Is axillary imaging for invasive lobular carcinoma accurate in determining clinical node staging?

PURPOSE: Preoperative evaluation of clinical N-stage (cN) is difficult in breast cancer patients with invasive lobular carcinoma (ILC). Our goal was to assess the predictive value of axillary imaging in ILC by comparing imaging cN and pathologic N-stage (pN). METHODS: A single-institution retrospective review was performed for newly diagnosed stage I-III ILC patients undergoing preoperative breast imaging from 2011 to 2016. Clinicopathologic factors; mammogram, MRI, and ultrasound findings; and surgical pathology data were reviewed. Sub-analysis for pN2-N3 patients was performed to determine imaging sensitivity for patients with a larger nodal disease burden. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality. RESULTS: Of the total 349 patients included, 70.5% were cN0, and 62% were pN0 (p = 0.03). For all patients, mammogram sensitivity was 7%, specificity 97%, PPV 50%, NPV 72%; ultrasound sensitivity was 26%, specificity 86%, PPV 52%, NPV 67%; MRI sensitivity was 7%, specificity 98%, PPV 80%, NPV 51%. For pN2/N3 patients, 38% were identified as cN0. Mammogram sensitivity was 10%; ultrasound 42%; MRI 65%. Pathology evaluation of N2/N3 patients indicated LN were replaced with ILC but maintained normal architecture. The average largest pathologic tumor deposit (1.5 ± 0.8 cm) correlated with average largest imaging LN size (1.4 ± 0.6 cm) (p = 0.58). CONCLUSION: A statistically significant difference between clinical and pathologic N-stage exists for ILC patients. MRI was most sensitive for identification of pN2-N3 patients and should be considered part of routine axillary imaging evaluation for ILC patients.

Genetic evidence of hybridization between Magellanic (Sphensicus magellanicus) and Humboldt (Spheniscus humboldti) penguins in the wild.

The process of hybridization between closely related species plays an important role in defining the genetic integrity and overall genetic diversity of species. The distribution range of Magellanic (Spheniscus magellanicus) and Humboldt (Spheniscus humboldti) penguins is predominantly allopatric; however, the species share a region of sympatry where they may hybridize. We analyzed four types of genetic markers (including nuclear and mitochondrial markers) to assess their utility in detecting hybridization events between Magellanic and Humboldt penguins. Genetic assessment of non-introgressed reference samples allowed us to identify three types of informative markers (microsatellites, major histocompatibility complex, and mitochondrial DNA) and detect positive evidence of introgressive hybridization in the wild. Four out of six putative hybrids showed positive evidence of hybridization, revealed by the detection of Humboldt mitochondrial DNA and Magellanic species-specific alleles from nuclear markers. Bayesian Structure analysis, including samples from the sympatric region of the species in the southern Pacific Ocean, confirmed the use of nuclear markers for detecting hybridization and genetic admixture of putative hybrids, but revealed relatively low levels of genetic introgression at the population level. These findings provide insights into the role of hybridization in regions of species sympatry and its potential consequences on the levels of genetic introgression, genetic diversity, and conservation of these penguin species.

Maize early endosperm growth and development: from fertilization through cell type differentiation.

UNLABELLED: • PREMISE OF THE STUDY: Given the worldwide economic importance of maize endosperm, it is surprising that its development is not the most comprehensively studied of the cereals. We present detailed morphometric and cytological descriptions of endosperm development in the maize inbred line B73, for which the genome has been sequenced, and compare its growth with four diverse Nested Association Mapping (NAM) founder lines.• METHODS: The first 12 d of B73 endosperm development were described using semithin sections of plastic-embedded kernels and confocal microscopy. Longitudinal sections were used to compare endosperm length, thickness, and area.• KEY RESULTS: Morphometric comparison between Arizona- and Michigan-grown B73 showed a common pattern. Early endosperm development was divided into four stages: coenocytic, cellularization through alveolation, cellularization through partitioning, and differentiation. We observed tightly synchronous nuclear divisions in the coenocyte, elucidated that the onset of cellularization was coincident with endosperm size, and identified a previously undefined cell type (basal intermediate zone, BIZ). NAM founders with small mature kernels had larger endosperms (0-6 d after pollination) than lines with large mature kernels.• CONCLUSIONS: Our B73-specific model of early endosperm growth links developmental events to relative endosperm size, while accounting for diverse growing conditions. Maize endosperm cellularizes through alveolation, then random partitioning of the central vacuole. This unique cellularization feature of maize contrasts with the smaller endosperms of Arabidopsis, barley, and rice that strictly cellularize through repeated alveolation. NAM analysis revealed differences in endosperm size during early development, which potentially relates to differences in timing of cellularization across diverse lines of maize.

The role of demographic history and selection in shaping genetic diversity of the Galápagos penguin (Spheniscus mendiculus).

Although many studies have documented the effects of demographic bottlenecks on the genetic diversity of natural populations, there is conflicting evidence of the roles that genetic drift and selection may play in driving changes in genetic variation at adaptive loci. We analyzed genetic variation at microsatellite and mitochondrial loci in conjunction with an adaptive MHC class II locus in the Galápagos penguin (Spheniscus mendiculus), a species that has undergone serial demographic bottlenecks associated with El Niño events through its evolutionary history. We compared levels of variation in the Galápagos penguin to those of its congener, the Magellanic penguin (Spheniscus magellanicus), which has consistently maintained a large population size and thus was used as a non-bottlenecked control. The comparison of neutral and adaptive markers in these two demographically distinct species allowed assessment of the potential role of balancing selection in maintaining levels of MHC variation during bottleneck events. Our analysis suggests that the lack of genetic diversity at both neutral and adaptive loci in the Galápagos penguin likely resulted from its restricted range, relatively low abundance, and history of demographic bottlenecks. The Galápagos penguin revealed two MHC alleles, one mitochondrial haplotype, and six alleles across five microsatellite loci, which represents only a small fraction of the diversity detected in Magellanic penguins. Despite the decreased genetic diversity in the Galápagos penguin, results revealed signals of balancing selection at the MHC, which suggest that selection can mitigate some of the effects of genetic drift during bottleneck events. Although Galápagos penguin populations have persisted for a long time, increased frequency of El Niño events due to global climate change, as well as the low diversity exhibited at immunological loci, may put this species at further risk of extinction.

Endometrial Scratch (Injury): Does Timing Matter?

Objective: To examine the timing of endometrial scratch in a patient's menstrual cycle and whether there is an association with subsequent implantation. Materials and methods: This study is a retrospective chart review on women, aged 18-45, seen in a reproductive endocrine clinic seeking conception. Timing of endometrial scratch was defined as proliferative (cycle day 1-9), periovulatory (CD11-16), or secretory (CD19+). All periovulatory biopsies were performed at time of oocyte retrieval in women freezing all oocytes/embryos for future use. Primary outcome of interest was positive beta-hCG within ninety days of the endometrial scratch. Results: Sixty-nine cases of endometrial scratch met the inclusion criteria. There were no statistically significant differences in baseline demographic characteristics between those who received endometrial injury in the three phases. There was no significant difference in frequency of positive beta-hCG within 90 days of endometrial scratch between the patients who received an endometrial scratch in the three phases (proliferative 65.6%, periovulatory 69.6%, secretory 64.3%; p = 0.9332). Conclusion: In contrast to prior studies which showed up to 65% decrease in implantation rate after endometrial scratch performed at time of oocyte retrieval, this study shows no significant difference in implantation when the injury is performed at the time of oocyte retrieval as compared to other phases of the menstrual cycle. Possible explanation may be that we did not perform a scratch if fresh embryo transfer was planned. As endometrial injury is associated with patient discomfort, performing the scratch while under conscious sedation for oocyte retrieval may be desirable in cycles where fresh embryo transfer is not planned. Future studies are needed to assess the validity of these findings.