Optimal designs for regional bridging studies using the Bayesian power prior method

As described in the ICH E5 guidelines, a bridging study is an additional study executed in a new geographical region or subpopulation to link or “build a bridge” from global clinical trial outcomes to the new region. The regulatory and scientific goals of a bridging study is to evaluate potential subpopulation differences while minimizing duplication of studies and meeting unmet medical needs expeditiously. Use of historical data (borrowing) from global studies is an attractive approach to meet these conflicting goals. Here, we propose a practical and relevant approach to guide the optimal borrowing rate (percent of subjects in earlier studies) and the number of subjects in the new regional bridging study. We address the limitations in global/regional exchangeability through use of a Bayesian power prior method and then optimize bridging study design with a return on investment viewpoint. The method is demonstrated using clinical data from global and Japanese trials in dapagliflozin for type 2 diabetes.     

Distance-d independent set problems for bipartite and chordal graphs

The paper studies a generalization of the Independent Set problem (IS for short). A distance- $d$ independent set for an integer $d\ge 2$ in an unweighted graph $G = (V, E)$ is a subset $S\subseteq V$ of vertices such that for any pair of vertices $u, v \in S$ , the distance between $u$ and $v$ is at least $d$ in $G$ . Given an unweighted graph $G$ and a positive integer $k$ , the Distance- $d$ Independent Set problem (D $d$ IS for short) is to decide whether $G$ contains a distance- $d$ independent set $S$ such that $|S| \ge k$ . D2IS is identical to the original IS. Thus D2IS is $\mathcal{NP}$ -complete even for planar graphs, but it is in $\mathcal{P}$ for bipartite graphs and chordal graphs. In this paper we investigate the computational complexity of D $d$ IS, its maximization version MaxD $d$ IS, and its parameterized version ParaD $d$ IS( $k$ ), where the parameter is the size of the distance- $d$ independent set: (1) We first prove that for any $\varepsilon >0$ and any fixed integer $d\ge 3$ , it is $\mathcal{NP}$ -hard to approximate MaxD $d$ IS to within a factor of $n^{1/2-\varepsilon }$ for bipartite graphs of $n$ vertices, and for any fixed integer $d\ge 3$ , ParaD $d$ IS( $k$ ) is $\mathcal{W}[1]$ -hard for bipartite graphs. Then, (2) we prove that for every fixed integer $d\ge 3$ , D $d$ IS remains $\mathcal{NP}$ -complete even for planar bipartite graphs of maximum degree three. Furthermore, (3) we show that if the input graph is restricted to chordal graphs, then D $d$ IS can be solved in polynomial time for any even $d\ge 2$ , whereas D $d$ IS is $\mathcal{NP}$ -complete for any odd $d\ge 3$ . Also, we show the hardness of approximation of MaxD $d$ IS and the $\mathcal{W}[1]$ -hardness of ParaD $d$ IS( $k$ ) on chordal graphs for any odd $d\ge 3$ .     

Approximation algorithms for the graph orientation minimizing the maximum weighted outdegree

Given a simple, undirected graph G=(V,E) and a weight function w:E→ℤ⁺, we consider the problem of orienting all edges in E so that the maximum weighted outdegree among all vertices is minimized. It has previously been shown that the unweighted version of the problem is solvable in polynomial time while the weighted version is (weakly) NP-hard. In this paper, we strengthen these results as follows: (1) We prove that the weighted version is strongly NP-hard even if all edge weights belong to the set {1,k}, where k is any fixed integer greater than or equal to 2, and that there exists no pseudo-polynomial time approximation algorithm for this problem whose approximation ratio is smaller than (1+1/k) unless P = NP; (2) we present a new polynomial-time algorithm that approximates the general version of the problem within a ratio of (2−1/k), where k is the maximum weight of an edge in G; (3) we show how to approximate the special case in which all edge weights belong to {1,k} within a ratio of 3/2 for k=2 (note that this matches the inapproximability bound above), and (2−2/(k+1)) for any k≥3, respectively, in polynomial time.     

Longitudinal assessment of social attention in preterm and term infants: Its relation to social communication and language outcome

Preterm birth has been reported to be associated with an increased risk of social communication and language problems. Recently, we found that preterm infants showed atypical patterns of social attention compared with term infants. However, it is still unknown how social attention develops and whether the individual differences are associated with developmental outcomes for social communication and language in preterm infants. The social attention of preterm and term infants at 6, 12, and 18 months was investigated using two types of social attention tasks (human-geometric preference task and gaze-following task). The Modified Checklist for Autism in Toddlers (M-CHAT) and the MacArthur Communicative Development Inventory adapted for Japanese were measured at 18 months. We found that compared with term infants, preterm infants spent less time looking toward dynamic human images and followed another's gaze directions less frequently through 6, 12, and 18 months. Moreover, hierarchical multiple regression analysis revealed that less preference for dynamic human images and gaze-following abilities was associated with high M-CHAT and low language scores in preterm and term infants, respectively. These findings suggest that birth status affects development of social attention through 18 months and individual differences in social attention reflect differences in social communication and language outcomes.     

Theorizing disaster communitas

Theory and Society - Disaster scholars have long complained that their field is theory light: they are much better at doing and saying than analyzing. The paucity of theory doubtless reflects an...