Experiences of living with chronic back pain: The physical disabilities

Purpose. Back-related functional limitations are largely assessed using lists of activities, each scored on a yes/no basis and the scores then summed. This provides little information about how chronic back pain (CBP) patients live with their condition. This study describes the consequences of living day-to-day with CBP and documents the 'insider' accounts of its impact on daily life. Method. Unstructured interviews, using the 'Framework' approach with topic guide, were recorded and transcribed verbatim. Subjects were sampled for age, sex, ethnicity and occupation from new referrals with back pain to a rheumatology outpatient clinic. Eleven subjects (5 male, 6 female) were interviewed either in English (n = 9) or their preferred language (n = 2). Interviews were read in-depth twice to identify the topics. Data were extracted in phrases and sentences using thematic content analysis. Results. Four themes emerged: sleep/rest, mobility, independence and leisure. All subjects reported issues about sleep and rest, nine about mobility, seven about independence and six on leisure. Most descriptions concerned loss and limitation in daily life. Strategies for coping with sleep disruption and physical limitations were described. Conclusions. Subjects provided graphic 'in-depth' descriptions of experiences living with CBP every day; expressed regret at the loss of capabilities and distress at the functional consequences of those losses. Facilitating 'adjustment' to 'loss' may be more helpful than inferring the potential for a life free of pain as a result of therapeutic endeavours

For What It's Worth: Humans Overwrite Their Economic Self-interest to Avoid Bargaining With AI Systems

As algorithms are increasingly augmenting and substituting human decision-making, understanding how the introduction of computational agents changes the fundamentals of human behavior becomes vital. This pertains to not only users, but also those parties who face the consequences of an algorithmic decision. In a controlled experiment with 480 participants, we exploit an extended version of two-player ultimatum bargaining where responders choose to bargain with either another human, another human with an AI decision aid or an autonomous AI-system acting on behalf of a passive human proposer. Our results show strong responder preferences against the algorithm, as most responders opt for a human opponent and demand higher compensation to reach a contract with autonomous agents. To map these preferences to economic expectations, we elicit incentivized subject beliefs about their opponent's behavior. The majority of responders maximize their expected value when this is line with approaching the human proposer. In contrast, responders predicting income maximization for the autonomous AI-system overwhelmingly override economic self-interest to avoid the algorithm

Motivation through gamification: A Self-Determination Theory perspective for the design of an adaptive reward system

Research on the nature and origins of human motivation has addressed the role of rewards in learning and behaviour. Gamification finds its raison d'être in being able to leverage motivational theories, to foster motivation in users through the use of game elements. One of the main criticisms moved to the use of gamification for learning purposes is related to the one-size-fits-all approach that tends to characterize many gamified applications. In this paper we explore the possibilities that can arise from the convergence of Self-Determination Theory principles and machine learning, to improve the efficacy of gamification reward systems

Three-Dimensional Cell and Tissue Patterning in a Strained Fibrin Gel System

Techniques developed for the in vitro reproduction of three-dimensional (3D) biomimetic tissue will be valuable for investigating changes in cell function in tissues and for fabricating cell/matrix composites for applications in tissue engineering techniques. In this study, we show that the simple application of a continuous strain to a fibrin gel facilitates the development of fibril alignment and bundle-like structures in the fibrin gel in the direction of the applied strain. Myoblasts cultured in this gel also exhibited well-aligned cell patterning in a direction parallel to the direction of the strain. Interestingly, the direction of cell proliferation was identical to that of cell alignment. Finally, the oriented cells formed linear groups that were aligned parallel to the direction of the strain and replicated the native skeletal muscle cell patterning. In addition, vein endothelial cells formed a linear, aligned vessel-like structure in this system. Thus, the system enables the in vitro reproduction of 3D aligned cell sets replicating biological tissue patterns

Targeted high throughput sequencing in clinical cancer Settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity

<p>Abstract</p> <p>Background</p> <p>Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings.</p> <p>Methods</p> <p>Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.</p> <p>Results</p> <p>We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance.</p> <p>Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations.</p> <p>Conclusions</p> <p>The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - in the long term - result in a more reliable prediction of individual cancer therapies.</p

Ca2+ Cycling in Heart Cells from Ground Squirrels: Adaptive Strategies for Intracellular Ca2+ Homeostasis

Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca2+ homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca2+ current (ICa) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of ICa did not compromise the Ca2+-induced Ca2+ release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of ICa. Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca2+ removal were more rapid in ground squirrels. Ca2+ sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high ICa threshold, low SR Ca2+ leak and rapid cytosolic Ca2+ clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca2+ homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca2+ overload-related heart diseases

Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort.We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity.These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection

Ephrin-A5 and EphA5 Interaction Induces Synaptogenesis during Early Hippocampal Development

Synaptogenesis is a fundamental step in neuronal development. For spiny glutamatergic synapses in hippocampus and cortex, synaptogenesis involves adhesion of pre and postsynaptic membranes, delivery and anchorage of pre and postsynaptic structures including scaffolds such as PSD-95 and NMDA and AMPA receptors, which are glutamate-gated ion channels, as well as the morphological maturation of spines. Although electrical activity-dependent mechanisms are established regulators of these processes, the mechanisms that function during early development, prior to the onset of electrical activity, are unclear. The Eph receptors and ephrins provide cell contact-dependent pathways that regulate axonal and dendritic development. Members of the ephrin-A family are glycosyl-phosphatidylinositol-anchored to the cell surface and activate EphA receptors, which are receptor tyrosine kinases.Here we show that ephrin-A5 interaction with the EphA5 receptor following neuron-neuron contact during early development of hippocampus induces a complex program of synaptogenic events, including expression of functional synaptic NMDA receptor-PSD-95 complexes plus morphological spine maturation and the emergence of electrical activity. The program depends upon voltage-sensitive calcium channel Ca2+ fluxes that activate PKA, CaMKII and PI3 kinase, leading to CREB phosphorylation and a synaptogenic program of gene expression. AMPA receptor subunits, their scaffolds and electrical activity are not induced. Strikingly, in contrast to wild type, stimulation of hippocampal slices from P6 EphA5 receptor functional knockout mice yielded no NMDA receptor currents.These studies suggest that ephrin-A5 and EphA5 signals play a necessary, activity-independent role in the initiation of the early phases of synaptogenesis. The coordinated expression of the NMDAR and PSD-95 induced by eprhin-A5 interaction with EphA5 receptors may be the developmental switch that induces expression of AMPAR and their interacting proteins and the transition to activity-dependent synaptic regulation