Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.

The scholarly networks of Albrecht von Haller and the Economic Society of Bern – a multi-level network analysis

Here, by the example of the transfer of cultivated plants in the context of the correspondence networks of Albrecht von Haller and the Economic Society, a multi-level network analysis is suggested. By a multi-level procedure, the chronological dynamics, the social structure, the spatial distribution and the functional networking are analyzed one after the other. These four levels of network analysis do not compete with each other but are mutually supporting. This aims at a deeper understanding of how these networks contributed to an international transfer of knowledge in the 18th century.

Networks of Information Exchange Under Uncertainty: The Case of Unconventional Gas Development in the United Kingdom

Modern policy-making is increasingly influenced by different types of uncertainty. Political actors are supposed to behave differently under the context of uncertainty then in “usual” decision-making processes. Actors exchange information in order to convince other actors and decision-makers, to coordinate their lobbying activities and form coalitions, and to get information and learn on the substantive issue. The literature suggests that preference similarity, social trust, perceived power and functional interdependence are particularly important drivers of information exchange. We assume that social trust as well as being connected to scientific actors is more important under uncertainty than in a setting with less uncertainty. To investigate information exchange under uncertainty analyze the case of unconventional shale gas development in the UK from 2008 till 2014. Our study will rely on statistical analyses of survey data on a diverse set of actors dealing with shale gas development and regulation in the UK.

Process and pattern in cichlid radiations - inferences for understanding unusually high rates of evolutionary diversification

The cichlid fish radiations in the African Great Lakes differ from all other known cases of rapid speciation in vertebrates by their spectacular trophic diversity and richness of sympatric species, comparable to the most rapid angiosperm radiations. I review factors that may have facilitated these radiations and compare these with insights from recent work on plant radiations. Work to date suggests that it was a coincidence of ecological opportunity, intrinsic ecological versatility and genomic flexibility, rapidly evolving behavioral mate choice and large amounts of standing genetic variation that permitted these spectacular fish radiations. I propose that spatially orthogonal gradients in the fit of phenotypes to the environment facilitate speciation because they allow colonization of alternative fitness peaks during clinal speciation despite local disruptive selection. Such gradients are manifold in lakes because of the interaction of water depth as an omnipresent third spatial dimension with other fitness-relevant variables. I introduce a conceptual model of adaptive radiation that integrates these elements and discuss its applicability to, and predictions for, plant radiations.

Chow–Liu trees are sufficient predictive models for reproducing key features of functional networks of periictal EEG time-series

Seizure freedom in patients suffering from pharmacoresistant epilepsies is still not achieved in 20–30% of all cases. Hence, current therapies need to be improved, based on a more complete understanding of ictogenesis. In this respect, the analysis of functional networks derived from intracranial electroencephalographic (iEEG) data has recently become a standard tool. Functional networks however are purely descriptive models and thus are conceptually unable to predict fundamental features of iEEG time-series, e.g., in the context of therapeutical brain stimulation. In this paper we present some first steps towards overcoming the limitations of functional network analysis, by showing that its results are implied by a simple predictive model of time-sliced iEEG time-series. More specifically, we learn distinct graphical models (so called Chow–Liu (CL) trees) as models for the spatial dependencies between iEEG signals. Bayesian inference is then applied to the CL trees, allowing for an analytic derivation/prediction of functional networks, based on thresholding of the absolute value Pearson correlation coefficient (CC) matrix. Using various measures, the thus obtained networks are then compared to those which were derived in the classical way from the empirical CC-matrix. In the high threshold limit we find (a) an excellent agreement between the two networks and (b) key features of periictal networks as they have previously been reported in the literature. Apart from functional networks, both matrices are also compared element-wise, showing that the CL approach leads to a sparse representation, by setting small correlations to values close to zero while preserving the larger ones. Overall, this paper shows the validity of CL-trees as simple, spatially predictive models for periictal iEEG data. Moreover, we suggest straightforward generalizations of the CL-approach for modeling also the temporal features of iEEG signals.

Identification of a new genomic hot spot of evolutionary diversification of protein function.

Establishment of phylogenetic relationships remains a challenging task because it is based on computational analysis of genomic hot spots that display species-specific sequence variations. Here, we identify a species-specific thymine-to-guanine sequence variation in the Glrb gene which gives rise to species-specific splice donor sites in the Glrb genes of mouse and bushbaby. The resulting splice insert in the receptor for the inhibitory neurotransmitter glycine (GlyR) conveys synaptic receptor clustering and specific association with a particular synaptic plasticity-related splice variant of the postsynaptic scaffold protein gephyrin. This study identifies a new genomic hot spot which contributes to phylogenetic diversification of protein function and advances our understanding of phylogenetic relationships.

Inference of evolutionary forces acting on human biological pathways

Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures.

Comparing the Networks of Ethnic Japanese and Ethnic Chinese in International Trade

In this paper I re-examined the trade enhancing effects of ethnic Chinese networks, found by Rauch and Trindade (2002), on a newer and extended data set. The effects are estimated by the gravity equation with the product of the population ratio (or absolute number) of the ethnic Chinese in both the importing and exporting countries, and are reaffirmed positive and statistically significant. I also compared the effects of two different ethnic Japanese networks, i.e., the networks of long-term Japanese stayers in foreign countries, and the networks of permanent Japanese residents in foreign countries. It is found that the former has stronger trade enhancing effects than the latter. This shows that the effects of ethnic networks on international trade can be generalized beyond the ethnic Chinese, and the ’cohesiveness’ of the ethnic network matters to the trade enhancing effects of the network.

A distributed end-to-end overload control mechanism for networks of SIP servers.

The Session Initiation Protocol (SIP) is an application-layer control protocol standardized by the IETF for creating, modifying and terminating multimedia sessions. With the increasing use of SIP in large deployments, the current SIP design cannot handle overload effectively, which may cause SIP networks to suffer from congestion collapse under heavy offered load. This paper introduces a distributed end-to-end overload control (DEOC) mechanism, which is deployed at the edge servers of SIP networks and is easy to implement. By applying overload control closest to the source of traf?c, DEOC can keep high throughput for SIP networks even when the offered load exceeds the capacity of the network. Besides, it responds quickly to the sudden variations of the offered load and achieves good fairness. Theoretic analysis and extensive simulations verify that DEOC is effective in controlling overload of SIP networks.