Psychiatric Illnesses as Disorders of Network Dynamics

This review provides a dynamical systems perspective on psychiatric symptoms and disease, and discusses its potential implications for diagnosis, prognosis, and treatment. After a brief introduction into the theory of dynamical systems, we will focus on the idea that cognitive and emotional functions are implemented in terms of dynamical systems phenomena in the brain, a common assumption in theoretical and computational neuroscience. Specific computational models, anchored in biophysics, for generating different types of network dynamics, and with a relation to psychiatric symptoms, will be briefly reviewed, as well as methodological approaches for reconstructing the system dynamics from observed time series (like fMRI or EEG recordings). We then attempt to outline how psychiatric phenomena, associated with schizophrenia, depression, PTSD, ADHD, phantom pain, and others, could be understood in dynamical systems terms. Most importantly, we will try to convey that the dynamical systems level may provide a central, hub-like level of convergence which unifies and links multiple biophysical and behavioral phenomena, in the sense that diverse biophysical changes can give rise to the same dynamical phenomena and, vice versa, similar changes in dynamics may yield different behavioral symptoms depending on the brain area where these changes manifest. If this assessment is correct, it may have profound implications for the diagnosis, prognosis, and treatment of psychiatric conditions, as it puts the focus on dynamics. We therefore argue that consideration of dynamics should play an important role in the choice and target of interventions

Living with the user: Design drama for dementia care through responsive scripted experiences in the home

Participation in forms of drama and narrative can provoke empathy and creativity in user-centred design processes. In this paper, we expand upon existing methods to explore the potential for responsive scripted experiences that are delivered through the combination of sensors and output devices placed in a home. The approach is being developed in the context of Dementia care, where the capacity for rich user participation in design activities is limited. In this case, a system can act as a proxy for a person with Dementia, allowing designers to gain experiences and insight as to what it is like to provide care for, and live with, this person. We describe the rationale behind the approach, a prototype system architecture, and our current work to explore the creation of scripted experiences for design, played out though UbiComp technologies.This research is funded by the Arts and Humanities Research Council UK, (AH/K00266X/1) and Horizon Digital Economy Research (RCUK grant EP/G065802/1)

Using cultural probes to inform the design of assistive technologies

This paper discusses the practical implications of applying cultural probes to drive the design of assistive technologies. Specifically we describe a study in which a probe was deployed with home-based carers of people with dementia in order to capture critical data and gain insights of integrating the technologies into this sensitive and socially complex design space. To represent and utilise the insights gained from the cultural probes, we created narratives based on the probe data to enhance the design of assistive technologies.This work was supported by the Arts and Humanities Research Council (AH/K00266X/1) and RCUK through the Horizon Digital Economy Research grant (EP/G065802/1)

Kinetic energy driven superconductivity, the origin of the Meissner effect, and the reductionist frontier

Is superconductivity associated with a lowering or an increase of the kinetic energy of the charge carriers? Conventional BCS theory predicts that the kinetic energy of carriers increases in the transition from the normal to the superconducting state. However, substantial experimental evidence obtained in recent years indicates that in at least some superconductors the opposite occurs. Motivated in part by these experiments many novel mechanisms of superconductivity have recently been proposed where the transition to superconductivity is associated with a lowering of the kinetic energy of the carriers. However none of these proposed unconventional mechanisms explores the fundamental reason for kinetic energy lowering nor its wider implications. Here I propose that kinetic energy lowering is at the root of the Meissner effect, the most fundamental property of superconductors. The physics can be understood at the level of a single electron atom: kinetic energy lowering and enhanced diamagnetic susceptibility are intimately connected. According to the theory of hole superconductivity, superconductors expel negative charge from their interior driven by kinetic energy lowering and in the process expel any magnetic field lines present in their interior. Associated with this we predict the existence of a macroscopic electric field in the interior of superconductors and the existence of macroscopic quantum zero-point motion in the form of a spin current in the ground state of superconductors (spin Meissner effect). In turn, the understanding of the role of kinetic energy lowering in superconductivity suggests a new way to understand the fundamental origin of kinetic energy lowering in quantum mechanics quite generally

An Acute Increase of Dietary Protein Intake Elicits Positive Cellular Metabolic Adaptations in Healthy Males

There is emerging literature demonstrating that restricting dietary carbohydrate (CHO) intake might upregulate cellular markers of mitochondrial biogenesis. Mitochondria quantity and density has been linked with increased endurance performance, reduction in type 2 diabetes and improved insulin sensitivity. A number of transcriptional cellular markers have been identified as key regulators of this process. PURPOSE: To determine the influence of 7 days dietary manipulation on resting metabolic rate (RMR), body composition and transcriptional markers of mitochondrial biogenesis. METHOD: Forty-six healthy male participants (mean ± SD; age (years), body mass (kg), height (cm); 28 ± 5, 75.6 ± 11.1, 178.0 ± 4.9, respectively) were recruited and randomised to one of four conditions: energy matched high protein (PRO-EM), energy restricted high protein (PRO-ER), energy matched high carbohydrate (CHO-EM) or energy restricted high carbohydrate (CHO-ER). Macronutrient ratios (PRO:CHO:FAT) of 40:30:30 and 60:10:30 were used for high protein and high carbohydrate conditions, respectively. Calorific intake for energy restricted groups was matched to RMR. Participants visited the laboratory on 3 occasions across 15 days. On days 0, 7 and 15 participants completed assessments of body composition (DEXA) and RMR (indirect calorimetry), prior to providing a muscle biopsy from the vastus lateralis for later analysis of transcriptional markers via real-time polymerase chain reaction. Between days 1 & 7 and 7 & 14 participants consumed their habitual and prescribed diets, respectively. Laboratory testing was completed following an overnight fast and at the same time of day on each occasion. RESULTS: No difference in RMR was observed in any group across all time points. AMPK, PGC-1a, SIRT1 and PPAR expression was increased in the PRO-ER group (1.32, 1.20, 1.45 and 1.41 fold, respectively). Transcriptional markers were not affected in either CHO group. The CHO-ER group demonstrated a greater loss in lean mass relative to the PRO-EM (-2.22 vs -0.35%,) and body mass loss relative to both CHO-EM and PRO-EM (-2.85 vs -0.95 vs -1.47%) (P < 0.05). CONCLUSION: A restriction energy intake combined with increased protein consumption for 7 days increases transcriptional markers of mitochondrial biogenesis

Evaluation of endogenous miRNA reference genes across different zebrafish strains, developmental stages and kidney disease models

The majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseases in vivo. Unfortunately, there is no consensus about a proper normalization strategy of RT-qPCR-based miRNA expression data in zebrafish. In this study we analyzed 9 preselected candidates dre-miR-92a-3p, dre-miR-206-3p, dre-miR-99-1, dre-miR-92b-3p, dre-miR-363-3p, dre-let-7e, dre-miR-454a, dre-miR-30c-5p, dre-miR-126a-5p for their capability as endogenous reference genes in zebrafish experiments. Expression levels of potential candidates were measured in 3 different zebrafish strains, different developmental stages, and in different kidney disease models by RT-qPCR. Expression values were analyzed with NormFinder, BestKeeper, GeNorm, and DeltaCt and were tested for inter-group differences. All candidates show an abundant expression throughout all samples and relatively high stability. The most stable candidate without significant inter-group differences was dre-miR-92b-3p making it a suitable endogenous reference gene for RT-qPCR-based miR expression zebrafish studies

Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS: Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS: (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION: This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors