[Work Participation after Multimodal Rehabilitation due to Cardiovascular Diseases - Representative Analyses using Routine Data of the German Pension Insurance]. / Berufliche Teilhabe nach einer medizinischen Rehabilitation aufgrund von kardiovaskulären Erkrankungen ­ Repräsentative Analysen auf Basis der Routinedaten der Deutschen Rentenversicherung.

PURPOSE: Cardiovascular diseases represent a large proportion of the disease burden of the adult population in Germany. Their importance in rehabilitation has increased continuously in recent years. Several studies have investigated return to work of cardiac patients after rehabilitation, which is relevant from the perspective of pension insurance. However, there is a lack of representative findings for the German region on employment trajectories and their influencing factors. METHODS: The rehabilitation statistics database of the German Pension Insurance (GPI) was used for this study. Subjects were patients with cardiovascular diseases undergoing rehabilitation in 2017. Analyses were performed for the total group and differentiated by relevant diagnosis groups. Occupational participation was operationalized via a monthly state variable up to 24 months after rehabilitation and the rate of all persons who were employed at the 12- and 24- month follow-up and in the 3 months before, respectively. Multiple logistic regression models were calculated to analyze the influencing factors. RESULTS: The total sample comprised 59,667 patients. The average age in all groups was between 53 and 56 years. Men were disproportionately represented; 70% of the services were provided as follow-up rehabilitations and 88% in the inpatient setting. Stable employment rates were 66% after one year and 63% after two years in the overall group (disease groups: 49% to 71%). The strongest influencing factors were the amount of pay and the number of sickness absence days before rehabilitation, active employment before rehabilitation, and age. CONCLUSION: For the first time, representative data on occupational participation following rehabilitation on behalf of the GPI are available for the disease groups considered. The analyses underline the need to focus on occupational perspectives already in medical rehabilitation or directly thereafter.

Network location and clustering of genetic mutations determine chronicity in a stylized model of genetic diseases.

In a highly simplified view, a disease can be seen as the phenotype emerging from the interplay of genetic predisposition and fluctuating environmental stimuli. We formalize this situation in a minimal model, where a network (representing cellular regulation) serves as an interface between an input layer (representing environment) and an output layer (representing functional phenotype). Genetic predisposition for a disease is represented as a loss of function of some network nodes. Reduced, but non-zero, output indicates disease. The simplicity of this genetic disease model and its deep relationship to percolation theory allows us to understand the interplay between disease, network topology and the location and clusters of affected network nodes. We find that our model generates two different characteristics of diseases, which can be interpreted as chronic and acute diseases. In its stylized form, our model provides a new view on the relationship between genetic mutations and the type and severity of a disease.

Collective patterns and stable misunderstandings in networks striving for consensus without a common value system.

Collective phenomena in systems of interacting agents have helped us understand diverse social, ecological and biological observations. The corresponding explanations are challenged by incorrect information processing. In particular, the models typically assume a shared understanding of signals or a common truth or value system, i.e., an agreement of whether the measurement or perception of information is 'right' or 'wrong'. It is an open question whether a collective consensus can emerge without these conditions. Here we introduce a model of interacting agents that strive for consensus, however, each with only a subjective perception of the world. Our communication model does not presuppose a definition of right or wrong and the actors can hence not distinguish between correct and incorrect observations. Depending on a single parameter that governs how responsive the agents are to changing their world-view we observe a transition between an unordered phase of individuals that are not able to communicate with each other and a phase of an emerging shared signalling framework. We find that there are two types of convention-aligned clusters: one, where all social actors in the cluster have the same set of conventions, and one, where neighbouring actors have different but compatible conventions ('stable misunderstandings').

Pipette Show: An Open Source Web Application to Support Pipetting into Microplates.

Despite increasing automation, manual pipetting remains a daily important task in life science laboratories. However, the creation of an efficient work plan is often time-consuming, and its completion is error-prone. Here, we present Pipette Show, a free Vue.js based application that optimizes the generation of an efficient work plan for pipetting into microplates and supports its reliable execution by visual guidance. The basis forms a graphical web interface with a module for building workflows as well as a module displaying the information for each pipetting step by illuminating wells of microplates placed on a tablet.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 1.

BACKGROUND: Although cardiovascular rehabilitation (CR) is well accepted in general, CR-attendance and delivery still considerably vary between the European countries. Moreover, clinical and prognostic effects of CR are not well established for a variety of cardiovascular diseases. METHODS: The guidelines address all aspects of CR including indications, contents and delivery. By processing the guidelines, every step was externally supervised and moderated by independent members of the "Association of the Scientific Medical Societies in Germany" (AWMF). Four meta-analyses were performed to evaluate the prognostic effect of CR after acute coronary syndrome (ACS), after coronary bypass grafting (CABG), in patients with severe chronic systolic heart failure (HFrEF), and to define the effect of psychological interventions during CR. All other indications for CR-delivery were based on a predefined semi-structured literature search and recommendations were established by a formal consenting process including all medical societies involved in guideline generation. RESULTS: Multidisciplinary CR is associated with a significant reduction in all-cause mortality in patients after ACS and after CABG, whereas HFrEF-patients (left ventricular ejection fraction <40%) especially benefit in terms of exercise capacity and health-related quality of life. Patients with other cardiovascular diseases also benefit from CR-participation, but the scientific evidence is less clear. There is increasing evidence that the beneficial effect of CR strongly depends on "treatment intensity" including medical supervision, treatment of cardiovascular risk factors, information and education, and a minimum of individually adapted exercise volume. Additional psychologic interventions should be performed on the basis of individual needs. CONCLUSIONS: These guidelines reinforce the substantial benefit of CR in specific clinical indications, but also describe remaining deficits in CR-delivery in clinical practice as well as in CR-science with respect to methodology and presentation.

Context in synthetic biology: Memory effects of environments with mono-molecular reactions.

Synthetic biology aims at designing modular genetic circuits that can be assembled according to the desired function. When embedded in a cell, a circuit module becomes a small subnetwork within a larger environmental network, and its dynamics is therefore affected by potentially unknown interactions with the environment. It is well-known that the presence of the environment not only causes extrinsic noise but also memory effects, which means that the dynamics of the subnetwork is affected by its past states via a memory function that is characteristic of the environment. We study several generic scenarios for the coupling between a small module and a larger environment, with the environment consisting of a chain of mono-molecular reactions. By mapping the dynamics of this coupled system onto random walks, we are able to give exact analytical expressions for the arising memory functions. Hence, our results give insights into the possible types of memory functions and thereby help to better predict subnetwork dynamics.

A tightly regulated and adjustable CRISPR-dCas9 based AND gate in yeast.

The robust and precise on and off switching of one or more genes of interest, followed by expression or repression is essential for many biological circuits as well as for industrial applications. However, many regulated systems published to date influence the viability of the host cell, show high basal expression or enable only the overexpression of the target gene without the possibility of fine regulation. Herein, we describe an AND gate designed to overcome these limitations by combining the advantages of three well established systems, namely the scaffold RNA CRISPR/dCas9 platform that is controlled by Gal10 as a natural and by LexA-ER-AD as heterologous transcription factor. We hence developed a predictable and modular, versatile expression control system. The selection of a reporter gene set up combining a gene of interest (GOI) with a fluorophore by the ribosomal skipping T2A sequence allows to adapt the system to any gene of interest without losing reporter function. In order to obtain a better understanding of the underlying principles and the functioning of our system, we backed our experimental findings with the development of a mathematical model and single-cell analysis.

[Rehabilitation of Patients with Peripheral Arterial Disease in the Context of Guideline Recommendations]. / Rehabilitation von Menschen mit einer peripheren arteriellen Verschlusskrankheit im Kontext aktueller Leitlinien. Eine Analyse auf Basis von Routinedaten.

BACKGROUND: The study examines the rehabilitation of patients with peripheral arterial disease (PAD) in the context of current guidelines. METHODOLOGY: All medical rehabilitations completed in 2014 with the initial diagnosis of PAD (ICD-10-GM: I70.2) were analyzed. Sociodemographic and socio-medical characteristics as well as the therapies received were evaluated and compared to current guideline recommendations. RESULTS: 1289 patients with PAD (mean age 56.1 years, 78.3% men) where included in the study. Social-medical parameters outline a fairly multimorbid cohort with poor prognosis for long-term occupational outcome and survival. Evidence-based therapies based on guideline recommendations (including supervised walking 58%, vascular training 63% and PAD-specific education lessons 64%) were performed to a lesser extent than expected. CONCLUSION: The results suggest an overall high standard of rehabilitation of patients with PAD. However, the poor socio-medical prognosis and the partial lack of compliance with guideline recommendations indicate the need for action. The development of specific recommendations for rehabilitation of PAD-patients could therefore be useful.

Analysis of stochastic bifurcations with phase portraits.

We propose a method to obtain phase portraits for stochastic systems. Starting from the Fokker-Planck equation, we separate the dynamics into a convective and a diffusive part. We show that stable and unstable fixed points of the convective field correspond to maxima and minima of the stationary probability distribution if the probability current vanishes at these points. Stochastic phase portraits, which are vector plots of the convective field, therefore indicate the extrema of the stationary distribution and can be used to identify stochastic bifurcations that change the number and stability of these extrema. We show that limit cycles in stochastic phase portraits can indicate ridges of the probability distribution, and we identify a novel type of stochastic bifurcation, where the probability maximum moves to the edge of the system through a gap between the two nullclines of the convective field.

[Need for Information about Medical Rehabilitation of Persons with German Pension Insurance: a Written Survey]. / Informationsbedürfnisse von Versicherten der Deutschen Rentenversicherung zur medizinischen Rehabilitation ­ eine schriftliche Befragung.

AIM: In order to acquire target group-specific information on rehabilitation for members of the German pension insurance, they were asked about their ideas about medical rehabilitation and desired information regarding subjects and kind of information transfer. METHOD: The core of the project was a written survey of members of the German pension insurance. N=600 insured people were invited to participate in the study. The questionnaire was developed in a qualitative pre-study. RESULTS: N=196 questionnaires were evaluated. Recovery of working ability was mentioned by most persons as the aim of medical rehabilitation. The most common idea regarding indication for rehabilitation was a specific operation. Physiotherapy was most often considered as therapy during medical rehabilitation. Information about formal steps, realistic aims and rehabilitation clinics were important. A conversation with their physician, written information material and a website were the preferred information pathways. Two-thirds of participants thought that information about medical rehabilitation was important even though they had no rehabilitation indication at the time of survey. CONCLUSION: The identified target-related information needs can be considered in a need-oriented development of information material. These can contribute to an informed decision for members of the German pension insurance for or against medical rehabilitation or an application for rehabilitation. Moreover, patient-oriented information can contribute to more successful rehabilitation participation, higher satisfaction with and a better rating of medical rehabilitation.

[Subjective Level of Information and Information Needs of Patients with an Approved Rehabilitation Application and Patients at the End of Rehabilitation Results of a Written Survey]. / Subjektiver Informationsstand und Informationsbedürfnisse von Versicherten mit bewilligtem Rehabilitationsantrag und Rehabilitanden am Ende der Rehabilitation Ergebnisse einer schriftlichen Befragung .

AimThe aim of the study was to identify the subjective level of information and information needs of patients with an approved rehabilitation application and patients at the end of rehabilitation with regard to preferred subjects and kind of information transfer. Method Written survey with N=283 patients with approved rehabilitation application and N=388 patients at the end of rehabilitation. ResultsBoth groups reported high information needs particularly regarding treatments during rehabilitation, rehabilitation aftercare and rehabilitation aims. A conversation with their physician, a brochure and a website are the preferred information pathways. Conclusion Taking into account the topics for which both groups require information and the preference regarding the kind of information transfer can make a valuable contribution for the development of needs-oriented information material.

[Return to Work after Acute Myocardial Infarction]. / Berufliche Wiedereingliederung nach akutem Herzinfarkt.

Vocational reintegration provides a key goal for patients after myocardial infarction both from social as well as from individual perspective. Return to work rate is determined by medical parameters such as left ventricular function, residual ischemia and rhythm stability, as well as by occupational requirement profile such as the blue or white collar work, night shifts and the way capacity. Psycho-social factors including depression, self-assessment of their own situation and pre-existing cognitive impairment to a large extent determine the reintegration. Optimally, re-employment should be performed immediately after cardiac rehabilitation in patient after uncomplicated myocardial infarction. After a long hospitalization phase a stepwise inclusion is recommended. In failed reintegration particularly in younger workers retraining should be considered.

A minimal model of burst-noise induced bistability.

We investigate the influence of intrinsic noise on stable states of a one-dimensional dynamical system that shows in its deterministic version a saddle-node bifurcation between monostable and bistable behaviour. The system is a modified version of the Schlögl model, which is a chemical reaction system with only one type of molecule. The strength of the intrinsic noise is varied without changing the deterministic description by introducing bursts in the autocatalytic production step. We study the transitions between monostable and bistable behavior in this system by evaluating the number of maxima of the stationary probability distribution. We find that changing the size of bursts can destroy and even induce saddle-node bifurcations. This means that a bursty production of molecules can qualitatively change the dynamics of a chemical reaction system even when the deterministic description remains unchanged.