Online Bivariate Outlier Detection in Final Test Using Kernel Density Estimation

In parametric IC testing, outlier detection is applied to filter out potential unreliable devices. Most outlier detection methods are used in an offline setting and hence are not applicable to Final Test, where immediate pass/fail decisions are required. Therefore, we developed a new bivariate online outlier detection method that is applicable to Final Test without making assumptions about a specific form of relations between two test parameters. An acceptance region is constructed using kernel density estimation. We use a grid discretization in order to enable a fast outlier decision. After each accepted device the grid is updated, hence the method is able to adapt to shifting measurements

TSE pathogenesis in cattle and sheep

Many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (TSE). Only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (BSE) and scrapie in their natural hosts. In this review, we summarize the most recent insights into the pathogenesis of BSE and scrapie starting from the initial uptake of TSE agents and crossing of the gut epithelium. Following replication in the gut-associated lymphoid tissues (GALT), TSE agents spread to the enteric nervous system (ENS) of the gut. Infection is then carried through the efferent fibers of the post-ganglionic neurons of the parasympathetic and sympathetic nervous system to the pre-ganglionic neurons in the medulla oblongata of the brain and the thoracic segments of the spinal cord. The differences between the pathogenesis of BSE in cattle and scrapie in sheep are discussed as well as the possible existence of additional pathogenetic routes

Differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and CH1641 scrapie

With increased awareness of the diversity of transmissible spongiform encephalopathy (TSE) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. Exposure to bovine spongiform encephalopathy (BSE) has been associated with the human TSE, variant Creutzfeldt–Jakob disease, emphasizing the necessity in distinguishing low-risk TSE types from BSE. TSE type discrimination in ruminants such as cattle, sheep, goats and deer, requires the application of several prion protein (PrP)-specific antibodies in parallel immunochemical tests on brain homogenates or tissue sections from infected animals. This study uses in a single incubation step, three PrP-specific antibodies and fluorescent Alexa dye-labelled anti-mouse Fabs on a Western blot. The usual amount of brain tissue needed is 0.5 mg. This multiplex application of antibodies directed towards three different PrP epitopes enabled differential diagnosis of all established main features of classical scrapie, BSE and Nor98-like scrapie in sheep and goats, as well as the currently known BSE types C, H and L in cattle. Moreover, due to an antibody-dependent dual PrP-banding pattern, for the first time CH1641 scrapie of sheep can be reliably discriminated from the other TSE isolate types in sheep

Outcomes after contemporary Fontan operation

Aims and outline of this thesis The aim of this thesis was to study medium to long term outcome in a large contemporary cohort of Fontan patients. These are patients that have been operated upon according to a modern technique (either ILT or ECC TCPC) in a staged manner. Furthermore, completion of the Fontan-circulation was performed before the age of 7. Special emphasis of this thesis will be the comparison of the ILT and ECC techniques. Main objectives were: - To compare and assess risk factors for mortality and morbidity for ECC and ILT patients - To study ventricular function and reserve and identify predictors for impaired function using echocardiography as well as CMR, including dobutamine-stress CMR. - To assess exercise capacity and identify predictors for deterioration of exercise capacity. - To assess rhythm status and the incidence of arrhythmias. - To determine the health related quality of life in modern Fontan patients and identify predictors for lower quality of life. - To study flow dynamics and power loss inside the TCPC pathway. - To study shear stress and growth of the pulmonary arteries after Fontan completion

Complete genome sequence and taxonomic position of anguillid herpesvirus 1

Eel herpesvirus or anguillid herpesvirus 1 (AngHV1) frequently causes disease in freshwater eels. The complete genome sequence of AngHV1 and its taxonomic position within the family Alloherpesviridae were determined. Shotgun sequencing revealed a 249 kbp genome including an 11 kbp terminal direct repeat that contains 7 of the 136 predicted protein-coding open reading frames. Twelve of these genes are conserved among other members of the family Alloherpesviridae and another 28 genes have clear homologues in cyprinid herpesvirus 3. Phylogenetic analyses based on amino acid sequences of five conserved genes, including the ATPase subunit of the terminase, confirm the position of AngHV1 within the family Alloherpesviridae, where it is most closely related to the cyprinid herpesviruses. Our analyses support a recent proposal to subdivide the family Alloherpesviridae into two sister clades, one containing AngHV1 and the cyprinid herpesviruses and the other containing Ictalurid herpesvirus 1 and the ranid herpesviruses

Gene expression profiling en association with prion-related lesions in the medulla oblongata of symptomatic natural scrapie animals.

The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed

The effect of an interactive cycling training on cognitive functioning in older adults with mild dementia: study protocol for a randomized controlled trial

Contains fulltext : 168861.pdf (publisher's version ) (Open Access)Background: To date there is no cure or an effective disease-modifying drug to treat dementia. Available acetylcholine-esterase inhibiting drugs or memantine only produce small benefits on cognitive and behavioural functioning and their clinical relevance remains controversial. Combined cognitive-aerobic interventions are an appealing alternative or add-on to current pharmacological treatments. The primary aim of this study is to investigate the efficacy of a combined cognitive-aerobic training and a single aerobic training compared to an active control group in older adults with mild dementia. We expect to find a beneficial effect on executive functioning in both training regimes, compared to the control intervention, with the largest effect in the combined cognitive-aerobic group. Secondary, intervention effects on cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty and quality of life are studied. Methods: The design is a single-blind, randomized controlled trial (RCT) with three groups: a combined cognitive-aerobic bicycle training (interactive cycling), a single aerobic bicycle training and a control intervention, which consists of stretching and toning exercises. Older adults with mild dementia follow a 12-week training program consisting of three training sessions of 30-40 min per week. The primary study outcome is objective executive functioning measured with a neuropsychological assessment. Secondary measures are objective cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty, mood and quality of life. The three groups are compared at baseline, after 6 and 12 weeks of training, and at 24-week follow-up. Discussion: This study will provide novel information on the effects of an interactive cycling training on executive function in older adults with mild dementia. Furthermore, since this study has both a combined cognitive-aerobic training and a single aerobic training group the effectiveness of the different components of the intervention can be identified. The results of this study may be used for physical and mental activity recommendations in older adults with dementia.8 p

Microarray and morphological analysis of early postnatal CRB2 mutant retinas on a pure C57BL/6J genetic background

In humans, the Crumbs homologue-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. Th

Prehospital Epidemiology and Treatment of Severe Traumatic Brain Injury:Unraveling the black box

In Chapter 2, the study protocol is described of the BRAIN-PROTECT study, the first Dutch prospective observational study on prehospital epidemiology and treatment of patients with severe traumatic brain injury (TBI). The main objective of this research project was to identify prehospital factors, in particular treatment strategies, associated with beneficial or detrimental outcomes in patients with suspected severe TBI. The BRAIN-PROTECT study inclusion started in 2012 and prehospital inclusion continued until December 2017 (Follow-up until December 2018). In total, 2,589 patients were included (Chapter 3The incidence rate of suspected severe TBI was 3.2 (per 100,000 inhabitants per year) and 2.7 for confirmed TBI. Age ranged between 1 and 97 years and 70.8% were male. The overall 30-day mortality was 39.0% for the overall population of severe TBI and for confirmed TBI 42.4%. In Chapter 5, the results of a retrospective study on neurological deterioration are presented. 13% of 808 patients with initial mild TBI showed a discrepancy between the initial assessment of TBI severity based on the GCS, and the actual TBI severity as determined post hoc. In Chapter 6 face-to-face and telephonic examination of the GOS-E - an extended score on neurological functioning after neurotrauma - were compared. These showed a kappa value of 0.79, which is commonly considered good or substantial agreement, and implies that telephonic assessment is a valid alternative. Most of the prehospital treatments for severe TBI lack a thorough base of evidence. Prehospital airway management is regularly performed, but it’s benefit is not yet fully established. In Chapter 7, a systematic review and meta-analysis was performed to address effects of Prehospital Intubation (PHI) on mortality in patients with severe TBI. Six studies met the inclusion criteria for the meta-analysis. The main finding is that effects of PHI depend on the level of experience of the Emergency Medical Service (EMS)-providers who perform the intervention, and that PHI by EMS-personnel with limited experience in performing PHI is associated with increased mortality. In Chapter 9, the results are described of an inquiry and analysis of the national trauma data registry of the Netherlands. Between 2015 and the end of 2019, almost 9000 patients with severe TBI were studied. In an unadjusted comparison between the groups, mortality was significantly higher when patients were intubated (prehospital) as compared to non-intubated patients. After adjusting for potential confounders, PHI was still significantly associated with an almost 2-fold increase in the odds of mortality in the complete case analysis. Furthermore, the analyses revealed that the relationship of PHI and mortality may depend on whether P-HEMS is involved in the treatment or not. In Chapter 10, analyses were performed on the BRAIN-PROTECT dataset in order to assess the most optimum end-tidal CO2 values regarding mortality. Analyses of the (unadjusted) effects of end-tidal CO2 levels on predicted mortality revealed a statistically significant “L-shaped” association. These results were robust as they were repeated in a multi variable model. This model revealed reasonable end-tidal CO2 values between 35-45mmHg. In Chapter 11, the results of a systematic review and meta-analysis are presented on fluid administration to patients with severe TBI. The meta-analysis on the effects of Hypertonic Saline with Dextran (HSD) versus normal saline on survival did not show any effect. This was the same for the effect of hypertonic saline versus crystalloid fluids. Finally, the role of Tranexamic Acid (TXA) as an anti-fibrinolytic agent was investigated. In the BRAIn-PROTECT study, an increased mortality was observed among patients with isolated severe TBI who had received TXA, whereas no evidence for a relationship between TXA and mortality was observed in the other cohorts after controlling for potential confounder