Active and Passive Immunization Protects against Lethal, Extreme Drug Resistant-Acinetobacter baumannii Infection

Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A. baumannii in mice. OmpA was >99% conserved at the amino acid level across clinical isolates harvested between 1951 and 2009 from cerebrospinal fluid, blood, lung, and wound infections, including carbapenem-resistant isolates, and was ≥89% conserved among other sequenced strains, but had minimal homology to the human proteome. Vaccination of diabetic mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival and reduced tissue bacterial burden in mice infected intravenously. Vaccination induced high titers of anti-OmpA antibodies, the levels of which correlated with survival in mice. Passive transfer with immune sera recapitulated protection. Immune sera did not enhance complement-mediated killing but did enhance opsonophagocytic killing of A. baumannii. These results define active and passive immunization strategies to prevent and treat highly lethal, XDR A. baumannii infections

Online collaboration and cooperation : the recurring importance of evidence, rationale and viability

This paper investigates collaboration in teaching and learning and draws out implications for the promotion of collaboration within online environments. It is divided into four sections. First the case for collaboration, including specifically cooperative approaches, is explored. This case revolves around the impact of collaboration on the quality of learning and on learning outcomes. Collaboration is seen as constrained by context but, if structured and rewarded, it will bring important motivational and cognitive benefits. Next, the case for online collaboration is examined. This is based on longstanding arguments about the benefits of working together albeit in an environment which offers greater reach; a mix of media; and archives of interaction. The third section of the paper compares perspectives on online collaboration with a longer tradition of research into collaboration in general; it critiques the idea that online mediation offers a paradigm change in teaching and learning. The fourth section of the paper considers future directions for promoting online collaboration

Implementation outcome instruments for use in physical healthcare settings: a systematic review

BACKGROUND: Implementation research aims to facilitate the timely and routine implementation and sustainment of evidence-based interventions and services. A glaring gap in this endeavour is the capability of researchers, healthcare practitioners and managers to quantitatively evaluate implementation efforts using psychometrically sound instruments. To encourage and support the use of precise and accurate implementation outcome measures, this systematic review aimed to identify and appraise studies that assess the measurement properties of quantitative implementation outcome instruments used in physical healthcare settings. METHOD: The following data sources were searched from inception to March 2019, with no language restrictions: MEDLINE, EMBASE, PsycINFO, HMIC, CINAHL and the Cochrane library. Studies that evaluated the measurement properties of implementation outcome instruments in physical healthcare settings were eligible for inclusion. Proctor et al.'s taxonomy of implementation outcomes was used to guide the inclusion of implementation outcomes: acceptability, appropriateness, feasibility, adoption, penetration, implementation cost and sustainability. Methodological quality of the included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Psychometric quality of the included instruments was assessed using the Contemporary Psychometrics checklist (ConPsy). Usability was determined by number of items per instrument. RESULTS: Fifty-eight publications reporting on the measurement properties of 55 implementation outcome instruments (65 scales) were identified. The majority of instruments assessed acceptability (n = 33), followed by appropriateness (n = 7), adoption (n = 4), feasibility (n = 4), penetration (n = 4) and sustainability (n = 3) of evidence-based practice. The methodological quality of individual scales was low, with few studies rated as 'excellent' for reliability (6/62) and validity (7/63), and both studies that assessed responsiveness rated as 'poor' (2/2). The psychometric quality of the scales was also low, with 12/65 scales scoring 7 or more out of 22, indicating greater psychometric strength. Six scales (6/65) rated as 'excellent' for usability. CONCLUSION: Investigators assessing implementation outcomes quantitatively should select instruments based on their methodological and psychometric quality to promote consistent and comparable implementation evaluations. Rather than developing ad hoc instruments, we encourage further psychometric testing of instruments with promising methodological and psychometric evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017 CRD42017065348

Complexity challenges in development of cyber-physical systems

In embarking towards Cyber-Physical Systems (CPS) withunprecedented capabilities it becomes essential to improve our understanding ofCPS complexity and how we can deal with it. We investigate facets of CPScomplexity and the limitations of Collaborating Information Processing Systems(CIPS) in dealing with those facets. By CIPS we refer to teams of humans andcomputer-aided engineering systems that are used to develop CPS. Furthermore,we specifically analyze characteristic differences among software and physicalparts within CPS. The analysis indicates that it will no longer be possible to relyonly on architectures and skilled people, or process and model/tool centeredapproaches. The tight integration of heterogeneous physical, cyber, CPS components,aspects and systems, results in a situation with interfaces and interrelationseverywhere, each requiring explicit consideration. The role of modelbasedand computer aided engineering will become even more essential, anddesign methodologies will need to deeply consider interwoven systems andsoftware aspects, including the hidden costs of software.QC 20181019</p