Improved Logrank-Type Tests for Survival Data Using Adaptive Weights

Summary .  For testing for treatment effects with time-to-event data, the logrank test is the most popular choice and has some optimality properties under proportional hazards alternatives. It may also be combined with other tests when a range of nonproportional alternatives are entertained. We introduce some versatile tests that use adaptively weighted logrank statistics. The adaptive weights utilize the hazard ratio obtained by fitting the model of Yang and Prentice (2005,  Biometrika   92 , 1–17). Extensive numerical studies have been performed under proportional and nonproportional alternatives, with a wide range of hazard ratios patterns. These studies show that these new tests typically improve the tests they are designed to modify. In particular, the adaptively weighted logrank test maintains optimality at the proportional alternatives, while improving the power over a wide range of nonproportional alternatives. The new tests are illustrated in several real data examples.     

Predicting beef carcass composition using tissue weights of a primal cut assessed by computed tomography

The potential of the composition of the forerib measured by X-ray computed tomography (CT) as a predictor of carcass composition was evaluated using data recorded on 30 Aberdeen Angus and 43 Limousin crossbred heifers and steers. The left sides of the carcasses were split into 20 cuts, which were CT scanned and fully dissected into fat, muscle and bone. Carcass and forerib tissue weights were assessed by dissection and CT. Carcass composition was assessed very accurately by CT scanning of the primal cuts (adj-R2 = 0.97 for the three tissues). CT scanning predicted weights of fat, muscle and bone of the forerib with adj-R2 of 0.95, 0.91 and 0.75, respectively. Single regression models with the weights of fat, muscle or bone in the forerib measured by CT as the only predictors to estimate fat, muscle or bone of the left carcass obtained by CT showed adjusted coefficients of determination (adj-R2) of 0.79, 0.60 and 0.52, respectively. By additionally fitting breed and sex, accuracy increased to 0.85, 0.73 and 0.67. Using carcass and forerib weights in addition to the previous predictors improved significantly the prediction accuracy of carcass fat and muscle weights to adj-R2 values of 0.92 and 0.96, respectively, while the highest value for carcass bone weight was 0.77. In general, equations derived using CT data had lower adj-R2 values for bone, but better accuracies for fat and muscle compared to those obtained using dissection. CT scanning could be considered as an alternative very accurate and fast method to assess beef carcass composition that could be very useful for breeding programmes and research studies involving a large number of animals, including the calibration of other indirect methods (e.g. in vivo and carcass video image analysis).     

When is connectivity important? A case study of the spatial pattern of sudden oak death

Although connectivity has been examined from many different angles and in many ecological disciplines, few studies have tested in which systems and under what conditions connectivity is important in determining ecological dynamics. Identifying general rules governing when connectivity is important is crucial not only for basic ecology, but also for our ability to manage natural systems, particularly as increasing fragmentation may change the degree to which connectivity influences ecological dynamics. In this study, we used statistical regression, least‐cost path analysis, and model selection techniques to test the relative importance of potential connectivity in determining the spatial pattern of sudden oak death, a tree disease that is killing millions of oak and tanoak trees along coastal forests of California and Oregon. We hypothesized that potential connectivity, in addition to environmental conditions, is important in determining the spatial distribution of sudden oak death, the importance of connectivity is more apparent when measured using biologically meaningful metrics that account for the effects of landscape structure on disease spread, and the relative importance of environmental variables and connectivity is approximately equal. Results demonstrate that potential connectivity was important in determining the spatial pattern of sudden oak death, though it was relatively less important than environmental variables. Moreover, connectivity was important only when using biologically meaningful metrics as opposed to simple distance‐based metrics that ignore landscape structure. These results demonstrate that connectivity can be important in systems not typically considered in connectivity studies – highlighting the importance of examining connectivity in a variety of different systems – and demonstrate that the manner in which connectivity is measured may govern our ability to detect its importance.     

Microbial metabolism of cannflavin A and B isolated from Cannabis sativa

Microbial metabolism of cannflavin A (1) and B (2), two biologically active flavonoids isolated from Cannabis sativa L., produced five metabolites (3–7). Incubation of 1 and 2 with Mucor ramannianus (ATCC 9628) and Beauveria bassiana (ATCC 13144), respectively, yielded 6″S,7″-dihydroxycannflavin A (3), 6″S,7″-dihydroxycannflavin A 7-sulfate (4) and 6″S,7″-dihydroxycannflavin A 4′-O-α-l-rhamnopyranoside (5), and cannflavin B 7-O-β-d-4?-O-methylglucopyranoside (6) and cannflavin B 7-sulfate (7), respectively. All compounds were evaluated for antimicrobial and antiprotozoal activity.     

Regulation of the gibberellin pathway by auxin and DELLA proteins

The synthesis and deactivation of bioactive gibberellins (GA) are regulated by auxin and by GA signalling. The effect of GA on its own pathway is mediated by DELLA proteins. Like auxin, the DELLAs promote GA synthesis and inhibit its deactivation. Here, we investigate the relationships between auxin and DELLA regulation of the GA pathway in stems, using a pea double mutant that is deficient in DELLA proteins. In general terms our results demonstrate that auxin and DELLAs independently regulate the GA pathway, contrary to some previous suggestions. The extent to which DELLA regulation was able to counteract the effects of auxin regulation varied from gene to gene. For Mendel’s LE gene (PsGA3ox1) no counteraction was observed. However, for another synthesis gene, a GA 20-oxidase, the effect of auxin was weak and in WT plants appeared to be completely over-ridden by DELLA regulation. For a key GA deactivation (2-oxidase) gene, PsGA2ox1, the up-regulation induced by auxin deficiency was reduced to some extent by DELLA regulation. A second pea 2-oxidase gene, PsGA2ox2, was up-regulated by auxin, in a DELLA-independent manner. In Arabidopsis also, one 2-oxidase gene was down-regulated by auxin while another was up-regulated. Monitoring the metabolism pattern of GA₂₀ showed that in Arabidopsis, as in pea, auxin can promote the accumulation of bioactive GA.     

Patterning of mutually interacting bacterial bodies: close contacts and airborne signals

Background  

Bacterial bodies (colonies) can develop complex patterns of color and structure. These patterns may arise as a result of both colony-autonomous developmental and regulatory processes (self-patterning) and environmental influences, including those generated by neighbor bodies. We have studied the interplay of intra-colony signaling (self-patterning) and inter-colony influences in related clones of Serratia rubidaea grown on rich media.     

Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon

Background  

MLL2, an epigenetic regulator in mammalian cells, mediates histone 3 lysine 4 tri-methylation (H3K4me3) through the formation of a multiprotein complex. MLL2 shares a high degree of structural similarity with MLL, which is frequently disrupted in leukemias via chromosomal translocations. However, this structural similarity is not accompanied by functional equivalence. In light of this difference, and previous reports on involvement of epigenetic regulators in malignancies, we investigated MLL2 expression in established cell lines from breast and colon tissues. We then investigated MLL2 in solid tumors of breast and colon by immunohistochemistry, and evaluated potential associations with established clinicopathologic variables.