PubPredict: Prediction of progression and survival in oncology leveraging publications and early efficacy data

In oncology/hematology early phase clinical trials, efficacies were often observed in terms of response rate, depth, timing, and duration. However, the true clinical benefits that eventually support registrational purpose are progression-free survival (PFS) and/or overall survival (OS), the follow-up of which are typically not long enough in early phase trials. This gap imposes challenges in strategies for late phase drug development. In this article, we tackle the question by leveraging published study to establish a quantitative link between early efficacy outcomes and late phase efficacy endpoints. We used solid tumor cancer as disease model. We modeled the disease course of a RECISTv1.1 assessed solid tumor with a continuous Markov chain (CMC) model. We parameterize the transition intensity matrix of a CMC model based on published aggregate-level summary statistics, and then simulate subject-level time-to-event data. The simulated data is shown to have good approximation to published studies. PFS and/or OS could be predicted with the transition intensity matrix modified given clinical knowledge to reflect various assumptions on response rate, depth, timing, and duration. The authors have built a R shiny application named PubPredict, the tool implements the algorithm described above and allows customized features including multiple response levels, treatment crossover and varying follow-up duration. This toolset has been applied to advise phase 3 trial design when only early efficacy data are available from phase 1 or 2 studies.     

Does Religious Attendance Moderate the Connection Between Pornography Consumption and Attitudes Toward Women?

Feminist theory and religious doctrines alike often suggest that pornography alters the attitudes of those who consume it, particularly with respect to how consumers view women. Many would assume that pornography would universally encourage sexism and female objectification, but recent evidence has linked pornography use with more gender egalitarian views. Using data from a large-scale, nationally representative survey, we argue that cognitive dissonance among pornography consumers could alter egalitarian attitudes. We found that those who reported consuming pornography had more egalitarian attitudes than those who did not, but this difference was stronger among those who attended religious services more regularly—those who would be likely to experience dissonance when consuming pornography. This pattern was consistent across the three egalitarian attitudes we examined: attitudes toward women in power, women in the workplace, and abortion. Our results suggest that pornography might foster progressive attitudes among those most likely to hold conservative beliefs.     

The new PR of states: How nation branding practices affect the security function of public diplomacy

This paper investigates how the role of public relations practice in public diplomacy is undergoing a transformation as a consequence of the influence from nation branding. A case study of the Danish government's response to the so-called Cartoon Crisis illustrates how the threat from international terrorism to national security initially served as a catalyst for new public diplomacy initiatives. But as the initiatives were implemented within a framework of nation branding the focus on risk reduction became subjected to a marketing logic and a new focus on economic objectives took over. The paper points to a possible future status of public diplomacy under the influence of nation branding: Public diplomacy may maintain a function pertinent to national security but as this function is incapable of managing real risks it will only serve as auto-communication that legitimizes security policy towards a domestic audience. In the public diplomacy efforts towards transnational publics the link to national security will completely disappear whereby the public relations of states is transformed to the marketing of states.     

Chronic avoidance helps explain the relationship between severity of childhood sexual abuse and psychological distress in adulthood

Recent studies have found that chronic avoidance of unpleasant internal experiences (e.g., thoughts, emotions, memories) is a maladaptive means of affect regulation often adopted by women with a history of sexual victimization in childhood. The primary aim of this study was to replicate and extend previous findings suggesting that higher levels of experiential avoidance may account for the relationship between childhood sexual abuse (CSA) and psychological distress in adulthood. It was hypothesized that, in a sample of undergraduate females (n = 151), the relationship between severity of CSA (e.g., frequency, nature of victimization) and trauma-related psychological distress would be mediated by avoidance. Results supported this hypothesis. Findings are consistent with previous studies, and further suggest that the general tendency to avoid or escape from unpleasant internal experiences may be a specific factor that exacerbates psychological distress among women with a history of sexual victimization in childhood.     

Dose intra-subject escalation to an event (DIETE): A new method for phase 1 dose-finding utilizing systematic intra-subject dose escalation with application to T-cell engagers

T-cell engagers are a class of oncology drugs which engage T-cells to initiate immune response against malignant cells. T-cell engagers have features that are unlike prior classes of oncology drugs (e.g., chemotherapies or targeted therapies), because (1) starting dose level often must be conservative due to immune-related side effects such as cytokine release syndrome (CRS); (2) dose level can usually be safely titrated higher as a result of subject's immune system adaptation after first exposure to lower dose; and (3) due to preventive management of CRS, these safety events rarely worsen to become dose limiting toxicities (DLTs). It is generally believed that for T-cell engagers the dose intensity of the starting dose and the peak dose intensity both correlate with improved efficacy. Existing dose finding methodologies are not designed to efficiently identify both the initial starting dose and peak dose intensity in a single trial. In this study, we propose a new trial design, dose intra-subject escalation to an event (DIETE) design, that can (1) estimate the maximum tolerated initial dose level (MTD1); and (2) incorporate systematic intra-subject dose-escalation to estimate the maximum tolerated dose level subsequent to adaptation induced by the initial dose level (MTD2) with a survival analysis approach. We compare our framework to similar methodologies and evaluate their key operating characteristics.     

Internet and the Political Public Sphere

The article addresses the main theory of the political public sphere generally, and the role of the Internet and Internet‐based media in the theory specifically. It first reviews briefly the initial social research on the Internet in the 1990s concerning political participation. After a presentation of Jürgen Habermas' theory of the contemporary public sphere, it proceeds to discuss the main problems concerning the Internet as a platform or infrastructure for public debate: segmentation and concentration. It argues that a general conclusion is that the public sphere differentiates and become more complex. A key task for future research, it argues, is to investigate the complex connections between Internet publics and mass media publics.     

On the foundation and early development of domestic and international new ventures

The founding and early development of Domestic New Ventures and International New Ventures is examined based upon a large scale survey of Danish manufacturing firms. The firms are classified into five different categories and compared with regard to their foundation and development within the first 3?years. The article contributes with a demonstration of differences between these categories of firms with regard to the number and mindset of founders, the growth of the firm, and the networks of firm.     

Psychosocial factors and safety behaviour as predictors of accidental work injuries in farming

Farming is one of the most hazardous occupations in terms of the incidence and seriousness of accidental injuries. Research with other occupational groups has drawn attention to the role of psychosocial factors and stress. Such research needs to be extended to agriculture. Since stress may be a problem faced by farmers, there is a particular need to investigate the associations between farm accidents and work stressors and stress reactions. Using multivariate logistic regression analyses, this study aimed to uncover the best psychosocial predictors of injury, while controlling for exposure-related confounders. From a randomly selected sample of 794 farms, 10% of all farms in Ringkoebing County, Denmark, 393 farmers completed completed weekly accident registration over 12 months. The study sample consisted of 310 farmers who also completed questionnaires on psychosocial factors. Results indicated that farm stressors (including perceived economic problems), stress symptoms, and safety behaviour were predictors of occupational farm accidents. Higher levels of stressors and stress symptoms and poor safety behaviour were all associated with an elevated risk of injury. In the case of stress symptoms, the relation with accidents occurred via an interaction with safety behaviour. The combination of high levels of stress symptoms and poor safety behaviour was associated with a particularly high accident risk.