Bayesian change-point analysis reveals developmental change in a classic theory of mind task

Although learning and development reflect changes situated in an individual brain, most discussions of behavioral change are based on the evidence of group averages. Our reliance on group-averaged data creates a dilemma. On the one hand, we need to use traditional inferential statistics. On the other hand, group averages are highly ambiguous when we need to understand change in the individual; the average pattern of change may characterize all, some, or none of the individuals in the group. Here we present a new method for statistically characterizing developmental change in each individual child we study. Using false-belief tasks, fifty-two children in two cohorts were repeatedly tested for varying lengths of time between 3 and 5 years of age. Using a novel Bayesian change point analysis, we determined both the presence and—just as importantly—the absence of change in individual longitudinal cumulative records. Whenever the analysis supports a change conclusion, it identifies in that child’s record the most likely point at which change occurred. Results show striking variability in patterns of change and stability across individual children. We then group the individuals by their various patterns of change or no change. The resulting patterns provide scarce support for sudden changes in competence and shed new light on the concepts of "passing" and "failing" in developmental studies.National Science Foundation (Grant IDs: BCS-0725169, BCS-0922184), Economic and Social Research Counci

Chondrocyte responses to neurovascular peptides, cytokines, and a 3D environment: focus on ADAMs

Chondrocyte exposure to inflammatory stimuli in several arthritic conditions, including osteoarthritis, results in the well-characterised induction of extracellular matrix (ECM) degrading proteinases, notably members of a disintegrin and metalloproteinase with thrombospondin domains (ADAMTS) and matrix metalloproteinase (MMP) families. Here we briefly review the less-studied a disintegrin and metalloproteinase (ADAM) family of proteinases in chondrocyte and cartilage biology. Following damage, cartilage is exposed to neurovascular peptides, and in this study we hypothesised that substance P and bradykinin, alongside inflammatory cytokines, may modulate chondrocyte steady state messenger RNA levels for the proteolytic ADAM family members as well as for key cytokines and neuropeptides. We compared chondrocytes cultured in both 2-dimensional (2D) and 3D environments and found that 3D culture generally resulted in repression of expression of the genes under investigation, with the exception of anti-inflammatory interleukin 10 (IL10) which was markedly up-regulated in a 3D environment. Substance P and bradykinin had little effect on ADAM family expression but further investigation revealed that a combination of bradykinin and cytokines led to enhanced expression of ADAM28 and a synergistic up-regulation of IL6, also observed under hypoxic conditions. Overall this data reveals wider chondrocyte responses to neurovascular peptides which may have an impact in an osteoarthritis context

Managing sustainable non-profit network organizations

We draw upon a case study conducted within a non-profit network organization to propose five dualities which are central to understanding effective management of non-profit networks. We then examine strategies that address these dualities, based on new approaches to leadership, performance measurement, governance, coaching and creative management of dualities

Investigating the effects of arousal state on cognitive performance in individuals with and without mild head injury

We examined the cognitive and emotional sequelae following mild head injury (MHI; e.g., concussion) in high-functioning individuals and whether persons with MHI pre~ent, both physiologically and via self-report, in a manner different from (i.e., underaroused) that of persons who have no history of head injury. We also investigated the effect arousal state ~as on the cognitive performance of this population. Using a quasiexperimental research design (N = 91), we examined changes in attention, working memory, and cognitive flexibility (subtests ofthe WAIS-III, 1997,WMS-III, 1997, & DKEFS, 2002) as a function of manipulated arousal (i.e., induced psychosocial stress/activation; reduced activation/relaxation). In addition to self-reported arousal and state anxiety (State-Trait Anxiety Inventory; Speilberger, 1983a) measures, physiological indices of arousal state (i.e., electrodermal responsivity, heart rate, and respiration activity) were recorded (via Polygraph Professional Suite, 2008) across a 2.5 hour interval while completing various cognitive tasks. Students also completed the Post-concussive Symptom Checklist (Gouvier et aI., 1992). The results demonstrate that university students who report a history ofMHI (i.e., "altered state of consciousness") experience significantly lower levels of anxiety, were physiologically underaroused, and were less responsive to stressors in their environment, compared to their non-~HI cohorts. As expected, cognitive flexibility (but not other neuropsychological measures of cognition) was advantaged with increased stress, and disadvantaged with reduced stress, in persons with reported MHI, but not for those without reported MHI which provided limited support for our hypothesis. Further, university students who had no complaints related to their previous MHI endorsed a greater number of traditional post-concussive symptoms in terms of intensity, duration and frequency as compared to students who did not report a MHI. The underarousal in traumatic brain injury has been associated with (ventromedial prefrontal cortex) VMPFC disruption and may be implicated in MHI generally. Students who report sustaining a previous MHI may be less able to physiologically respond and/or cognitively appraise, stressful experiences as compared to their no-MHI cohort and experience persistent, long-lasting consequences despite the subtle nature of a history of head injury

Health literacy, health status, and healthcare utilization of Taiwanese adults: results from a national survey

Abstract Background Low health literacy is considered a worldwide health threat. The purpose of this study is to assess the prevalence and socio-demographic covariates of low health literacy in Taiwanese adults and to investigate the relationships between health literacy and health status and health care utilization. Methods A national survey of 1493 adults was conducted in 2008. Health literacy was measured using the Mandarin Health Literacy Scale. Health status was measured based on self-rated physical and mental health. Health care utilization was measured based on self-reported outpatient clinic visits, emergency room visits, and hospitalizations. Results Approximately thirty percent of adults were found to have low (inadequate or marginal) health literacy. They tended to be older, have fewer years of schooling, lower household income, and reside in less populated areas. Inadequate health literacy was associated with poorer mental health (OR, 0.57; 95% CI, 0.35-0.91). No association was found between health literacy and health care utilization even after adjusting for other covariates. Conclusions Low (inadequate and marginal) health literacy is prevalent in Taiwan. High prevalence of low health literacy is not necessarily indicative of the need for interventions. Systematic efforts to evaluate the impact of low health literacy on health outcomes in other countries would help to illuminate features of health care delivery and financing systems that may mitigate the adverse health effects of low health literacy.http://deepblue.lib.umich.edu/bitstream/2027.42/78252/1/1471-2458-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78252/2/1471-2458-10-614.pdfPeer Reviewe

Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons.

Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH) neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs). Here, we demonstrate that in homozygous Sox10(lacZ/lacZ) mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting). Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.This work was supported by the Wellcome Trust [grant 091555 to C.V.H.B. and P.B.], a Griffith University Encouragement Research grant to J.A.S., and Deutsche Forschungsgemeinschaft [grant We1326/9 to M.W.].This is the final version of the article. It was first available from The Company of Biologists via http://dx.doi.org/10.1242/bio.2013524

Intranasal immunisation with Outer Membrane Vesicles (OMV) protects against airway colonisation and systemic infection with Acinetobacter baumannii.

OBJECTIVES: The multi-drug resistant bacteria Acinetobacter baumannii is a major cause of hospital associated infection; a vaccine could significantly reduce this burden. The aim was to develop a clinically relevant model of A. baumannii respiratory tract infection and to test the impact of different immunisation routes on protective immunity provided by an outer membrane vesicle (OMV) vaccine. METHODS: BALB/c mice were intranasally challenged with isolates of oxa23-positive global clone GC2 A. baumannii from the lungs of patients with ventilator associated pneumonia. Mice were immunised with OMVs by the intramuscular, subcutaneous or intranasal routes; protection was determined by measuring local and systemic bacterial load. RESULTS: Infection with A. baumannii clinical isolates led to a more disseminated infection than the prototype A. baumannii strain ATCC17978; with bacteria detectable in upper and lower airways and the spleen. Intramuscular immunisation induced an antibody response but did not protect against bacterial infection. However, intranasal immunisation significantly reduced airway colonisation and prevented systemic bacterial dissemination. CONCLUSION: Use of clinically relevant isolates of A. baumannii provides stringent model for vaccine development. Intranasal immunisation with OMVs was an effective route for providing protection, demonstrating that local immunity is important in preventing A. baumannii infection