Lichenometric dating: a commentary, in the light of some recent statistical studies

This commentary article discusses the relative merits of new mathematical approaches to lichenometry. It highlights their strong reliance on complex statistics; their user un-friendliness; and their occasional mistreatment of existing lichenometric techniques. The article proposes that the success of lichenometric dating over the past 50 years has stemmed from its relative simplicity, transparency, and general field applicability. It concludes that any new techniques which ignore these principles are likely to be unjustified, unsuitable to the user community and inappropriate for the subject matter. Furthermore, the article raises a more general philosophical question: can statistical complexity and high precision in a ‘geobotanical’ dating technique, fraught with high degrees of environmental variability and in-built uncertainty, ever be scientifically valid

Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors

Objective: CD4+ T-cells mediate inflammation in atherosclerosis, but additive genetic effects on associated pathways of Th1 and Th2 immune response have not been described. We sought to characterize heritability, pleiotropy, and QTL effects on the expression of genes implicated in Th1 and Th2 immune response in a baboon model of risk factors for atherosclerosis. Methods: We employed a maximum likelihood-based variance decomposition approach to estimate additive genetic effects on transcript levels generated from a gene expression profile of lymphocytes in 499 pedigreed baboons maintained on a basal diet. Transcript levels for 57 genes implicated in Th1 and Th2 immune response were selected for analysis based on significant heritability in this profile. Multipoint whole genome scans were conducted on heritable transcript levels to localize QTLs influencing these measures. To evaluate pleiotropic effects on transcript levels, we estimated genetic and phenotypic correlations among transcript measures, and assessed their correspondence using a Mantel test. Network analysis using GeneGo's MetaCore™ software was conducted to characterize known interaction among coded proteins.Results: Heritabilities for candidate gene transcript levels ranged from 0.092–0.786 (median h2 = 0.278, P = 4.72 × 10−4). Linkage analyses yielded significant evidence (LOD ≥ 2.73) for 14 eQTLs (LOD score range 2.76–14.87, genome-wide P = 4.9 × 10−2–1.03 × 10−14). Estimates of genetic correlation supported shared additive genetic effects incorporating all 57 transcripts (null hypothesis of ρG = 0 rejected at FDR ≤ 0.05 for 522 of 1596 estimates), and accounted for most of the observed phenotypic correlation among transcripts (Mantel test, r[ρP],[ρG] = 0.781, P < 0.0001). Network analysis revealed direct interactions among 54 of the 57 coded proteins. Conclusions: We conclude that major genetic effects influence expression levels of multiple genes implicated in Th1 and Th2 immune response. Additionally, we find that expression levels of these candidate genes are characterized by extensive pleiotropy, consistent with known interaction among their coded proteins, many of which are independently associated with atherosclerosis

The mechanisms of coronary restenosis: insights from experimental models

Since its introduction into clinical practice, more than 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) has proven to be an effective, minimally invasive alternative to coronary artery bypass grafting (CABG). During this time there have been great improvements in the design of balloon catheters, operative procedures and adjuvant drug therapy, and this has resulted in low rates of primary failure and short-term complications. However, the potential benefits of angioplasty are diminished by the high rate of recurrent disease. Up to 40% of patients undergoing angioplasty develop clinically significant restenosis within a year of the procedure. Although the deployment of endovascular stents at the time of angioplasty improves the short-term outcome, ‘in-stent’ stenosis remains an enduring problem. In order to gain an insight into the mechanisms of restenosis, several experimental models of angioplasty have been developed. These have been used together with the tools provided by recent advances in molecular biology and catheter design to investigate restenosis in detail. It is now possible to deliver highly specific molecular antagonists, such as antisense gene sequences, to the site of injury. The knowledge provided by these studies may ultimately lead to novel forms of intervention. The present review is a synopsis of our current understanding of the pathological mechanisms of restenosis