Eigenvalue Distributions for a Class of Covariance Matrices with Applications to Bienenstock-Cooper-Munro Neurons Under Noisy Conditions

We analyze the effects of noise correlations in the input to, or among, BCM neurons using the Wigner semicircular law to construct random, positive-definite symmetric correlation matrices and compute their eigenvalue distributions. In the finite dimensional case, we compare our analytic results with numerical simulations and show the effects of correlations on the lifetimes of synaptic strengths in various visual environments. These correlations can be due either to correlations in the noise from the input LGN neurons, or correlations in the variability of lateral connections in a network of neurons. In particular, we find that for fixed dimensionality, a large noise variance can give rise to long lifetimes of synaptic strengths. This may be of physiological significance.Comment: 7 pages, 7 figure

T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study.

The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring. A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3-11.0). Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

A stakeholder co-design approach for developing a community pharmacy service to enhance screening and management of atrial fibrillation

The authors would like to thank all participants in this research for their valuable input into the co-design process.Background: Community pharmacies provide a suitable setting to promote self-screening programs aimed at enhancing the early detection of atrial fibrillation (AF). Developing and implementing novel community pharmacy services (CPSs) is a complex and acknowledged challenge, which requires comprehensive planning and the participation of relevant stakeholders. Co-design processes are participatory research approaches that can enhance the development, evaluation and implementation of health services. The aim of this study was to co-design a pharmacist-led CPS aimed at enhancing self-monitoring/screening of AF. Methods: A 3-step co-design process was conducted using qualitative methods: (1) interviews and focus group with potential service users (n = 8) to identify key needs and concerns; (2) focus group with a mixed group of stakeholders (n = 8) to generate a preliminary model of the service; and (3) focus group with community pharmacy owners and managers (n = 4) to explore the feasibility and appropriateness of the model. Data were analysed qualitatively to identify themes and intersections between themes. The JeMa2 model to conceptualize pharmacybased health programs was used to build a theoretical model of the service. Results: Stakeholders delineated: a clear target population (i.e., individuals ≥65 years old, with hypertension, with or without previous AF or stroke); the components of the service (i.e., patient education; self-monitoring at home; results evaluation, referral and follow-up); and a set of circumstances that may influence the implementation of the service (e.g., quality of the service, competency of the pharmacist, inter-professional relationships, etc.). A number of strategies were recommended to enable implementation (e.g.,. endorsement by leading cardiovascular organizations, appropriate communication methods and channels between the pharmacy and the general medical practice settings, etc.). Conclusion: A novel and preliminary model of a CPS aimed at enhancing the management of AF was generated from this participatory process. This model can be used to inform decision making processes aimed at adopting and piloting of the service. It is expected the co-designed service has been adapted to suit existing needs of patients and current care practices, which, in turn, may increase the feasibility and acceptance of the service when it is implemented into a real setting.This work was funded by Covidien Pty Ltd. (Medtronic Australasia Pty Ltd) [UTS Project code: PRO16–0688], which is the company that has the rights to distribute the device Microlife BP A200 AFIB in Australia. Also, funding for this research has been provided by a UTS Chancellor’s postdoctoral fellowship awarded to the first author of this article (ID number: 2013001605)