User-Centered Design of a National Medical Registry for Tick-Borne Diseases

Tick-borne diseases are increasing in a global perspective, with Lyme disease and tick-borne encephalitis as the most frequent. The Norwegian National Ad-visory Unit on Tick-borne Diseases is preparing the development of a national medical registry for clinical follow-up of patients with tick-borne diseases based on the best practice guidelines and for research purposes. This paper presents the methodological approach of a user-centered design process applied in the in-itial phase of the registry development. A user workshop identified user needs, requirements and proposed a service workflow for the registry operation. As the next step, a simulation of the proposed service workflow was performed in a clinical laboratory together with end-user groups. The main contribution of this paper lies on the methodological descriptions of the user-centered design pro-cess, and how to facilitate the active contribution of end-users in a technical de-velopment process within a health care context.User-Centered Design of a National Medical Registry for Tick-Borne DiseasesacceptedVersionNivå

Exploring the Dynamic Range of the Kinetic Exclusion Assay in Characterizing Antigen-Antibody Interactions

Therapeutic antibodies are often engineered or selected to have high on-target binding affinities that can be challenging to determine precisely by most biophysical methods. Here, we explore the dynamic range of the kinetic exclusion assay (KinExA) by exploiting the interactions of an anti-DKK antibody with a panel of DKK antigens as a model system. By tailoring the KinExA to each studied antigen, we obtained apparent equilibrium dissociation constants (KD values) spanning six orders of magnitude, from approximately 100 fM to 100 nM. Using a previously calibrated antibody concentration and working in a suitable concentration range, we show that a single experiment can yield accurate and precise values for both the apparent KD and the apparent active concentration of the antigen, thereby increasing the information content of an assay and decreasing sample consumption. Orthogonal measurements obtained on Biacore and Octet label-free biosensor platforms further validated our KinExA-derived affinity and active concentration determinations. We obtained excellent agreement in the apparent affinities obtained across platforms and within the KinExA method irrespective of the assay orientation employed or the purity of the recombinant or native antigens

Neutrino Signatures From Young Neutron Stars

After a successful core collapse supernova (CCSN) explosion, a hot dense proto-neutron star (PNS) is left as a remnant. Over a time of 20 or so seconds, this PNS emits the majority of the neutrinos that come from the CCSN, contracts, and loses most of its lepton number. This is the process by which all neutron stars in our galaxy are likely born. The emitted neutrinos were detected from supernova (SN) 1987A, and they will be detected in much greater numbers from any future galactic CCSN. These detections can provide a direct window into the properties of the dense matter encountered inside neutron stars, and they can affect nucleosynthesis in the material ejected during the CCSN. In this chapter, we review the basic physics of PNS cooling, including the basic equations of PNS structure and neutrino diffusion in dense matter. We then discuss how the nuclear equation of state, neutrino opacities in dense matter, and convection can shape the temporal behavior of the neutrino signal. We also discuss what was learned from the late-time SN 1987A neutrinos, the prospects for detection of these neutrinos from future galactic CCSNe, and the effects these neutrinos can have on nucleosynthesis

Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structures

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Ocean Acidification at High Latitudes: Potential Effects on Functioning of the Antarctic Bivalve Laternula elliptica

Ocean acidification is a well recognised threat to marine ecosystems. High latitude regions are predicted to be particularly affected due to cold waters and naturally low carbonate saturation levels. This is of concern for organisms utilising calcium carbonate (CaCO3) to generate shells or skeletons. Studies of potential effects of future levels of pCO2 on high latitude calcifiers are at present limited, and there is little understanding of their potential to acclimate to these changes. We describe a laboratory experiment to compare physiological and metabolic responses of a key benthic bivalve, Laternula elliptica, at pCO2 levels of their natural environment (430 µatm, pH 7.99; based on field measurements) with those predicted for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH 8.32). Adult L. elliptica basal metabolism (oxygen consumption rates) and heat shock protein HSP70 gene expression levels increased in response both to lowering and elevation of pH. Expression of chitin synthase (CHS), a key enzyme involved in synthesis of bivalve shells, was significantly up-regulated in individuals at pH 7.78, indicating L. elliptica were working harder to calcify in seawater undersaturated in aragonite (ΩAr = 0.71), the CaCO3 polymorph of which their shells are comprised. The different response variables were influenced by pH in differing ways, highlighting the importance of assessing a variety of factors to determine the likely impact of pH change. In combination, the results indicate a negative effect of ocean acidification on whole-organism functioning of L. elliptica over relatively short terms (weeks-months) that may be energetically difficult to maintain over longer time periods. Importantly, however, the observed changes in L. elliptica CHS gene expression provides evidence for biological control over the shell formation process, which may enable some degree of adaptation or acclimation to future ocean acidification scenarios

The intellectual structure and substance of the knowledge utilization field: A longitudinal author co-citation analysis, 1945 to 2004

<p>Abstract</p> <p>Background</p> <p>It has been argued that science and society are in the midst of a far-reaching renegotiation of the social contract between science and society, with society becoming a far more active partner in the creation of knowledge. On the one hand, new forms of knowledge production are emerging, and on the other, both science and society are experiencing a rapid acceleration in new forms of knowledge utilization. Concomitantly since the Second World War, the science underpinning the knowledge utilization field has had exponential growth. Few in-depth examinations of this field exist, and no comprehensive analyses have used bibliometric methods.</p> <p>Methods</p> <p>Using bibliometric analysis, specifically first author co-citation analysis, our group undertook a domain analysis of the knowledge utilization field, tracing its historical development between 1945 and 2004. Our purposes were to map the historical development of knowledge utilization as a field, and to identify the changing intellectual structure of its scientific domains. We analyzed more than 5,000 articles using citation data drawn from the Web of Science^®. Search terms were combinations of knowledge, research, evidence, guidelines, ideas, science, innovation, technology, information theory and use, utilization, and uptake.</p> <p>Results</p> <p>We provide an overview of the intellectual structure and how it changed over six decades. The field does not become large enough to represent with a co-citation map until the mid-1960s. Our findings demonstrate vigorous growth from the mid-1960s through 2004, as well as the emergence of specialized domains reflecting distinct collectives of intellectual activity and thought. Until the mid-1980s, the major domains were focused on innovation diffusion, technology transfer, and knowledge utilization. Beginning slowly in the mid-1980s and then growing rapidly, a fourth scientific domain, evidence-based medicine, emerged. The field is dominated in all decades by one individual, Everett Rogers, and by one paradigm, innovation diffusion.</p> <p>Conclusion</p> <p>We conclude that the received view that social science disciplines are in a state where no accepted set of principles or theories guide research (<it>i.e.</it>, that they are pre-paradigmatic) could not be supported for this field. Second, we document the emergence of a new domain within the knowledge utilization field, evidence-based medicine. Third, we conclude that Everett Rogers was the dominant figure in the field and, until the emergence of evidence-based medicine, his representation of the general diffusion model was the dominant paradigm in the field.</p

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders