A simulation study of methods for selecting subgroup‐specific doses in phase 1 trials

Patient heterogeneity may complicate dose‐finding in phase 1 clinical trials if the dose‐toxicity curves differ between subgroups. Conducting separate trials within subgroups may lead to infeasibly small sample sizes in subgroups having low prevalence. Alternatively,it is not obvious how to conduct a single trial while accounting for heterogeneity. To address this problem,we consider a generalization of the continual reassessment method on the basis of a hierarchical Bayesian dose‐toxicity model that borrows strength between subgroups under the assumption that the subgroups are exchangeable. We evaluate a design using this model that includes subgroup‐specific dose selection and safety rules. A simulation study is presented that includes comparison of this method to 3 alternative approaches,on the basis of nonhierarchical models,that make different types of assumptions about within‐subgroup dose‐toxicity curves. The simulations show that the hierarchical model‐based method is recommended in settings where the dose‐toxicity curves are exchangeable between subgroups. We present practical guidelines for application and provide computer programs for trial simulation and conduct.     

Estimation and Inference for Linear Panel Data Models Under Misspecification When Both n and T are Large

This article considers fixed effects (FE) estimation for linear panel data models under possible model misspecification when both the number of individuals, n, and the number of time periods, T, are large. We first clarify the probability limit of the FE estimator and argue that this probability limit can be regarded as a pseudo-true parameter. We then establish the asymptotic distributional properties of the FE estimator around the pseudo-true parameter when n and T jointly go to infinity. Notably, we show that the FE estimator suffers from the incidental parameters bias of which the top order is O(T^{? 1}), and even after the incidental parameters bias is completely removed, the rate of convergence of the FE estimator depends on the degree of model misspecification and is either (nT)^{? 1/2} or n^{? 1/2}. Second, we establish asymptotically valid inference on the (pseudo-true) parameter. Specifically, we derive the asymptotic properties of the clustered covariance matrix (CCM) estimator and the cross-section bootstrap, and show that they are robust to model misspecification. This establishes a rigorous theoretical ground for the use of the CCM estimator and the cross-section bootstrap when model misspecification and the incidental parameters bias (in the coefficient estimate) are present. We conduct Monte Carlo simulations to evaluate the finite sample performance of the estimators and inference methods, together with a simple application to the unemployment dynamics in the U.S.     

A Generalization of the Childs-Moran Result for Orthoscheme Probabilities

van der Vaart (1953, 1955) introduced the orthoscheme probability R_n (c ₁,..., c_n−1 ), meaning the orthant probability of an n -dimensional normal random vector with zero mean and tridiagonal correlation matrix with elements c ₁,..., c_n−1 on the upper diagonal. Childs (1967) conjectured and Moran (1983) proved that the generating function of { R_n (½,...,½)} equals tan z + sin z . This paper derives the generating function of { R_n (τ,½,...,½)}.     

The union-intersection principle applied to the test of dimensionality

In the first section Anderson-Rao-Fujikoshi's test statistics for testing the hypothesis of dimensionality are reviewed and then Olkin-Tomsky's generalized union-intersection principle is applied to show that a new class of test statistics for testing the hypothesis of dimensionality are derived which includes the likelihood ratio test statistics, the trace test statistics and a version of ROY'S maximum root test statistics.     

Not Just the Price of Food: Challenges of an Urban Agriculture Organization in Engaging Local Residents

This case study of a community‐supported agriculture (CSA) organization in New Orleans focuses on the lack of participation in the CSA market by the local residents despite its intentions, and how various constituencies diagnose the causes of the disengagement. Interview and ethnographic observation data indicate a general consensus on the economic constraints, but some non‐resident supporters of the organization attributed the issue to lack of knowledge about the food system or the benefits of local food consumption. The residents, on the other hand, pointed to spatial and sociocultural barriers that made the market and its location less accessible to them, including the produce selection and purchase options, convenience of access to the market, and the race‐related historical and spatial context of the market's location. These findings suggest that the food access concerns of the food justice movement may be more easily addressed than the food sovereignty concerns. Food as a unique resource poses an additional challenge for the movement to construct an effective food justice frame.     

Effects of parasitoid community structure upon the population dynamics of the honeysuckle leafminer,Chromatomyia suikazurae (Diptera: Agromyzidae)

Population dynamics of a leafminer,Chromatomyia suikazurae (Agromyzidae, Diptera) and its parasitoid community were studied for ten years at seven natural populations along an altitudinal gradient in Japan. This species which mines leaves of a forest shrub,Lonicera gracilipes (Caprifoliaceae), was attacked by 25 hymenopterous parasitoid species. Annually, the parasitoid community structure varied less within a population than among populations. The seven parasitoid communities were clustered into three groups corresponding to the altitudinal gradient: (a) lowland communities dominated by late-attacking, generalist pupal idiobiont eulophids and with highest species diversity, (b) hillside communities dominated by an early-attacking, specialist larval-pupal koinobiont braconid and (c) highland communities dominated by an early-attacking, generalist larval idiobiont eulophid. Annual changes of the host larval densities among the local populations were largely synchronous rather than cyclic. Among these populations, host density levels and mortality patterns greatly varied. By analyzing these inter-populational differences of host mortality patterns, the following conclusions were drawn: (1) The host mortality patterns were determined by the host utilization patterns of the locally dominant species. (2) The host pupal mortality but not larval mortality was related to species diversity but not to species richness itself of each parasitoid community. (3) Density dependence was detected only in pupal mortality at a lowland population dominated by late-attacking pupal parasitoids. These results suggest that interspecific interactions of parasitoids add additive effects to host population dynamics dissimilarly among local populations with different parasitoid communities.     

Fetal movement frequency and the effect of associated perinatal factors: Multicenter study

Background

Decreased fetal movements are associated with adverse perinatal outcomes, including stillbirth. Delayed maternal visits to a health care provider after perceiving decreased fetal movements are frequently observed in stillbirths. Informing pregnant women of the normal range of fetal movement frequency is essential in their earlier visits in order to prevent stillbirth.

An assessment framework based on social perspectives and Analytic Hierarchy Process: A case study on sustainability in the Japanese concrete industry

This research introduces a framework for assessing concrete sustainability which is based upon the concept that technology is defined by stakeholders’ perspectives and which applied Analytic Hierarchy Process to translate these perspectives into quantifiable assessment values. A survey was conducted to identify important criteria, and several “design scenarios” were introduced which represent different value systems by varying criteria importance. Concrete materials with varying environmental impact were then assessed to observe the effect of different value systems and material properties, and it was found that the concrete with better properties was generally selected as most sustainable regardless of the design scenario.     

Seasonality and vertical structure of light-attracted insect communities in a dipterocarp forest in Sarawak

Nocturnal flying insects were collected monthly for 13 months using ultra violet light-traps set at various vertical levels in a weakly-seasonal, tropical lowland dipterocarp forest in Sarawak, Malaysia. Abundance, faunal composition, size distribution and guild structure of these samples were analyzed with respect to temperal and vertical distributions. The nocturnal flying insect community in the canopy level was highly dominated by fig wasps (84%) in individual number, and by scarabaeid beetles (28%) in weight. A principal component analysis on monthly catches detected non-random, seasonal trends of insect abundance. The first two principal trends were an alternation of wetter (September to January) and less wet seasons (February to August) and an alternation between the least wet (January to March) and the other seasons. Many insect groups were less abundant in the least wet season than the other seasons, whilst inverse patterns were found in Scarabaeidae and Tenebrionidae. Significantly positive and negative correlations between monthly catch and rainfall were detected only in ovule-feeders and in phloem-feeders, respectively. Delayed, significant negative correlations between monthly catch and 1–3 month preceding rainfall were more frequently detected in phytophages, phloem-feeders, seed-feeders, wood-borers and scavengers. The peak in abundance along vertical levels were found at the canopy level (35 m) for phloem-, ovule-, seed-, root-, fungal-feeders and nectar collectors, at an upper subcanopy level (25 m) for scavengers and aquatic predators, and at a middle subcanopy level (17 m) for ants. Catches at the emergent level (45 m) did not exceed those at the canopy level.