Citations

Abstract The determination of HER2 amplification is critical to selecting appropriate patients for HER2 targeted therapy in breast cancer. Dual in situ hybridization (DISH), an alternative to fluorescence in situ hybridization (FISH) and immunohistochemistry, is now available. To compare the FISH and DISH methods, we tested 251 samples enriched for common or difficult-to-assess HER2 anomalies. Seven samples failed DISH testing. There was a 64% (156/244) concordance between FISH and DISH by anomaly (κ = 0.58, 95% confidence interval, 0.51-0.65; P < .0001) and an 83% (203/244) concordance by amplification status (κ = 0.58; 95% confidence interval, 0.47-0.69; P < .0001). DISH resulted in lower estimates of HER2/ centromere 17 ratios than FISH, and many cases that were equivocal with FISH were normal with DISH. DISH did not detect any case with coamplification of HER2 and centromere 17. Using a cohort of difficult specimens, we observed less than 95% concordance between FISH and DISH. DISH may underestimate the HER2/chromosome 17 ratio, or FISH may overestimate this ratio.

Abstract Background: Our genome-wide association study (GWAS) of chronic lymphocytic leukemia (CLL) identified 4 highly correlated intronic variants within the IRF8 gene that were associated with CLL. These results were further supported by a recent meta-analysis of our GWAS with two other GWAS of CLL, supporting the IRF8 gene as a strong candidate for CLL risk. Methods: To refine the genetic association of CLL risk, we conducted Sanger sequencing of IRF8 in 94 CLL cases and 96 controls. We then conducted fine mapping by genotyping 39 variants (of which 10 were identified from sequencing) in 745 CLL cases and 1,521 controls. We also assessed these associations with risk of other non-Hodgkin lymphoma (NHL) subtypes. Results: The strongest association with CLL risk was observed with a common single-nucleotide polymorphism (SNP) located within the 3′ untranslated region (UTR) of IRF8 (rs1044873, log additive OR = 0.7, P = 1.81 × 10−6). This SNP was not associated with the other NHL subtypes (all P > 0.05). Conclusions: We provide evidence that rs1044873 in the IRF8 gene accounts for the initial GWAS signal for CLL risk. This association appears to be unique to CLL with little support for association with other common NHL subtypes. Future work is needed to assess functional role of IRF8 in CLL etiology. Impact: These data provide support that a functional variant within the 3′UTR of IRF8 may be driving the GWAS signal seen on 16q24.1 for CLL risk. Cancer Epidemiol Biomarkers Prev; 22(3); 461–6. ©2013 AACR.

Cardiac channelopathies are potentially lethal inherited arrhythmia syndromes and an important cause of sudden cardiac death (SCD) in young athletes. Other cardiac rhythm and conduction disturbances also may indicate the presence of an underlying cardiac disorder. The 12-lead ECG is utilised as both a screening and a diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of a pathological cardiac disease. This article describes ECG findings present in primary electrical diseases afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.

Purpose The purpose of this prospective randomized study was to compare the outcomes of arthroscopic labral repair and selective labral debridement in female patients undergoing arthroscopy for the treatment of pincer‐type or combined pincer‐ and cam‐type femoroacetabular impingement. Methods Between June 2007 and June 2009, 36 female patients undergoing arthroscopic hip treatment for pincer‐ or combined‐type femoroacetabular impingement were randomized to 2 treatment groups at the time of surgery: labral repair or labral debridement. The repair group comprised 18 patients with a mean age of 38; the debridement group comprised 18 patients with a mean age of 39. All patients underwent the same rehabilitation protocol postoperatively. At a minimum of 1 year, all patients were assessed using a validated Hip Outcome Score (HOS) to determine hip function, and also completed a simple subjective outcome measure. Results All 36 patients were available for follow‐up at an average time of 32 months (range, 12 to 48). In both groups, HOSs for activities of daily living (ADL) and sports improved significantly from before surgery to the final follow‐up ( P < .05). The postoperative ADL HOS was significantly better in the repair group (91.2; range, 73 to 100) compared with the debridement group (80.9; range, 42.6 to 100; P < .05). Similarly, the postoperative sports HOS was significantly greater in the repair group (88.7; range, 28.6 to 100) than in the debridement group (76.3; range, 28.6 to 100; P < .05). Additionally, patient subjective outcome was significantly better in the labral repair group ( P = .046). Conclusions Arthroscopic treatment of femoroacetabular impingement with labral repair in female patients resulted in superior improvement in hip functional outcomes compared with labral debridement. In addition, a greater number of patients in the repair group subjectively rated their hip function as normal or nearly normal after surgery compared with the labral debridement group. Level of Evidence Level I, prospective randomized study.

ABSTRACT Identification of anaerobic bacteria using phenotypic methods is often time-consuming; methods such as 16S rRNA gene sequencing are costly and may not be readily available. We evaluated 253 clinical isolates of anaerobic bacteria using the Bruker MALDI Biotyper (Bruker Daltonics, Billerica, MA) matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) system with a user-supplemented database and an on-plate formic acid-based preparation method and compared results to those of conventional identification using biochemical testing or 16S rRNA gene sequencing. A total of 179 (70.8%) and 232 (91.7%) isolates were correctly identified to the species and genus levels, respectively, using manufacturer-recommended score cutoffs. MALDI-TOF MS offers a rapid, inexpensive method for identification of anaerobic bacteria.

In this study, we compared gains in student content learning over a 10-yr period in which the introductory biology laboratory curriculum was changed in two ways: an increase of inquiry and a reduction of content. Three laboratory formats were tested: traditional 1-wk-long cookbook laboratories, two 7-wk-long inquiry laboratories, and one 14-wk-long inquiry laboratory. As the level of inquiry increased, student learning gains on content exams trended upward even while traditional content coverage taught decreased. In a quantitative assessment of content knowledge, students who participated in the 14-wk-long inquiry laboratory format outscored their peers in both 7- and 1-wk-long lab formats on Medical College Admissions Test exam questions (scores of 64.73%, 61.97%, and 53.48%, respectively, P < 0.01). In a qualitative study of student opinions, surveys conducted at the end of semesters where traditional 1-wk laboratories ( n = 167 students) were used had low response rates and predominately negative opinions (only 20% of responses were positive), whereas those who participated in 7-wk ( n = 543) or 14-wk ( n = 308) inquiry laboratories had high response rates and 71% and 96% positive reviews, respectively. In an assessment of traditional content coverage in courses, three indexes were averaged to calculate traditional forms of coverage and showed a decrease by 44% over the study period. We believe that the quantitative and qualitative data support greater student-driven inquiry in the classroom laboratory, which leads to deeper learning in fewer topic areas (less teaching) and can reap gains in scientific thinking and fundamental understanding applicable to a broader range of topic areas (more learning) in introductory biology.