BMBF-Verbund-Projekt: "Interdisziplinarität von Wissenschaftseinrichtungen - Strukturen und Effekte" (INTERDIS), Teilvorhaben "Detailanalysen zur MPG"

1 Einleitung 3 2 Datenquellen und Methoden 4 2.1 Externe Datenquellen 4 2.2 Datenaufbereitung und Auswahl 5 2.3 Fachklassifikationen 7 2.4 Topic-Modelling 8 2.4.1 Latent Dirichlet Allocation 8 2.4.2 Korpora 8 2.4.3 Linguistische Vorverarbeitung der Textdokumente 8 2.4.4 LDA-Modellierung 9 2.5 Indikatoren der Interdisziplinarität 10 2.5.1 Teilmengen (Sets) 10 2.5.2 Einfache Indikatoren 10 2.5.3 Auf Zitationsnetzwerken basierende Indikatoren 10 2.6 Statistik, Visualisierung, Archivierung 11 3 Ergebnisse 12 3.1 Klassische Bibliometrische Indikatoren zur Messung der Interdisziplinarität 12 3.1.1 Überblick Deutschland 12 3.1.2 Teilgruppen der Max Planck Gesellschaft 15 3.2 Neue Methoden zur Messung von Interdisziplinarität 17 3.2.1 Patente 17 3.2.2 Kooperationsprojekte 19 3.2.3 Personal 21 3.2.4 Text-basierte Indikatoren 23 3.3 Synthese der Indikatoren 26 4 Diskussion 28 Literatur und Software 3

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The status of the environmentally sensitive dynamic model of the human physiology used in the V-HAB LSS simulation

The Virtual Habitat project (V-HAB) at the Technical University of Munich (TUM) aims to develop a simulation environment for spacecraft life support systems (LSS). The tool is implemented using the object orientated programming (OOP) approach to enable a highly modular structure. This allows engineers to combine different LSS technologies and elements in a straight-forward and exible way and perform dynamic simulations of open-or closed-loop as well as non-regenerative or regenerative LSS. In addition to providing a toolbox that can be used to create physical/chemical systems out of their basic components and biological modules to simulate plants and algae, the environmentally sensitive dynamic model of the human physiology is crucial part of the V-HAB simulation. The V-HAB human model was developed to provide the relevant metabolic inputs and outputs that respectively serve as outputs and inputs for the LSS, and to correlate these interactions to each other. To achieve that goal, it was necessary to enable the human model to react to environmental and operational influences. The V-HAB human not only tracks mass inputs and outputs, but also includes mechanical work and heat produced as a function of its load level and state. However, no prediction of pathological effects is included, as the calculations are based on high-level physiological relationships, not detailed medical issues. But if desired, some illnesses and the reaction to certain off-nominal conditions can be modeled; they just have to be triggered manually. The V-HAB human is broken into five distinct sub-models (layers) of metabolism, respiration, water, digestion, thermal that where developed in recent years. This paper focusses on how the individual layers have been integrated to one comprehensive model. This was done by linking the important interfaces between the layers to each other. Moreover, the model's reaction to exercise and hypoxic/hyperoxic conditions was verified mainly for the metabolic and respiratory layers using experimental data cited in the literature. Also, a description of the newly developed meta-model, which can be used to introduce additional physiological effects, is given

A New Human Thermal Model for the Dynamic Life Support System Simulation V-HAB

The Virtual Habitat project (V-HAB) at the Technical University of Munich (TUM) aims to develop a dynamic simulation environment for life support systems (LSS). Within V-HAB a dynamic human model interacts with the LSS by relevant metabolic inputs and outputs based on internal, environmental and operational factors. The human model is separated into five sub-models (called layers) representing metabolism, respiration, thermoregulation, water balance and digestion. As V-HAB is evolving, new requirements emerge for the human model, as it is used for the simulation of both short term (e.g. EVA) and long term (e.g. space station) missions. These requirements call for different fidelity levels for each of the layers of the model (to allow for faster or more detailed simulations) and a more precise calculation of heat production and heat exchange within a subject and with its environment. The current version of the thermoregulation focuses on the trunk temperature and warmer environments, containing six thermal nodes. However, for a scenario like EVAs, the resolution of this model especially in the extremities is too low. Therefore, the Wissler thermal model was converted from Fortran to C#, also introducing a more modularized structure and a standalone graphical user interface (GUI). Currently, a initial interface to V-HAB is being implemented, making it possible to use the model in V-HAB. To fully integrate the Wissler model with the V-HAB simulation, the fluid and thermal solver framework in V-HAB has to be used to solve the equations provided by the Wissler model. This will allow a close interaction between the human thermal layer and the environment defined in V-HAB. This is necessary to allow using the model not only in normal environments, but also connect it to e.g. the model of the liquid cooling garment implemented in V-HAB. While this integration is ongoing, the currently implemented arm model and initial validation results are presented

Chancen und Grenzen einer Friedenserziehung im Schulfach Politik/Sozialkunde

Frieden ist eine wichtige Kategorie der politischen Bildung. Der Beitrag versucht, den fachlichen Beitrag des Schulfachs Politik/Sozialkunde für die Aufgaben der Friedenserziehung zu bestimmen. Der Politikunterricht hat die Aufgabe, den politischen Prozess und das Handeln der Akteure in aktuellen Konfliktfällen zu rekonstruieren und zu interpretieren. Die Anschaulichkeit der Politik wird durch unterrichtliche Fallanalysen erhöht. Der friedenspädagogische Ertrag des Politikunterrichts liegt darin, dass die Schülerinnen und Schüler eine reflektierende Einstellung gegenüber den Akteuren gewinnen können

PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis

ObjectivesPEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. MethodsPEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. ResultsA total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. ConclusionsNoninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines