Objective The first objective was to assess the psychometric properties of the 92-item Dutch Naming Test (DNT-92), developed to assess word finding difficulties in people with aphasia, using Item Response Theory (IRT). The second objective was to select suitable items for a short version with a discriminative purpose. Method This study has a retrospective, psychometric research design, in which 510 DNT-92-forms of people with aphasia and 192 DNT-forms of healthy participants were used for analyses. An IRT analysis was performed and information on the item- and person parameters was obtained. Item selection for the short version was based on a combination of the discriminative ability of the items and their estimated theta or difficulty. Items with the highest information load, and a difficulty parameter in the range of overlap between the sample of people with aphasia and healthy participants were selected. Results A 2-PL IRT analysis showed best fit to the data. Assumptions of unidimensionality, local independence, and monotonicity were met. Items were removed incrementally, whilst checking sensitivity and specificity of the remaining short form. A selection of six items proved optimal in terms of sensitivity and specificity, with an area under the curve value of 0.85. Differences were found between participants younger than 70 and older. Conclusions The IRT assumptions for the DNT-92 were met, indicating that the test has good psychometric properties. A reduction of items to just six items proved possible, leading to a reliable six item short form with a discriminatory purpose.
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Background: Magnetic resonance imaging (MRI) is being used extensively in the search for pathoanatomical factors contributing to low back pain (LBP) such as Modic changes (MC). However, it remains unclear whether clinical findings can identify patients with MC. The purpose of this explorative study was to assess the predictive value of six clinical tests and three questionnaires commonly used with patients with low-back pain (LBP) on the presence of Modic changes (MC).Methods: A retrospective cohort study was performed using data from Dutch military personnel in the period between April 2013 and July 2016. Questionnaires included the Roland Morris Disability Questionnaire, Numeric Pain Rating Scale, and Pain Self-Efficacy Questionnaire. The clinical examination included (i) range of motion, (ii) presence of pain during flexion and extension, (iii) Prone Instability Test, and (iv) straight leg raise. Backward stepwise regression was used to estimate predictive value for the presence of MC and the type of MC. The exploration of clinical tests was performed by univariable logistic regression models.Results: Two hundred eighty-six patients were allocated for the study, and 112 cases with medical records and MRI scans were available; 60 cases with MC and 52 without MC. Age was significantly higher in the MC group. The univariate regression analysis showed a significantly increased odds ratio for pain during flexion movement (2.57 [95% confidence interval (CI): 1.08-6.08]) in the group with MC. Multivariable logistic regression of all clinical symptoms and signs showed no significant association for any of the variables. The diagnostic value of the clinical tests expressed by sensitivity, specificity, positive predictive, and negative predictive values showed, for all the combinations, a low area under the curve (AUC) score, ranging from 0.41 to 0.53. Single-test sensitivity was the highest for pain in flexion: 60% (95% CI: 48.3-70.4).Conclusion: No model to predict the presence of MC, based on clinical tests, could be demonstrated. It is therefore not likely that LBP patients with MC are very different from other LBP patients and that they form a specific subgroup. However, the study only explored a limited number of clinical findings and it is possible that larger samples allowing for more variables would conclude differently.
This report presents the highlights of the 7th European Meeting on Molecular Diagnostics held in Scheveningen, The Hague, The Netherlands, 12-14 October 2011. The areas covered included molecular diagnostics applications in medical microbiology, virology, pathology, hemato-oncology,clinical genetics and forensics. Novel real-time amplification approaches, novel diagnostic applications and new technologies, such as next-generation sequencing, PCR lectrospray-ionization TOF mass spectrometry and techniques based on the detection of proteins or other molecules, were discussed. Furthermore, diagnostic companies presented their future visions for molecular diagnostics in human healthcare.
Structural colour (SC) is created by light interacting with regular nanostructures in angle-dependent ways resulting in vivid hues. This form of intense colouration offers commercial and industrial benefits over dyes and other pigments. Advantages include durability, efficient use of light, anti-fade properties and the potential to be created from low cost materials (e.g. cellulose fibres). SC is widely found in nature, examples include butterflies, squid, beetles, plants and even bacteria. Flavobacterium IR1 is a Gram-negative, gliding bacterium isolated from Rotterdam harbour. IR1 is able to rapidly self-assemble into a 2D photonic crystal (a form of SC) on hydrated surfaces. Colonies of IR1 are able to display intense, angle-dependent colours when illuminated with white light. The process of assembly from a disordered structure to intense hues, that reflect the ordering of the cells, is possible within 10-20 minutes. This bacterium can be stored long-term by freeze drying and then rapidly activated by hydration. We see these properties as suiting a cellular reporter system quite distinct from those on the market, SC is intended to be “the new Green Fluorescent Protein”. The ability to understand the genomics and genetics of SC is the unique selling point to be exploited in product development. We propose exploiting SC in IR1 to create microbial biosensors to detect, in the first instance, volatile compounds that are damaging to health and the environment over the long term. Examples include petroleum or plastic derivatives that cause cancer, birth defects and allergies, indicate explosives or other insidious hazards. Hoekmine, working with staff and students within the Hogeschool Utrecht and iLab, has developed the tools to do these tasks. We intend to create a freeze-dried disposable product (disposables) that, when rehydrated, allow IR1 strains to sense and report multiple hazardous vapours alerting industries and individuals to threats. The data, visible as brightly coloured patches of bacteria, will be captured and quantified by mobile phone creating a system that can be used in any location by any user without prior training. Access to advice, assay results and other information will be via a custom designed APP. This work will be performed in parallel with the creation of a business plan and market/IP investigation to prepare the ground for seed investment. The vision is to make a widely usable series of tests to allow robust environmental monitoring for all to improve the quality of life. In the future, this technology will be applied to other areas of diagnostics.
Pre-eclampsia (PE) is a common and severe pregnancy complication and is associated with substantial perinatal morbidity and mortality in mothers and infants. The disease is often characterized by a non-specific presentation which makes it challenging for physician to diagnose PE during regular pregnancy check-ups. To date, there are no diagnostic tests on the market for detection of PE early in pregnancy (first trimester). In this project, we will develop a platform to sensitively analyse calcium-binding proteins (CBPs) which will unlock the full potential of CBPs as predictive PE markers. The technology will also be applicable for other diseases (e.g., dementia and cancer) where CBPs are also known to play a key role in disease pathophysiology. We will develop with phage display antibodies that can recognize calcium binding to specific motifs in proteins. To this end we will synthesize peptide motifs with and without calcium to select antibodies that are specific for calcium bound proteins. These antibodies will be validated for their clinical use. For this goal we will use serum samples from the Improved studie (EU subsidised study) to determine if we can recognize pre-eclampsia in a very early stage. This knowledge can lead to a better treatment of pregnant women suffering from this disease and also will probably increase the well-being for the baby born and the development further in life.
The missing link in diagnostic testing for rheumatoid arthritis (RA) is an agglutination assay, easy to perform and dedicated to decentralized testing. Approximately 75% of RA patients produce autoantibodies to citrullinated proteins (ACPA), which can be detected using an agglutination-based diagnostic test. Such a diagnostic test will be cheaper, less laborious and faster than current tests and does not require sophisticated equipment. Novio Catalpa is developing this alternative test for ACPA in collaboration with Radboud University. To develop this test, specifically tagged and citrullinated nanobodies are needed, but the production is still challenging. Current methods for the production of ACPA diagnostics involve chemical synthesis, in which a variety of toxic chemicals are used in each step. The alternative assay involves nanobodies fused with RA-biomarker target entities, which can be completely produced by ‘green synthesis’ in the yeast Pichia pastoris using the expertise of HAN BioCentre. The yeast P. pastoris has proven to be able to produce nanobodies and is a fast and cost-effective platform that often results in high protein yields. Goal of the project is therefore to determine the feasibility and best green route to produce purified nanobodies tagged with citrullinated ACPA targets that can be used for developing an agglutination assay for RA. P. pastoris does not produce endogenous PAD enzymes which are needed for citrullination of the nanobodies in order to be able to use it in a RA agglutination test. Therefore, PAD enzymes from other sources need to be tested and applied. The project results will be directly used by Novio Catalpa to further develop the innovative test for RA. This project will contribute to and finally result in a single-step agglutination assay suitable for both point-of-care testing and automation in clinical laboratories.
