Investigating psychometric properties and dimensional structure of an educational environment measure (DREEM) using Mokken scale analysis - A pragmatic approach

© 2018 The Author(s). Background: Questionnaires and surveys are used throughout medical education. Nevertheless, measuring psychological attributes such as perceptions of a phenomenon among individuals may be difficult. The aim of this paper is to introduce the basic principles of Mokken scale analysis (MSA) as a method for the analysis of questionnaire data and to empirically apply MSA to a real-data example. Methods: MSA provides a set of statistical tools for exploring the relationship between items and latent traits. MSA is a scaling method of item selection algorithms used to partition an array of items into scales. It employs various methods to probe the assumptions of two nonparametric item response theory models: the monotone homogeneity model and the double monotonicity model. The background and theoretical framework underlying MSA are outlined in the paper. MSA for polytomous items was applied to a real-life data example of 222 undergraduate students who had completed a 50-item self-administered inventory measuring the educational environment, the Dundee Ready Educational Measure (DREEM). Results: A pragmatic and parsimonious approach to exploring questionnaires and surveys from an item response theory (IRT) perspective is outlined. The use of MSA to explore the psychometric properties of the Swedish version of the DREEM failed to yield strong support for the scalability and dimensional structure of the instrument. Conclusions: MSA, a class of simple nonparametric IRT models - for which estimates can be easily obtained and whose fit to data is relatively easily investigated - was introduced, presented, and tested. Our real-data example suggests that the psychometric properties of DREEM are not adequately supported. Thus, the empirical application depicted a potential and feasible approach whereby MSA could be used as a valuable method for exploring the behavior of scaled items in response to varying levels of a latent trait in medical education research

Serological evaluation of possible exposure to Ljungan virus and related parechovirus in autoimmune (type 1) diabetes in children.

Exposure to Ljungan virus (LV) is implicated in the risk of autoimmune (type 1) diabetes but possible contribution by other parechoviruses is not ruled out. The aim was to compare children diagnosed with type 1 diabetes in 2005-2011 (n = 69) with healthy controls (n = 294), all from the Jämtland County in Sweden, using an exploratory suspension multiplex immunoassay for IgM and IgG against 26 peptides of LV, human parechoviruses (HPeV), Aichi virus and poliovirus in relation to a radiobinding assay (RBA) for antibodies against LV and InfluenzaA/H1N1pdm09. Islet autoantibodies and HLA-DQ genotypes were also determined. 1) All five LV-peptide antibodies correlated to each other (P < 0.001) in the suspension multiplex IgM- and IgG-antibody assay; 2) The LV-VP1_31-60-IgG correlated with insulin autoantibodies alone (P = 0.007) and in combination with HLA-DQ8 overall (P = 0.022) as well as with HLA-DQ 8/8 and 8/X subjects (P = 0.013); 3) RBA detected LV antibodies correlated with young age at diagnosis (P < 0.001) and with insulin autoantibodies (P < 0.001) especially in young HLA-DQ8 subjects (P = 0.004); 4) LV-peptide-VP1_31-60-IgG correlated to RBA LV antibodies (P = 0.009); 5) HPeV3-peptide-IgM and -IgG showed inter-peptide correlations (P < 0.001) but only HPeV3-VP1_1-30-IgG (P < 0.001) and VP1_95-124-IgG (P = 0.009) were related to RBA LV antibodies without relation to insulin autoantibody positivity (P = 0.072 and P = 0.486, respectively). Both exploratory suspension multiplex IgG to LV-peptide VP1_31-60 and RBA detected LV antibodies correlated with insulin autoantibodies and HLA-DQ8 suggesting possible role in type 1 diabetes. It remains to be determined if cross-reactivity or concomitant exposure to LV and HPeV3 contributes to the seroprevalence. J. Med. Virol. © 2015 Wiley Periodicals, Inc

In vitro evaluation of iron oxide nanoparticle-induced thromboinflammatory response using a combined human whole blood and endothelial cell model

Iron oxide nanoparticles (IONPs) are widely used in diagnostic and therapeutic settings. Upon systemic administration, however, they are rapidly recognized by components of innate immunity, which limit their therapeutic capacity and can potentially lead to adverse side effects. IONPs were previously found to induce the inflammatory response in human whole blood, including activation of the complement system and increased secretion of cytokines. Here, we investigated the thromboinflammatory response of 10-30 nm IONPs in lepirudin anticoagulated whole blood in interplay with endothelial cells and evaluated the therapeutic effect of applying complement inhibitors to limit adverse effects related to thromboinflammation. We found that IONPs induced complement activation, primarily at the C3-level, in whole blood incubated for up to four hours at 37°C with and without human microvascular endothelial cells. Furthermore, IONPs mediated a strong thromboinflammatory response, as seen by the significantly increased release of 21 of the 27 analyzed cytokines (p&lt;0.05). IONPs also significantly increased cell-activation markers of endothelial cells [ICAM-1 (p&lt;0.0001), P/E-selectin (p&lt;0.05)], monocytes, and granulocytes [CD11b (p&lt;0.001)], and platelets [CD62P (p&lt;0.05), CD63 (p&lt;0.05), NAP-2 (p&lt;0.01), PF4 (p&lt;0.05)], and showed cytotoxic effects, as seen by increased LDH (p&lt;0.001) and heme (p&lt;0.0001) levels. We found that inflammation and endothelial cell activation were partly complement-dependent and inhibition of complement at the level of C3 by compstatin Cp40 significantly attenuated expression of ICAM-1 (p&lt;0.01) and selectins (p&lt;0.05). We show that complement activation plays an important role in the IONPs-induced thromboinflammatory response and that complement inhibition is promising in improving IONPs biocompatibility

Mass spectrometry imaging of cassette-dosed drugs for higher throughput pharmacokinetic and biodistribution analysis

Cassette dosing of compounds for preclinical drug plasma pharmacokinetic analysis has been shown to be a powerful strategy within the pharmaceutical industry for increasing throughput while decreasing the number of animals used. Presented here for the first time is data on the application of a cassette dosing strategy for label-free tissue distribution studies. The aim of the study was to image the spatial distribution of eight nonproprietary drugs (haloperidol, bufuralol, midazolam, clozapine, terfenadine, erlotinib, olanzapine, and moxifloxacin) in multiple tissues after oral and intravenous cassette dosing (four compounds per dose route). An array of mass spectrometry imaging technologies, including matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), liquid extraction surface analysis tandem mass spectrometry (LESA-MS/MS), and desorption electrospray ionization mass spectrometry (DESI-MS) was used. Tissue analysis following intravenous and oral administration of discretely and cassette-dosed compounds demonstrated similar relative abundances across a range of tissues indicating that a cassette dosing approach was applicable. MALDI MSI was unsuccessful in detecting all of the target compounds; therefore, DESI MSI, a complementary mass spectrometry imaging technique, was used to detect additional target compounds. In addition, by adapting technology used for tissue profiling (LESA-MS/MS) low spatial resolution mass spectrometry imaging (∼1 mm) was possible for all targets across all tissues. This study exemplifies the power of multiplatform MSI analysis within a pharmaceutical research and development (R&D) environment. Furthermore, we have illustrated that the cassette dosing approach can be readily applied to provide combined, label-free pharmacokinetic and drug distribution data at an early stage of the drug discovery/development process while minimizing animal usage

Non-randomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes

BACKGROUND: Laparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial. METHODS: Characteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy. RESULTS: During the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older – and had more complications from gallstone disease, higher co-morbidity, and higher ASA – score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy. CONCLUSION: Non-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials

Deformation independent open brane metrics and generalized theta parameters

We investigate the consequences of generalizing certain well established properties of the open string metric to the conjectured open membrane and open Dp-brane metrics. By imposing deformation independence on these metrics their functional dependence on the background fields can be determined including the notorious conformal factor. In analogy with the non-commutativity parameter $\Theta^{\mu\nu}$ in the string case, we also obtain `generalized' theta parameters which are rank q+1 antisymmetric tensors (polyvectors) for open Dq-branes and rank 3 for the open membrane case. The expressions we obtain for the open membrane quantities are expected to be valid for general background field configurations, while the open D-brane quantities are only valid for one parameter deformations. By reducing the open membrane data to five dimensions, we show that they, modulo a subtlety with implications for the relation between OM-theory and NCYM, correctly generate the open string and open D2-data.Comment: 24 pages, LaTe