Experiments from unfinished Registered Reports in the Reproducibility Project: Cancer Biology.

As part of the Reproducibility Project: Cancer Biology, we published Registered Reports that described how we intended to replicate selected experiments from 29 high-impact preclinical cancer biology papers published between 2010 and 2012. Replication experiments were completed and Replication Studies reporting the results were submitted for 18 papers, of which 17 were accepted and published by eLife with the rejected paper posted as a preprint. Here, we report the status and outcomes obtained for the remaining 11 papers. Four papers initiated experimental work but were stopped without any experimental outcomes. Two papers resulted in incomplete outcomes due to unanticipated challenges when conducting the experiments. For the remaining five papers only some of the experiments were completed with the other experiments incomplete due to mundane technical or unanticipated methodological challenges. The experiments from these papers, along with the other experiments attempted as part of the Reproducibility Project: Cancer Biology, provides evidence about the challenges of repeating preclinical cancer biology experiments and the replicability of the completed experiments.

Anatomic Reasons for Failure to Visualize the Appendix With Graded Compression Sonography: Insights From Contemporaneous CT.

OBJECTIVE: The purpose of this study is to identify the anatomic locations of appendixes on CT when graded compression sonography fails to visualize the appendix. MATERIALS AND METHODS: The study included 197 patients with suspected appendicitis whose appendixes were not visualized on graded compression sonography performed with typically used transducers of at least 10 MHz, who underwent CT within 48 hours following graded compression sonography, and who had available either pathologic examination following surgery or 6-week follow-up if surgery was not performed. Appendixes were retrospectively localized using four transverse quadrants (including the posteromedial quadrant) centered on the ileocecal valve and projected vertically, the craniocaudal level relative to the iliac crests, and the depth of the appendix as measured from the surface of the skin. Data were assessed using the Fisher exact test, t test, multinomial test, binomial distribution, ANOVA, and linear regression. RESULTS: Appendixes were most frequently located in the posteromedial quadrant (123 of 197 patients [62.4%]; 95% CI, 55.3-69.2%) at a statistically significantly greater frequency than that expected by chance (p < 0.00001). Appendixes were located above the iliac crests in 19.8% of patients (39/197; 95% CI, 14.5-26.1%) and at depths exceeding the penetration of typical transducers of at least 10 MHz in 19.3% of patients (38/197; 95% CI, 14.0-25.5%). All appendixes (95% CI, 98.1-100.0%) were located within the range of 6-MHz transducers. CONCLUSION: Appendixes that are not visualized on graded compression sonography are most frequently located in the posteromedial quadrant and are often located above the iliac crests or at depths too great for visualization with typically used transducers of at least 10 MHz. Accordingly, when the appendix is not visualized on graded compression sonography, targeted scanning of the posteromedial quadrant and the region above the iliac crests, and scanning with 6-MHz transducers, may enable visualization of the appendix and are recommended additions to scanning protocols.

Benign Gynecologic Conditions of the Uterus.

In this article, the authors review the anatomy, pathophysiology, MR imaging features, and diagnostic criteria for benign uterine conditions, including adenomyosis, uterine leiomyomas, retained products of conception, and uterine arteriovenous malformations. Pearls, pitfalls, and variants are discussed for each entity as well as important imaging features that can affect management decisions.

When Timing Is Everything: Are Placental MRI Examinations Performed Before 24 Weeks' Gestational Age Reliable?

OBJECTIVE: The objective of our study was to determine if placental MRI examinations performed for the detection of abnormal placentation earlier than 24 weeks' gestational age (GA) are more or less reliable than examinations performed at a later GA. MATERIALS AND METHODS: Two radiologists blinded to clinical, surgical, and pathologic reports retrospectively and independently reviewed 69 placental MRI examinations for nine imaging signs associated with abnormal placentation. A consensus of the suspicion of abnormal placentation (including accreta, increta, or percreta) was determined using a 5-point (low to high suspicion) Likert scale and compared with pathologic or surgical findings or both. RESULTS: Seventeen placental MRI examinations were performed at GA 14-23 weeks, and 52 placental MRI examinations were performed at GA 24-41 weeks. Reviewer agreement (Cronbach alpha) among the nine imaging signs was 0.86 (95% CI, 0.72-0.92) and 0.92 (95% CI, 0.92-0.94) for MRI examinations at GA 14-23 weeks and GA 24-41 weeks, respectively. Pathologic or surgical evidence of abnormal placentation was found in 41% and 65% of the cases between GA 14-23 weeks and GA 24-41 weeks, respectively. The AUC for the MRI-based consensus score and the presence of abnormal placentation for GA 14-23 weeks was 0.49 (95% CI, 0.21-0.78) compared with 0.92 (95% CI, 0.83-1.0) for GA 24-41 weeks (p = 0.002). CONCLUSION: Placental MRI examinations performed before 24 weeks' GA unreliably predict abnormal placentation.

Normal epiphyseal cartilage measurements in the knee in children: an alternative sonographic approach.

OBJECTIVES: The purpose of this study was to validate previously reported distal femoral cartilage measurements in healthy children of different ages using an alternative sonographic imaging plane and patient position than previously reported and to provide preliminary proximal tibial epiphyseal cartilage measurements in healthy children. METHODS: Distal femoral and proximal tibial epiphyseal cartilage thickness was measured using sonography in a cohort of healthy children based on a coronal image at the medial aspect of the femorotibial joint with the knee in 30° of flexion. The average of 3 measurements of femoral and tibial epiphyseal cartilage was obtained and correlated with age and sex. Femoral epiphyseal cartilage measurements were compared to recently reported measurements at the patellofemoral joint. RESULTS: Sixty children (31 boys and 29 girls; newborn to 21 years; mean, 9 years; median, 7 years 11 months) were imaged. Seventy-four percent of distal femoral cartilage epiphyseal measurements fell into the 95% confidence intervals predicted by previously published reports. At age ranges outside those previously reported, there was less concordance between measured cartilage thickness values and those predicted. CONCLUSIONS: Values of distal femoral epiphyseal cartilage thickness measured by sonography of the femorotibial joint are similar to those reported at the patellofemoral joint. We propose that femoral epiphyseal cartilage thickness be measured on the basis of a coronal image at the medial femorotibial joint. This technique requires less knee flexion, which may prove advantageous when evaluating cartilage in patients with joint inflammation and a limited range of motion. It also allows concurrent measurement of tibial epiphyseal cartilage and thus provides another parameter for assessing cartilage loss.

Detection of active disease in juvenile idiopathic arthritis: sensitivity and specificity of the physical examination vs ultrasound.

OBJECTIVE: To determine sensitivity and specificity of the physical examination (PE) for identifying synovitis in the knee and ankle joints of children with juvenile idiopathic arthritis (JIA), and to identify cases in which ultrasound (US) screening augments the PE. METHODS: Nineteen patients with JIA were referred for US. Both knees and ankles were examined using US with and without power Doppler. Active arthritis on PE was defined as (1) non-bony swelling or (2) limitation of motion with either pain on motion or tenderness to palpation. Active arthritis on US was defined as synovial hyperplasia, effusion, or increased vascularity on power Doppler scan. RESULTS: There was agreement between US and PE in 75% of cases. PE was 64% sensitive and 86% specific for identifying active arthritis. PE was 100% specific if (1) the patient was positive for both PE criteria or (2) if arthritis was present on PE in the knees. When the PE was negative and the US was positive, 21.4% developed active disease on PE within 6 months. In cases where the PE was positive and US was negative, the joint involved was most often the ankle and frequently the subtalar joint. CONCLUSION: PE is neither highly sensitive nor specific for identifying active synovitis when compared to US, and screening with US can identify subclinical disease. In joints with both non-bony swelling and limitation of motion with pain on motion or tenderness, and in the knee joint, little additional information is gained by US. This has implications for classification and treatment of JIA.

Hereditary hemorrhagic telangiectasia and juvenile polyposis: an overlap of syndromes.

Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu syndrome) is a syndrome characterized by multiorgan telangiectases and arteriovenous malformations. A subset of patients with a mutation in the MADH4 gene on chromosome 18 exhibits an overlapping syndrome of HHT and juvenile polyposis (JPS). We present one such family. Genetic testing is warranted when either HHT or JPS is diagnosed, as early recognition of this syndrome overlap allows appropriate management of these patients.

Scatter radiation from chest radiographs: is there a risk to infants in a typical NICU?

OBJECTIVE: To evaluate the dose of scatter radiation to infants in a NICU in order to determine the minimal safe distance between isolettes. MATERIALS AND METHODS: Dose secondary to scattered radiation from an acrylic phantom exposed to vertical and horizontal beam exposures at 56 kVp was measured at 93 cm and 125 cm from the center of the phantom. This corresponds to 2 and 3 ft between standard isolettes, respectively. For horizontal exposures, the dosimeter was placed directly behind a CR plate and scatter dose at 90-degrees and 135-degrees from the incident beam was also measured. Exposures were obtained at 160 mAs and the results were extrapolated to correspond to 2.5 mAs. Four measurements were taken at each point and averaged. RESULTS: At 125 cm and 93 cm there was minimal scatter compared to daily natural background radiation dose (8.493 microGy). Greatest scatter dose obtained from a horizontal beam exposure at 135 degrees from the incident beam was still far below background radiation. CONCLUSION: Scatter radiation dose from a single exposure as well as cumulative scatter dose from numerous exposures is significantly below natural background radiation. Infants in neighboring isolettes are not at added risk from radiation scatter as long as the isolettes are separated by at least 2 ft.

Learning drives differential clustering of axodendritic contacts in the barn owl auditory system.

Computational models predict that experience-driven clustering of coactive synapses is a mechanism for information storage. This prediction has remained untested, because it is difficult to approach through time-lapse analysis. Here, we exploit a unique feature of the barn owl auditory localization pathway that permits retrospective analysis of prelearned and postlearned circuitry: owls reared wearing prismatic spectacles develop an adaptive microcircuit that coexists with the native one but can be analyzed independently based on topographic location. To visualize the clustering of axodendritic contacts (potential synapses) within these zones, coactive axons were labeled by focal injection of fluorescent tracer and their target dendrites labeled with an antibody directed against CaMKII (calcium/calmodulin-dependent protein kinase type II, alpha subunit). Using high-resolution confocal imaging, we measured the distance from each contact to its nearest neighbor on the same branch of dendrite. We found that the distribution of intercontact distances for the adaptive zone was shifted dramatically toward smaller values compared with distributions for either the maladaptive zone of the same animals or the adaptive zone of normal juveniles, which indicates that a dynamic clustering of contacts had occurred. Moreover, clustering in the normal zone was greater in normal juveniles than in prism-adapted owls, indicative of declustering. These data demonstrate that clustering is bidirectionally adjustable and tuned by behaviorally relevant experience. The microanatomical configurations in all zones of both experimental groups matched the functional circuit strengths that were assessed by in vivo electrophysiological mapping. Thus, the observed changes in clustering are appropriately positioned to contribute to the adaptive strengthening and weakening of auditory-driven responses.