Low-energy electronic properties of clean CaRuO3_3: elusive Landau quasiparticles

We have prepared high-quality epitaxial thin films of CaRuO$_3$ with residual resistivity ratios up to 55. Shubnikov-de Haas oscillations in the magnetoresistance and a $T^2$ temperature dependence in the electrical resistivity only below 1.5 K, whose coefficient is substantially suppressed in large magnetic fields, establish CaRuO$_3$ as a Fermi liquid (FL) with anomalously low coherence scale. Non-Fermi liquid (NFL) $T^{3/2}$ dependence is found between 2 and 25 K. The high sample quality allows access to the intrinsic electronic properties via THz spectroscopy. For frequencies below 0.6 THz, the conductivity is Drude-like and can be modeled by FL concepts, while for higher frequencies non-Drude behavior, inconsistent with FL predictions, is found. This establishes CaRuO$_3$ as a prime example of optical NFL behavior in the THz range.Comment: 12 pages, 21 figures including supplemental materia

Digital three-dimensional imaging techniques provide new analytical pathways for malacological research

Author Posting. © BioOne Complete, 2019. This article is posted here by permission of BioOne Complete for personal use, not for redistribution. The definitive version was published in Ziegler, A., Bock, C., Ketten, D. R., Mair, R. W., Mueller, S., Nagelmann, N., Pracht, E. D., & Schroeder, L. Digital three-dimensional imaging techniques provide new analytical pathways for malacological research. American Malacological Bulletin, 36(2), (2018):248-273, doi:10.4003/006.036.0205.Research on molluscan specimens is increasingly being carried out using high-throughput molecular techniques. Due to their efficiency, these technologies have effectively resulted in a strong bias towards genotypic analyses. Therefore, the future large-scale correlation of such data with the phenotype will require a significant increase in the output of morphological studies. Three-dimensional (3D) scanning techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) can achieve this goal as they permit rapidly obtaining digital data non-destructively or even entirely non-invasively from living, fixed, and fossil samples. With a large number of species and a relatively complex morphology, the Mollusca would profit from a more widespread application of digital 3D imaging techniques. In order to provide an overview of the capacity of various MRI and CT techniques to visualize internal and external structures of molluscs, more than twenty specimens ranging in size from a few millimeters to well over one meter were scanned in vivo as well as ex vivo. The results show that all major molluscan organ systems can be successfully visualized using both MRI and CT. The choice of a suitable imaging technique depends primarily on the specimen's life condition, its size, the required resolution, and possible invasiveness of the approach. Apart from visual examples derived from more than two dozen scans, the present article provides guidelines and best practices for digital 3D imaging of a broad range of molluscan taxa. Furthermore, a comprehensive overview of studies that previously have employed MRI or CT techniques in malacological research is given.We would like to express our gratitude to Adam J. Baldinger, Thomas Bartolomaeus, Patrick Beckers, Rüdiger Bieler, Roger T. Hanlon, Carsten Lüter, Iliana Ruiz-Cooley, Tom Schiøtte, Andreas Schmidt-Rhaesa, and Sid Staubach for help with specimen collection or for providing access to museum material. Cornelius Faber, Julia Koch, Tony Stöcker, and W. Caroline West kindly facilitated use of scanning systems. We would also like to thank Julie Arruda, Scott Cramer, Jörg Döpfert, Charlotte Eymann, Bastian Maus, Malte Ogurreck, Christina L. Sagorny, Gillian Trombke, and Christopher Witte for support with data acquisition and analysis. We are particularly grateful to Elizabeth K. Shea for inviting the present contribution and for her extensive commentary on the manuscript. We also thank two anonymous reviewers for their helpful criticisms. Funding for this study was provided by the Ocean Life Institute, the Office of Naval Research, the Seaver Institute, and the Deutsche Forschungsgemeinschaft (INST 217/849-1 FUGG)

Cruise Report Poseidon 229a/b Kolbeinsey Ridge, Akureyri - Reykjavik, 22.05.1997 - 11.06.1997

General Subject of research: Detailed study of the shallow water hydrothermal system around Kolbeinsey and Grimsey island

Overall survival and objective response in advanced unresectable hepatocellular carcinoma: A subanalysis of the REFLECT study

Background & Aims: Validated surrogate endpoints for overall survival (OS) are important for expediting the clinical study and drug-development processes. Herein, we aimed to validate objective response as an independent predictor of OS in individuals with unresectable hepatocellular carcinoma (HCC) receiving systemic anti-angiogenic therapy. Methods: We investigated the association between objective response (investigator-assessed mRECIST, independent radiologic review [IRR] mRECIST and RECIST v1.1) and OS in REFLECT, a phase III study of lenvatinib vs. sorafenib. We conducted landmark analyses (Simon-Makuch) of OS by objective response at 2, 4, and 6 months after randomization. Results: Median OS was 21.6 months (95% CI 18.6–24.5) for responders (investigator-assessed mRECIST) vs. 11.9 months (95% CI 10.7–12.8) for non-responders (hazard ratio [HR] 0.61; 95% CI 0.49–0.76; p <0.001). Objective response by IRR per mRECIST and RECIST v1.1 supported the association with OS (HR 0.61; 95% CI 0.51–0.72; p <0.001 and HR 0.50; 95% CI 0.39–0.65; p <0.001, respectively). OS was significantly prolonged for responders vs. non-responders (investigator-assessed mRECIST) at the 2-month (HR 0.61; 95% CI 0.49–0.76; p <0.001), 4-month (HR 0.63; 95% CI 0.51–0.80; p <0.001), and 6-month (HR 0.68; 95% CI 0.54–0.86; p <0.001) landmarks. Results were similar when assessed by IRR, with both mRECIST and RECIST v1.1. An exploratory multivariate Cox regression analysis identified objective response by investigator-assessed mRECIST (HR 0.55; 95% CI 0.44–0.68; p <0.0001) and IRR-assessed RECIST v1.1 (HR 0.49; 95% CI, 0.38–0.64; p <0.0001) as independent predictors of OS in individuals with unresectable HCC. Conclusions: Objective response was an independent predictor of OS in individuals with unresectable HCC in REFLECT; additional studies are needed to confirm surrogacy. Participants achieving a complete or partial response by mRECIST or RECIST v1.1 had significantly longer survival vs. those with stable/progressive/non-evaluable disease. ClinicalTrials.gov number: NCT01761266. Impact and implications: This analysis of data taken from a completed clinical trial (REFLECT) looked for any link between objective response and overall survival time in individuals with unresectable HCC receiving anti-angiogenic treatments. Significantly longer median overall survival was found for responders (21.6 months) vs. non-responders (11.9 months). Overall survival was also significantly longer for responders vs. non-responders (based on objective response status at 2, 4, and 6 months) in the landmark analysis. Our results indicate that objective response is an independent predictor of overall survival in this setting, confirming its validity as a rapid marker of efficacy that can be applied in phase II trials; however, further validation is required to determine is validity for other systemic treatments (e.g. immunotherapies), or as a surrogate of overall survival

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma

PURPOSE The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti-PD-1 antibody) in unresectable HCC (uHCC). PATIENTS AND METHODS In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight $60 kg, 12 mg; , 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21- day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase). RESULTS A total of 104 patients were enrolled. No DLTs were reported (n 5 6) in the DLT phase; 100 patients (expansion phase; included n 5 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n 5 29) or C disease (n 5 71). At data cutoff, 37$ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified. CONCLUSION Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals

Regionalisation of trauma care in England

Aims We aimed to determine whether there is evidence of improved patient outcomes in Major Trauma Centres following the regionalisation of trauma care in England. Patients and Methods An observational study was undertaken using the Trauma Audit and Research Network (TARN), Hospital Episode Statistics (HES) and national death registrations. The outcome measures were indicators of the quality of trauma care, such as treatment by a senior doctor and clinical outcomes, such as mortality in hospital. Results and Conclusion A total of 20 181 major trauma cases were reported to TARN during the study period, which was 270 days before and after each hospital became a Major Trauma Centre. Following regionalisation of trauma services, all indicators of the quality of care improved, fewer patients required secondary transfer between hospitals and a greater proportion were discharged with a Glasgow Outcome Score of “good recovery”. In this early post-implementation analysis, there were a number of apparent process improvements (e.g. time to CT) but no differences in either crude or adjusted mortality. The overall number of deaths following trauma in England did not change following the national reconfiguration of trauma services. Evidence from other countries that have regionalised trauma services suggests that further benefits may become apparent after a period of maturing of the trauma system

A Metalloproteinase Secreted by Streptococcus pneumoniae Removes Membrane Mucin MUC16 from the Epithelial Glycocalyx Barrier

The majority of bacterial infections occur across wet-surfaced mucosal epithelia, including those that cover the eye, respiratory tract, gastrointestinal tract and genitourinary tract. The apical surface of all these mucosal epithelia is covered by a heavily glycosylated glycocalyx, a major component of which are membrane-associated mucins (MAMs). MAMs form a barrier that serves as one of the first lines of defense against invading bacteria. While opportunistic bacteria rely on pre-existing defects or wounds to gain entry to epithelia, non opportunistic bacteria, especially the epidemic disease-causing ones, gain access to epithelial cells without evidence of predisposing injury. The molecular mechanisms employed by these non opportunistic pathogens to breach the MAM barrier remain unknown. To test the hypothesis that disease-causing non opportunistic bacteria gain access to the epithelium by removal of MAMs, corneal, conjunctival, and tracheobronchial epithelial cells, cultured to differentiate to express the MAMs, MUCs 1, 4, and 16, were exposed to a non encapsulated, non typeable strain of Streptococcus pneumoniae (SP168), which causes epidemic conjunctivitis. The ability of strain SP168 to induce MAM ectodomain release from epithelia was compared to that of other strains of S. pneumoniae, as well as the opportunistic pathogen Staphylococcus aureus. The experiments reported herein demonstrate that the epidemic disease-causing S. pneumoniae species secretes a metalloproteinase, ZmpC, which selectively induces ectodomain shedding of the MAM MUC16. Furthermore, ZmpC-induced removal of MUC16 from the epithelium leads to loss of the glycocalyx barrier function and enhanced internalization of the bacterium. These data suggest that removal of MAMs by bacterial enzymes may be an important virulence mechanism employed by disease-causing non opportunistic bacteria to gain access to epithelial cells to cause infection

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers