Logistic retainment interval dose exploration design for Phase I clinical trials of cytotoxic agents

Phase I studies of a cytotoxic agent often aim to identify the dose that provides an investigator specified target dose-limiting toxicity (DLT) probability. In practice, an initial cohort receives a dose with a putative low DLT probability, and subsequent dosing follows by consecutively deciding whether to retain the current dose, escalate to the adjacent higher dose, or de-escalate to the adjacent lower dose. This article proposes a Phase I design derived using a Bayesian decision-theoretic approach to this sequential decision-making process. The design consecutively chooses the action that minimizes posterior expected loss where the loss reflects the distance on the log-odds scale between the target and the DLT probability of the dose that would be given to the next cohort under the corresponding action. A logistic model is assumed for the log odds of a DLT at the current dose with a weakly informative t-distribution prior centered at the target. The key design parameters are the pre-specified odds ratios for the DLT probabilities at the adjacent higher and lower doses. Dosing rules may be pre-tabulated, as these only depend on the outcomes at the current dose, which greatly facilitates implementation. The recommended default version of the proposed design improves dose selection relative to many established designs across a variety of scenarios.     

Piketty comes to South Africa

One of the most valuable features of Capital and Ideology is its concern to take history seriously and consider how the emergence of different political and economic regimes relate to discourses about fairness and justice across time. This paper pushes this agenda further by acknowledging that the experience of a few developed nations should not be taken as the template for the generalized study of inequality dynamics across time and space. In this paper, we interrogate Piketty's analysis and policy proposals against specificities that are central to understanding the production and reproduction of inequalities within South Africa. We reflect on the South African case, the structure of inequality and its changes since 1994. We review a battery of policy interventions that have been implemented to address inequality in the last 25 years. We emphasize that the long shadow cast by centuries of colonialism and various forms of apartheid strongly affirm Piketty's emphasis on understanding history. But this is both affirmation and critique given the foundational, imbedded impact that this specific legacy has had on post‐apartheid society and its policies. Piketty is aware that the levels of inequality in South Africa are so high that this is “unknown territory.” We map out some of this territory to reveal how these extreme initial wealth and racial inequities inform the reproduction of inequalities in all dimensions and undermine well intentioned policies. We claim that understanding extractive histories, imbedded wealth inequalities, and complex social and political institutions allows us to understand and confront some of the reasons why even in light of progressive policies, many of which are in line with the proposals from Piketty, government interventions have thus far failed to reduce inequality.     

'Anti-Oppressiveness': Critical Comments on a Discourse and its Context

This paper identifies and aims to explain an apparent dissonancebetween the dominance in Britain of ‘anti-oppressive’social work discourse and the socio-political context surroundingits use; a context often claimed to feature excessive regulationand control. Pursuing this, some politically radical aims associatedwith ‘anti-oppressiveness’ are spelt out, and thedifficulty of achieving these in an unconducive climate is discussed.Then, a distinction made by Robert Merton between ‘latent’and ‘manifest’ functions is used to suggest thatthe manifest radicalism of ‘anti-oppressive’ discoursecan helpfully be distinguished from some latent largely unrecognisedconsequences of its use – not consequences with politicallyradical impact, but with a social meaning congruent with a climateof control. It is concluded that the ‘success’ ofanti-oppressive discourse might well be viewed as requiringmore of the kind of critical analysis that the discourse itselfwas supposed to espouse.     

A note on connectedness in fixed effects manova and gmanova models withmissing cells

Murray and Smith (1985) and Hocking (1985) give a generalized definition and test of connectedness in the case of missing cells using the univariate cell-means model with linear restrictions on the cell-means. The test of connectedness is here extended to multivariate fixed effects models, including the usual MANOVA model with linear restrictions, the MANOVA model with double linear restrictions, and the GMANOVA model.     

Title Index

Abstract

This article describes how electronic resources have impacted the University of Nevada, Las Vegas (UNLV) Libraries' binding operation and how the libraries have responded to the resulting challenges, including the need for updated collection development and preservation/conservation policies, a comprehensive bindery contract, and a fully functional in-house binding capability. The evaluation of the binding process must continue as libraries move from a predominantly print to a predominantly electronic environment. Librarians, scholars, and binders should work together to preserve and bind library collections that will be valuable to future generations.     

Recursive location and scale estimators

It is shown that a recursive estimator with the same asymptotic properties as the median has convergence properties in finite samples which depend heavily on the scale of the data. A simple modification which adjusts for the scale is suggested and its application illustrated on simulated data. The modified estimator has much improved properties which are similar to those of the sample (non-recursive) median.     

Computing equilibrium in network utility-sharing and discrete election games

Journal of Combinatorial Optimization - This paper studies the computation of pure Nash equilibrium (PNE) in network utility-sharing and discretized Hotelling–Downs games, and the interplay...