Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05).

OBJECTIVES Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND METHODS Fifty patients with baseline and 24 h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). RESULTS Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). CONCLUSION Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.

Individual Video Training iVT - Development of a National Infrastructure for Video-Supported Learning

Introduction: Video‐Supported Learning is particularly effective when it comes to skills and behaviors. Video registration of patient‐physician interviews, class room instruction or practical skills allow it to learners themselves, their peers, and their tutors to assess the quality of the learner's performance, to give specific feedback, and to make suggestions for improvement. Methods: In Switzerland, four pedagogical universities and two medical faculties joined to initiate the development of a national infrastructure for Video Supported Learning. The goal was to have a system that is simple to use, has most steps automated, provides the videos over the Internet, and has a sophisticated access control. Together with SWITCH, the national IT‐Support‐Organisation for Swiss Universities, the program iVT (Individual Video Training) was developed by integrating two preexisting technologies. The first technology is SWITCHcast, a podcast system. With SWITCHcast, videos are automatically uploaded to a server as soon as the registration is over. There the videos are processed and converted to different formats. The second technology is the national Single Logon System AAI (Authentification and Authorization Infrastructure) that enables iVT to link each video with the corresponding learner. The learner starts the registration with his Single Logon. Thus, the video can unambiguously be assigned. Via his institution's Learning Management System (LMS), the learner can access his video and give access to his video to peers and tutors. Results: iVT is now used at all involved institutions. The system works flawlessly. In Bern, we use iVT for the communications skills training in the forth and sixth year. Since students meet with patient actors alone, iVT is also used to certify attendance. Students are encouraged to watch the videos of the interview and the feedback of the patient actor. The offer to discuss a video with a tutor was not used by the students. Discussion: We plan to expand the use of iVT by making peer assessment compulsory. To support this, annotation capabilities are currently added to iVT. We also want to use iVT in training of practical skills, again for self as well as for peer assessment.  At present, we use iVT for quality control of patient actor's performance.

CO2 Electroreduction on Cu-Modified Platinum Single Crystal Electrodes in Aprotic Media

Techniques of electrode modification by copper deposits are developed that allow obtaining compact bulk quasi-epitaxial deposits on basal Pt(hkl) single crystal faces. The issues of the deposit roughness and characterization are discussed. Problems of drying and transferring electrodes with copper deposits into other solutions are considered. The obtained deposits are used for CO2 electroreduction in propylene carbonate and acetonitrile solutions of 0.1 M TBAPF6, and the relationship between the electrode surface structure and its electrocatalytic activity in CO2 electroreduction is discussed. We also demonstrate that the restructuring of Cu deposits occurs upon CO2 electroreduction. Complementary reactivity studies are presented for bare Pt(hkl) and Cu(hkl) single crystal electrodes. Cu-modified Pt(hkl) electrodes display the highest activity as compared to bare Pt(hkl) and Cu(hkl). Particularly, the Cu/Pt(110) electrode shows the highest activity among the electrodes under study. Such high activity of Cu/Pt(hkl) electrodes can be explained not only by the increasing actual surface area but also by structural effects, namely by the presence of a large amount of specific defect sites (steps, kinks) on Cu crystallites.

Evidence-supported psychosocial treatment for dual disorder patients

Results on the effectiveness of psychosocial treatments for patients with comorbid psychiatric and substance use disorders (dual disorders) will be discussed based on relevant meta-analyses and comprehensive reviews. Findings pertaining to severe (e.g., schizophrenia) and mild to moderate (e.g., anxiety disorders) dual disorders will be presented. The heterogeneity in patient characteristics, treatments, settings, and measured outcomes within the studies hinders the extraction of simple conclusions regarding how to effectively integrate psychiatric and addiction-oriented services into one psychosocial treatment. However, promising treatment strategies and interventions include integrative programs that comprise motivational interviewing; disorder-specific cognitive-behavioral interventions; substance use reduction interventions such as relapse prevention or contingency management; and/or family interventions. Such programs are generally superior to control groups (e.g., waiting list, treatment as usual) and are sometimes superior to other active treatments (e.g., skills training) in outcomes of substance use, psychiatric disorders, and social functioning.

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part I: Single crowns (SCs).

OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported single crowns (SCs) and to describe the incidence of biological, technical and esthetic complications. METHODS Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported fixed dental prostheses (FDPs) with a mean follow-up of at least 3 years. This was complimented by an additional hand search and the inclusion of 34 studies from a previous systematic review [1,2]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS Sixty-seven studies reporting on 4663 metal-ceramic and 9434 all-ceramic SCs fulfilled the inclusion criteria. Seventeen studies reported on metal-ceramic crowns, and 54 studies reported on all-ceramic crowns. Meta-analysis of the included studies indicated an estimated survival rate of metal-ceramic SCs of 94.7% (95% CI: 94.1-96.9%) after 5 years. This was similar to the estimated 5-year survival rate of leucit or lithium-disilicate reinforced glass ceramic SCs (96.6%; 95% CI: 94.9-96.7%), of glass infiltrated alumina SCs (94.6%; 95% CI: 92.7-96%) and densely sintered alumina and zirconia SCs (96%; 95% CI: 93.8-97.5%; 92.1%; 95% CI: 82.8-95.6%). In contrast, the 5-year survival rates of feldspathic/silica-based ceramic crowns were lower (p<0.001). When the outcomes in anterior and posterior regions were compared feldspathic/silica-based ceramic and zirconia crowns exhibited significantly lower survival rates in the posterior region (p<0.0001), the other crown types performed similarly. Densely sintered zirconia SCs were more frequently lost due to veneering ceramic fractures than metal-ceramic SCs (p<0.001), and had significantly more loss of retention (p<0.001). In total higher 5 year rates of framework fracture were reported for the all-ceramic SCs than for metal-ceramic SCs. CONCLUSIONS Survival rates of most types of all-ceramic SCs were similar to those reported for metal-ceramic SCs, both in anterior and posterior regions. Weaker feldspathic/silica-based ceramics should be limited to applications in the anterior region. Zirconia-based SCs should not be considered as primary option due to their high incidence of technical problems.

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part II: Multiple-unit FDPs.

OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported fixed dental prostheses (FDPs) and to describe the incidence of biological, technical and esthetic complications. METHODS Medline (PubMed), Embase and Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported FDPs with a mean follow-up of at least 3 years. This was complemented by an additional hand search and the inclusion of 10 studies from a previous systematic review [1]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS Forty studies reporting on 1796 metal-ceramic and 1110 all-ceramic FDPs fulfilled the inclusion criteria. Meta-analysis of the included studies indicated an estimated 5-year survival rate of metal-ceramic FDPs of 94.4% (95% CI: 91.2-96.5%). The estimated survival rate of reinforced glass ceramic FDPs was 89.1% (95% CI: 80.4-94.0%), the survival rate of glass-infiltrated alumina FDPs was 86.2% (95% CI: 69.3-94.2%) and the survival rate of densely sintered zirconia FDPs was 90.4% (95% CI: 84.8-94.0%) in 5 years of function. Even though the survival rate of all-ceramic FDPs was lower than for metal-ceramic FDPs, the differences did not reach statistical significance except for the glass-infiltrated alumina FDPs (p=0.05). A significantly higher incidence of caries in abutment teeth was observed for densely sintered zirconia FDPs compared to metal-ceramic FDPs. Significantly more framework fractures were reported for reinforced glass ceramic FDPs (8.0%) and glass-infiltrated alumina FDPs (12.9%) compared to metal-ceramic FDPs (0.6%) and densely sintered zirconia FDPs (1.9%) in 5 years in function. However, the incidence of ceramic fractures and loss of retention was significantly (p=0.018 and 0.028 respectively) higher for densely sintered zirconia FDPs compared to all other types of FDPs. CONCLUSIONS Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramic FDPs. The incidence of framework fractures was significantly higher for reinforced glass ceramic FDPs and infiltrated glass ceramic FDPs, and the incidence for ceramic fractures and loss of retention was significantly higher for densely sintered zirconia FDPs compared to metal-ceramic FDPs.

Implant-supported mandibular overdentures and cortical bone formation: clinical and radiographic results

PURPOSE: The aim of this study was to evaluate the hard and soft tissue parameters around implants supporting overdentures and the possible influence of increased periimplant bone density (IPBD) on implant success. MATERIALS AND METHODS: A total of 44 dental implants placed in the mandible of 12 patients were included in the study. Implants were divided in 2 groups in relation to the optically detected IPBD. Periimplant clinical and radiographic variables were collected over the period of 5 years. RESULTS: Periimplant clinical and radiographic parameters for all implants did not change significantly throughout the observation period (P > 0.05). Significant differences were observed between implants with and without IPBD for periimplant soft tissue parameters and Periotest values (P < 0.05). Implants with and without IPBD at 5-year control showed mean bone loss of 0.04 ± 0.48 mm and 0.55 ± 0.96 mm, respectively (P = 0.026). All density values decreased throughout the observation period, except maximal values for implants with IPBD that overcome the initial values at the 5-year control. CONCLUSIONS: Implants supporting overdentures were clinically successful over the period of follow-up. IPBD may be related to the maintenance of the periimplant bone level.

A potential application of sludge-based catalysts for the anaerobic bio-decolorization of tartrazine dye.

Two highly efficient (K2CO3/sludge carbon and ZnCl2/sludge carbon) solids were prepared by chemical addition following carbonization at 800 °C and were tested for anaerobic reduction of tartrazine dye in a continuous upflow packed-bed biological reactor, and their performance was compared to that of commercial activated carbon (CAC). The chemical and structural information of the solids was subjected to various characterizations in order to understand the mechanism for anaerobic decolorization, and efficiency for SBCZN800 and SBCPC800 materials was 87% and 74%, respectively, at a short space time (τ) of 2.0 min. A first-order kinetic model fitted the experimental points and kinetic constants of 0.40, 0.92 and 1.46 min(-1) were obtained for SBCZN800, SBCPC800 and CAC, respectively. The experimental results revealed that performance of solids in the anaerobic reduction of tartrazine dye can depend on several factors including chemical agents, carbonization, microbial population, chemical groups and surface chemistry. The Langmuir and Freundlich models are successfully described in the batch adsorption data. Based on these observations, a cost-effective sludge-based catalyst can be produced from harmful sewage sludge for the treatment of industrial effluents.

Synthesis and Structural Elucidation of Triazolylmolybdenum(VI) Oxide Hybrids and Their Behavior as Oxidation Catalysts

A large family of bifunctional 1,2,4-triazole molecular tectons (tr) has been explored for engineering molybdenum(VI) oxide hybrid solids. Specifically, tr ligands bearing auxiliary basic or acidic groups were of the type amine, pyrazole, 1H-tetrazole, and 1,2,4-triazole. The organically templated molybdenum(VI) oxide solids with the general compositions [MoO3(tr)], [Mo2O6(tr)], and [Mo2O6(tr)(H2O)2] were prepared under mild hydrothermal conditions or by refluxing in water. Their crystal structures consist of zigzag chains, ribbons, or helixes of alternating cis-{MoO4N2} or {MoO5N} polyhedra stapled by short [N–N]-tr bridges that for bitriazole ligands convert the motifs into 2D or 3D frameworks. The high thermal (235–350 °C) and chemical stability observed for the materials makes them promising for catalytic applications. The molybdenum(VI) oxide hybrids were successfully explored as versatile oxidation catalysts with tert-butyl hydroperoxide (TBHP) or aqueous H2O2 as an oxygen source, at 70 °C. Catalytic performances were influenced by the different acidic–basic properties and steric hindrances of coordinating organic ligands as well as the structural dimensionality of the hybrid.

Monitoring the Chemical State of Catalysts for CO 2 Electroreduction: An In Operando Study

A major concern of electrocatalysis research is to assess the structural and chemical changes that a catalyst may itself undergo in the course of the catalyzed process. These changes can influence not only the activity of the studied catalyst but also its selectivity toward the formation of a certain product. An illustrative example is the electroreduction of carbon dioxide on tin oxide nanoparticles, where under the operating conditions of the electrolysis (that is, at cathodic potentials), the catalyst undergoes structural changes which, in an extreme case, involve its reduction to metallic tin. This results in a decreased Faradaic efficiency (FE) for the production of formate (HCOO–) that is otherwise the main product of CO2 reduction on SnOx surfaces. In this study, we utilized potential- and time-dependent in operando Raman spectroscopy in order to monitor the oxidation state changes of SnO2 that accompany CO2 reduction. Investigations were carried out at different alkaline pH levels, and a strong correlation between the oxidation state of the surface and the FE of HCOO– formation was found. At moderately cathodic potentials, SnO2 exhibits a high FE for the production of formate, while at very negative potentials the oxide is reduced to metallic Sn, and the efficiency of formate production is significantly decreased. Interestingly, the highest FE of formate production is measured at potentials where SnO2 is thermodynamically unstable; however, its reduction is kinetically hindered.

Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

Are claims made in orthodontic journal advertisements evidence-supported?

OBJECTIVE To examine the supporting evidence of advertisements published in six leading orthodontic journals. MATERIALS AND METHODS The 2012-2013 printed issues of American Journal of Orthodontics and Dentofacial Orthopedics, Australian Orthodontic Journal, Journal of Orthodontics, European Journal of Orthodontics, Journal of Clinical Orthodontics, and Journal of Orofacial Orthopedics were screened for advertisements implying superior performance compared with competitor products. Advertisements were classified according to type of product, availability, and currency of supporting references. RESULTS A total of 99 unique advertisements claiming clinical benefit or superiority were identified. The overwhelming majority of the identified advertisements promoted appliance products (62.6%), orthodontic materials (14.1%), and dental operatory equipment, including imaging systems (12.1%). Advertisements were found to provide references or not regardless of the product type. Half of the advertisements referred to at least one peer-reviewed publication, whereas unpublished studies were cited by 25% of the advertisements. Most of the referenced articles were published within the past 5 years. CONCLUSIONS The scientific background of advertisements in the orthodontic literature appears limited. While surveillance of journal advertising needs to be regulated, clinicians are urged to critically appraise the claims being made in orthodontic print advertisements by consulting the associated existing evidence.