Rheology of gelling polymers in the Zimm model

In order to study rheological properties of gelling systems in dilute solution, we investigate the viscosity and the normal stresses in the Zimm model for randomly crosslinked monomers. The distribution of cluster topologies and sizes is assumed to be given either by Erd\H os-R\'enyi random graphs or three-dimensional bond percolation. Within this model the critical behaviour of the viscosity and of the first normal stress coefficient is determined by the power-law scaling of their averages over clusters of a given size $n$ with $n$. We investigate these Mark--Houwink like scaling relations numerically and conclude that the scaling exponents are independent of the hydrodynamic interaction strength. The numerically determined exponents agree well with experimental data for branched polymers. However, we show that this traditional model of polymer physics is not able to yield a critical divergence at the gel point of the viscosity for a polydisperse dilute solution of gelation clusters. A generally accepted scaling relation for the Zimm exponent of the viscosity is thereby disproved.Comment: 9 pages, 2 figure

Functional somatic disorders: discussion paper for a new common classification for research and clinical use

Background Functional somatic symptoms and disorders are common and complex phenomena involving both bodily and brain processes. They pose major challenges across medical specialties. These disorders are common and have significant impacts on patients’ quality of life and healthcare costs. Main body We outline five problems pointing to the need for a new classification: (1) developments in understanding aetiological mechanisms; (2) the current division of disorders according to the treating specialist; (3) failure of current classifications to cover the variety of disorders and their severity (for example, patients with symptoms from multiple organs systems); (4) the need to find acceptable categories and labels for patients that promote therapeutic partnership; and (5) the need to develop clinical services and research for people with severe disorders. We propose ‘functional somatic disorders’ (FSD) as an umbrella term for various conditions characterised by persistent and troublesome physical symptoms. FSDs are diagnosed clinically, on the basis of characteristic symptom patterns. As with all diagnoses, a diagnosis of FSD should be made after considering other possible somatic and mental differential diagnoses. We propose that FSD should occupy a neutral space within disease classifications, favouring neither somatic disease aetiology, nor mental disorder. FSD should be subclassified as (a) multisystem, (b) single system, or (c) single symptom. While additional specifiers may be added to take account of psychological features or co-occurring diseases, neither of these is sufficient or necessary to make the diagnosis. We recommend that FSD criteria are written so as to harmonise with existing syndrome diagnoses. Where currently defined syndromes fall within the FSD spectrum – and also within organ system-specific chapters of a classification – they should be afforded dual parentage (for example, irritable bowel syndrome can belong to both gastrointestinal disorders and FSD). Conclusion We propose a new classification, ‘functional somatic disorder’, which is neither purely somatic nor purely mental, but occupies a neutral space between these two historical poles. This classification reflects both emerging aetiological evidence of the complex interactions between brain and body and the need to resolve the historical split between somatic and mental disorders

Abrupt and spontaneous strategy switches emerge in simple regularised neural networks

Humans sometimes have an insight that leads to a sudden and drastic performance improvement on the task they are working on. Sudden strategy adaptations are often linked to insights, considered to be a unique aspect of human cognition tied to complex processes such as creativity or meta-cognitive reasoning. Here, we take a learning perspective and ask whether insight-like behaviour can occur in simple artificial neural networks, even when the models only learn to form input-output associations through gradual gradient descent. We compared learning dynamics in humans and regularised neural networks in a perceptual decision task that included a hidden regularity to solve the task more efficiently. Our results show that only some humans discover this regularity, whose behaviour was marked by a sudden and abrupt strategy switch that reflects an aha-moment. Notably, we find that simple neural networks with a gradual learning rule and a constant learning rate closely mimicked behavioural characteristics of human insight-like switches, exhibiting delay of insight, suddenness and selective occurrence in only some networks. Analyses of network architectures and learning dynamics revealed that insight-like behaviour crucially depended on a regularised gating mechanism and noise added to gradient updates, which allowed the networks to accumulate "silent knowledge" that is initially suppressed by regularised (attentional) gating. This suggests that insight-like behaviour can arise naturally from gradual learning in simple neural networks, where it reflects the combined influences of noise, gating and regularisation.Comment: 17 pages, 5 figure

Hierarchical Graph Transformation

If systems are specified by graph transformation, large graphs should be structured in order to be comprehensible. In this paper, we present an approach for the rule-based transformation of hierarchically structured (hyper)graphs. In these graphs, distinguished hyperedges contain graphs that can be hierarchical again. Our framework extends the well-known double-pushout approach from at to hierarchical graphs. In particular, we show how pushouts and pushout complements of hierarchical graphs and graph morphisms can be constructed recursively. Moreover, we make rules more expressive by introducing variables which allow to copy and to remove hierarchical subgraphs in a single rule application

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978

Validation of the Fibromyalgia Survey Questionnaire within a Cross-Sectional Survey

The Fibromyalgia Survey Questionnaire (FSQ) assesses the key symptoms of fibromyalgia syndrome. The FSQ can be administrated in survey research and settings where the use of interviews to evaluate the number of pain sites and extent of somatic symptom intensity and tender point examination would be difficult. We validated the FSQ in a cross-sectional survey with FMS patients. In a cross-sectional survey, participants with physician diagnosis of FMS were recruited by FMS-self help organisations and nine clinical institutions of different levels of care. Participants answered the FSQ (composed by the Widespread Pain Index [WPI] and the Somatic Severity Score [SSS]) assessing the Fibromyalgia Survey Diagnostic Criteria (FSDC) and the Patient Health Questionnaire PHQ 4. American College of Rheumatology 1990 classification criteria were assessed in a subgroup of participants. 1,651 persons diagnosed with FMS were included into analysis. The acceptance of the FSQ-items ranged between 78.9 to 98.1% completed items. The internal consistency of the items of the SSS ranged between 0.75–0.82. 85.5% of the study participants met the FSDC. The concordance rate of the FSDC and ACR 1990 criteria was 72.7% in a subsample of 128 patients. The Pearson correlation of the SSS with the PHQ 4 depression score was 0.52 (p<0.0001) and with the PHQ anxiety score was 0.51 (p<0.0001) (convergent validity). 64/202 (31.7%) of the participants not meeting the FSDC criteria and 152/1283 (11.8%) of the participants meeting the FSDC criteria reported an improvement (slightly too very much better) in their health status since FMS-diagnosis (Chi2 = 55, p<0.0001) (discriminant validity). The study demonstrated the feasibility of the FSQ in a cross-sectional survey with FMS-patients. The reliability, convergent and discriminant validity of the FSQ were good. Further validation studies of the FSQ in clinical and general population settings are necessary

Critical Dynamics of Gelation

Shear relaxation and dynamic density fluctuations are studied within a Rouse model, generalized to include the effects of permanent random crosslinks. We derive an exact correspondence between the static shear viscosity and the resistance of a random resistor network. This relation allows us to compute the static shear viscosity exactly for uncorrelated crosslinks. For more general percolation models, which are amenable to a scaling description, it yields the scaling relation $k=\phi-\beta$ for the critical exponent of the shear viscosity. Here $\beta$ is the thermal exponent for the gel fraction and $\phi$ is the crossover exponent of the resistor network. The results on the shear viscosity are also used in deriving upper and lower bounds on the incoherent scattering function in the long-time limit, thereby corroborating previous results.Comment: 34 pages, 2 figures (revtex, amssymb); revised version (minor changes

Dynamics of gelling liquids: a short survey

The dynamics of randomly crosslinked liquids is addressed via a Rouse- and a Zimm-type model with crosslink statistics taken either from bond percolation or Erdoes-Renyi random graphs. While the Rouse-type model isolates the effects of the random connectivity on the dynamics of molecular clusters, the Zimm-type model also accounts for hydrodynamic interactions on a preaveraged level. The incoherent intermediate scattering function is computed in thermal equilibrium, its critical behaviour near the sol-gel transition is analysed and related to the scaling of cluster diffusion constants at the critical point. Second, non-equilibrium dynamics is studied by looking at stress relaxation in a simple shear flow. Anomalous stress relaxation and critical rheological properties are derived. Some of the results contradict long-standing scaling arguments, which are shown to be flawed by inconsistencies.Comment: 21 pages, 3 figures; Dedicated to Lothar Schaefer on the occasion of his 60th birthday; Changes: added comments on the gel phase and some reference

The ANTOP study: focal psychodynamic psychotherapy, cognitive-behavioural therapy, and treatment-as-usual in outpatients with anorexia nervosa - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Anorexia nervosa is a serious eating disorder leading to high morbidity and mortality as a result of both malnutrition and suicide. The seriousness of the disorder requires extensive knowledge of effective treatment options. However, evidence for treatment efficacy in this area is remarkably weak. A recent Cochrane review states that there is an urgent need for large, well-designed treatment studies for patients with anorexia nervosa. The aim of this particular multi-centre study is to evaluate the efficacy of two standardized outpatient treatments for patients with anorexia nervosa: focal psychodynamic (FPT) and cognitive behavioural therapy (CBT). Each therapeutic approach is compared to a "treatment-as-usual" control group.</p> <p>Methods/Design</p> <p>237 patients meeting eligibility criteria are randomly and evenly assigned to the three groups – two intervention groups (CBT and FPT) and one control group. The treatment period for each intervention group is 10 months, consisting of 40 sessions respectively. Body weight, eating disorder related symptoms, and variables of therapeutic alliance are measured during the course of treatment. Psychotherapy sessions are audiotaped for adherence monitoring. The treatment in the control group, both the dosage and type of therapy, is not regulated in the study protocol, but rather reflects the current practice of established outpatient care. The primary outcome measure is the body mass index (BMI) at the end of the treatment (10 months after randomization).</p> <p>Discussion</p> <p>The study design surmounts the disadvantages of previous studies in that it provides a randomized controlled design, a large sample size, adequate inclusion criteria, an adequate treatment protocol, and a clear separation of the treatment conditions in order to avoid contamination. Nevertheless, the study has to deal with difficulties specific to the psychopathology of anorexia nervosa. The treatment protocol allows for dealing with the typically occurring medical complications without dropping patients from the protocol. However, because patients are difficult to recruit and often ambivalent about treatment, a drop-out rate of 30% is assumed for sample size calculation. Due to the ethical problem of denying active treatment to patients with anorexia nervosa, the control group is defined as "treatment-as-usual".</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN72809357</p