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.     

In search of excellence: a case study of the first excellence initiative of Germany

As higher education policies are often associated with intense public spending, the evaluation and performance measurement of respective initiatives becomes increasingly crucial. An extensive and fruitful strand of literature has dealt with the assessment of university performance, yet mainly focused on point-in-time rather than period-of-time examinations. This study investigates the effects of Germany’s first Excellence Initiative, a political measure aimed at building up world-class universities to be able to compete in the globalizing research world. Relying on both qualitative and quantitative measures, taking into account a 15-year period from 1998 to 2012, we analyze the selection process and how and whether the Excellence Initiative fulfilled its ambitious goals. Our results suggest that not the political initiative per se, i.e. the treatment, but the announcement of the treatment triggered diverging performance paths within the German higher education system, thus positively contributed to augmented research performance of the promoted universities. Based on these findings, we provide policy recommendations and avenues for future research.     

Teil-autonome Arbeitsteams oder tayloristische Produktionslinie? Welche Erkenntnisgewinne bieten simulationsbasierte Work Design Trainings

Digitalisation, flexible job markets, new technologies and innovative forms of collaboration constitute increasing challenges for employers and the design of modern work. But how can we deal with these challenges and what do we know about the effect of good versus bad work design? Based on the job demands-resources model (JRM), we present a simulation-based training during which participants experience the effects of different work characteristics. We focus on the moderating effects of job control and job demands: The JRM assumes that job demands and job control interactively affect employee exhaustion and work engagement: Jobs with high control can buffer the strain-enhancing effect of job demands (buffer hypothesis) and increase work engagement (active learning hypothesis). We test these hypotheses in a workplace simulation during which participants have to produce ice-cream. Our results support the buffer hypothesis but not the active learning hypothesis. We discuss the added value of work design simulations for organisations, practitioners, and HR professionals.     

RISK AVERSION RELATES TO COGNITIVE ABILITY: PREFERENCES OR NOISE?

Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation may be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice tasks that vary the bias induced by random choices, we are able to generate both negative and positive correlations between risk aversion and cognitive ability. Our results suggest that cognitive ability is related to random decision making rather than to risk preferences. (JEL: C81, C91, D12, D81)     

How Do Classes Make Use of Their Incomes?

Against the backdrop of occasional claims by social scientists that class analysis is no longer relevant this article will study the consumption patterns of different classes. Two hypotheses are derived and tested. These are to assume that classes' consumption differences are due to processes of social closure, or are of a cultural kind. This is investigated using a Swedish family expenditure data-set from 1992. The focus is on classes' different uses of their incomes regarding basic expenditures, expenditures on non-durables and ownership of durables. The most striking result is that 'higher' classes tend to spend a great deal of money on activities outside the home, 'appearance' and information, while other classes' consumption resembles the 'higher' classes, to different degrees. Moreover, the class hierarchy, constructed theoretically from employment factors, resembles a hierarchy constructed from similarities in patterns of consumption. The main conclusion is that class matters, in interesting ways, for consumption, though there are also other powerful factors. The closure hypothesis receives support, even though a combination of the two hypotheses seems sound.     

Loan repayment plans as sequences of instalments

Loan repayment can be viewed as a sequence of instalments. Instalments can either fall over time (i.e., repaying more in the beginning and less in the end), rise or stay constant. Three studies investigated whether the well-established preference for improvement (i.e., falling profiles) can also be observed in a loan context. Results show that consumers do prefer falling profiles over rising profiles; however, also a strong preference for constant profiles was found. These preferences for improvement and spreading even outweigh financial benefits. Consumers, hence, may sometimes opt for the financially worse loan option. Financial capability programs could benefit from including information about the perception of sequences.     

Transition secured? A follow-up study of adolescents who have left secure residential care

Many adolescents who make the transition to adulthood experience problems after their departure from secure residential care. Research suggests that these young people are often in need of support after they have left secure care. Little is known about the experiences and perceptions of adolescents during and after this transition. The aim of this article is to assess these experiences for a group of 24 adolescents in the Netherlands that have left secure residential care. The results show, in line with previous studies, that many adolescents experience problems during their transition from secure care, especially with regard to finances, school and employment, and living arrangements. In contrast to other studies, a majority of the adolescents reports to have received support in the year following their departure. Relatively few adolescents move to independence after their departure, which suggests that many adolescents are not ready for making a true transition into adulthood yet.     

Trade Credit and the Propagation of Corporate Failure: An Empirical Analysis

Using an exhaustive data set on claims held by trade creditors (suppliers) on failed trade debtors (customers), we quantify the importance of trade credit chains for the propagation of corporate bankruptcy. We show that trade creditors experience significant trade credit losses due to trade debtor failures and that creditors' bankruptcy risks increase in the size of incurred losses. By exploring the roles of financial constraints and creditor‐debtor dependences, we infer that the trade credit failure propagation mechanism is driven by both credit losses and demand shrinkage. Finally, we show that the documented propagation mechanism constitutes a significant part of the overall bankruptcy frequency, suggesting that it has measurable implications for the aggregate level.     

Weight matrices for social influence analysis: An investigation of measurement errors and their effect on model identification and estimation quality

Weight matrices, such as used in network autocorrelation models, are useful to investigate social influence processes. The objective of this paper is to investigate a key topic that has received relatively little attention in previous research, namely the issues that arise when observational limitations lead to measurement errors in these weight matrices. Measurement errors are investigated from two perspectives: when relevant ties are omitted, and when irrelevant ties are erroneously included as part of the matrix. The paper first shows analytically that these two situations result in biased estimates. Next, a simulation experiment provides evidence of the effect of erroneously coding the weight matrix on model performance and the ability of a network autocorrelation test to identify social influence effects. The results suggest that depending on the level of autocorrelation and the topology attributes of the underlying matrix, there is a window of opportunity to identify and model social influence processes even in situations where the ties in a matrix cannot be accurately observed.