Estimation of the odds ratio in a proportional odds model with censored time-lagged outcome in a randomized clinical trial

In many randomized clinical trials of therapeutics for COVID-19, the primary outcome is an ordinal categorical variable, and interest focuses on the odds ratio (OR; active agent vs control) under the assumption of a proportional odds model. Although at the final analysis the outcome will be determined for all subjects, at an interim analysis, the status of some participants may not yet be determined, for example, because ascertainment of the outcome may not be possible until some prespecified follow-up time. Accordingly, the outcome from these subjects can be viewed as censored. A valid interim analysis can be based on data only from those subjects with full follow-up; however, this approach is inefficient, as it does not exploit additional information that may be available on those for whom the outcome is not yet available at the time of the interim analysis. Appealing to the theory of semiparametrics, we propose an estimator for the OR in a proportional odds model with censored, time-lagged categorical outcome that incorporates additional baseline and time-dependent covariate information and demonstrate that it can result in considerable gains in efficiency relative to simpler approaches. A byproduct of the approach is a covariate-adjusted estimator for the OR based on the full data that would be available at a final analysis.     

A new molecular phylogeny offers hope for a stable family level classification of the Noctuoidea (Lepidoptera)

Zahiri, R., Kitching, I. J., Lafontaine, J. D., Mutanen, M., Kaila, L., Holloway, J. D. & Wahlberg, N. (2010). A new molecular phylogeny offers hope for a stable family level classification of the Noctuoidea (Lepidoptera). —Zoologica Scripta, 40, 158–173. To examine the higher level phylogeny and evolutionary affinities of the megadiverse superfamily Noctuoidea, an extensive molecular systematic study was undertaken with special emphasis on Noctuidae, the most controversial group in Noctuoidea and arguably the entire Lepidoptera. DNA sequence data for one mitochondrial gene (cytochrome oxidase subunit I) and seven nuclear genes (Elongation Factor‐1α, wingless, Ribosomal protein S5, Isocitrate dehydrogenase, Cytosolic malate dehydrogenase, Glyceraldehyde‐3‐phosphate dehydrogenase and Carbamoylphosphate synthase domain protein) were analysed for 152 taxa of principally type genera/species for family group taxa. Data matrices (6407 bp total) were analysed by parsimony with equal weighting and model‐based evolutionary methods (maximum likelihood), which revealed a new high‐level phylogenetic hypothesis comprising six major, well‐supported lineages that we here interpret as families: Oenosandridae, Notodontidae, Erebidae, Nolidae, Euteliidae and Noctuidae.     

Photochemical instability of 1-nitropyrene, 3-nitrofluoranthene, 1,8-dinitropyrene and their parent polycyclic aromatic hydrocarbons

The environmental contaminants pyrene, 1-nitropyrene, 1,8-dinitropyrene, fluoranthene, and 3-nitrofluoranthene were exposed to light (greater than or equal to 310 nm) either in DMSO, or following coating onto silica. Under all conditions tested the pyrenyl were less stable than the fluoranthenyl compounds. During irradiation in DMSO or on silica, 1-nitropyrene had half-lives of 1.2 and 6 days, while those of 3-nitrofluoranthene were 12.5 and greater than 20 days, respectively. The photodecomposition of 1,8-dinitropyrene resembled that of 1-nitropyrene with half-lives of 0.7 and 5.7 days. A principle photodecomposition product of 1,8-dinitropyrene was identified as 1-nitropyren-8-ol. It was also found that when the nitroarenes were exposed to light, the loss of compound was associated with a concomitant loss of mutagenicity in Salmonella typhimurium strain TA98. The mechanism of nitrated polycyclic aromatic hydrocarbon decomposition and 1-nitropyren-8-ol formation, and the relevance to the atmospheric disposition of these compounds are discussed.     

Sexual dimorphism of the human corpus callosum from three independent samples: Relative size of the corpus callosum

Three independent autopsy samples of brains without apparent neuropathology were studied to ascertain whether there was sexual dimorphism in the human corpus callosum (CC). Using planimetric measurements on midsagittal brain sections, several morphometric features of the CC were studied: total callosal area, maximum dorsoventral splenial width, the posterior one fifth of the total area of the CC (mostly splenium), and brain weight. Ratio data correcting for brain size were also studied. In all samples, absolute brain size was larger in males, and significantly so. Measurements of splenial dorsoventral width were higher in females than males, but not significantly, except in the Australian sample. Total callosal area was absolutely higher in the Australian female sample than in males, and almost equal in the two American samples, without statistically significant differences. The posterior one-fifth area (splenium) was larger for females in each of the samples. The variables which were corrected for brain size were usually significantly larger in females, although this pattern varied in each sample. The statistical pattern of sexual dimorphism for the human CC differs from that found in most other neural structures, such as the amygdaloid nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these structures are always significantly larger in males. When corrected for brain size, the relative sizes are not significantly larger. The CC is the only structure to show a larger set of relative measures in females. © 1993 Wiley-Liss, Inc.     

A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality--and tolerance of segmental aneuploidy--in humans.

The distribution of simple autosomal duplications associated with congenital malformations has been analyzed by means of data contained in the Human Cytogenetics Database. For each of the 47 malformations, the frequency of duplication of a given chromosome band associated with the malformation was compared with the overall frequency of duplication of that band recorded in the database. In total, there were 143 malformation-associated chromosomal regions (MACR); 21 of these contained at least one band with a highly significant (P<.001) association. The average number of bands per MACR was 3.1. Eight bands, representing 2.1% of haploid autosomal length, were not involved in any duplication, and we suggest that these are potentially triplolethal. This compares with 31 bands, representing 11% of haploid autosomal length, that were identified in the previously reported deletion map and that were not involved in any deletion and are potentially haplolethal. In both cases, approximately half of these bands are pericentromeric. The longest duplication involves 4.3% of haploid autosomal length, and the longest deletion involves 2.7%.