Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.

Studies have demonstrated that the effects of two well-known predictors of adolescent substance use, family monitoring and antisocial peers, are not static but change over the course of adolescence. Moreover, these effects may differ for different groups of youth. The current study uses time-varying effect modeling to examine the changes in the association between family monitoring and antisocial peers and marijuana use from ages 11 to 19, and to compare these associations by gender and levels of behavioral disinhibition. Data are drawn from the Raising Healthy Children study, a longitudinal panel of 1,040 youth. The strength of association between family monitoring and antisocial peers and marijuana use was mostly steady over adolescence, and was greater for girls than for boys. Differences in the strength of the association were also evident by levels of behavioral disinhibition: youth with lower levels of disinhibition were more susceptible to the influence of parents and peers. Stronger influence of family monitoring on girls and less disinhibited youth was most evident in middle adolescence, whereas the stronger effect of antisocial peers was significant during middle and late adolescence. Implications for the timing and targeting of marijuana preventive interventions are discussed.

Environmental variation (VE) in a quantitative trait – variation in phenotype that cannot be explained by genetic variation or identifiable genetic differences – can be regarded as being under some degree of genetic control. Such variation may be either between repeated expressions of the same trait within individuals (e.g. for bilateral traits), in the phenotype of different individuals, where variation within families may differ, or in both components. We consider alternative models for defining the distribution of phenotypes to include a component due to heterogeneity of VE. We review evidence for the presence of genetic variation in VE and estimates of its magnitude. Typically the heritability of VE is under 10%, but its genetic coefficient of variation is typically 20% or more. We consider experimental designs appropriate for estimating genetic variance in VE and review alternative methods of estimation. We consider the effects of stabilizing and directional selection on VE and review both the forces that might be maintaining levels of VE and heritability found in populations. We also evaluate the opportunities for reducing VE in breeding programmes. Although empirical and theoretical studies have increased our understanding of genetic control of environmental variance, many issues remain unresolved.

This paper describes the results of two seasons of excavation and associated palaeoenvironmental analyses of a wetland site on Beccles Marshes, Beccles, Suffolk. The site has been identified as a triple post alignment of oak timbers (0.6–2.0 m long), over 100 m in length, and 3–4 m wide, running north-west to south-east towards the River Waveney. It was constructed in a single phase which has been dated dendrochronologically to 75 BC, although discrete brushwood features identified as possible short trackways have been dated by radiocarbon to both before and after the alignment was built. It is unclear if the posts ever supported a superstructure but notches (‘halving lap joints’) in some of the posts appear to have held timbers to support the posts and/or aid in their insertion. In addition, fragments of both Iron Age and Romano-British pottery were recovered. A substantial assemblage of worked wooden remains appears to reflect the construction of the post row itself and perhaps the on-site clearance of floodplain vegetation. This assemblage also contains waste material derived from the reduction splitting of timbers larger than the posts of the alignment, but which have not been recovered from the site. Environmental analyses indicate that the current landscape context of the site with respect to the River Waveney is probably similar to that which pertained in prehistory. The coleoptera (beetle) record illustrates a series of changes in the on-site vegetation in the period before, during and after the main phase of human activity which may be related to a range of factors including floodplain hydrology and anthropogenic utilisation of Beccles Marshes. The possible form and function of the site is discussed in relation to the later prehistoric period in Suffolk.

Methods for estimating probability of identity by descent (f) are derived for data on numbers of genotypes at single loci and at pairs of loci with many alleles at each locus. The methods are general, but are specifically applied to data on genotype frequencies in zygotes of the malaria parasite sampled from its mosquito host in order to find the extent of outcrossing in the parasite and the degree of clonality in populations. It is assumed that zygotes are the outcome either of gametes of the same clone, in which they are identical at all loci, or are products of two random, unrelated clones. From the estimate of f an effective number of clones per human host can also be derived. For Plasmodium falciparum from a Tanzanian village, estimates of f are 0·33 from data on zygote frequencies at two multiallelic loci, indicating that two-thirds of zygotes produce recombinant types.

A method is proposed for estimating effective population size (N) from data on linkage disequilibrium among neutral genes at several polymorphic loci or restriction sites. The efficiency of the method increases with larger sample size and more tightly linked genes; but for very tightly linked genes estimates of N are more dependent on long-term than on recent population history. Two sets of data are analysed as examples.

Expressions for the probability and average time of detection of a recessive visible gene in populations where there is partial selfing or partial full-sib mating are presented. A small increase in the proportion of inbred matings greatly reduces the average time until detection and increases the proportion detected. Unless the proportion of inbred matings or the population size is very small, the time and proportion detected are approximately independent of the population size.

The effects of mutation on mean and variance of response to selection for quantitative traits are investigated. The mutants are assumed to be unlinked, to be additive, and to have their effects symmetrically distributed about zero, with absolute values of effects having a gamma distribution. It is shown that the ratio of expected cumulative response to generation t from mutants, , and expected response over one generation from one generation of mutants, , is a function of t/N, where t is generations and N is effective population size. Similarly, , is a function of t/N, where is the increment in genetic variance from one generation of mutants. The mean and standard deviation of response from mutations relative to that from initial variation in the population, in the first generation, are functions of . Evaluation of these formulae for a range of parameters quantifies the important role that population size can play in response to long-term selection.

Quantitative variation in traits that change with age is important to both evolutionary biologists and breeders. We present three new methods for estimating the phenotypic and additive genetic covariance functions of a trait that changes with age, and illustrate them using data on daily lactation records from British Holstein—Friesian dairy cattle. First, a new technique is developed to fit a continuous covariance function to a covariance matrix. Secondly, this technique is used to estimate and correct for a bias that inflates estimates of phenotypic variances. Thirdly, we offer a numerical method for estimating the eigenvalues and eigenfunctions of covariance functions. Although the algorithms are moderately complex, they have been implemented in a software package that is made freely available.

Analysis of lactation shows the advantages of the new methods over earlier ones. Results suggest that phenotypic variances are inflated by as much as 39 % above the underlying covariance structure by measurement error and short term environmental effects. Analysis of additive genetic variation indicates that about 90 % of the additive genetic variation for lactation during the first 10 months is associated with an eigenfunction that corresponds to increased (or decreased) production at all ages. Genetic tradeoffs between early and late milk yield are seen in the second eigenfunction, but it accounts for less than 8 % of the additive variance. This illustrates that selection is expected to increase production throughout lactation.