The Empower project : a new way of assessing and monitoring test comparability and stability

Background: Manufacturers and laboratories might benefit from using a modern integrated tool for quality management/assurance. The tool should not be confounded by commutability issues and focus on the intrinsic analytical quality and comparability of assays as performed in routine laboratories. In addition, it should enable monitoring of long-term stability of performance, with the possibility to quasi "real-time" remedial action. Therefore, we developed the "Empower" project. Methods: The project comprises four pillars: (i) master comparisons with panels of frozen single-donation samples, (ii) monitoring of patient percentiles and (iii) internal quality control data, and (iv) conceptual and statistical education about analytical quality. In the pillars described here (i and ii), state-of-the-art as well as biologically derived specifications are used. Results: In the 2014 master comparisons survey, 125 laboratories forming 8 peer groups participated. It showed not only good intrinsic analytical quality of assays but also assay biases/non-comparability. Although laboratory performance was mostly satisfactory, sometimes huge between-laboratory differences were observed. In patient percentile monitoring, currently, 100 laboratories participate with 182 devices. Particularly, laboratories with a high daily throughput and low patient population variation show a stable moving median in time with good between-instrument concordance. Shifts/drifts due to lot changes are sometimes revealed. There is evidence that outpatient medians mirror the calibration set-points shown in the master comparisons. Conclusions: The Empower project gives manufacturers and laboratories a realistic view on assay quality/comparability as well as stability of performance and/or the reasons for increased variation. Therefore, it is a modern tool for quality management/assurance toward improved patient care

Estimating the level of carbamoylated plasma non-high-density lipoproteins using infrared spectroscopy

Background: The increased cardiovascular morbidity and mortality observed in chronic kidney disease (CKD) patients can be partly explained by the presence of carbamoylated lipoproteins. Lipid profiles can be determined with infrared spectroscopy. In this paper, the effects of carbamoylation on spectral changes of non-high-density lipoproteins (non-HDL) were studied. Methods: In the present study, fasting serum samples were obtained from 84 CKD patients (CKD stage 3-5: n = 37 and CKD stage 5d (hemodialysis): n = 47) and from 45 healthy subjects. In vitro carbamoylation of serum lipoproteins from healthy subjects was performed using increasing concentrations of potassium cyanate. Lipoprotein-containing pellets were isolated by precipitation of non-HDL. The amount of carbamoylated serum non-HDL was estimated using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, followed by soft independent modelling by class analogy analysis. Results: Carbamoylation resulted in a small increase of the amide I band (1714-1589 cm(-1)) of the infrared spectroscopy (IR) spectrum. A significant difference in the amide II/amide I area under the curves (AUC) ratio was observed between healthy subjects and CKD patients, as well as between the two CKD groups (non-dialysis versus hemodialysis patients). Conclusions: ATR-FTIR spectroscopy can be considered as a novel method to detect non-HDL carbamoylation

Developmental screening in South Africa : comparing the national developmental checklist to a standardized tool

Background: Worldwide, more than 200 million children in low- and middle-income countries have developmental delays and/or disabilities. In South Africa the only nationally implemented developmental 'screening' tool is integrated as part of 'The Road to Health Booklet (RTHB). Method: The study employed a comparative cross-sectional within-subject design to evaluate the accuracy of the RTHB developmental checklist against a standardized international tool i.e. the PEDS tools, consisting of the PEDS and PEDS: DM. A total of 201 participants were included through convenience sampling at primary health care facilities in Tshwane, South Africa. Results: Sensitivity of the RTHB developmental checklist is low, but specificity is high. The RTHB developmental checklist failed to identify more than half the infants at risk of delays or disorders. The nationally implemented developmental checklist is ineffective to identify at-risk infants. It should be adapted and validated or replaced in order to improve identification of at-risk infants

Using 'big data' to describe the effect of seasonal variation in thyroid-stimulating hormone

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Early detection of communication delays with the PEDS tools in at-risk South African infants

Background: Prevalence of communication delays or disorders is increasing, possibly because of various environmental risk factors. Selection and implementation of effective screening tools are important to detect at-risk infants as early as possible. This study aimed to evaluate the accuracy of the Parents' Evaluation of Developmental Status (PEDS), PEDS-Developmental Milestones and PEDS tools to detect communication delays in infants (6-12 months) in a South African primary healthcare context. Method: A comparative study design evaluated the accuracy of the PEDS tools to detect communication delays, using an internationally accepted diagnostic assessment tool, the Rossetti Infant-Toddler Language Scale (RITLS). A convenience sample of 201 infants was selected at primary healthcare clinics. Results: Expressive and receptive language sensitivity scores were low across all three screens (ranging between 14% and 44%). The PEDS tools had high sensitivity (71%) and specificity (73%) ratings for the receptive and expressive language and socio-emotional domain in combination. Conclusion: In the sample population, the PEDS tools did not accurately detect receptive and expressive language delays; however, communication delays in general were identified. Future research determining accuracy of the PEDS, PEDS-Developmental Milestones and PEDS tools for children aged 2-5 years in detecting communication delays should be prioritised

Single-molecule localization microscopy analysis with ImageJ

ImageJ is a versatile and powerful tool for quantitative image analysis in microscopy. It is open-source software, platform-independent and enables students and researchers to obtain an easy but thorough introduction into image analysis. Especially the image processing package Fiji is a valuable and powerful extension of ImageJ. Several plugins and macros for single-molecule localization microscopy (SMLM) have been developed during the last decade. These novel tools cover the steps from single-molecule localization and image reconstruction to SMLM data postprocessing such as density analysis, image registration or resolution estimation. This article describes how ImageJ/Fiji can be used for image analysis, reviews existing extensions for SMLM, and aims at introducing and motivating novices and advanced SMLM users alike to explore the possibilities of ImageJ/Fiji for automated and quantitative data analysis

Immunotherapy and beta-cell replacement in type I diabetes mellitus

Control of allo- and auto-immunity is important for pancreas and islet transplantations. In chapter 2 different mechanism of actions of humanized monoclonal antibodies against CD3 and CD25 versus ATG are described. ATG leads to depletion of auto-reactive T-cells by ADCC, CDC and apoptosis induction, while anti-CD3 and daclizumab inhibited T-cell autoreactivity in a non-depleting fashion. In chapter 3, our experience with induction therapy with ATG and daclizumab was reported. ATG Fresenius or daclizumab were well tolerated and equally effective in reducing the incidence of acute rejections in simultaneous pancreas kidney transplantation. Data in Chapter 4 imply that daclizumab is more specifically affecting diabetes related immune responses compared to ATG. Islet transplantation provides an attractive and less invasive alternative to whole-organ pancreas transplantation. In chapter 5 we demonstrated the ability of our T-cell monitoring methods to determine the fate of repeated islet allografts transplanted into patients that express repeated mismatches. In most pancreas transplantations the enteric drainage is favoured exocrine duct management. Facing a higher risk on anastomotic complications in enteric drained pancreas transplantations, primary bladder drainage may be the preferred option. In Chapter 6, we demonstrated that primary bladder drainage followed by enteric conversion is a safe and effective procedure.UBL - phd migration 201

Stability criteria for a pyramidal shaped asperity ploughing through a plastically deforming substrate

In two body abrasion processes hard asperities plough through a soft surface. If the asperities can resist the forces that act on it, scratches will develop in the soft material. If the asperities cannot withstand these forces, they will break off and not cause direct abrasion damage. The same is the case for galling, where lumps develop on one of the surfaces because of material transfer. These lumps will abrade the counter surface, if the lumps are strong enough to withstand the forces that act on it. In order to describe these phenomena, simple criteria are desired to describe the mechanical stability of asperities and lumps.\ud \ud In this work, an analytical model is presented for the mechanical stability of asperities. In the analysis, a pyramidal asperity shape will be assumed. Given the pyramidal asperity shape, several cases will be studied: the load is carried by a pyramid with a triangular base, a pyramid with a triangular base and an extended backside and the case where a crack has developed. Based on these models stability criteria of ploughing pyramidal asperities will be developed. Important results of the model will be discussed in the context of abrasion and adhesive wear processes