Brexit: The road ahead for EU-UK trade

The countdown to Brexit has started. Given the short timeframe to Brexit and the large trading volumes, the authors investigate which certainties and uncertainties exist regarding the future trade relationship between the European Union (EU) and the United Kingdom (UK). Certain is that the UK is leaving the EU on 29 March 2019. On the basis of the recently presented draft withdrawal agreement, however, the chances are apparent that the UK will not leave the EU Customs Union and the internal market during a transition period ending in December 2020. Taking into account a possible transition period, the authors discuss the most likely scenarios and their impact on trade between the EU and the UK, in particular from a customs perspective

Staatsvakken en kerkelijke vakken aan openbare universiteiten

Theology at the state universities in the Netherlands since 1876: State disciplines and church disciplines: In three contributions the organisation of (protestant) theology in the Netherlands since 1876 has been described. In this first part the Dutch law on higher education (1876) is dealt with, its background (especially separation of state and church and equal treatment of religious traditions). This law has established a dual system ("duplex ordo"): "state professors" and "church professors", all paid by the government. Various evaluations of this arrangement are discussed and its recent modification and the motifs thereof are given. In practice, the theological faculties at the state universities have been mostly reformed faculties.Continued 2001 as 'Verbum et Ecclesia'Spine cut of Journal binding and pages scanned on flatbed EPSON Expression 10000 XL; 400dpi; text/lineart - black and white - stored to Tiff Derivation: Abbyy Fine Reader v.9 work with PNG-format (black and white); Photoshop CS3; Adobe Acrobat v.9 Web display format PDFhttp://explore.up.ac.za/record=b102527

Overexpression of EGFR and c-erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts

AbstractOverexpression of EGFR and c-erbB2 frequently occurs in human breast cancers, correlating with poor prognosis. Here we show that overexpression of EGFR and c-erbB2 in cell lines increases cell migration, an important step in metastasis formation. The effect of EGFR on migration is dependent on the addition of EGF to the cells. In contrast, c-erbB2 seems to act independently of its ligand in these assays. Overexpression of this receptor is sufficient to induce cell migration. In addition, we investigated the involvement of a number of signal transduction pathways known to be activated by the EGFR. We found that inactivation of MAPKK results in a decreased migration, while inactivation of PI3K increases migration

Translational and Regulatory Challenges for Exon Skipping Therapies

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.status: publishe

The influence of body composition on therapeutic hypothermia: a prospective observational study of patients after cardiac arrest

Introduction Patients after out-of-hospital cardiac arrest (OHCA) benefit from therapeutic hypothermia for 24 hours. The time needed to reach hypothermia (target temperature of 32 degrees C to 34 degrees C) varies widely. In this study, we explore the relation between measures of body composition and the time needed to reach target temperature with hypothermia. Method We conducted a prospective observational study in patients treated with hypothermia after OHCA. Data collected included weight and height, body composition by anthropometric measures and by single-frequency body impedance, and waist-to-hip ratio. Analysis of concordance between impedance and anthropometric measures and hazard ratios of achieving target temperature (event) corrected for different body composition measures. Results Twenty-seven patients were included. The median (interquartile range) time to reach target temperature after admission to the intensive care unit was 191 (105 to 382) minutes. Intraclass correlation for total body fat (TBF) measures was 0.94 (95% confidence interval [CI] 0.89 to 0.97). Only TBF percentage (anthropometrics by the Durnin's table) appeared to be associated with time to reach target temperature: 0.93 (95% CI 0.87 to 0.99; P = 0.03). Conclusion The body composition measures from single-frequency impedance and anthropometrics appear to be very concordant. Only TBF percentage (anthropometrics) showed a significant but clinically irrelevant influence on time needed to achieve target temperature with hypothermia. We conclude that there are no indications to adjust current cooling practice toward the body composition of patient

Tracheotomy does not affect reducing sedation requirements of patients in intensive care – a retrospective study

INTRODUCTION: Translaryngeal intubated and ventilated patients often need sedation to treat anxiety, agitation and/or pain. Current opinion is that tracheotomy reduces sedation requirements. We determined sedation needs before and after tracheotomy of intubated and mechanically ventilated patients. METHODS: We performed a retrospective analysis of the use of morphine, midazolam and propofol in patients before and after tracheotomy. RESULTS: Of 1,788 patients admitted to our intensive care unit during the study period, 129 (7%) were tracheotomized. After the exclusion of patients who received a tracheotomy before or at the day of admittance, 117 patients were left for analysis. The daily dose (DD; the amount of sedatives for each day) divided by the mean daily dose (MDD; the mean amount of sedatives per day for the study period) in the week before and the week after tracheotomy was 1.07 ± 0.93 DD/MDD versus 0.30 ± 0.65 for morphine, 0.84 ± 1.03 versus 0.11 ± 0.46 for midazolam, and 0.62 ± 1.05 versus 0.15 ± 0.45 for propofol (p < 0.01). However, when we focused on a shorter time interval (two days before and after tracheotomy), there were no differences in prescribed doses of morphine and midazolam. Studying the course in DD/MDD from seven days before the placement of tracheotomy, we found a significant decline in dosage. From day -7 to day -1, morphine dosage (DD/MDD) declined by 3.34 (95% confidence interval -1.61 to -6.24), midazolam dosage by 2.95 (-1.49 to -5.29) and propofol dosage by 1.05 (-0.41 to -2.01). After tracheotomy, no further decrease in DD/MDD was observed and the dosage remained stable for all sedatives. Patients in the non-surgical and acute surgical groups received higher dosages of midazolam than patients in the elective surgical group. Time until tracheotomy did not influence sedation requirements. In addition, there was no significant difference in sedation between different patient groups. CONCLUSION: In our intensive care unit, sedation requirements were not further reduced after tracheotomy. Sedation requirements were already sharply declining before tracheotomy was performed

Typha latifolia paludiculture effectively improves water quality and reduces greenhouse gas emissions in rewetted peatlands

Paludiculture, the cultivation of crops on wet or rewetted agricultural peatlands, sustainably integrates productive land use with the provision of multiple ecosystem services. Paludiculture crops thrive under waterlogged conditions that stimulate nitrogen (N) and phosphorus (P) removal from soil and water and convert serious drainage-induced carbon (C) losses to C sequestration. Nutrient uptake by paludicrops can prevent mobilisation after rewetting and provide opportunities for purification of nutrient-rich water. Uncertainty remains, however, if and to what extent N loading and a subsequent increase in biomass productivity affect nutrient cycling as well as emissions of the potent greenhouse gases methane (CH4) and nitrous oxide (N2O). In this study, we use mesocosms with rewetted peat to investigate the effect of different N sources in surface water on biomass production of Typha latifolia, a typical paludiculture crop, and the emissions of CH4 and N2O. Organic (Azolla filiculoides; urea) or mineral (KNO3 ; NH4NO) N was supplied either a single time (steady state) or repeatedly (pulse) to simulate a total surface water load of 150 kg N ha(-1) . We found that N stimulated aboveground and belowground biomass production and nutrient uptake by T. latifolia. These effects were absent in Azolla treatments. Whereas after two months CH4 emissions arose to substantial amounts (> 10 mg CH4 m(-2) day(-1)) in unvegetated mesocosms loaded with organic N, they remained very low (<1 mg CH4 m(-2) day(-1)) in vegetated mesocosms, despite the labile C pool in the extensive belowground biomass and organic N loading. Overall, N2O emissions were close to zero and were only detected episodically after NO(3)(- )loading, irrespective of plant presence. Our findings support that T. latifolia as a paludicrop effectively removes various forms of N and P when harvested, and strongly mitigates CH4 emission after the rewetting of agricultural peat soils compared to unvegetated conditions