Production and characterization of recombinant human lactoferrin

Human lactoferrin (hLF) is an iron-binding glycoprotein of Mr 77,000 that belongs to the transferrin family. Based on extensive research showing antimicrobial, anti-inflammatory and immunomodulatory activities of hLF, the molecule is postulated to be involved in the innate host defence against infection and severe inflammation. The diverse biological properties of hLF may allow for a variety of applications in human healthcare. However, the limited availability of (human milk-derived) natural hLF has been a major hurdle for (clinical) studies on potential applications. To overcome this limitation the feasibility of large-scale production of functional recombinant hLF (rhLF) was studied. This thesis reports on the use of transgenic cows as protein production technology for rhLF and describes the characterization and safety testing of the purified molecule. The bovine mammary gland appears to be an attractive vehicle for producing large amounts of rhLF as constant expression levels, in the gram per liter range, have been obtained without affecting normal milk parameters. Characterization of purified rhLF revealed that the molecule closely matches the structure of natural hLF except for differences in glycosylation. The differential glycosylation pattern did not result in difference between rhLF and natural hLF in any of the employed in vitro and in vivo assay systems. Furthermore, various preclinical toxicity studies and a Phase I clinical study revealed that rhLF is safe and well tolerated. Taken together, transgenic cows are a valuable platform for large-scale production of rhLF for application in human healthcare.UBL - phd migration 201

Gebromeerde vlamvertrager gehaltes en DR-CALUX respons in sediment en zwevende stof van de Noordzeekustzone

In het kader van het RIKZ project ‘Lakmoes’ wordt de waterkwaliteit van de Waddenzee aan de hand van chemische parameters onderzocht. Omdat de ‘nieuwe milieuvervuilers’, de gebromeerde vlamvertragers al eerder zijn aangetoond in dit gebied [Zegers e.a. 2003], is het belangrijk om inzicht te krijgen in de verspreiding en gehaltes van deze verbindingen

Performance of triage systems in emergency care: a systematic review and meta-analysis

Objective To assess and compare the performance of triage systems for identifying high and low-urgency patients in the emergency department (ED). Design Systematic review and meta-analysis. Data sources EMBASE, Medline OvidSP, Cochrane central, Web of science and CINAHL databases from 1980 to 2016 with the final update in December 2018. Eligibility criteria Studies that evaluated an emergency medical triage system, assessed validity using any reference standard as proxy for true patient urgency and were written in English. Studies conducted in low(er) income countries, based on case scenarios or involving less than 100 patients were excluded. Review methods Reviewers identified studies, extracted data and assessed the quality of the evidence independently and in duplicate. The Quality Assessment of studies of Diagnostic Accuracy included in Systematic Reviews -2 checklist was used to assess risk of bias. Raw data were extracted to create 2×2 tables and calculate sensitivity and specificity. ED patient volume and casemix severity of illness were investigated as determinants of triage systems’ performance. Results Sixty-six eligible studies evaluated 33 different triage systems. Comparisons were restricted to the three triage systems that had at least multiple evaluations using the same reference standard (Canadian Triage and Acuity Scale, Emergency Severity Index and Manchester Triage System). Overall, validity of each triage system to identify high and low-urgency patients was moderate to good, but performance was highly variable. In a subgroup analysis, no clear association was found between ED patient volume or casemix severity of illness and triage systems’ performance. Conclusions Established triage systems show a reasonable validity for the triage of patients at the ED, but performance varies considerably. Important research questions that remain are what determinants influence triage systems’ performance and how the performance of existing triage systems can be improved

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). Method: MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. Results: We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Conclusions: Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. Key Points: • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI

Viking Age garden plants from southern Scandinavia: diversity, taphonomy and cultural aspects

Plant finds recovered from archaeological sites in southern Scandinavia dated to the Viking Age reflect the diversity of useful plants that were cultivated and collected. This review presents the results of 14 investigations of deposits that are dated between AD 775 and 1050. The site types are categorized as agrarian, urban, military and burials. Garden plants are unevenly distributed, as the greatest diversity is recorded in features from urban contexts. We argue that taphonomic processes played an important role in the picture displayed. Archaeobotanical research results from neighbouring regions suggest that Viking Age horticulture has its roots in older traditions, and that the spectrum of garden plants is influenced by central and north-western European horticultural customs, which were to a great extent shaped by Roman occupation

Multifunctionele landbouw in Nederland : meer dan boeren alleen

Multifunctionele landbouw combineert verschillende functies op het boerenbedrijf: een agrarische tak met bijvoorbeeld huisverkoop of zorglandbouw. Inmiddels vormt de sector met bijna een half miljard euro omzet, die vergelijkbaar is met de bollensector, een sterke economische drager van het platteland. In het boek komen thema’s aan bod als economie, ondernemerschap, verbinding, vers voedsel en beleving. Verder worden de belangrijkste deelsectoren belicht: kinderopvang, boerderijverkoop, zorglandbouw, agrarisch natuurbeheer, recreatie/toerisme en boerderij-educatie. In tien ‘dubbelportretten’ komen mensen aan het woord die via de multifunctionele landbouw met elkaar in verbinding staan, zoals gastvrouw en gast, leverancier en verwerker, educatieboerin en docent