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RATIONALE: Lung clearance index (LCI) has good intravisit repeatability with better sensitivity in detecting lung disease on computed tomography scan compared with forced expiratory volume in 1 second (FEV(1)) in adults with bronchiectasis. Alternative multiple-breath washout parameters have not been systematically studied in bronchiectasis. OBJECTIVES: To determine the validity, repeatability, sensitivity, specificity, and feasibility of standard LCI (LCI(2.5)), shortened LCI (LCI(5.0)), ventilation heterogeneity arising within proximal conducting airways (S(cond)VT), and ventilation heterogeneity arising within the acinar airways (S(acin)VT) in a cross-sectional observational cohort of adults with bronchiectasis. METHODS: Cross-sectional multiple-breath nitrogen washout data (Exhalyzer D; Eco Medics AG) from 132 patients with bronchiectasis across five United Kingdom centers (BronchUK Clinimetrics study) and 88 healthy control subjects were analyzed. RESULTS: Within-test repeatability (mean coefficient of variation) was 2) but in normal FEV(1) (z-score

When escapee farmed Atlantic salmon Salmo salar interbreed with wild fish, the introgression of maladaptive genes can lower wild population productivity and alter key life history traits. To date, only a few European studies have compared wild, farm, and hybrid salmon under common conditions in the wild, isolating the influence of genetics on survival and fitness-related traits. Here, we examined the performance of experimentally derived Atlantic salmon fry from 4 cross types (wild, farm, and reciprocal F1 hybrids) during the first summer of growth at 3 locations in southern Newfoundland. Overall survival was high, with the cross type rank order consistent across sites (mean percent recaptured: wild-mother hybrids 26.2% ≈ wild 26.0% > farm 19.2% > farm-mother hybrids 12.8%). Wild fish were smaller than wild-mother hybrids and farm fish, though differed less in size from farm-mother hybrids. At 2 out of 3 sites, wild-mother hybrids were larger than wild and farm-mother hybrid fish but had only a small size advantage over farm fish. Shape differences were small and mainly related to body depth, with the largest differences between wild and farm fish. Wild-mother hybrids had fewer parr marks than other cross types at a single site, and though differences in the size of marks were minimal, farm fish tended to have the narrowest marks. Overall, these results show that genetic differences exist for fitness-related traits among wild, farm, and hybrid juveniles, even over short temporal scales and under favourable environmental conditions, and may contribute to patterns of reduced farm-mother hybrid and feral farm survival in the wild.

Supplementary Figure S1. Distribution of HER2 expression (measured by HERmark) in all patients (left) and in 3+ IHC cohort patients (right). All patient: n=324; IHC3+: n=232.

Supplementary Table S1. Multivariate Models in the IHC 3+ Subgroup

Purpose: Expression of p95HER2 has been associated with resistance to trastuzumab-based therapy in patients with metastatic breast cancer. Conversely, high levels of HER2 have been linked with increased clinical benefit from anti-HER2 therapy. In this work, we aimed to investigate whether the levels of p95HER2 and HER2 can predict response to anti-HER2 therapy in patients with breast cancer.Experimental Design: We measured p95HER2 and HER2 by VeraTag and HERmark, respectively, in primary tumors of patients enrolled in the neoadjuvant phase III study NeoALTTO and correlated these variables with pathologic complete response (pCR) and progression-free survival (PFS) following lapatinib (L), trastuzumab (T), or the combination of both agents (L+T).Results: A positive correlation between p95HER2 and HER2 levels was found in the 274 cases (60%) in which quantification of both markers was possible. High levels of these markers were predictive for pCR, especially in the hormone receptor (HR)–positive subset of patients. High HER2 expression was associated with increased pCR rate upon L+T irrespective of the HR status. To examine whether the levels of either p95HER2 or HER2 could predict for PFS in patients treated with lapatinib, trastuzumab or L+T, we fit to the PFS data in Cox models containing log2(p95HER2) or log2(HER2). Both variables correlated with longer PFS.Conclusions: Increasing HER2 protein expression correlated with increased benefit of adding lapatinib to trastuzumab. HER2 expression is a stronger predictor of pCR and PFS than p95HER2 for response to lapatinib, trastuzumab and, more significantly, L+T. Clin Cancer Res; 21(3); 569–76. ©2014 AACR.

Supergenes are sets of genes that are inherited as a single marker and encode complex phenotypes through their joint action. They are identified in an increasing number of organisms, yet their origins and evolution remain enigmatic. In Atlantic cod, four megabase-scale supergenes have been identified and linked to migratory lifestyle and environmental adaptations. Here we investigate the origin and maintenance of these four supergenes through analysis of whole-genome-sequencing data, including a new long-read-based genome assembly for a non-migratory Atlantic cod individual. We corroborate the finding that chromosomal inversions underlie all four supergenes, and we show that they originated at different times between 0.40 and 1.66 million years ago. We reveal gene flux between supergene haplotypes where migratory and stationary Atlantic cod co-occur and conclude that this gene flux is driven by gene conversion, on the basis of an increase in GC content in exchanged sites. Additionally, we find evidence for double crossover between supergene haplotypes, leading to the exchange of an ~275 kilobase fragment with genes potentially involved in adaptation to low salinity in the Baltic Sea. Our results suggest that supergenes can be maintained over long timescales in the same way as hybridizing species, through the selective purging of introduced genetic variation.