Stimulation of neutrophil functions by C5adesArg: an in vitro model of haemodialysis

Cuprophane membranes during haemodialysis significantly increase the plasma levels of C5adesArg (maximal 55 μg C5aadesArg/1 blood after 30 min) whereas Hemophane or Polysulphonemembranes induce only low plasma levels of C5adesArg. C5adesArg generated in vitro by yeast incubation of autologous plasma stimulates PMN chemotaxis and oxidative metabolism but has no effect on enzyme release. Preincubation of whole blood with C5adesArg causes aggregation and changed oxidative burst activity of the isolated PMN. These changes are similar to those found in cells from patients after haemodialysis with cuprophane membranes. So the elevated plasma levels of C5adesArg after haemodialysis explain some of the changes in PMN functions, but additional mechanisms have to be assumed

Openness in Teachers' Digital Competence Frameworks: Looking for the Open Educator

There has been a wide variety of definitions of digital competence, from early narrow and technology-focused explanations to more recent attempts , such as the one by Ferrari (2013), who describes it as a complex concept encompassing a wide set of skills, attitudes and knowledge when performing tasks with Information and Communication Technologies (ICT). Furthermore, there have been various different attempts to describe teachers’ digital competence, as the literature review by McGarr and McDonagh (2019) demonstrates. These authors evidence that models either depict teachers’ digital competence in diverse taxonomies of areas and dimensions, or as a hierarchical and progressive evolution from low to high levels of awareness and ability. They observe that openness does not have a presence in most of the taxonomic models and thus they propose openness as a dimension of their four-part model, under the label of attitudes. In this current work, we analyse international and national teachers’ digital competence frameworks and review whether openness has been included in them, and, if so, how it is described. In the case of frameworks that offer a model of increasing performance, we observe the levels at which open-related concepts appear. An initial review of the frameworks by the European Commission, UNESCO, ISTE (US) and INTEF (Spain) indicates that ‘openness’ typically does not constitute a dimension in itself and tends to appear at intermediate and high levels of teachers’ digital competence, except from the UNESCO framework, where access to OER (Open Educational Resources) is present already at the lowest level. In this paper we reflect on the need for international and national frameworks of teacher professional development to boost openness: in particular, for open educational practices to be included at lower levels of teachers’ pre-service and in-service professional education. We argue that becoming an open educator requires both the development of the dispositions associated with reflective practice and the confidence to challenge neo-liberal educational assumptions in order to embrace participatory, equitable and open educational practices from the early stages of the development of teachers’ digital competence

Identifying Overlapping and Hierarchical Thematic Structures in Networks of Scholarly Papers: A Comparison of Three Approaches

We implemented three recently proposed approaches to the identification of overlapping and hierarchical substructures in graphs and applied the corresponding algorithms to a network of 492 information-science papers coupled via their cited sources. The thematic substructures obtained and overlaps produced by the three hierarchical cluster algorithms were compared to a content-based categorisation, which we based on the interpretation of titles and keywords. We defined sets of papers dealing with three topics located on different levels of aggregation: h-index, webometrics, and bibliometrics. We identified these topics with branches in the dendrograms produced by the three cluster algorithms and compared the overlapping topics they detected with one another and with the three pre-defined paper sets. We discuss the advantages and drawbacks of applying the three approaches to paper networks in research fields.Comment: 18 pages, 9 figure

Shortwave spectral radiative signatures and their physical controls

The spectrum of reflected solar radiation emerging at the top of the atmosphere is rich with Earth system information. To identify spectral signatures in the reflected solar radiation and directly relate them to the underlying physical properties controlling their structure, over 90,000 solar reflectance spectra are computed over West Africa in 2010 using a fast radiation code employing the spectral characteristics of the SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY). Cluster analysis applied to the computed spectra reveals spectral signatures related to distinct surface properties, and cloud regimes distinguished by their spectral short-wave cloud radiative effect (SWCRE). The cloud regimes exhibit a diverse variety of mean broadband SWCREs, and offer an alternative approach to define cloud type for SWCRE applications that does not require any prior assumptions. The direct link between spectral signatures and distinct physical properties extracted from clustering remains robust between spatial scales of 1, 20 and 240 km, and presents an excellent opportunity to understand the underlying properties controlling real spectral reflectance observations. Observed SCIAMACHY spectra are assigned to the calculated spectral clusters, showing that cloud regimes are most frequent during the active West African monsoon season of June–October in 2010, and all cloud regimes have a higher frequency of occurrence during the active monsoon season of 2003 compared with the inactive monsoon season of 2004. Overall, the distinct underlying physical properties controlling spectral signatures show great promise for monitoring evolution of the Earth system directly from solar spectral reflectance observations

Venlafaxine’s therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis

Introduction The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet. Objectives We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression. Methods Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal. Results High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75–225 mg/day). The population-based concentration ranges (25–75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225–450 ng/ml for the AM and (ii) 144–302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140–600 ng/ml. Conclusion VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN’s dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations

Open Data as Open Educational Resources: Case studies of emerging practice

This collection presents the stories of our contributors’ experiences and insights, in order to demonstrate the enormous potential for openly-licensed and accessible datasets (Open Data) to be used as Open Educational Resources (OER). Open Data is an umbrella term describing openly-licensed, interoperable, and reusable datasets which have been created and made available to the public by national or local governments, academic researchers, or other organisations. These datasets can be accessed, used and shared without restrictions other than attribution of the intellectual property of their creators1.While there are various definitions of OER, these are generally understood as openly-licensed digital resources that can be used in teaching and learning. On the basis of these definitions, it is reasonable to assert that while Open Data is not always OER, it certainly becomes OER when used within pedagogical contexts. Yet while the question may appear already settled at the level of definition, the potential and actual pedagogical uses of Open Data appear to have been under-discussed. As open education researchers who take a wider interest in the various open ‘movements’, we have observed that linkages between them are not always strong, in spite of shared and interconnecting values. So, Open Data tends to be discussed primarily in relation to its production, storage, licensing and accessibility, but less often in relation to its practical subsequent uses. And, in spite of widespread understanding that use of the term ‘OER’ is actually context-dependent, and, therefore, could be almost all-encompassing, the focus of OER practice and research has tended to be on educator-produced learning materials. The search for relevant research literature in the early stages of this project turned up sources which discuss the benefits of opening data, and others advocating improving student engagement with data3, but on the topic of Open Data as an educational resource specifically, there appeared to be something of a gap

World citation and collaboration networks: uncovering the role of geography in science

Modern information and communication technologies, especially the Internet, have diminished the role of spatial distances and territorial boundaries on the access and transmissibility of information. This has enabled scientists for closer collaboration and internationalization. Nevertheless, geography remains an important factor affecting the dynamics of science. Here we present a systematic analysis of citation and collaboration networks between cities and countries, by assigning papers to the geographic locations of their authors' affiliations. The citation flows as well as the collaboration strengths between cities decrease with the distance between them and follow gravity laws. In addition, the total research impact of a country grows linearly with the amount of national funding for research & development. However, the average impact reveals a peculiar threshold effect: the scientific output of a country may reach an impact larger than the world average only if the country invests more than about 100,000 USD per researcher annually.Comment: Published version. 9 pages, 5 figures + Appendix, The world citation and collaboration networks at both city and country level are available at http://becs.aalto.fi/~rajkp/datasets.htm

Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods: The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated. Results: Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions: High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers

Knowledge Integration and Diffusion: Measures and Mapping of Diversity and Coherence

I present a framework based on the concepts of diversity and coherence for the analysis of knowledge integration and diffusion. Visualisations that help understand insights gained are also introduced. The key novelty offered by this framework compared to previous approaches is the inclusion of cognitive distance (or proximity) between the categories that characterise the body of knowledge under study. I briefly discuss the different methods to map the cognitive dimension