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A physically anchored consensus map is foundational to modern genomics research; however, construction of such a map in oat (Avena sativa L., 2 n = 6 x = 42) has been hindered by the size and complexity of the genome, the scarcity of robust molecular markers, and the lack of aneuploid stocks. Resources developed in this study include a modified SNP discovery method for complex genomes, a diverse set of oat SNP markers, and a novel chromosome-deficient SNP anchoring strategy. These resources were applied to build the first complete, physically-anchored consensus map of hexaploid oat. Approximately 11,000 high-confidence in silico SNPs were discovered based on nine million inter-varietal sequence reads of genomic and cDNA origin. GoldenGate genotyping of 3,072 SNP assays yielded 1,311 robust markers, of which 985 were mapped in 390 recombinant-inbred lines from six bi-parental mapping populations ranging in size from 49 to 97 progeny. The consensus map included 985 SNPs and 68 previously-published markers, resolving 21 linkage groups with a total map distance of 1,838.8 cM. Consensus linkage groups were assigned to 21 chromosomes using SNP deletion analysis of chromosome-deficient monosomic hybrid stocks. Alignments with sequenced genomes of rice and Brachypodium provide evidence for extensive conservation of genomic regions, and renewed encouragement for orthology-based genomic discovery in this important hexaploid species. These results also provide a framework for high-resolution genetic analysis in oat, and a model for marker development and map construction in other species with complex genomes and limited resources.

The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant treatment for early breast cancer. We investigated prospectively predictive biomarkers of anthracycline benefit including HER2 and TOP2A. 1941 tumours from 2391 women recruited to NEAT/BR9601 were analysed on tissue microarrays for HER2 and TOP2A amplification and deletion, HER1–3 and Ki67 expression, and duplication of chromosome 17 centromere enumeration probe (Ch17CEP). Log-rank analyses identified factors affecting relapse-free and overall survival, and regression models tested independent prognostic effect of markers, with adjustment for known prognostic factors (age, nodal status, oestrogen-receptor status, grade, and tumour size). The predictive value of markers was tested by treatment interactions for relapse-free and overall survival. 1762 patients were analysed. 21% of tumours (n=367) were HER2 amplified, 10% were TOP2A amplified (n=169), 11% showed TOP2A deleted (n=191), 23% showed Ch17CEP duplication (n=406), and 61% had high (>13·0%) Ki67 (n=1136). In univariate analyses, only HER2 amplification and TOP2A deletion were significant prognostic factors for relapse-free (hazard ratio [HR] 1·59, 95% CI 1·32–1·92, p<0·0001; and 1·52, 1·20–1·92, p=0·0006, respectively) and overall survival (1·79, 1·47–2·19, p<0·0001; and 1·62, 1·26–2·08, p=0·0002 respectively). We detected no significant interaction with anthracycline benefit for Ki67, HER2, HER1–3, or TOP2A. By contrast, in multivariate analyses, Ch17CEP duplication was associated with significant improvements in both relapse-free (HR 0·92, 95% CI 0·72–1·18 for tumours with normal Ch17CEP vs 0·52, 0·34–0·81 for tumours with abnormal Ch17CEP; p for interaction=0·004) and overall survival (0·94, 0·72–1·24 vs 0·57, 0·36–0·92; p for interaction=0·02) with anthracycline use. In women with early breast cancer receiving adjuvant chemotherapy, the most powerful predictor of benefit from anthracyclines is Ch17CEP duplication. In view of the location of HER2/TOP2A on chromosome 17, Ch17CEP duplication might explain the inconsistencies in previous studies of factors predicting benefit from anthracyclines. Cancer Research UK and the Scottish Breast Cancer Clinical Trials Group.

Background: The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. Methods: National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. Results: In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65–0.86), P <0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65–0.89), P =0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. Conclusion: Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.

White-tailed deer (Odocoileus virginianus) create positive and negative effects incurred by stakeholders throughout the midwestern United States. Knowledge of deer ecology and stakeholder values for deer are needed to match the level of acceptable impacts with the capabilities of management. To address this challenge, we 1) quantified how landscape characteristics in southwestern and south-central Michigan, USA affect the distribution and population characteristics of deer throughout agro-forested landscapes, 2) quantified factors affecting stakeholder acceptance capacity for deer, and 3) present a deer management framework based on desired levels of impacts in relation to existing conditions. We investigated ecological components by radiocollaring deer during 2001–2006 and analyzed their movements, survival, and mortality factors in landscapes with diverse land-ownerships. Sociological components were investigated through interviews and questionnaires sent to 3,520 households. Southern Michigan residents identified a visible deer herd (a perceptual cue to the naturalness of the area) as a positive impact. Concerns about deer, especially deer–vehicle collisions, were weighed against positive impacts in determining acceptable levels of deer–human interactions. Nonhunting, nonfarming rural residents, a stakeholder of increasing size and influence, perceived impacts distinct from those perceived by hunters and farmers. Small annual home ranges of yearlings–adults (77–202 ha) and fawns (60–116 ha) and high survival rates (yearling–adult = 0.40–0.94, fawns = 0.51–0.76) may be attributed to the parcelization of land, habitat quality, and positive values stakeholders hold for deer. Knowledge of the impacts perceived and the effect of impacts on acceptance capacity for deer may enable managers to develop management actions that complement existing programs and address stakeholder values. Knowledge of deer ecology, landscape characteristics, and responses of stakeholders to deer are critical for managing the impacts of white-tailed deer.

Despite the common use of Clover traps to capture white-tailed deer (Odocoileus virginianus), little published information exists quantifying trap success, trap selectivity (sex-age selection), or weather correlates of trap success. We quantified these relationships using white-tailed deer data from 3 study sites in the Lower Peninsula of Michigan, USA, during winters 2001–2007. We captured 610 deer in 8,569 trap-nights; pooled capture success was 0.07 deer/trap-night, although site-year success varied from 0.021 to 0.086. We compared sex-age classes (fawn [pooled by sex], ad M, ad F) captured with sex-age classes estimated to be available on each study site during each capture season. We used generalized linear mixed modeling to construct 19 a priori models to describe probability of capture success as a function of weather covariates (daily min. temp [° C], daily snowfall [cm], daily snow depth [cm]), Julian day, site, and year. General selection patterns included fawns captured more than expected and adult males captured less than expected; adult females were generally neutrally selected. The quasi-Akaike's Information Criterion best model within our set was described by the global model without Julian day and contained all 3 weather covariates and site-year effects. Our model provided some evidence that as daily snow depth increased, probability of capture increased; the positive effect of daily snowfall on capture probability was dependent on decreasing daily minimum temperature. Our results may be used to increase efficacy of deer capture programs by researchers and managers through informed decision-making about when to allocate effort (e.g., if extreme winter weather conditions are predicted) and when to consider alternative methods (e.g., if capture of ad M is an objective).

On Sep 26, 2007, the Appeals Board of the Pension Benefit Guaranty Corp (PBGC) issued an opinion in which it determined that a private equity fund (and each of its controlled portfolio companies) could be jointly and severally liable to the PBGC for the unfunded benefit liabilities of a pension plan that had been terminated by one of its controlled portfolio companies. Generally, the Employee Retirement Income Security Act of 1974 (ERISA) imposes joint and several liability on all members of a pension plan sponsor's \"controlled group\" upon a termination of the pension plan. While the decision by the PBGC Appeals Board involved an analysis of whether or not a specific fund was engaged in a trade or business, the facts on which the decision was based are generally applicable across the private equity industry. The PBGC's position may affect the way in which lenders conduct due diligence of ERISA liabilities of their potential borrowers, and lenders should examine their loan documents.