Local competition for space across a wide array of taxa typically involves three mechanisms that we denote here as expansion (spreading into unoccupied habitat), lottery (replacing dead competitors), and overgrowth (encroaching on competitors along zones of contact). By formulating and analysing a simple, general model incorporating these features, we identify ecological conditions and life-history features that lead to stable coexistence or competitive exclusion (with or without initial-condition dependence) and gain insight by linking these to case studies in the literature. We demonstrate the importance of contact inhibition, a little-studied feature of overgrowth, and we show how life-history tradeoffs may influence and be influenced by local competition for space. The general model we present can help indicate whether local interactions are sufficient to explain patterns of coexistence or exclusion and can serve as the foundation for more specific, realistic models of spatial competition.

Background-Single-nucleotide polymorphisms (SNPs) within the regulatory ␤2 subunit of the voltage-gated calcium channel (CACNB2) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results-SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a ␤-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter AϾG SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes (P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; Pϭ0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79; Pϭ0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11; Pϭ0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele. Conclusions-These data suggest that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00133692. (Circ Cardiovasc Genet. 2010;3:548-555.)

Heart failure is an increasingly common disease associated with significant morbidity and mortality in the aging population. Recent advances in heart failure pharmacotherapy have established a number of agents as beneficial to disease progression and outcomes. However, current consensus guideline recommended pharmacotherapy may not represent an optimal treatment strategy in all heart failure patients. Specifically, individuals with genetic variation in regions central to mediation of beneficial response to standard heart failure agents may not receive optimal benefit from these drugs. Additionally, targeted approaches in Phase III clinical trials that select patients for inclusion based on the genotype most likely to respond might advance the currently stalled drug development pipeline in heart failure. This article reviews the literature in heart failure pharmacogenetics to date, opportunities for discovery in recent and upcoming clinical trials, as well as future directions in this field.