Preventive maintenance and rehabilitation of rigid pavements

Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in engl. und bulg. SpracheDie Herausforderung für Straßenbetreiber mit einem gut ausgebauten Straßennetz wird sich in Zukunft immer stärker in Richtung Erhaltung verschieben. Nur im Rahmen eines systematischen Erhaltungsmanagements ist es möglich die Verfügbarkeit des Bestandes dauerhaft zu sichern. Dazu ist es notwendig die richtige Maßnahme zur richtigen Zeit im Rahmen knapper werdender Budgets zu setzen.Die vorliegende Diplomarbeit befasst sich mit der systematischen Instandhaltung und Instandsetzung von Betonfahrbahnen. Ausgehend von einer Literaturrecherche sowie Befragung von Spezialisten im Betonstraßenbau wird ein Überblick über die Grundzüge eines systematischen Erhaltungsmanagements gegeben. Weiters werden die bestehenden Schadenskataloge für Betonfahrbahnen überprüft und ergänzt.Der eigentliche Kern der Arbeit ist jedoch die Ausarbeitung von Instandhaltungs- und Instandsetzungsmaßnahmenkatalogen zur Behebung dieser Schäden. Ausgehend von einer Schadens- und Maßnahmenmatrix, in der den einzelnen Schäden mögliche Maßnahmen zugewiesen werden, erfolgt eine Konkretisierung der Maßnahmen bis hin zur Auflistung der einzelnen Arbeitsschritte und Leistungspositionen. Abgerundet wird die Arbeit durch Information und Ansätzen für die wirtschaftliche Umsetzung und Optimierung der ausgearbeiteten Maßnahmen. Für die wirtschaftliche Optimierung bei einem gegebenen Schadensbild sind die möglichen Maßnahmen durch die Schadens/Maßnahmenmatrix definiert. Aus dem Vergleich der notwendigen Maßnahmen und ihrer erzielbaren Wirkdauer ergibt sich eine Annuität (Kosten pro Jahr). Die Erhaltungsmaßnahme oder Kombination von Maßnahmen mit der geringsten Annuität ist wirtschaftlich optimal im Rahmen der Erhaltungsstrategie.Durch die systematische Zusammenstellung von der Zustandserfassung bis hin zur Maßnahmenplanung und Budgetierung in der vorliegenden Arbeit wird eine erfolgreiche Umsetzung in der Praxis wesentlich erleichtert.Nachdem sich die Bautechnik weiterentwickelt, wird es sinnvoll sein die Schadens- und Maßnahmenkataloge fortzuschreiben und die Wirkung der Maßnahmen durch empirische Untersuchungen weiter zu erhärten.The challenges for transportation agencies and road administrations are getting focused more and more on the preservation of the existing road network. Only a well-designed program roadway preventive maintenance and rehabilitation can provide satisfactory performance of the pavement during its design life and actually extend it. The main prerequisite for this is the timely selection of a technologically and economically appropriate and proven method and strategy for maintenance. The thesis addresses the systematic preventive maintenance and rehabilitation of rigid pavements. Based on a literature review and a survey among specialists in this field, it provides an overview of the basics of systematic roadway preservation and rehabilitation management.The common distresses for rigid pavements are summarized in the form of a cataloge, which serves as a basis for further analyses. The rehabilitation measures, which could be applied for treating each distress type, are defined in matrix form. The main part of the thesis gives instructions and specific practice descriptions of the maintenance techniques. A cataloge is developed for every measurement technique, which be-sides short description of the measure it also includes data on important components for further economic analysis, such as costs, expected service life, construction timeframe and section length. Possible treatments for each distress type can be defined by the "Distress type/ maintenance technique"- matrix. For the economic optimization rehabilitation alternatives are compared, based on their annual costs (annuity), which can be calculated using the unit costs and expected service life, as well as the interest rate. The measure, or the combination of several measures, with the lowest annuity, is considered to provide the most economic value over time. The systematic presentation of the main stages of one pavement preservation strategy makes its implementation in practice much easier.Taking into account the fact, that technologies in roadway engineering are continually being developed, it would be reasonable to periodically update these distress and preservation measurement catalogs and also to include empirical analysis of the effect of the proposed solutions.11

Montgomery‐Åsberg Depression Rating Scale factors in treatment‐resistant depression at onset of treatment: Derivation, replication, and change over time during treatment with esketamine

Abstract Objective Derive and confirm factor structure of the Montgomery‐Åsberg Depression Rating Scale (MADRS) in patients with treatment‐resistant depression (TRD) and evaluate how the factors evident at baseline change over 4 weeks of esketamine treatment. Methods Two similarly‐designed, short‐term TRANSFORM trials randomized adults to esketamine or matching placebo nasal spray, each with a newly‐initiated oral antidepressant, for 4 weeks (TRANSFORM‐1: N = 342 patients; TRANSFORM‐2: N = 223 patients). The factor structure of MADRS item scores at baseline was determined by exploratory factor analysis in TRANSFORM‐2 and corroborated by confirmatory factor analysis in TRANSFORM‐1. Change in MADRS factor scores from baseline (day 1) to the end of the 28‐day double‐blind treatment phase of TRANSFORM‐2 was analyzed using a mixed‐effects model for repeated measures (MMRM). Results Three factors were identified based on analysis of MADRS items: Factor 1 labeled affective and anhedonic symptoms (apparent sadness, reported sadness, lassitude, inability to feel), Factor 2 labeled anxiety and vegetative symptoms (inner tension, reduced sleep, reduced appetite, concentration difficulties), and Factor 3 labeled hopelessness (pessimistic thoughts, suicidal thoughts). The three‐factor structure observed in TRANSFORM‐2 was verified in TRANSFORM‐1. Treatment benefit at 24 h with esketamine versus placebo was observed on all 3 factors and continued throughout the 4‐week double‐blind treatment period. Conclusions A three‐factor structure for MADRS appears to generalize to TRD. All three factors improved over 4 weeks of treatment with esketamine nasal spray

Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field