Social-ecological analysis of climate induced changes in biodiversity – outline of a research concept

The interactions of changes in climate and biodiversity with societal actions, structures and processes are a priority topic within the international scientific debate – and thus, a relevant subject matter for BiKF’s work. This paper outlines a concept for transdisciplinary research within BiKF. It focuses on the analysis of social-ecological systems supporting society with biodiversity driven ecosystem services. Such research is considering different issues: defining sustainable societal adaptations to climate induced biodiversity changes; permitting adequate understanding of the social-ecological reproduction of ecosystem functions, including their conservation and restoration; analysing the societal values and socio-economic utilisation of ecosystem services. Gaining knowledge in these areas provides an improved basis for decision-making in biodiversity and resource management

Algorithms to identify COPD in health systems with and without access to ICD coding: a systematic review

Background Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide. Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected. This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute. The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available. Methods A systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters. Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables. Results In total, the systematic search yielded 151 publications. After title and abstract screening, 38 publications were included into the systematic assessment. In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits. Only four out of 38 studies used methods other than ICD coding. In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided. Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies. Only five studies used spirometry, two used surgery and one used oxygen therapy. Conclusions A variety of different criteria is used for the identification of COPD from routine data. The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data. Further health services research should focus on the application of more systematic internal and/or external validation approaches

Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online

Background: Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. Methods: A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Results: Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Conclusions: Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM. Electronic supplementary material The online version of this article (10.1186/s12885-017-3603-z) contains supplementary material, which is available to authorized users

Risks and benefits for use of dolutegravir-based antiretroviral drug regimens in sub Saharan Africa: a modelling study

Background: The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains. Methods: We used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted. Findings: The greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving. Interpretation: Using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks. Funding: Bill & Melinda Gates Foundation

Structural and Mutational Analysis of Functional Differentiation between Synaptotagmins-1 and -7

Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7). Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 Å resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences

Achieving highest proton intensities with a laser-based ion beamline

This thesis reports on a test beamline which combines laser-driven ion sources with conventional accelerator elements realized at GSI Helmholtzzentrum für Schwerionenforschung GmbH. The Petawatt High-Energy Laser for Heavy Ion EXperiments (PHELIX) drove a Target Normal Sheath Acceleration (TNSA) source which delivered an exponentially decaying proton spectrum up to ≈ 21.5 MeV. In the next step, the generated proton beam is collimated by a pulsed high-field solenoid, which selected a specific energy range. Through this setting, the central energy was defined, which was transported through the whole beamline. In this thesis, the aim was a central energy value of E0 = 8 MeV and solenoid magnetic field strength of 6.5 T. Proton numbers of the order of 10^9 were measured in an energy interval of (8.5 ± 0.25) MeV. Afterwards, the collimated proton bunch entered a radiofrequency (rf) cavity operated at 108.4 MHz. Inside this element, the particle bunch was compressed in longitudinal phase space around its central energy by a certain angle. At an rf power of 6.26 V, the proton bunch was temporally focused to a bunch duration of (458 ± 40) ps at full width at half maximum (FWHM) in 6 m distance from the source. The measurement was performed with a specially developed diamond membrane detector, which had a time resolution of (113 ± 11) ps (FWHM). Finally, a second pulsed high-field solenoid was built-in as a final focusing system. In consequence, the beam was focused down to a focal spot size of 1.1 mm x 1.2 mm at FWHM

Sustainable science in the anthropocene

The anthropocene – the epoch of humankind – is currently a topic of great interest. What consequences does the idea of humanity as a geological force have for the undertaken path of sustainable development? What new questions are arising for sustainability science? Diagnosing contemporary society from an anthropocene perspective could change the relationship between natural and social sciences, as well as between society and science: science will be needed even more as a critical authority and must be organized to an even greater extent in a transdisciplinary manner. New forms of social participation in the process of producing scientifically legitimated knowledge are indispensable.∗ More than ten years ago the Dutch chemist and Nobel laureate Paul Crutzen coined the term “Anthropocene” to describe the period during which humans have begun to significantly influence biological, geological and atmospheric processes, thus becoming a relevant geological force on planet Earth (Crutzen and Stoermer 2000, Crutzen 2002). In the earth sciences the anthropocene represents nothing less than a transition to a new epoch and is therefore being discussed intensively. Until 2016 data have been collected by geologists from the International Commission on Stratigraphy (ICS) to provide evidence that might help answer the question whether a turning point has been reached in the history of the Earth (Zalasiewicz et al. 2011). A decision will be made as to whether and when a new epoch in Earth history has begun. The significance and consequences outside the geoscientific discourse of identifying an “epoch of humans” (Zalasiewicz 2013) has, so far, only been understood to a small extent. Yet this change of perspective is one of the most important in the last 100 hundred years, for it means society and nature have become so closely intertwined that they can no longer be studied independently of each other. Natural spheres and societal spheres have merged into one large system (Guillaume 2015, Becker und Jahn 2006). A well-founded acceptance of the concept of the anthropocene, however, has been lacking, especially where transitions to a sustainable development are being researched. It remains unclear whether the concept of the Anthropocene will lead to a new fundamental understanding of the relationships between nature and society and, if so, what opportunities this new understanding might open for shaping these relationships in a more sustainable manner. And lastly, and equally importantly, it is still unclear whether science’s role and responsibilities will change in the course of developing visions of the future. With this article we hope to stimulate further discussions of these issues

Skill acquisition in the use of driver information systems

Fahrerinformations- und Fahrerassistenzsysteme (FIS/FAS), die während der Fahrt zusätzliche, den Fahrer entlastende Funktionen anbieten, können durch damit verbundene Bedienvorgänge Aufmerksamkeit beanspruchen und in der Folge durch visuelle Ablenkung und mentale Beanspruchung unerwünschte sicherheitsrelevante Veränderungen des Fahrverhaltens hervorrufen. Allerdings stellt die Interaktion mit Fahrerinformationssystemen bei fortschreitender Übung zunehmend geringere Aufmerksamkeitsanforderungen. Dieser Effekt des Kompetenzerwerbs ist bei der Beurteilung der sicherheitskritischen Fahrerbeanspruchung zu beachten. In einem Fahrversuch wurde die Veränderung von Ablenkungswirkungen als Folge des Kompetenzerwerbs in der Bedienung von Fahrerinformationssystemen untersucht. Als Aufgabe wurde die Zieleingabe in ein Navigationssystem gewählt. Zwei Navigationssysteme mit unterschiedlichen Mensch-Maschine-Schnittstellen wurden dabei eingesetzt. Mit denselben Systemen wurden in weiteren Trainingsstudien Daten zum Kompetenzerwerb für drei Altersgruppen erhoben. Als Methode zur kondensierten Beschreibung der Kompetenzerwerbsverläufe wurde die Schätzung von Potenzfunktionsparametern verwendet. Aufgrund unterschiedlicher Bedienelemente und abweichend konzipierter Eingabedialoge führten die Systeme wie erwartet zu deutlichen Unterschieden in der Fahrerbeanspruchung. Auch der Lernverlauf von Fahrern mittleren Alters und von älteren Fahrern wich erheblich voneinander ab. Jüngere Fahrer erreichten deutlich kürzere Bearbeitungszeiten mit beiden Systemen. Auswertungen des Blickverhaltens im Fahrversuch ergaben umfangreiche Datensätze zur visuellen Ablenkung in verschiedenen Fahrbedingungen. Der Kompetenzerhalt nach einigen Monaten war außer in der Gruppe älterer Fahrer fast vollständig. Es war kein Transfer zwischen den deutlich verschiedenen Systemen festzustellen. Die Schätzung von Potenzfunktionsparametern hat sich insgesamt als Methode zur Beschreibung des Kompetenzerwerbs bewährt. In einer weiteren Studie wurde die erste Phase des Kompetenzerwerbs für vier unterschiedliche Navigationssysteme mit der Okklusionsmethode untersucht, die als Bewertungsverfahren der visuellen Beanspruchung durch Fahrerinformationssysteme vorgeschlagen ist. Die Projektstudien leisten damit auch einen Beitrag zur Methodenentwicklung und zur Einschätzung der sicherheitsrelevanten Auswirkungen von Fahrerinformationssystemen.Driver information and driver assistance systems (Fahrerinformations- und Fahrerassistenzsysteme - FIS/FAS) have functions which can be used during journeys to reduce demands made on drivers; operating these systems can, however, claim the driver- attention, causing visual distraction and making mental demands of the driver which can in turn lead to undesired, safety-relevant changes in driver behaviour. However, the amount of attention required to interact with driver information systems decreases with continued practice. Account must be taken of this skill acquisition effect when assessing whether demands placed on the driver endanger safety. Tests of driver behaviour were carried out to investigate how the degree of distraction changed due to skill acquisition in the operation of driver information systems. Entering the destination into a navigation system was selected as the task for investigation. Two navigation systems with different people-machine interfaces were used. Other training studies used the same systems to record data on skill acquisition in three age groups. The estimation of power function parameters was used as a method for condensed description of the skills-acquisition development process. As expected, the different operating elements and the differently designed input dialogues of the two systems meant that the demands made on the drivers differed. The learning development process of middle-aged drivers also deviated considerably from that of older drivers. Younger drivers recorded significantly shorter processing times with both systems. Assessment of eye behaviour in the driving-behaviour tests produced extensive data records on visual distraction in different driving circumstances. Apart from the group of older drivers, almost all the skills gained had been maintained when tested after a period of some months. No transfer was detected between the significantly different systems. Overall, the estimation of power function parameters proved itself as a method to describe skill acquisition. A further study used the occlusion method to investigate the first phase of skill acquisition for four different navigations systems; it is proposed that this method should be used to evaluate the visual demands made by driver information systems. The project studies therefore also contribute to the development of methodology and to estimating the safety-relevant effects of driver information systems

Social Ecology as Critical, Transdisciplinary Science - Conceptualizing, Analyzing and Shaping Societal Relations to Nature

The sustainability discourse is, essentially, centered on the question of how complex relations between nature and society can be conceptualized, analyzed and shaped. In this paper, we present a specific interpretation of social ecology as an attempt to address this question. For this purpose, we establish Frankfurt Social Ecology (FSE) as a formal research program, which is based on the concept of societal relations to nature (SRN). The basic idea of the SRN concept is to put the modern distinction between nature and society at the start of a critical analysis. Such an analysis, we argue, has to focus on the interplay between what we call patterns and modes of regulation. Whereas patterns of regulation stand for the material and symbolic aspects of the organization of the individual and societal satisfaction of needs, modes of regulation mirror the norms and power structures of a society. Using an approach that is based on reformulating social-ecological systems as provisioning systems, we show how this interplay can be analyzed empirically. Finally, we propose critical transdisciplinarity as the research mode of choice of FSE. To conclude, we discuss how FSE can contribute to the development of a research program for a sustainable Anthropocene