Can outcome prediction data change patient outcomes and organizational outcomes?

PURPOSE OF REVIEW: Intensive care medicine consumes a high share of healthcare costs, and there is growing pressure to use the scarce resources efficiently. Accordingly, organizational issues and quality management have become an important focus of interest in recent years. Here, we will review current concepts of how outcome data can be used to identify areas requiring action. RECENT FINDINGS: Using recently established models of outcome assessment, wide variability between individual ICUs is found, both with respect to outcome and resource use. Such variability implies that there are large differences in patient care processes not only within the ICU but also in pre-ICU and post-ICU care. Indeed, measures to improve the patient process in the ICU (including care of the critically ill, patient safety, and management of the ICU) have been presented in a number of recently published papers. SUMMARY: Outcome assessment models provide an important framework for benchmarking. They may help the individual ICU to spot appropriate fields of action, plan and initiate quality improvement projects, and monitor the consequences of such activity.

Colonization history of the Swiss Rhine basin by the bullhead (Cottus gobio): inference under a Bayesian spatially explicit framework

The present distribution of freshwater fish in the Alpine region has been strongly affected by colonization events occurring after the last glacial maximum (LGM), some 20,000 years ago. We use here a spatially explicit simulation framework to model and better understand their colonization dynamics in the Swiss Rhine basin. This approach is applied to the European bullhead (Cottus gobio), which is an ideal model organism to study fish past demographic processes since it has not been managed by humans. The molecular diversity of eight sampled populations is simulated and compared to observed data at six microsatellite loci under an approximate Bayesian computation framework to estimate the parameters of the colonization process. Our demographic estimates fit well with current knowledge about the biology of this species, but they suggest that the Swiss Rhine basin was colonized very recently, after the Younger Dryas some 6600 years ago. We discuss the implication of this result, as well as the strengths and limits of the spatially explicit approach coupled to the approximate Bayesian computation framework.

MARVIN: a medical research application framework based on open source software

This paper describes the open source framework MARVIN for rapid application development in the field of biomedical and clinical research. MARVIN applications consist of modules that can be plugged together in order to provide the functionality required for a specific experimental scenario. Application modules work on a common patient database that is used to store and organize medical data as well as derived data. MARVIN provides a flexible input/output system with support for many file formats including DICOM, various 2D image formats and surface mesh data. Furthermore, it implements an advanced visualization system and interfaces to a wide range of 3D tracking hardware. Since it uses only highly portable libraries, MARVIN applications run on Unix/Linux, Mac OS X and Microsoft Windows.

Evaluation of early tissue reactions after lumbar intertransverse process fusion using CT in a rabbit

OBJECTIVE: The objective of the study was to evaluate tissue reactions such as bone genesis, cartilage genesis and graft materials in the early phase of lumbar intertransverse process fusion in a rabbit model using computed tomography (CT) imaging with CT intensity (Hounsfield units) measurement, and to compare these data with histological results. MATERIALS AND METHODS: Lumbar intertransverse process fusion was performed on 18 rabbits. Four graft materials were used: autograft bone (n = 3); collagen membrane soaked with recombinant human bone morphogenetic protein-2 (rhBMP-2) (n = 5); granular calcium phosphate (n = 5); and granular calcium phosphate coated with rhBMP-2 (n = 5). All rabbits were euthanized 3 weeks post-operatively and lumbar spines were removed for CT imaging and histological examination. RESULTS: Computed tomography imaging demonstrated that each fusion mass component had the appropriate CT intensity range. CT also showed the different distributions and intensities of bone genesis in the fusion masses between the groups. Each component of tissue reactions was identified successfully on CT images using the CT intensity difference. Using CT color mapping, these observations could be easily visualized, and the results correlated well with histological findings. CONCLUSIONS: The use of CT intensity is an effective approach for observing and comparing early tissue reactions such as newly synthesized bone, newly synthesized cartilage, and graft materials after lumbar intertransverse process fusion in a rabbit model.

Individual patient data meta-analysis of diagnostic and prognostic studies in obstetrics, gynaecology and reproductive medicine

BACKGROUND: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine. METHODS/DESIGN: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians. DISCUSSION: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

Conserved leucine residue in the head region of morbillivirus fusion protein regulates the large conformational change during fusion activity

Paramyxovirus cell entry is controlled by the concerted action of two viral envelope glycoproteins, the fusion (F) and the receptor-binding (H) proteins, which together with a cell surface receptor mediate plasma membrane fusion activity. The paramyxovirus F protein belongs to class I viral fusion proteins which typically contain two heptad repeat regions (HR). Particular to paramyxovirus F proteins is a long intervening sequence (IS) located between both HR domains. To investigate the role of the IS domain in regulating fusogenicity, we mutated in the canine distemper virus (CDV) F protein IS domain a highly conserved leucine residue (L372) previously reported to cause a hyperfusogenic phenotype. Beside one F mutant, which elicited significant defects in processing, transport competence, and fusogenicity, all remaining mutants were characterized by enhanced fusion activity despite normal or slightly impaired processing and cell surface targeting. Using anti-CDV-F monoclonal antibodies, modified conformational F states were detected in F mutants compared to the parental protein. Despite these structural differences, coimmunoprecipitation assays did not reveal any drastic modulation in F/H avidity of interaction. However, we found that F mutants had significantly enhanced fusogenicity at low temperature only, suggesting that they folded into conformations requiring less energy to activate fusion. Together, these data provide strong biochemical and functional evidence that the conserved leucine 372 at the base of the HRA coiled-coil of F(wt) controls the stabilization of the prefusogenic state, restraining the conformational switch and thereby preventing extensive cell-cell fusion activity.

Overview of data assimilation methods

We present the data assimilation approach, which provides a framework for combining observations and model simulations of the climate system, and has led to a new field of applications for paleoclimatology. The three subsequent articles explore specific applications in more detail.

Illusions of fusions: assessing cervical vertebral fusion on lateral cephalograms, multidetector computed tomographs, and cone-beam computed tomographs

INTRODUCTION The aims of this study were to compare lateral cephalograms with other radiologic methods for diagnosing suspected fusions of the cervical spine and to validate the assessment of congenital fusions and osteoarthritic changes against the anatomic truth. METHODS Four cadaver heads were selected with fusion of vertebrae C2 and C3 seen on a lateral cephalogram. Multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) were performed and assessed by 5 general radiologists and 5 oral radiologists, respectively. Vertebrae C2 and C3 were examined for osseous fusions, and the left and right facet joints were diagnosed for osteoarthritis. Subsequently, the C2 and C3 were macerated and appraised by a pathologist. Descriptive analysis was performed, and interrater agreements between and within the groups were computed. RESULTS All macerated specimens showed osteoarthritic findings of varying degrees, but no congenital bony fusion. All observers agreed that no fusion was found on MDCT or CBCT. They disagreed on the prevalence of osteoarthritic deformities (general radiologists/MDCT, 100%; oral radiologists/CBCT, 93.3%) and joint space assessment in the facet joints (kappa = 0.452). The agreement within the rater groups differed considerably (general radiologists/MDCT, kappa = 0.612; oral radiologists/CBCT, kappa = 0.240). CONCLUSIONS Lateral cephalograms do not provide dependable data to assess the cervical spine for fusions and cause false-positive detections. Both MDCT interpreted by general radiologists and CBCT interpreted by oral radiologists are reliable methods to exclude potential fusions. Degenerative osteoarthritic changes are diagnosed more accurately and consistently by general radiologists evaluating MDCT.

Opportunistic Content-Centric Data Transmission During Short Network Contacts

In this paper, we investigate content-centric data transmission in the context of short opportunistic contacts and base our work on an existing content-centric networking architecture. In case of short interconnection times, file transfers may not be completed and the received information is discarded. Caches in content-centric networks are used for short-term storage and do not guarantee persistence. We implemented a mechanism to extend caching on persistent storage enabling the completion of disrupted content transfers. The mechanisms have been implemented in the CCNx framework and have been evaluated on wireless mesh nodes. Our evaluations using multicast and unicast communication show that the implementation can support content transfers in opportunistic environments without significant processing and storing overhead.

Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion

It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91-115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111-118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism.

Description of the ERA-CLIM historical upper-air data

Historical, i.e. pre-1957, upper-air data are a valuable source of information on the state of the atmosphere, in some parts of the world dating back to the early 20th century. However, to date, reanalyses have only partially made use of these data, and only of observations made after 1948. Even for the period between 1948 (the starting year of the NCEP/NCAR (National Centers for Environmental Prediction/National Center for Atmospheric Research) reanalysis) and the International Geophysical Year in 1957 (the starting year of the ERA-40 reanalysis), when the global upper-air coverage reached more or less its current status, many observations have not yet been digitised. The Comprehensive Historical Upper-Air Network (CHUAN) already compiled a large collection of pre-1957 upper-air data. In the framework of the European project ERA-CLIM (European Reanalysis of Global Climate Observations), significant amounts of additional upper-air data have been catalogued (> 1.3 million station days), imaged (> 200 000 images) and digitised (> 700 000 station days) in order to prepare a new input data set for upcoming reanalyses. The records cover large parts of the globe, focussing on, so far, less well covered regions such as the tropics, the polar regions and the oceans, and on very early upper-air data from Europe and the US. The total number of digitised/inventoried records is 61/101 for moving upper-air data, i.e. data from ships, etc., and 735/1783 for fixed upper-air stations. Here, we give a detailed description of the resulting data set including the metadata and the quality checking procedures applied. The data will be included in the next version of CHUAN. The data are available at doi:10.1594/PANGAEA.821222

Increasing the Antitumor Effect of an EpCAM-Targeting Fusion Toxin by Facile Click PEGylation

Fusion toxins used for cancer-related therapy have demonstrated short circulation half-lives, which impairs tumor localization and, hence, efficacy. Here, we demonstrate that the pharmacokinetics of a fusion toxin composed of a designed ankyrin repeat protein (DARPin) and domain I–truncated Pseudomonas Exotoxin A (PE40/ETA″) can be significantly improved by facile bioorthogonal conjugation with a polyethylene glycol (PEG) polymer at a unique position. Fusion of the anti-EpCAM DARPin Ec1 to ETA″ and expression in methionine-auxotrophic E. coli enabled introduction of the nonnatural amino acid azidohomoalanine (Aha) at position 1 for strain-promoted click PEGylation. PEGylated Ec1-ETA″ was characterized by detailed biochemical analysis, and its potential for tumor targeting was assessed using carcinoma cell lines of various histotypes in vitro, and subcutaneous and orthotopic tumor xenografts in vivo. The mild click reaction resulted in a well-defined mono-PEGylated product, which could be readily purified to homogeneity. Despite an increased hydrodynamic radius resulting from the polymer, the fusion toxin demonstrated high EpCAM-binding activity and retained cytotoxicity in the femtomolar range. Pharmacologic analysis in mice unveiled an almost 6-fold increase in the elimination half-life (14 vs. 82 minutes) and a more than 7-fold increase in the area under the curve (AUC) compared with non-PEGylated Ec1-ETA″, which directly translated in increased and longer-lasting effects on established tumor xenografts. Our data underline the great potential of combining the inherent advantages of the DARPin format with bioorthogonal click chemistry to overcome the limitations of engineering fusion toxins with enhanced efficacy for cancer-related therapy.

Approximate decoding approaches for network coded correlated data

This paper considers a framework where data from correlated sources are transmitted with the help of network coding in ad hoc network topologies. The correlated data are encoded independently at sensors and network coding is employed in the intermediate nodes in order to improve the data delivery performance. In such settings, we focus on the problem of reconstructing the sources at decoder when perfect decoding is not possible due to losses or bandwidth variations. We show that the source data similarity can be used at decoder to permit decoding based on a novel and simple approximate decoding scheme. We analyze the influence of the network coding parameters and in particular the size of finite coding fields on the decoding performance. We further determine the optimal field size that maximizes the expected decoding performance as a trade-off between information loss incurred by limiting the resolution of the source data and the error probability in the reconstructed data. Moreover, we show that the performance of the approximate decoding improves when the accuracy of the source model increases even with simple approximate decoding techniques. We provide illustrative examples showing how the proposed algorithm can be deployed in sensor networks and distributed imaging applications.

A Concept of Semantics Extraction from Web Data by Induction of Fuzzy Ontologies

Traditionally, ontologies describe knowledge representation in a denotational, formalized, and deductive way. In addition, in this paper, we propose a semiotic, inductive, and approximate approach to ontology creation. We define a conceptual framework, a semantics extraction algorithm, and a first proof of concept applying the algorithm to a small set of Wikipedia documents. Intended as an extension to the prevailing top-down ontologies, we introduce an inductive fuzzy grassroots ontology, which organizes itself organically from existing natural language Web content. Using inductive and approximate reasoning to reflect the natural way in which knowledge is processed, the ontology’s bottom-up build process creates emergent semantics learned from the Web. By this means, the ontology acts as a hub for computing with words described in natural language. For Web users, the structural semantics are visualized as inductive fuzzy cognitive maps, allowing an initial form of intelligence amplification. Eventually, we present an implementation of our inductive fuzzy grassroots ontology Thus,this paper contributes an algorithm for the extraction of fuzzy grassroots ontologies from Web data by inductive fuzzy classification.

The FORA Framework - A Fuzzy Grassroots Ontology for Online Reputation Management

Online reputation management deals with monitoring and influencing the online record of a person, an organization or a product. The Social Web offers increasingly simple ways to publish and disseminate personal or opinionated information, which can rapidly have a disastrous influence on the online reputation of some of the entities. This dissertation can be split into three parts: In the first part, possible fuzzy clustering applications for the Social Semantic Web are investigated. The second part explores promising Social Semantic Web elements for organizational applications,while in the third part the former two parts are brought together and a fuzzy online reputation analysis framework is introduced and evaluated. Theentire PhD thesis is based on literature reviews as well as on argumentative-deductive analyses.The possible applications of Social Semantic Web elements within organizations have been researched using a scenario and an additional case study together with two ancillary case studies—based on qualitative interviews. For the conception and implementation of the online reputation analysis application, a conceptual framework was developed. Employing test installations and prototyping, the essential parts of the framework have been implemented.By following a design sciences research approach, this PhD has created two artifacts: a frameworkand a prototype as proof of concept. Bothartifactshinge on twocoreelements: a (cluster analysis-based) translation of tags used in the Social Web to a computer-understandable fuzzy grassroots ontology for the Semantic Web, and a (Topic Maps-based) knowledge representation system, which facilitates a natural interaction with the fuzzy grassroots ontology. This is beneficial to the identification of unknown but essential Web data that could not be realized through conventional online reputation analysis. Theinherent structure of natural language supports humans not only in communication but also in the perception of the world. Fuzziness is a promising tool for transforming those human perceptions intocomputer artifacts. Through fuzzy grassroots ontologies, the Social Semantic Web becomes more naturally and thus can streamline online reputation management.