Measuring Spatial Presence: Introducing and Validating the Pictorial Presence SAM

The aim of the present study was to develop a pictorial presence scale using selfassessment- manikins (SAM). The instrument assesses presence sub-dimensions (selflocation and possible actions) as well as presence determinants (attention allocation, spatial situation model, higher cognitive involvement, and suspension of disbelief). To qualitatively validate the scale, think-aloud protocols and interviews (n = 12) were conducted. The results reveal that the SAM items are quickly filled out as well as easily, intuitively, and unambiguously understood. Furthermore, the instrument’s validity and sensitivity was quantitatively examined in a two-factorial design (n = 317). Factors were medium (written story, audio book, video, and computer game) and distraction (non-distraction vs. distraction). Factor analyses reveal that the SAM presence dimensions and determinants closely correspond to those of the MEC Spatial Presence Questionnaire, which was used as a comparison measure. The findings of the qualitative and quantitative validation procedures show that the Pictorial Presence SAM successfully assesses spatial presence. In contrast to the verbal questionnaire data (MEC), the significant distraction effect suggests that the new scale is even more sensitive. This points out that the scale can be a useful alternative to existing verbal presence selfreport measures.

Space-time clustering of childhood cancers in Switzerland: A nationwide study.

The aetiology of childhood cancers remains largely unknown. It has been hypothesized that infections may be involved and that mini-epidemics thereof could result in space-time clustering of incident cases. Most previous studies support spatio-temporal clustering for leukaemia, while results for other diagnostic groups remain mixed. Few studies have corrected for uneven regional population shifts which can lead to spurious detection of clustering. We examined whether there is space-time clustering of childhood cancers in Switzerland identifying cases diagnosed at age <16 years between 1985 and 2010 from the Swiss Childhood Cancer Registry. Knox tests were performed on geocoded residence at birth and diagnosis separately for leukaemia, acute lymphoid leukaemia (ALL), lymphomas, tumours of the central nervous system, neuroblastomas and soft tissue sarcomas. We used Baker's Max statistic to correct for multiple testing and randomly sampled time-, sex- and age-matched controls from the resident population to correct for uneven regional population shifts. We observed space-time clustering of childhood leukaemia at birth (Baker's Max p = 0.045) but not at diagnosis (p = 0.98). Clustering was strongest for a spatial lag of <1 km and a temporal lag of <2 years (Observed/expected close pairs: 124/98; p Knox test = 0.003). A similar clustering pattern was observed for ALL though overall evidence was weaker (Baker's Max p = 0.13). Little evidence of clustering was found for other diagnostic groups (p > 0.2). Our study suggests that childhood leukaemia tends to cluster in space-time due to an etiologic factor present in early life.

A Process Model of the Formation of Spatial Presence Experiences

In order to bridge interdisciplinary differences in Presence research and to establish connections between Presence and “older” concepts of psychology and communication, a theoretical model of the formation of Spatial Presence is proposed. It is applicable to the exposure to different media and intended to unify the existing efforts to develop a theory of Presence. The model includes assumptions about attention allocation, mental models, and involvement, and considers the role of media factors and user characteristics as well, thus incorporating much previous work. It is argued that a commonly accepted model of Spatial Presence is the only solution to secure further progress within the international, interdisciplinary and multiple-paradigm community of Presence research.

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.

Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural mass model

Generalised epileptic seizures are frequently accompanied by sudden, reversible transitions from low amplitude, irregular background activity to high amplitude, regular spike-wave discharges (SWD) in the EEG. The underlying mechanisms responsible for SWD generation and for the apparently spontaneous transitions to SWD and back again are still not fully understood. Specifically, the role of spatial cortico-cortical interactions in ictogenesis is not well studied. We present a macroscopic, neural mass model of a cortical column which includes two distinct time scales of inhibition. This model can produce both an oscillatory background and a pathological SWD rhythm. We demonstrate that coupling two of these cortical columns can lead to a bistability between out-of-phase, low amplitude background dynamics and in-phase, high amplitude SWD activity. Stimuli can cause state-dependent transitions from background into SWD. In an extended local area of cortex, spatial heterogeneities in a model parameter can lead to spontaneous reversible transitions from a desynchronised background to synchronous SWD due to intermittency. The deterministic model is therefore capable of producing absence seizure-like events without any time dependent adjustment of model parameters. The emergence of such mechanisms due to spatial coupling demonstrates the importance of spatial interactions in modelling ictal dynamics, and in the study of ictogenesis.

The Ras inhibitors caveolin-1 and docking protein 1 activate peroxisome proliferator-activated receptor ? through spatial relocalization at helix 7 of its ligand-binding domain

Peroxisome proliferator-activated receptor ? (PPAR?) is a transcription factor that promotes differentiation and cell survival in the stomach. PPAR? upregulates and interacts with caveolin-1 (Cav1), a scaffold protein of Ras/mitogen-activated protein kinases (MAPKs). The cytoplasmic-to-nuclear localization of PPAR? is altered in gastric cancer (GC) patients, suggesting a so-far-unknown role for Cav1 in spatial regulation of PPAR? signaling. We show here that loss of Cav1 accelerated proliferation of normal stomach and GC cells in vitro and in vivo. Downregulation of Cav1 increased Ras/MAPK-dependent phosphorylation of serine 84 in PPAR? and enhanced nuclear translocation and ligand-independent transcription of PPAR? target genes. In contrast, Cav1 overexpression sequestered PPAR? in the cytosol through interaction of the Cav1 scaffolding domain (CSD) with a conserved hydrophobic motif in helix 7 of PPAR?'s ligand-binding domain. Cav1 cooperated with the endogenous Ras/MAPK inhibitor docking protein 1 (Dok1) to promote the ligand-dependent transcriptional activity of PPAR? and to inhibit cell proliferation. Ligand-activated PPAR? also reduced tumor growth and upregulated the Ras/MAPK inhibitors Cav1 and Dok1 in a murine model of GC. These results suggest a novel mechanism of PPAR? regulation by which Ras/MAPK inhibitors act as scaffold proteins that sequester and sensitize PPAR? to ligands, limiting proliferation of gastric epithelial cells.

Self-organised transients in a neural mass model of epileptogenic tissue dynamics

Stimulation of human epileptic tissue can induce rhythmic, self-terminating responses on the EEG or ECoG. These responses play a potentially important role in localising tissue involved in the generation of seizure activity, yet the underlying mechanisms are unknown. However, in vitro evidence suggests that self-terminating oscillations in nervous tissue are underpinned by non-trivial spatio-temporal dynamics in an excitable medium. In this study, we investigate this hypothesis in spatial extensions to a neural mass model for epileptiform dynamics. We demonstrate that spatial extensions to this model in one and two dimensions display propagating travelling waves but also more complex transient dynamics in response to local perturbations. The neural mass formulation with local excitatory and inhibitory circuits, allows the direct incorporation of spatially distributed, functional heterogeneities into the model. We show that such heterogeneities can lead to prolonged reverberating responses to a single pulse perturbation, depending upon the location at which the stimulus is delivered. This leads to the hypothesis that prolonged rhythmic responses to local stimulation in epileptogenic tissue result from repeated self-excitation of regions of tissue with diminished inhibitory capabilities. Combined with previous models of the dynamics of focal seizures this macroscopic framework is a first step towards an explicit spatial formulation of the concept of the epileptogenic zone. Ultimately, an improved understanding of the pathophysiologic mechanisms of the epileptogenic zone will help to improve diagnostic and therapeutic measures for treating epilepsy.

An Urn Model for Cascading Failures on a Lattice

A cascading failure is a failure in a system of interconnected parts, in which the breakdown of one element can lead to the subsequent collapse of the others. The aim of this paper is to introduce a simple combinatorial model for the study of cascading failures. In particular, having in mind particle systems and Markov random fields, we take into consideration a network of interacting urns displaced over a lattice. Every urn is Pólya-like and its reinforcement matrix is not only a function of time (time contagion) but also of the behavior of the neighboring urns (spatial contagion), and of a random component, which can represent either simple fate or the impact of exogenous factors. In this way a non-trivial dependence structure among the urns is built, and it is used to study default avalanches over the lattice. Thanks to its flexibility and its interesting probabilistic properties, the given construction may be used to model different phenomena characterized by cascading failures such as power grids and financial networks.

Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity

Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.

Cortical and subcortical correlates of electroencephalographic alpha rhythm modulation

Neural correlates of electroencephalographic (EEG) alpha rhythm are poorly understood. Here, we related EEG alpha rhythm in awake humans to blood-oxygen-level-dependent (BOLD) signal change determined by functional magnetic resonance imaging (fMRI). Topographical EEG was recorded simultaneously with fMRI during an open versus closed eyes and an auditory stimulation versus silence condition. EEG was separated into spatial components of maximal temporal independence using independent component analysis. Alpha component amplitudes and stimulus conditions served as general linear model regressors of the fMRI signal time course. In both paradigms, EEG alpha component amplitudes were associated with BOLD signal decreases in occipital areas, but not in thalamus, when a standard BOLD response curve (maximum effect at approximately 6 s) was assumed. The part of the alpha regressor independent of the protocol condition, however, revealed significant positive thalamic and mesencephalic correlations with a mean time delay of approximately 2.5 s between EEG and BOLD signals. The inverse relationship between EEG alpha amplitude and BOLD signals in primary and secondary visual areas suggests that widespread thalamocortical synchronization is associated with decreased brain metabolism. While the temporal relationship of this association is consistent with metabolic changes occurring simultaneously with changes in the alpha rhythm, sites in the medial thalamus and in the anterior midbrain were found to correlate with short time lag. Assuming a canonical hemodynamic response function, this finding is indicative of activity preceding the actual EEG change by some seconds.

Spatial Assessment of Erosion and its Impact on Soil Fertility in the Tajik Foothills

Efficient planning of soil conservation measures requires, first, to understand the impact of soil erosion on soil fertility with regard to local land cover classes; and second, to identify hot spots of soil erosion and bright spots of soil conservation in a spatially explicit manner. Soil organic carbon (SOC) is an important indicator of soil fertility. The aim of this study was to conduct a spatial assessment of erosion and its impact on SOC for specific land cover classes. Input data consisted of extensive ground truth, a digital elevation model and Landsat 7 imagery from two different seasons. Soil spectral reflectance readings were taken from soil samples in the laboratory and calibrated with results of SOC chemical analysis using regression tree modelling. The resulting model statistics for soil degradation assessments are promising (R2=0.71, RMSEV=0.32). Since the area includes rugged terrain and small agricultural plots, the decision tree models allowed mapping of land cover classes, soil erosion incidence and SOC content classes at an acceptable level of accuracy for preliminary studies. The various datasets were linked in the hot-bright spot matrix, which was developed to combine soil erosion incidence information and SOC content levels (for uniform land cover classes) in a scatter plot. The quarters of the plot show different stages of degradation, from well conserved land to hot spots of soil degradation. The approach helps to gain a better understanding of the impact of soil erosion on soil fertility and to identify hot and bright spots in a spatially explicit manner. The results show distinctly lower SOC content levels on large parts of the test areas, where annual crop cultivation was dominant in the 1990s and where cultivation has now been abandoned. On the other hand, there are strong indications that afforestations and fruit orchards established in the 1980s have been successful in conserving soil resources.

The cranial bone window model: studying angiogenesis of primary and secondary bone tumors by intravital microscopy

The successful treatment of primary and secondary bone tumors in a huge number of cases remains one of the major unsolved challenges in modern medicine. Malignant primary bone tumor growth predominantly occurs in younger people, whereas older people predominantly suffer from secondary bone tumors since up to 85% of the most frequently occurring malignant solid tumors, such as lung, mammary, and prostate carcinomas, metastasize into the bone. It is well known that a tumor's course may be altered by its surrounding tissue. For this reason, reported here is the protocol for the surgical preparation of a cranial bone window in mice as well as the method to implant tumors in this bone window for further investigations of angiogenesis and other microcirculatory parameters in orthotopically growing primary or secondary bone tumors using intravital microscopy. Intravital microscopy represents an internationally accepted and sophisticated experimental method to study angiogenesis, microcirculation, and many other parameters in a wide variety of neoplastic and nonneoplastic tissues. Since most physiologic and pathophysiologic processes are active and dynamic events, one of the major strengths of chronic animal models using intravital microscopy is the possibility of monitoring the regions of interest in vivo continuously up to several weeks with high spatial and temporal resolution. In addition, after the termination of experiments, tissue samples can be excised easily and further examined by various in vitro methods such as histology, immunohistochemistry, and molecular biology.