Deterministic and Stochastic Resilience Analysis of Minimum-time-controlled Discrete-time Systems

The resilience of discrete-time systems subject to minimum-time control is analysed for both deterministic and stochastic control gain perturbations. Lyapunov analysis is used to determine a tight upper bound on the control gain perturbations to maintain asymptotic stability

Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future

Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients

Consilient knowledge in fisheries: a case study of three species of wolffish (Anarhichadidae) listed under the Canadian Species at Risk Act

Three species of wolffish have been listed under Canada’s Species at Risk Act with consequences for commercial fisheries. Because harvester based local ecological knowledge (LEK) and science knowledge differ in goals, spatial and temporal scale, and mode of generalization, the current system struggles with including LEK along with traditional assessments in species at risk (SARA) processes. The differences in LEK and science led us to consider the concept of consilience in the sense of strengthened inductive knowledge via convergence or concordance of evidence from disparate sources. We used three criteria when considering consilience: a general concurrence of data, presence of unexplained inconsistencies, and a degree of complementarity between two disparate sources. Using wolffish in the northern Gulf of St. Lawrence we examined the feasibility of applying these criteria to two disparate sources of information: scientific stock assessments and data from structured fish harvester local ecological knowledge (LEK) interviews. We found that for wolffish there was consistency in observed trends and locations of high wolffish catch rates from both harvester LEK interviews and fishery-independent survey data. There was inconsistency between observed variability in catch sizes in harvester interviews and stock assessment maps. The science and LEK evidence were complementary in that observations took place at different spatial and temporal scales. They were complementary in that LEK was inshore, compared to science data from offshore. The explicit criteria we developed permit use of fishers’ knowledge that, in the past, has often been discounted to zero, often thereby reducing trust by harvesters in the results of species at risk assessments. The concept of consilience shifts the focus from controversy to dialogue in the use of evidence and, so, is important in rebuilding marine fishing communities

Interest coalitions and multilateral aid allocation

This paper analyzes multilateral aid allocation in the European Union (EU). We argue that EU members can influence the aid allocation process toward their national interests if they form powerful coalitions that bias the European Commission's development policies. When EU members' preferences over aid allocation are heterogeneous, the Commission can implement multilateral aid according to its programmatic goals. Greater homogeneity of EU members' goals, however, increases the likelihood that members can form powerful interest coalitions and induce the Commission to allocate aid according to their own national interests. The empirical analysis provides robust support for our theoretical argument, and the findings generally indicate that interest coalitions play an important role in multilateral aid allocation

Early Maladaptive Schemas as Predictors of Child Anxiety: The Role of Child and Mother Schemas

This study investigated the relationship between symptoms of anxiety in children and early maladaptive schemas in children and their mothers. Early maladaptive schemas are dysfunctional ways of thinking, feeling and behaving that develop as a result of adverse experiences with significant others in childhood, and lead to a higher risk of psychopathology. A sample of 200 non-clinical children (aged 9-13 years) completed the SCARED (Birmaher et al., 1997) and SIC (Rijkeboer and De Boo, 2010), their mothers completed the YSQ-SF (Young 1998). The psychometric properties of the SCARED separation anxiety and social phobia scales were inadequate. Regression analyses found that child anxiety scores were mainly predicted by the child schemas of loneliness, submission and vulnerability, which are similar to the anxiety predictors identified in adult samples. The failure schema was strongly related to anxiety symptoms in girls. Differences in schema predictors were found between girls and boys, and between different anxiety scales. Mother schemas were generally poor predictors of child anxiety symptoms. Support was found for the proposal that the schemas of self-sacrifice and enmeshment may not be maladaptive in children. This study identified several early maladaptive schemas that are significantly related to child anxiety symptoms, but further research is required to establish the causal direction of these relationships. Research in clinical samples is recommended to determine whether specific child schemas can differentiate between different types of psychopathology. The reliability and validity of the SCARED in Iranian children is questionable, and requires further examination.

The tripartite associations between bacteriophage, Wolbachia, and arthropods

© 2006 Bordenstein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Pathogens 2(2006): e43, doi:10.1371/journal.ppat.0020043.By manipulating arthropod reproduction worldwide, the heritable endosymbiont Wolbachia has spread to pandemic levels. Little is known about the microbial basis of cytoplasmic incompatibility (CI) except that bacterial densities and percentages of infected sperm cysts associate with incompatibility strength. The recent discovery of a temperate bacteriophage (WO-B) of Wolbachia containing ankyrin-encoding genes and virulence factors has led to intensifying debate that bacteriophage WO-B induces CI. However, current hypotheses have not considered the separate roles that lytic and lysogenic phage might have on bacterial fitness and phenotype. Here we describe a set of quantitative approaches to characterize phage densities and its associations with bacterial densities and CI. We enumerated genome copy number of phage WO-B and Wolbachia and CI penetrance in supergroup A- and B-infected males of the parasitoid wasp Nasonia vitripennis. We report several findings: (1) variability in CI strength for A-infected males is positively associated with bacterial densities, as expected under the bacterial density model of CI, (2) phage and bacterial densities have a significant inverse association, as expected for an active lytic infection, and (3) CI strength and phage densities are inversely related in A-infected males; similarly, males expressing incomplete CI have significantly higher phage densities than males expressing complete CI. Ultrastructural analyses indicate that approximately 12% of the A Wolbachia have phage particles, and aggregations of these particles can putatively occur outside the Wolbachia cell. Physical interactions were observed between approximately 16% of the Wolbachia cells and spermatid tails. The results support a low to moderate frequency of lytic development in Wolbachia and an overall negative density relationship between bacteriophage and Wolbachia. The findings motivate a novel phage density model of CI in which lytic phage repress Wolbachia densities and therefore reproductive parasitism. We conclude that phage, Wolbachia, and arthropods form a tripartite symbiotic association in which all three are integral to understanding the biology of this widespread endosymbiosis. Clarifying the roles of lytic and lysogenic phage development in Wolbachia biology will effectively structure inquiries into this research topic.This work was supported by grants from the NASA Astrobiology Institute (NNA04CC04A) and National Institutes of Health (R01 GM62626-01) to JJW, and by the Marine Biological Laboratory's Program in Global Infectious Diseases, funded by the Ellison Medical Foundation, to SRB

Alpha-synuclein ferrireductase activity is detectible in vivo, is altered in Parkinson's disease and increases the neurotoxicity of DOPAL

© 2017 Elsevier Inc. The normal cellular role of α-synuclein is of potential importance in understanding diseases in which an aggregated form of the protein has been implicated. A potential loss or change in the normal function of α-synuclein could play a role in the aetiology of diseases such as Parkinson's disease. Recently, it has been suggested that α-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Experiments were carried out to determine if such activity could be measured in vivo. Experiments with rats overexpressing human α-synuclein in nigral dopaminergic neurons demonstrated a correlation between α-synuclein expression and ferrireductase activity. Furthermore, studies on tissue from Parkinson's disease patient brains showed a significant decrease in ferrireductase activity, possibly due to deposition of large amounts of inactive protein. Cellular studies suggest that increase ferrireductase activity results in increased levels of dopamine metabolites and increased sensitivity to the toxicity of DOPAL. These findings demonstrate that α-synuclein ferrireductase activity is present in vivo and its alteration may play a role in neuron loss in disease