Through the Looking Glass: \u3cem\u3eDer Spiegel’s\u3c/em\u3e Presentation of America’s Image in the Iraq War

Der Spiegel, the weekly German news magazine, offered extensive coverage of the beginnings of the Iraq War. The magazine blended historical fact and cinematic and historical comparisons to present its decidedly negative view of the conflict. The twofold purpose of this thesis is to illuminate the German attitudes towards the war and the American culture from which it sprang and to explore some of the comparisons and metaphors and the visuals used to communicate this viewpoint. The intent is to examine the gap between the abstract position the magazine expresses and the wider scope of meaning created by the metaphors and visuals. Chapter I concentrates on the magazine\u27s presentation of a perceived history of failures on the part of the American CIA and the manner in which this is combined with allusions to the Rambo image. Through the use of the Rambo figure and other references to film characters (James Bond), the magazine suggests that both U.S. leaders such as George W. Bush and the population at large are victims of their own cinematic myths and vastly overestimate their own capacity to determine the world\u27s fate. Sharply contrasting portraits of two CIA agents who were casualties of the war, Alabama born Michael Spann and German born Helge Philipp Boes, cast the American as an inept blunderer and the German as an idealistic and sensitive defender of Western freedoms. Chapter II concerns the way in which historical comparisons are used to illuminate the conflict. The magazine suggests that the U.S. is an empire in decline. The very heterogeneous selection of examples offered in defense of this argument (e.g. the Roman, British, and Soviet empires) all spring from material that would be familiar to German readers. They offer cursory and arguably superficial analogies to explain today\u27s complex situation. Part II of the chapter explores the use of images from 20th century history, particularly World War II, to explain events. Very often the comparisons seem overblown and particularly inappropriate (e.g. Stalingrad and the Battle of Baghdad; the bombing of Dresden and the bombing of Baghdad). Rhetorically the magazine sometimes distances itself from these questionable analogies by attributing them to others (anonymous observers ). Such comparisons speak to a specifically German historical sensibility and the deep emotions these events evoke in German readers rather than to the explanatory power of the examples

Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021 : a national vaccine surveillance platform self-controlled case series study

Background Post-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines. Aim To estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands. Methods We used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021. Results Within 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3–7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91–0.94 and RI: 0.96; 95% CI: 0.94–0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95–0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00–1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28–1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97–1.78). Conclusion COVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety

Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study

Objectives To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. Design We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. Setting England, UK. Participants Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. Main outcome measures AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. Results A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3–7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91–0.94) and 0.96; 95% CI: 0.94–0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95–0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00–1.44)). Conclusions COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety

CD200 promotes immunosuppression in the pancreatic tumor microenvironment

Background A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive to immunotherapy. Our supporting data provide evidence that CD200, a regulator of myeloid cell activity, is expressed in the PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with PDAC express elevated levels of the CD200 receptor (CD200R). Thus, we hypothesize that CD200 expression in the PDAC microenvironment limits responses to immunotherapy by promoting expansion and activity of MDSC.Methods Immunofluorescent staining was used to determine expression of CD200 in murine and human PDAC tissue. Flow cytometry was utilized to test for CD200R expression by immune populations in patient blood samples. In vivo antibody blocking of CD200 was conducted in subcutaneous MT-5 tumor-bearing mice and in a genetically engineered PDAC model (KPC-Brca2 mice). Peripheral blood mononuclear cells (PBMC) from patients with PDAC were analyzed by single-cell RNA sequencing. MDSC expansion assays were completed using healthy donor PBMC stimulated with IL-6/GM-CSF in the presence of recombinant CD200 protein.Results We found expression of CD200 by human pancreatic cell lines (BxPC3, MiaPaca2, and PANC-1) as well as on primary epithelial pancreatic tumor cells and smooth muscle actin+ stromal cells. CD200R expression was found to be elevated on CD11b+CD33+HLA-DRlo/− MDSC immune populations from patients with PDAC (p=0.0106). Higher expression levels of CD200R were observed in CD15+ MDSC compared with CD14+ MDSC (p<0.001). In vivo studies demonstrated that CD200 antibody blockade limited tumor progression in MT-5 subcutaneous tumor-bearing and in KPC-Brca2 mice (p<0.05). The percentage of intratumoral MDSC was significantly reduced in anti-CD200 treated mice compared with controls. Additionally, in vivo blockade of CD200 can also significantly enhance the efficacy of PD-1 checkpoint antibodies compared with single antibody therapies (p<0.05). Single-cell RNA sequencing of PBMC from patients revealed that CD200R+ MDSC expressed genes involved in cytokine signaling and MDSC expansion. Further, in vitro cytokine-driven expansion and the suppressive activity of human MDSC was enhanced when cocultured with recombinant CD200 protein.Conclusions These results indicate that CD200 expression in the PDAC microenvironment may regulate MDSC expansion and that targeting CD200 may enhance activity of checkpoint immunotherapy

DICER1/Alu RNA Dysmetabolism Induces Caspase-8-Mediated Cell Death in Age-Related Macular Degeneration

Geographic atrophy, an advanced form of age-related macular degeneration (AMD) characterized by death of the retinal pigmented epithelium (RPE), causes untreatable blindness in millions worldwide. The RPE of human eyes with geographic atrophy accumulates toxic Alu RNA in response to a deficit in the enzyme DICER1, which in turn leads to activation of the NLRP3 inflammasome and elaboration of IL-18. Despite these recent insights, it is still unclear how RPE cells die during the course of the disease. In this study, we implicate the involvement of Caspase-8 as a critical mediator of RPE degeneration. Here we show that DICER1 deficiency, Alu RNA accumulation, and IL-18 up-regulation lead to RPE cell death via activation of Caspase-8 through a Fas ligand-dependent mechanism. Coupled with our observation of increased Caspase-8 expression in the RPE of human eyes with geographic atrophy, our findings provide a rationale for targeting this apoptotic pathway in this disease

A study of quasar selection in the supernova fields of the Dark Energy Survey

We present a study of quasar selection using the supernova fields of the Dark Energy Survey (DES). We used a quasar catalog from an overlapping portion of the SDSS Stripe 82 region to quantify the completeness and efficiency of selection methods involving color, probabilistic modeling, variability, and combinations of color/ probabilistic modeling with variability. In all cases, we considered only objects that appear as point sources in the DES images. We examine color selection methods based on the Wide-field Infrared Survey Explorer (WISE) mid- IR W1 - W2 color, a mixture of WISE and DES colors (g − i and i - W1), and a mixture of Vista Hemisphere Survey and DES colors (g − i and i − K ). For probabilistic quasar selection, we used XDQSO, an algorithm that employs an empirical multi-wavelength flux model of quasars to assign quasar probabilities. Our variability selection uses the multi-band χ2-probability that sources are constant in the DES Year 1 griz-band light curves. The completeness and efficiency are calculated relative to an underlying sample of point sources that are detected in the required selection bands and pass our data quality and photometric error cuts. We conduct our analyses at two magnitude limits, i85% for both i-band magnitude limits and efficiencies of >80% to the bright limit and >60% to the faint limit; however, the giW1 and giW1+variability methods give the highest quasar surface densities. The XDQSOz method and combinations of W1W2/giW1/XDQSOz with variability are among the better selection methods when both high completeness and high efficiency are desired. We also present the OzDES Quasar Catalog of 1263 spectroscopically confirmed quasars from three years of OzDES observation in the 30 deg2 of the DES supernova fields. The catalog includes quasars with redshifts up to z4 and brighter than i = 22 mag, although the catalog is not complete up to this magnitude limit

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness