REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE

We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscle's contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients (n = 11). The topology of linear relationships (| r | ≥ 0.7, P ≤ 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects (n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.

Nonrandomness, nonlinear dependence, and nonstationarity of electroencephalographic recordings from epilepsy patients

To derive tests for randomness, nonlinear-independence, and stationarity, we combine surrogates with a nonlinear prediction error, a nonlinear interdependence measure, and linear variability measures, respectively. We apply these tests to intracranial electroencephalographic recordings (EEG) from patients suffering from pharmacoresistant focal-onset epilepsy. These recordings had been performed prior to and independent from our study as part of the epilepsy diagnostics. The clinical purpose of these recordings was to delineate the brain areas to be surgically removed in each individual patient in order to achieve seizure control. This allowed us to define two distinct sets of signals: One set of signals recorded from brain areas where the first ictal EEG signal changes were detected as judged by expert visual inspection ("focal signals") and one set of signals recorded from brain areas that were not involved at seizure onset ("nonfocal signals"). We find more rejections for both the randomness and the nonlinear-independence test for focal versus nonfocal signals. In contrast more rejections of the stationarity test are found for nonfocal signals. Furthermore, while for nonfocal signals the rejection of the stationarity test increases the rejection probability of the randomness and nonlinear-independence test substantially, we find a much weaker influence for the focal signals. In consequence, the contrast between the focal and nonfocal signals obtained from the randomness and nonlinear-independence test is further enhanced when we exclude signals for which the stationarity test is rejected. To study the dependence between the randomness and nonlinear-independence test we include only focal signals for which the stationarity test is not rejected. We show that the rejection of these two tests correlates across signals. The rejection of either test is, however, neither necessary nor sufficient for the rejection of the other test. Thus, our results suggest that EEG signals from epileptogenic brain areas are less random, more nonlinear-dependent, and more stationary compared to signals recorded from nonepileptogenic brain areas. We provide the data, source code, and detailed results in the public domain.

Governing the Local: Sovereignty, Social Governance and Community Safety

There has been much commentary about the re-ordering of the relations between nation state government, geographical territory, and populations in the advanced liberal democracies. This is seen as a product of: increasing demographic and cultural diversity due to legal and illegal migration; economic, cultural, and political global interdependence; footloose mobility of capital and the outsourcing of jobs to poorer countries; the growing power of international corporations and financial markets; and the growth of supra-national bodies like the European Union and The North Atlantic Free Trade Association, the World Trade Organisation, and (debatably), the UN. These developments are held to be associated with the gradual demise of the model of the increasingly secular nation state first crystallised by the Treaty of Westphalia in 1648. This conception provided a mutual, guarantee of states’ jurisdiction over territory and populations through their legitimated attempts to monopolise the use of force. Though, the relations between these states have always been asymmetrical and often challenged (Hunter 1998).

Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naïve patients with schizophrenia: preliminary results

We explored and refined the hypothesis that during a first episode of acute schizophrenia a disorganization of brain functioning is present. A novel EEG measure was introduced, Global Field Synchronization (GFS), that estimates functional connectivity of brain processes in different EEG frequency bands. The measure was applied to EEG's from 11 never-treated, first-episode, young patients with an acute, positive, schizophrenic symptomatology and from 19 controls, residing in Bern, Switzerland. In comparison to age- and sex- matched controls, patients had significantly decreased GFS in the theta EEG frequency band, indicating a loosened functional connectivity of processes in this frequency. The result was confirmed in an independent, comparable patient group from Osaka, Japan (9 patients and 9 controls), thus making a total of 20 analyzed patients. Previous EEG research in healthy, awake subjects indicated a positive correlation of theta activity with memory functions. Thus, our result suggests a loss of mutual interdependence of memory functions in patients with acute schizophrenia, which agrees well with previous reports of working memory dysfunction in schizophrenia.

Actor and partner effects of self-esteem on relationship satisfaction and the mediating role of secure attachment between the partners

We examined actor and partner effects of self-esteem on relationship satisfaction, using the actor-partner interdependence model and data from five independent samples of couples. The results indicated that self-esteem predicted the individual’s own relationship satisfaction (i.e., an actor effect) and the relationship satisfaction of his or her partner (i.e., a partner effect), controlling for the effect of the partner’s selfesteem. Gender, age, and length of relationship did not moderate the effect sizes. Moreover, using one of the samples, we tested whether secure attachment to the current partner (assessed as low attachment-related anxiety and avoidance) mediated the effects. The results showed that attachment-related anxiety and avoidance independently mediated both the actor and the partner effect of self-esteem on relationship satisfaction.

How large are actor and partner effects of personality on relationship satisfaction? The importance of controlling for shared method variance

Previous research suggests that the personality of a relationship partner predicts not only the individual’s own satisfaction with the relationship but also the partner’s satisfaction. Based on the actor–partner interdependence model, the present research tested whether actor and partner effects of personality are biased when the same method (e.g., self-report) is used for the assessment of personality and relationship satisfaction and, consequently, shared method variance is not controlled for. Data came from 186 couples, of whom both partners provided self- and partner reports on the Big Five personality traits. Depending on the research design, actor effects were larger than partner effects (when using only self-reports), smaller than partner effects (when using only partner reports), or of about the same size as partner effects (when using self- and partner reports). The findings attest to the importance of controlling for shared method variance in dyadic data analysis.

Computer simulation of glioma growth and morphology.

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.

Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

BACKGROUND Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. METHODS Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. RESULTS The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; p<0.05). CONCLUSIONS An interdependence between acute mental stress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels.

Multimodal viral communication: a social semiotic analysis of the popular Spanish "Ola ke ase" meme

Multimodality – the interdependence of semiotic resources in text – is an existential element of today’s media. The term multimodality attends systematically to the social interpretation of a wide range of communicational forms used in meaning making. A primary focus of social- semiotic multimodal analysis is on mapping how modal resources are used by people in a given social context. In November 2012 the “Ola ke ase” catchphrase, which is a play on “Hola ¿qué hace?”, appeared for the first time in Spain and immediately has been adopted as a Twitter hashtag and an image macro series. Its viral spread on social networks has been tremendous, being a trending topic in various Spanish-speaking countries. The objective of analysis is how language and image work together in the “Ola ke ase” meme. The interplay between text and image in one of the original memes and some of its variations is quantitatively analysed applying a social-semiotic approach. Results demonstrate how the “Ola ke ase” meme functions through its multimodal character and the non-standard orthography. The spread of uncountable variations of the meme shows the social process that goes on in the meaning making of the semiotic elements.

Computer simulation of glioma growth and morphology.

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.

Family change theory: A preliminary evaluation on the basis of recent cross-cultural studies

Family change theory (Kagitcibasi, 1996, 2007) is an approach which can be used to explain how modernisation and globalisation processes affect the family. The most important assumption of the theory is that when traditional interdependent cultures modernise, they need not necessarily develop in the direction of the independent family model typical of Western individualistic societies. Instead, they may develop towards a family model of emotional interdependence that combines continuing emotional interdependencies in the family with declining material interdependencies and with rising personal autonomy. In this chapter a preliminary evaluation of the empirical status of family change theory is given based on a review of recent cross-cultural studies. It will be shown to what extent the few studies that have been systematically conducted in this respect have found results either supporting or not supporting aspects ofthe theory, and where the strengths and problems of this research lie.

Intergenerational support: A comparison between Russian and German adult daughters

The aim of this study is a Russian-German cross-cultural comparison of the actual support and the readiness for support that adult daughters give to their parents as well as of the conditions for this support. Compared to Russia, Germany can be characterized by a more individualistic value system and a fully developed social-welfare system. Therefore, the extent of intergenerational support should be less in Germany than in Russia. Furthermore, the study attempts to test if the support-related differences between the two countries are mediated by differences in cultural values. The participants were German and Russian adult daughters who at the same time were mothers of adolescent children. The cross-cultural comparisons showed that compared to their German counterparts, Russian adult daughters reported more current support as well as a higher readiness for future support. These differences were mediated through a higher emotional interdependence (intimacy) of the Russian adult daughters, as well as through their considerably higher family values and norm-oriented motives for support. The results are discussed with regard to theoretical approaches regarding parent-child relations and the culture-specific meaning of intergenerational support in Russia and Germany.

Values of children and family models of adolescents: An eleven-culture study

Starting from Kagitcibasi's (2007) conceptualization of family models, this study compared N = 2961 adolescents' values across eleven cultures and explored whether patterns of values were related to the three proposed family models through cluster analyses. Three clusters with value profiles corresponding to the family models of interdependence, emotional interdependence, and independence were identified on the cultural as well as on the individual level. Furthermore, individual-level clusters corresponded to culture-level clusters in terms of individual cluster membership. The results largely support Kagitcibasi's proposition of changing family models and demonstrate their representation as individual-level value profiles across cultures.

Higher emotional distress in female partners of cancer patients: prevalence and patient-partner interdependencies in a 3-year cohort

OBJECTIVE: Assessment and treatment of psychological distress in cancer patients was recognized as a major challenge. The role of spouses, caregivers, and significant others became of salient importance not only because of their supportive functions but also in respect to their own burden. The purpose of this study was to assess the amount of distress in a mixed sample of cancer patients and their partners and to explore the dyadic interdependence. METHODS: An initial sample of 154 dyads was recruited, and distress questionnaires (Hospital Anxiety and Depression Scale, Symptom Checklist 9-Item Short Version and 12-Item Short Form Health Survey) were assessed over four time points. Linear mixed models and actor-partner interdependence models were applied. RESULTS: A significant proportion of patients and their partners (up to 40%) reported high levels of anxiety, depression, psychological distress, and low quality of life over the course of the investigation. Mixed model analyses revealed that higher risks for clinical relevant anxiety and depression in couples exist for female patients and especially for female partners. Although psychological strain decreased over time, the risk for elevated distress in female partners remained. Modeling patient-partner interdependence over time stratified by patients' gender revealed specific effects: a moderate correlation between distress in patients and partners, and a transmission of distress from male patients to their female partners. CONCLUSIONS: Our findings provide empirical support for gender-specific transmission of distress in dyads coping with cancer. This should be considered as an important starting point for planning systemic psycho-oncological interventions and conceptualizing further research.

Rethinking science for sustainable development: Reflexive interaction for a paradigm transformation

If we postulate a need for the transformation of society towards sustainable development, we also need to transform science and overcome the fact/value split that makes it impossible for science to be accountable to society. The orientation of this paradigm transformation in science has been under debate for four decades, generating important theoretical concepts, but they have had limited impact until now. This is due to a contradictory normative science policy framing that science has difficulties dealing with, not least of all because the dominant framing creates a lock-in. We postulate that in addition to introducing transdisciplinarity, science needs to strive for integration of the normative aspect of sustainable development at the meta-level. This requires a strategically managed niche within which scholars and practitioners from many different disciplines can engage in a long-term common learning process, in order to become a “thought collective” (Fleck) capable of initiating the paradigm transformation. Arguing with Piaget that “decentration” is essential to achieve normative orientation and coherence in a learning collective, we introduce a learning approach—Cohn's “Theme-Centred Interaction”—which provides a methodology for explicitly working with the objectivity and subjectivity of statements and positions in a “real-world” context, and for consciously integrating concerns of individuals in their interdependence with the world. This should enable a thought collective to address the epistemological and ethical barriers to science for sustainable development.