The Impact of Party Competition on the Individual Vote Decision: The Case of Extreme Right Parties

Since the early 1980s, Western Europe has witnessed the rising success of niche parties and a simultaneous decline in the vote share of mainstream parties. While for one group of these niche parties, namely the left-libertarian and green parties, this success is commonly explained by the rise of a ‘new politics’ or ‘post-materialist’ dimension, the causes for the emergence of Extreme Right Parties (ERPs) are still disputed. The continuous electoral support for ERPs at the national, regional and local level was unexpected and has induced a great deal of scientific attention and effort to explain the different fortunes of these parties at the polls. Previous research on the factors influencing the electoral success of ERPs has emphasized the importance of voter characteristics and party competition for the electoral fortunes of ERPs. With regard to the first, ERP voters have been found to share common policy preferences and are related to distinct socio-economic groups. With regard to party competition, scholars have pointed to the role of the electoral programmatic of ERPs as well as their mainstream competitors for the electoral support of ERPs. While existing studies come to the overall conclusion that both voter preferences and patterns of party competition do influence the electoral fortunes of ERPs, the question of how party competition influences the vote decision for an ERP is still a matter of academic dispute. The single contributions of this dissertation contribute to the existing literature on the impact of party competition on the vote decision for an ERP by (1) focusing on the interplay between the political preferences of ERP voters and party competition, (2) applying a two-dimensional approach to the political opportunity structure of ERPs, and (3) incorporating the findings into a formal theory on how party competition influences the decision of individual voters, be they ERP voters or supporters of any other party in Western Europe

Influence of Patient-Specific Covariates on Test Validity of Two Delirium Screening Instruments in Neurocritical Care Patients (DEMON-ICU)

Background: Delirium screening instruments (DSIs) should be used to detect delirium, but they only show moderate sensitivity in patients with neurocritical illness. We explored whether, for these patients, DSI validity is impacted by patient-specific covariates. Methods: Data were prospectively collected in a single-center quality improvement project. Patients were screened for delirium once daily using the Intensive Care Delirium Screening Checklist (ICDSC) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference was the daily assessment using criteria from the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR). In a two-step receiver operating characteristics regression analysis adjusting for repeated measurements, the impact of acute diagnosis of stroke or transient ischemic attack (TIA), neurosurgical intervention, Richmond Agitation Sedation Scale, and ventilation status on test validity was determined. Results: Of 181 patients screened, 101 went into final analysis. Delirium incidence according to DSM-IV-TR was 29.7%. For the first complete assessment series (CAM-ICU, ICDSC, and DSM-IV-TR), sensitivity for the CAM-ICU and the ICDSC was 73.3% and 66.7%, and specificity was 91.8% and 94.1%, respectively. Consideration of daily repeated measurements increased sensitivity for the CAM-ICU and ICDSC to 75.7% and 73.4%, and specificity to 97.3% and 98.9%, respectively. Receiver operating characteristics regression revealed that lower Richmond Agitation Sedation Scale levels significantly impaired validity of the ICDSC (p = 0.029) and the CAM-ICU in its severity scale version (p = 0.004). Neither acute diagnosis of stroke or TIA nor neurosurgical intervention or mechanical ventilation significantly influenced DSI validity. Conclusions: The CAM-ICU and ICDSC perform well in patients requiring neurocritical care, regardless of the presence of acute stroke, TIA, or neurosurgical interventions. Yet, even very light or moderate sedation can significantly impair DSI performance

The paediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU): Translation and cognitive debriefing for the German-speaking area

Purpose: To date there are only a few studies published, dealing with delirium in critically ill patients. The problem with these studies is that prevalence rates of delirium could only be estimated because of the lack of validated delirium assessment tools for the paediatric intensive care unit (PICU). The paediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU) was specifically developed and validated for the detection of delirium in PICU patients. The purpose of this study was the translation of the English pCAM-ICU into German according to international validated guidelines

Reinitiated viral RNA-dependent RNA polymerase resumes replication at a reduced rate

RNA-dependent RNA polymerases (RdRP) form an important class of enzymes that is responsible for genome replication and transcription in RNA viruses and involved in the regulation of RNA interference in plants and fungi. The RdRP kinetics have been extensively studied, but pausing, an important regulatory mechanism for RNA polymerases that has also been implicated in RNA recombination, has not been considered. Here, we report that RdRP experience a dramatic, long-lived decrease in its elongation rate when it is reinitiated following stalling. The rate decrease has an intriguingly weak temperature dependence, is independent of both the nucleotide concentration during stalling and the length of the RNA transcribed prior to stalling; however it is sensitive to RNA structure. This allows us to delineate the potential factors underlying this irreversible conversion of the elongation complex to a less active mode

DNA mechanics as a tool to probe helicase and translocase activity

Helicases and translocases are proteins that use the energy derived from ATP hydrolysis to move along or pump nucleic acid substrates. Single molecule manipulation has proved to be a powerful tool to investigate the mechanochemistry of these motors. Here we first describe the basic mechanical properties of DNA unraveled by single molecule manipulation techniques. Then we demonstrate how the knowledge of these properties has been used to design single molecule assays to address the enzymatic mechanisms of different translocases. We report on four single molecule manipulation systems addressing the mechanism of different helicases using specifically designed DNA substrates: UvrD enzyme activity detection on a stretched nicked DNA molecule, HCV NS3 helicase unwinding of a RNA hairpin under tension, the observation of RecBCD helicase/nuclease forward and backward motion, and T7 gp4 helicase mediated opening of a synthetic DNA replication fork. We then discuss experiments on two dsDNA translocases: the RuvAB motor studied on its natural substrate, the Holliday junction, and the chromosome-segregation motor FtsK, showing its unusual coupling to DNA supercoiling

Discovery and Annotation of Functional Chromatin Signatures in the Human Genome

Transcriptional regulation in human cells is a complex process involving a multitude of regulatory elements encoded by the genome. Recent studies have shown that distinct chromatin signatures mark a variety of functional genomic elements and that subtle variations of these signatures mark elements with different functions. To identify novel chromatin signatures in the human genome, we apply a de novo pattern-finding algorithm to genome-wide maps of histone modifications. We recover previously known chromatin signatures associated with promoters and enhancers. We also observe several chromatin signatures with strong enrichment of H3K36me3 marking exons. Closer examination reveals that H3K36me3 is found on well-positioned nucleosomes at exon 5′ ends, and that this modification is a global mark of exon expression that also correlates with alternative splicing. Additionally, we observe strong enrichment of H2BK5me1 and H4K20me1 at highly expressed exons near the 5′ end, in contrast to the opposite distribution of H3K36me3-marked exons. Finally, we also recover frequently occurring chromatin signatures displaying enrichment of repressive histone modifications. These signatures mark distinct repeat sequences and are associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation

Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands:the COVID-OLD study

BACKGROUND: as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. OBJECTIVE: to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. METHODS: this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. RESULTS: a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28–51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. CONCLUSIONS: compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality. The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands:the COVID-OLD study

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms

Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans.

BACKGROUND: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. METHODS: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. RESULTS: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. CONCLUSION: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely