A network model of language policy and planning: The United Nations as a case study

This paper contributes to recent critical discussion of ‘agency’ in LPP research and practice. It argues that whilst scholars have widened their purview to consider the impact of individual actors on LPP in different contexts, the field has not developed or embraced theoretical and methodological frameworks which satisfactorily model or investigate the network of actor impact on LPP. This article analyses the current status of LPP at the United Nations (UN). Taking the ‘Actor-Stage Model’ (Zhao & Baldauf, 2012) as a theoretical point of departure, the paper discusses and analyses the most recent review of LPP within the UN. It becomes apparent that a network of agents is responsible for LPP development, influence and implementation within the organisation. This ‘web of influence’ is schematised using a network model which accounts for the implicit and explicit responsibility of multiple actors/’experts’ within and outside of the organisation. A sub-analysis of institutional LPP goals reveals the ‘polycentric’ and ‘relational’ nature of influence within and across multiple ’nodes’. It is argued that the network model and the concept of ‘web of influence’ is crucial in de- and re-constructing particular LPP goals and serves as a useful heuristic for those investigating or working within similar sites of inter/transnational integration as well as LPP in other macro, meso or micro-contexts

Systemic Safety in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration: A Patient-Level Pooled Analysis

Topic This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham ± verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.3 mg with sham and ranibizumab 0.5 mg to 0.3 mg were performed. Clinical Relevance Intravitreal anti–vascular endothelial growth factor (VEGF) agents carry potential increased systemic risks, including cardiovascular or cerebrovascular events. Pooled safety analyses allow better interpretation of safety outcomes seen in individual clinical trials, especially for less common events. To our knowledge, this is the largest patient-level pooled analysis of patients with nAMD treated with ranibizumab. Methods Patient-level pooled analysis of data from 7 Genentech- and Novartis-sponsored phase II, III, and IV studies in nAMD that were completed by December 31, 2013. Pairwise comparisons (primary comparison: ranibizumab 0.5 mg [globally approved dose for nAMD] vs. sham or verteporfin) were performed using Cox proportional hazard regression (hazard ratios [HRs], 95% confidence intervals [CIs]) and rates per 100 patient-years. Standardized Medical Dictionary for Regulatory Activities queries (SMQs) and extended searches were used to identify relevant safety endpoints, including arterial thromboembolic events (ATEs), myocardial infarction (MI), stroke or transient ischemic attack (TIA), stroke (excluding TIA), vascular deaths, and major vascular events as defined by the Antiplatelet Trialists' Collaboration (APTC). Results The HRs (95% CIs) for the primary comparison of ranibizumab 0.5 mg (n=480) versus sham or verteporfin (n=462) were 1.16 (0.72–1.88) for ATE, 1.33 (0.59–2.97) for MI, 1.43 (0.54–3.77) for stroke excluding TIA, 1.25 (0.61–2.55) for stroke or TIA, 0.57 (0.18–1.78) for vascular death, and 1.12 (0.64–1.98) for APTC events. Hazard ratio 95% CIs included 1, indicating no significant treatment differences, for all endpoints for comparison of ranibizumab 0.5 mg versus sham or verteporfin. Conclusions The rates of cardiovascular and cerebrovascular events were low in these patients with nAMD and not clinically meaningfully different for patients treated with ranibizumab 0.5 mg versus sham or verteporfin, which supports the favorable benefit–risk profile of ranibizumab in the patient population with nAMD. Pooling these studies allows an analysis with higher power and precision compared with individual study analyses

Ziffern und ihre Anordnung im Flankerexperiment

Flankerexperimente tragen als weit verbreitetes Paradigma zur Aufklärung der Struktur visueller Aufmerksamkeit bei. Diese Studie untersucht in Anlehnung an frühere Studien die räumliche Struktur der Aufmerksamkeit in einem Flankerexperiment mit Ziffern in horizontaler und vertikaler Anordnung. Dazu wurden die Daten von 75 Probanden (40 männlich, 35 weiblich) im Alter zwischen 18 und 64 Jahren ausgewertet. Für die typischen Reaktionszeiten und die Fehlerraten wurden separate 2x2x2-faktorielle Varianzanalysen mit den Faktoren Anordnung und den beiden Flankerkompatibilitäten durchgeführt. Das Bild der Reaktionszeiten bestätigt frühere Befunde zur räumlichen Struktur der Aufmerksamkeit auch für die Verwendung von Ziffern: Horizontale Flanker haben einen stärkeren Effekt als vertikale Flanker und in Leserichtung vorhergehende (linke bzw. obere) Flanker haben einen stärkeren Effekt als nachfolgende (rechte bzw. untere) Flanker. In den Fehlerquoten ergibt sich in vertikaler Anordnung ein umgekehrtes Bild: Der untere Flanker hat einen stärkeren Einfluss auf die Fehlerrate als der obere Flanker. Die Befunde werden mit Bezug zu Lesegewohnheiten in die Verarbeitungskette aus Wahrnehmung, Klassifikation, Reaktionsgenerierung und Reaktionauswahl bei Flankerexperimenten eingeordnet und mit unterschiedlichen Wirkmechanismen auf Reaktionszeit und Fehlerrate erklärt. Weiterführende Experimente werden zur weiteren Untersuchung der Befunde vorgeschlagen

Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos

Responsive genes for fish embryos have been identified so far for some endocrine pathways but not for androgens. Using transcriptome analysis and multiple concentration–response modeling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05–5000 nM 11-ketotestosterone for 24 h. Four selected genes with sigmoidal concentration-dependent expression profiles (EC₅₀ = 6.5–30.0 nM) were characterized in detail. The expression of <i>cyp2k22</i> and <i>slco1f4</i> was demonstrated in the pronephros; <i>lipca</i> was detected in the liver, and <i>sult2st3</i> was found in the olfactory organs and choroid plexus. Their expression domains, the function of human orthologs, and a pathway analysis suggested a role of these genes in the metabolism of hormones. Hence, it was hypothesized that they were induced to compensate for elevated hormone levels. The induction of <i>sult2st3</i> and <i>cyp2k22</i> by 11-ketotestosterone was repressed by co-exposure to the androgen receptor antagonist nilutamide supporting a potential androgen receptor mediated regulation. Sensitivity (expressed as EC₅₀ values) of <i>sult2st3</i> and <i>cyp2k22</i> gene expression induction after exposure to other steroidal hormones (11-ketotestosterone ∼ testosterone > progesterone > cortisol > ethinylestradiol) correlated with their known binding affinities to zebrafish androgen receptor. Hence, these genes might represent potential markers for screening of androgenic compounds in the zebrafish embryo

Biostratigraphy of ODP Leg 108 sites

Leg 108 cored 12 sites in the eastern equatorial Atlantic and along the northwest African continental margin to investigate the late Neogene and Quaternary oceanographic and climatic history of these regions. Sediments recovered during Leg 108 provide in part a high-resolution stratigraphic record for the upper Pliocene through Holocene interval. The bio- and magnetostratigraphy are intercalibrated where possible and provide a useful chronostratigraphy for paleoceanographic studies