Politics, Economics, and Testing: Some Reflections

Luncheon Keynote Addres

C57BL/6J, DBA/2J, and DBA/2J.Gpnmb+ mice have different visual signal processing in the inner retina

To characterize differences in retinal ganglion cell (RGC) function in mouse strains relevant to disease models. C57BL/6J (B6) and DBA/2J (D2) are the two most common mouse strains; D2 has two mutated genes, tyrosinase-related protein 1 (Tyrp1) and glycoprotein non-metastatic melanoma protein B (Gpnmb), causing iris disease and intraocular pressure (IOP) elevation after 6 months of age that results in RGC degeneration, and is the most widely used model of glaucoma. DBA/2J.Gpnmb(+) (D2.Gpnmb(+)) is the wild type for the Gpnmb mutation and does not develop IOP elevation and glaucoma. Young (2-4 months of age) B6, D2, and D2.Gpnmb(+) mice (n=6 for each group) were tested with pattern electroretinogram (PERG) in response to different contrasts and spatial frequencies. PERG amplitude and latency dependencies on stimulus parameters (transfer functions) were established for each mouse strain, together with corresponding thresholds for contrast and spatial resolution. PERG analysis showed that B6, D2, and D2.Gpnmb(+) mice had comparable contrast threshold and spatial resolution. Suprathreshold spatial contrast processing, however, had different characteristics in the three strains. PERG amplitude and latency changes with increasing contrast were different between B6 and D2 as well as between D2 and D2.Gpnmb(+). B6, D2, and D2.Gpnmb(+) mice have different characteristics of PERG spatial contrast processing consistent with different mechanisms of contrast gain control. This may imply differences in the activity of underlying PERG generators and synaptic circuitry in the inner retina

What makes for prize-winning television?

We investigate the determinants of success in four international television awards festivals between 1994 and 2012. We find that countries with larger markets and greater expenditure on public broadcasting tend to win more awards, but that the degree of concentration in the market for television and rates of penetration of pay-per-view television are unrelated to success. These findings are consistent with general industrial organisation literature on quality and market size, and with media policy literature on public service broadcasting acting as a force for quality. However, we also find that ‘home countries’ enjoy a strong advantage in these festivals, which is not consistent with festival success acting as a pure proxy for television quality

Dallas with balls: televized sport, soap opera and male and female pleasures

Two of the most popular of television genres, soap opera and sports coverage have been very much differentiated along gender lines in terms of their audiences. Soap opera has been regarded very much as a 'gynocentric' genre with a large female viewing audience while the audiences for television sport have been predominantly male. Gender differentiation between the genres has had implications for the popular image of each. Soap opera has been perceived as inferior; as mere fantasy and escapism for women while television sports has been perceived as a legitimate, even edifying experience for men. In this article the authors challenge the view that soap opera and television sport are radically different and argue that they are, in fact, very similar in a number of significant ways. They suggest that both genres invoke similar structures of feeling and sensibility in their respective audiences and that television sport is a 'male soap opera'. They consider the ways in which the viewing context of each genre is related to domestic life and leisure, the ways in which the textual structure and conventions of each genre invoke emotional identification, and finally, the ways in which both genres re-affirm gender identities

(G)hosting television: Ghostwatch and its medium

This article’s subject is Ghostwatch (BBC, 1992), a drama broadcast on Halloween night of 1992 which adopted the rhetoric of live non-fiction programming, and attracted controversy and ultimately censure from the Broadcasting Standards Council. In what follows, we argue that Ghostwatch must be understood as a televisually-specific artwork and artefact. We discuss the programme’s ludic relationship with some key features of television during what Ellis (2000) has termed its era of ‘availability’, principally liveness, mass simultaneous viewing, and the flow of the television super-text. We trace the programme’s television-specific historicity whilst acknowledging its allusions and debts to other media (most notably film and radio). We explore the sophisticated ways in which Ghostwatch’s visual grammar and vocabulary and deployment of ‘broadcast talk’ (Scannell 1991) variously ape, comment upon and subvert the rhetoric of factual programming, and the ends to which these strategies are put. We hope that these arguments collectively demonstrate the aesthetic and historical significance of Ghostwatch and identify its relationship to its medium and that medium’s history. We offer the programme as an historically-reflexive artefact, and as an exemplary instance of the work of art in television’s age of broadcasting, liveness and co-presence

Long-Term Incidence And Timing Of Intraocular Hypertension After Intravitreal Triamcinolone Acetonide Injection

Purpose: To describe the long-term incidence and timing of steroid-induced ocular hypertension after intravitreal triamcinolone acetonide (IVTA) therapy. Design: Retrospective case series of 929 eyes of 841 patients. Participants: Patients with a variety of posterior segment disorders in a single group practice. Intervention: Pars plana injection of IVTA. Main Outcome Measures: Intraocular pressure (IOP) and requirement for glaucoma surgery. Results: Overall, 929 eyes received ≥1 injections (mean, 1.6) of 4 mg of IVTA. During a mean follow-up period of 14±6.9 months, the Kaplan-Meier cumulative incidences of IOP elevations \u3e21 mmHg at 6, 12, 18, and 24 months post-injection were 28.2%, 34.6%, 41.2%, and 44.6%, respectively; similarly, the incidences of eyes with IOP measurements \u3e25 mmHg were 14.6%, 19.1%, 24.1%, and 28.2%, respectively. At the same time points, lOP-lowering medications were required byl3.0%, 16.9%, 20.7%, and 24.2% of eyes, respectively. Only 3 eyes (0.3%) required lOP-lowering surgery. Preexisting glaucoma, younger age, and a history of an IOP elevation after a previous IVTA injection were risk factors for IOP elevations after IVTA injection. The minimum and maximum follow-up were 3 weeks and 37 months. The mean rate of attrition in this study was 3% per month. Conclusions: Elevations in IOP after IVTA injection are common. Younger patients and eyes with preexisting glaucoma or a history of a steroid response should be monitored more closely for IOP elevations after IVTA therapy

Evidence-based sizing of non-inferiority trials using decision models

Abstract Background There are significant challenges to the successful conduct of non-inferiority trials because they require large numbers to demonstrate that an alternative intervention is “not too much worse” than the standard. In this paper, we present a novel strategy for designing non-inferiority trials using an approach for determining the appropriate non-inferiority margin (δ), which explicitly balances the benefits of interventions in the two arms of the study (e.g. lower recurrence rate or better survival) with the burden of interventions (e.g. toxicity, pain), and early and late-term morbidity. Methods We use a decision analytic approach to simulate a trial using a fixed value for the trial outcome of interest (e.g. cancer incidence or recurrence) under the standard intervention (pS) and systematically varying the incidence of the outcome in the alternative intervention (pA). The non-inferiority margin, pA – pS = δ, is reached when the lower event rate of the standard therapy counterbalances the higher event rate but improved morbidity burden of the alternative. We consider the appropriate non-inferiority margin as the tipping point at which the quality-adjusted life-years saved in the two arms are equal. Results Using the European Polyp Surveillance non-inferiority trial as an example, our decision analytic approach suggests an appropriate non-inferiority margin, defined here as the difference between the two study arms in the 10-year risk of being diagnosed with colorectal cancer, of 0.42% rather than the 0.50% used to design the trial. The size of the non-inferiority margin was smaller for higher assumed burden of colonoscopies. Conclusions The example demonstrates that applying our proposed method appears feasible in real-world settings and offers the benefits of more explicit and rigorous quantification of the various considerations relevant for determining a non-inferiority margin and associated trial sample size.https://deepblue.lib.umich.edu/bitstream/2027.42/146777/1/12874_2018_Article_643.pd

Coxsackievirus B3 Inhibits Antigen Presentation In Vivo, Exerting a Profound and Selective Effect on the MHC Class I Pathway

Many viruses encode proteins whose major function is to evade or disable the host T cell response. Nevertheless, most viruses are readily detected by host T cells, and induce relatively strong T cell responses. Herein, we employ transgenic CD4+ and CD8+ T cells as sensors to evaluate in vitro and in vivo antigen presentation by coxsackievirus B3 (CVB3), and we show that this virus almost completely inhibits antigen presentation via the MHC class I pathway, thereby evading CD8+ T cell immunity. In contrast, the presentation of CVB3-encoded MHC class II epitopes is relatively unencumbered, and CVB3 induces in vivo CD4+ T cell responses that are, by several criteria, phenotypically normal. The cells display an effector phenotype and mature into multi-functional CVB3-specific memory CD4+ T cells that expand dramatically following challenge infection and rapidly differentiate into secondary effector cells capable of secreting multiple cytokines. Our findings have implications for the efficiency of antigen cross-presentation during coxsackievirus infection

Combining Information from Two Surveys to Estimate County-Level Prevalence Rates of Cancer Risk Factors and Screening

Cancer surveillance requires estimates of the prevalence of cancer risk factors and screening for small areas such as counties. Two popular data sources are the Behavioral Risk Factor Surveillance System (BRFSS), a telephone survey conducted by state agencies, and the National Health Interview Survey (NHIS), an area probability sample survey conducted through face-to-face interviews. Both data sources have advantages and disadvantages. The BRFSS is a larger survey, and almost every county is included in the survey; but it has lower response rates as is typical with telephone surveys, and it does not include subjects who live in households with no telephones. On the other hand, the NHIS is a smaller survey, with the majority of counties not included; but it includes both telephone and non-telephone households and has higher response rates. A preliminary analysis shows that the distributions of cancer screening and risk factors are different for telephone and non-telephone households. Thus, information from the two surveys may be combined to address both nonresponse and noncoverage errors. A hierarchical Bayesian approach that combines information from both surveys is used to construct county-level estimates. The proposed model incorporates potential noncoverage and nonresponse biases in the BRFSS as well as complex sample design features of both surveys. A Markov Chain Monte Carlo method is used to simulate draws from the joint posterior distribution of unknown quantities in the model based on the design-based direct estimates and county-level covariates. Yearly prevalence estimates at the county level for 49 states, as well as for the entire state of Alaska and the District of Columbia, are developed for six outcomes using BRFSS and NHIS data from the years 1997-2000. The outcomes include smoking and use of common cancer screening procedures. The NHIS/BRFSS combined county-level estimates are substantially different from those based on BRFSS alone