Tacitus on Principate and Empire: from the Agricola to the Annales.

This dissertation is a holistic examination of the relationship and interactions between Tacitus’ early monographs (the Agricola, Germania, and Dialogus de Oratoribus) and his later historical works Historiae and Annales. The study serves in part to confront several preconceptions about Tacitus and his writings that have informed much scholarship on the historian in the past century. In particular, it takes issue with the assumption that the opera minora are immature and essentially preliminary to the historical works, with the claim that Tacitus’ outlook on the Principate and the Empire shifts throughout his literary career, and with the generic determination on his corpus common in modern scholarship. One consequence of the above assumptions and approaches has been that the different texts often are read in isolation; the historical works receive most attention, while the shorter works continue to be comparatively marginalized. By reading the different works in conjunction and illustrating the thematic and conceptual consistency across them, I show that the corpus forms an integrated project, in which the different works interact with and build on one another, rather than being disparate intellectual attempts. I argue that, in the Agricola, Germania, and Dialogus, Tacitus sets out theories of the Roman state, imperial rule, and the nature of historical analysis, respectively, theories which he subsequently applies to his account of the early Principate in the historical works. The Agricola, Germania, and Dialogus formulate a series of well articulated topics that will continue to draw Tacitus’ attention in the Historiae and the Annales. What emerges from the approach I take is that Tacitus’ thinking progressively develops, while his methods of analysis largely remain consistent. In advocating this approach, I engage with scholarship that has tended to see Tacitus reaching full maturity as a thinker only in his Annales. My method of looking at thematic and conceptual continuity across the different works further serves to suggest that particular aspects of Roman thought are environmentally determined rather than, as is often the case now, dictated by the form in which they are composed, prompting us to reconsider the nature of genre.PhDClassical StudiesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120889/1/bltenber_1.pdfDescription of bltenber_1.pdf : Restricted to UM users only

Three-Dimensional Stereophotogrammetry Assessment of Facial Asymmetry in Facial Palsy

Three-dimensional stereophotogrammetry is not much used in assessing facial palsy and a comprehensive understanding of sources of variation in these measurements is lacking. The present study assessed intra- and interobserver reliability of a novel three-dimensional stereophotogrammetry measurement of facial asymmetry and examined sources of variation in these outcomes. Three photographs (rest, closed mouth smile, and maximum smile) were made of 60 participants, 30 facial palsy patients and 30 control subjects. All images were analyzed twice by 2 observers independently, to determine intra- and interobserver reliability. Variance component analysis was performed to investigate sources of variation in the outcomes. Intraobserver reliability was good with intraclass correlation coefficients ranging from 0.715 to 0.999. Interobserver reliability ranged from 0.442 to 0.929. Reliability of the smile image measurements was not clearly different from the rest images. Variation in measurement results was largely due to the status of a participant, facial palsy versus control. When splitting the sample, the facial expression was a major source of variation. Acceptable reliability of the proposed 3D facial asymmetry measurement was found, in facial palsy patients and control subjects. Interobserver reliability was marked less compared to intraobserver reliability. For follow-up data only one observer should assess 3D stereophotogrammetry measurements

AGER expression and alternative splicing in bronchial biopsies of smokers and never smokers

Abstract Cigarette smoking is one of the major risk factors for the development of chronic obstructive pulmonary disease (COPD). Evidence is accumulating that Receptor for Advanced Glycation-End products (RAGE)-signaling is a key pathway in the pathophysiology of COPD. To date, it is unknown how smoking affects RAGE expression. In the current study, we investigated the effect of smoking on AGER, the gene encoding RAGE, expression and on alternative splicing of AGER. To this end, we conducted RNA-Seq on bronchial biopsies for asymptomatic smokers (n = 36) and never smokers (n = 40). Total AGER gene expression was accessed using DESeq2, while alternative splicing was investigated by measuring the number of specific split reads spanning exon-exon junctions and the total split reads. One of the major isoforms of RAGE is endogenous soluble (es) RAGE, an anti-inflammatory decoy receptor, making up for approximately 10% of the total amount of soluble (s)RAGE. We found that smokers show decreased total gene expression of AGER in bronchial biopsies, while the relative abundance of the esRAGE isoform is increased. Furthermore, no difference in the serum levels of total sRAGE were observed between smokers and non-smokers. Our data indicates that smoking initiates a protective anti-inflammatory mechanism with decreased expression of the pro-inflammatory gene AGER and increased relative abundance of the anti-inflammatory isoform esRAGE

A population-based study describing characteristics, survival and the effect of TKI treatment on patients with EGFR mutated stage IV NSCLC in the Netherlands

INTRODUCTION: Since 2011, treatment guidelines advise targeted therapy (tyrosine kinase inhibitor, TKI) for patients with activating epidermal growth factor receptor (EGFR) mutations (EGFR+) in non-small cell lung cancer (NSCLC). We describe characteristics, first line treatment and survival of patients diagnosed with EGFR+ NSCLC in a European population, focussing on age, gender and trends over time and compare to the whole group and EGFR-. METHODS: All patients with non-squamous NSCLC stage IV, diagnosed 2011-2018, were identified from the population-based Netherlands Cancer Registry (N = 31,291). RESULTS: Among all, 7.0% were registered to be EGFR+, with highest prevalence in females 65 years to 23.6 months in the EGFR+ group <50 years treated with TKI. Over time, OS for the whole group increased by 0.6 months, of which 33% due to TKI treatment in EGFR+. The increase was strongest in females <50 years, where median OS almost doubled to 12.4 months. In the EGFR+, multivariable hazard of death was most strongly associated with the use of TKI (HR 0.45(0.41-0.49)). Of the patients with EGFR+ this space need or not, 71% received TKI treatment. Being young reduced the hazard of death (HR 0.71(95%CI:0.59-0.85)) irrespective of treatment, while male gender increased the hazard of death (HR 1.22(95%CI:1.11-1.33)). CONCLUSION: At population level, TKI treatment in patients with non-squamous NSCLC stage IV EGFR+ has very strong beneficial effects on outcome. Of the improvement in OS that was made over the years for the whole group, about one third seems to be attributed to TKI treatment in EGFR+ patients

A meta-analysis of the effects of agricultural management on soil physical quality for different farm typologies across Europe

Póster presentado en la Conferencia EGU 2014, 27 Abril - 7 Mayo 2014, Viena, Austri

Periostin:contributor to abnormal airway epithelial function in asthma?

Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus.Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion