solar cells. Well passivated by the SiO2 dielectric matrix, they are expected to overcome the difficulty of carrier separation encountered in the case of isolated crystalline quantum dots. In this study PECVD grown SRO were irradiated by a cw Ar⁺ laser. Raman spectroscopy has been used to assess the crystallinity of the Si nanostructures and thus to optimize the annealing conditions as dwell times and power densities. In addition, Si plasmon imaging in the transmission electron microscope was applied to identify the sponge-like structure of phase-separated silicon.

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.

Folate and colorectal cancer prevention.

Anti-folate chemotherapy agents such as methotrexate and fluorouracil reduce proliferation of neoplastic cells by inhibiting DNA synthesis. Paradoxically epidemiological data suggests an inverse relationship between dietary folate intake and incidence of colorectal cancer (CRC). On the basis of this and other putative health benefits around 35% of the North American population take folic acid supplements, in addition to natural food folates and fortified flour and cereal grains. Recently, randomised controlled trials investigating folic acid as a secondary preventative agent in colorectal neoplasia have shed further light on the relationship between folate and colorectal carcinogenesis, corroborating data from animal models indicating opposing effects dependent on the timing of exposure in relation to the development of neoplastic foci. A 'dual-modulator' role for folate in colorectal carcinogenesis has been proposed in which moderate dietary increases initiated before the establishment of neoplastic foci have a protective influence, whereas excessive intake or increased intake once early lesions are established increases tumorigenesis. Functional polymorphic variants in genes encoding key enzymes in the folate metabolic pathway add a further layer of complexity to the relationship between folate and CRC risk. Here, we review the evidence concerning the efficacy and safety of folate as a potential CRC chemopreventive agent.

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.

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.