Developing the "next generation" of genetic association databases for complex diseases

Tens of thousands of genetic association studies investigating the influence of common polymorphisms on disease susceptibility have been published to date. These include similar to 1,000 genome-wide association studies (GWAS). This vast amount of data in the field of complex genetics is becoming increasingly difficult to follow and interpret. It can be expected that the situation will become even more complex with the advent of association projects using next-generation technologies. One of the aims of the Human Variome Project is to concatenate such data in meaningful ways, for example, within the context of publicly available field synopses. Here, we present various examples of online genetic association databases developed by our group for neuropsychiatric disorders. One integral part of this model is the systematic inclusion of data from large-scale genotyping projects, for example, GWAS, while respecting the privacy of data contributors. We believe that our database approach may serve as a viable model that can be readily applied to other fields and ultimately improve our understanding of the genetic forces driving common human conditions. Hum Mutat 33:1366-1372, 2012. (c) 2012 Wiley Periodicals, Inc

Disaster Resilience Education and Research Roadmap for Europe 2030 : ANDROID Report

A disaster resilience education and research roadmap for Europe 2030 has been launched. This roadmap represents an important output of the ANDROID disaster resilience network, bringing together existing literature in the field, as well as the results of various analysis and study projects undertaken by project partners.The roadmap sets out five key challenges and opportunities in moving from 2015 to 2030 and aimed at addressing the challenges of the recently announced Sendai Framework for Disaster Risk Reduction 2015-2030. This roadmap was developed as part of the ANDROID Disaster Resilience Network, led by Professor Richard Haigh of the Global Disaster Resilience Centre (www.hud.ac.uk/gdrc ) at the School of Art, Design and Architecture at the University of Huddersfield, UK. The ANDROID consortium of applied, human, social and natural scientists, supported by international organisations and a stakeholder board, worked together to map the field in disaster resilience education, pool their results and findings, develop interdisciplinary explanations, develop capacity, move forward innovative education agendas, discuss methods, and inform policy development. Further information on ANDROID Disaster Resilience network is available at: http://www.disaster-resilience.netAn ANDROID Disaster Resilience Network ReportANDROI

Metabolic Heat: A New Way of Looking at How Controlled Atmospheres Kill Insects

The use of calorimetry as a tool to understand the effects of controlled atmospheres (CA) on insects is briefly reviewed. A variety of data are presented to illustrate the various types of information that calorimetry can make available to researchers. The use of a calorimeter connected to a mass spectrometer to determine the occurrence of anaerobic respiration is described and reported. We conclude that calorimetry is a useful tool to simplify the experimental options when developing new insecticidal CA treatments. It can also be used for development of other treatments such as fumigants

Cultivating a Team Mindset about Productivity with a Nudge: A Field Study in Hybrid Development Teams

While there has been significant study of both individuals and teams of knowledge workers, research has focused largely on one or the other, with less focus on the interaction between the two. In this paper, we explore the tensions between the individual and their team, focusing on the choices an individual makes towards their own productivity versus their team's productivity. We developed a technology probe with a team nudge that fosters recurring reflection and prompts individuals to consider how their team helps them to be productive. We examined its impact through a longitudinal field study with 48 participants. We chose to undertake this study with software development teams as they are examples of knowledge workers who collaborate on a shared set of tasks with specific goals. Our exploration took place with hybrid development teams, which have increasingly become the norm. Our analysis of a total of 8338 hourly self-reports and 1389 daily diary entries found that the team nudge increased participants' productivity ratings and team awareness, led to participants spending more time on their own tasks, reshaped their perceptions of themselves and their team, yet, in general, did not increase team cohesion or affect well-being

Is there any advantage in placing an additional calcar screw in locked nailing of proximal humeral fractures?

AbstractBackgroundThe objective of this study was to evaluate the biomechanical effect of an additional unlocked calcar screw compared to a standard setting with three proximal humeral head screws alone for fixation of an unstable 2-part fracture of the surgical neck.HypothesisThe additional calcar screw improves stiffness and failure load.MethodsFourteen fresh frozen humeri were randomized into two equal sized groups. An unstable 2-part fracture of the surgical neck was simulated and all specimens were fixed with the MultiLoc®-nail. Group I represented a basic screw setup, with three locked head screws and two unlocked shaft screws. Group II was identical with a supplemental unlocked calcar screw (CS). Stiffness tests were performed in torsional loading, as well as in axial and in 20° abduction/20° adduction modes. Subsequently cyclic loading and load-to-failure tests were performed. Resulting stiffness, displacement under cyclic load and ultimate load were compared between groups using the t-test for independent variables (α=0.05).ResultsNo significant differences were observed between the groups in any of the biomechanical parameters. Backing out of the CS was observed in three cases.DiscussionThe use of an additional unlocked calcar screw does not provide mechanical benefit in locked nailing of an unstable 2-part fracture of the surgical neck.Level of evidenceLevel III. Experimental biomechanical study with human specimen

The skin mucosal barrier of lumpfish (Cyclopterus lumpus L.) is weakened by exposure to potential aquaculture production related stressors

Various cleaner fish species, such as the lumpfish (Cyclopterus lumpus L.), are used in the sea cage production of Atlantic salmon (Salmo salar L.) as a control measure against the ectoparasitic salmon louse (Lepeophtheirus salmonis). However, during severe lice infestation, alternative treatments are required to control parasitic burden. The aim of this study was to gain insight into how lumpfish skin responds to different chemicals used to treat parasites. We collected skin from lumpfish from both research facilities (tank reared fish) and commercial production (cage reared fish), and used operational welfare indicators (OWIs), in vitro models, histology and transcriptomics to study how the skin responded to two anti-parasitic oxidative chemicals, hydrogen peroxide (H2O2) and peracetic acid (PAA). Lumpfish sampled from the farm were classified as clinically healthy or weak according to their morbidity status, and fish from each category were used to gain insight into how the therapeutics affect the skin barrier. Differences between healthy and weakened (moribund) fish, and between treated fish from each of the two groups, were observed. Histological examination showed an overall reduced skin quality in fish characterized as moribund, including different grades of exposed bony plates. In vitro oxidant-treated lumpfish skin had reduced migration capacity of keratocytes, a weakened epidermal barrier and altered gene transcription, changes that are known predisposing factors to secondary infections. Skin from non-treated, healthy fish sampled from commercial farms exhibited similar features and attributes to oxidant-exposed tank reared fish from a research facility, suggesting that apparently healthy cage-held lumpfish exhibited stress responses in the epidermal barrier. The results of the study outline the risks and consequences lumpfish can face if accidentally subjected to potential anti-parasitic oxidant treatments aimed at Atlantic salmon. It also strengthens the evidence behind the requirement that lumpfish should be removed from the cages before being potentially exposed to this type of treatment and outlines the potential risks of differing husbandry practices upon lumpfish health, welfare and resilience.The skin mucosal barrier of lumpfish (Cyclopterus lumpus L.) is weakened by exposure to potential aquaculture production related stressorspublishedVersio

Peripheral blood RNA gene expression profiling in patients with bacterial meningitis

Objectives: The aim of present study was to find genetic pathways activated during infection with bacterial meningitis (BM) and potentially influencing the course of the infection using genome-wide RNA expression profiling combined with pathway analysis and functional annotation of the differential transcription. Methods: We analyzed 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed using GeneChip Human Gene 1.0 ST Arrays which can assess the transcription of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling. Functional annotation of the enriched gene sets was used to define the altered genetic networks. We also analyzed whether gene expression profiles depend on the clinical course and outcome. In order to verify the microarray results, the expression levels of ten functionally relevant genes with high statistical significance (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, and IL7R) were confirmed by quantitative real-time (qRT) PCR. Results: There were 8569 genes displaying differential expression at a significance level of p < 0.05. Following False Discovery Rate (FDR) correction, a total of 5500 genes remained significant at a p-value of < 0.01. Quantitative RT-PCR confirmed the differential expression in 10 selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation of humoral and cellular immune responses (enrichment score 43). Those changes were found in both adults and in children with BM compared to the healthy controls. The gene expression profiles did not significantly depend on the clinical outcome, but there was a strong influence of the specific type of pathogen underlying BM. Conclusion: This study demonstrates that there is a very strong activation of immune response at the transcriptional level during BM and that the type of pathogen influences this transcriptional activation

Nasal responses to elevated temperature and Francisella noatunensis infection in Atlantic cod (Gadus morhua)

We report the histological and transcriptomic changes in the olfactory organ of Atlantic cod exposed to Francisella noatunensis. Experimental infection was performed at either 12oC or 17oC. Infected fish presented the classic gross pathologies of francisellosis. Nasal morpho-phenotypic parameters were not significantly affected by temperature and infection, except for the number of mucus cells in the 12oC group seven weeks after the challenge. A higher number of genes were altered through time in the group reared at 17oC. At termination, the nasal transcriptome of infected fish in both groups was similar to the control. When both infected groups were compared, 754 DEGs were identified, many of which were involved in signalling, defence, transmembrane and enzymatic processes. In conclusion, the study reveals that elevated temperature could trigger responses in the olfactory organ of Atlantic cod and shape the nasal response to F. noatunensis infection.Nasal responses to elevated temperature and Francisella noatunensis infection in Atlantic cod (Gadus morhua)publishedVersio

Genetic associations with learning over 100 days of practice

Cognitive performance is both heritable and sensitive to environmental inputs and sustained practice over time. However, it is currently unclear how genetic effects on cognitive performance change over the course of learning. We examine how polygenic scores (PGS) created from genome-wide association studies of educational attainment and cognitive performance are related to improvements in performance across nine cognitive tests (measuring perceptual speed, working memory, and episodic memory) administered to 131 adults (N = 51, ages = 20–31, and N = 80, ages = 65–80 years) repeatedly across 100 days. We observe that PGS associations with performance on a given task can change over the course of learning, with the specific pattern of change in associations differing across tasks. PGS correlations with pre-test to post-test scores may mask variability in how soon learning occurs over the course of practice. The associations between PGS and learning do not appear to simply reconstitute patterns of association between baseline performance and subsequent learning. Associations involving PGSs, however, were small with large confidence intervals. Intensive longitudinal research such as that described here may be of substantial value for clarifying the genetics of learning when implemented as far larger scale