Analyzing patterns of staining in immunohistochemical studies: application to a study of prostate cancer recurrence.

BACKGROUND: Immunohistochemical studies use antibodies to stain tissues with the goal of quantifying protein expression. However, protein expression is often heterogeneous resulting in variable degrees and patterns of staining. This problem is particularly acute in prostate cancer, where tumors are infiltrative and heterogeneous in nature. In this article, we introduce analytic approaches that explicitly consider both the frequency and intensity of tissue staining. METHODS: Compositional data analysis is a technique used to analyze vectors of unit-sum proportions, such as those obtained from soil sample studies or species abundance surveys. We summarized specimen staining patterns by the proportion of cells staining at mild, moderate, and intense levels and used compositional data analysis to summarize and compare the resulting staining profiles. RESULTS: In a study of Syndecan-1 staining patterns among 44 localized prostate cancer cases with Gleason score 7 disease, compositional data analysis did not detect a statistically significant difference between the staining patterns in recurrent (n = 22) versus nonrecurrent (n = 22) patients. Results indicated only modest increases in the proportion of cells staining at a moderate intensity in the recurrent group. In contrast, an analysis that compared quantitative scores across groups indicated a (borderline) significant increase in staining in the recurrent group (P = 0.05, t test). CONCLUSIONS: Compositional data analysis offers a novel analytic approach for immunohistochemical studies, providing greater insight into differences in staining patterns between groups, but possibly lower statistical power than existing, score-based methods. When appropriate, we recommend conducting a compositional data analysis in addition to a standard score-based analysis.     

UK guidelines for the management of bone sarcomas

This document is an update of the British Sarcoma Group guidelines published in 2010. The aim is to provide a reference standard for the clinical care of patients in the UK with bone sarcomas. Recent recommendations by the European Society of Medical Oncology, The National Comprehensive Cancer Network and The National Institute for Health and Care Excellence have been incorporated, and the literature since 2010 reviewed. The standards represent a consensus amongst British Sarcoma Group members in 2015. It is acknowledged that these guidelines will need further updates as care evolves. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and that patients with clinico-radiological findings suggestive of a primary bone tumour at any site in the skeleton should be referred to a specialist centre and managed by a fully accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow up schedules are suggested.     

Transepidermal Water Loss in Newborns Within the First 24 Hours of Life: Baseline Values and Comparison with Adults

The measurement of transepidermal water loss (TEWL) is important for evaluating the integrity of the barrier function of the stratum corneum. Normal TEWL values in healthy adults and in children ages 2 and older are well known, but few studies have been performed in infants and neonates. TEWL in healthy neonates younger than 24 hours old was assessed and compared with that of an adult study population. We also studied possible correlations between this parameter, gestational age, and mode of delivery. A prospective study was conducted in healthy newborns. The areas tested were the volar forearm and the popliteal fossa. Ninety‐nine healthy newborns were enrolled and 33 healthy adults were analyzed as controls. Statistically significant differences were noted between newborns and adults in TEWL (p < 0.01). Newborns had a much higher mean TEWL than adults. Differences in the morphology and physiology between newborn and mature skin can explain the higher TEWL in newborns. Higher TEWL could also be due to the sudden functional adaptation of the skin immediately after delivery, when the newborn transits from a liquid to the dry, gaseous extrauterine environment. Functional evaluation of the neonatal skin barrier is important mainly because maintaining skin integrity facilitates cutaneous adaptation.     

Looking at a predator with the left or right eye: Asymmetry of response in lizards

Studies carried out with the common wall lizard (Podarcis muralis) revealed preferential use of the left eye during responses to predatory threat in laboratory settings and in the wild. Here we tested lizards under monocular conditions of vision, using temporary eye-patching. Lizards were facing a (simulated) predatory threat laterally, from the side of the non-patched eye. Results showed that lizards with the left eye uncovered during predatory threat used the left eye to monitor the predator, whereas lizards with the right eye uncovered nonetheless tried to use the covered left eye. Moreover, lizards frequently tried to change the eye exposition, making a body C-bend behaviour. Right-eyed lizards showed more frequent and faster C-bending responses than left-eyed lizards, trying to monitor the predator with the left eye even though it was patched. Results fit with asymmetries in spontaneous eye use observed in laboratory conditions and in the wild in this species, confirming that structures located on the right side of the brain (mainly served by the left eye) predominantly attend to predatory threat.     

Retinal Laser Damage Thresholds as a Function of Image Diameter

The eyes of rhesus monkeys were exposed to argon (514.5 nm) and ruby (694.3 nm) laser irradiation using various retinal image diameters which were estimated by microphotometric techniques. The experimental design for both wavelengths produced image diameters of 40μ to 50μ for the “minimal” case and approximately 500μ to 1,000μ for the larger irradiance series employed. Extramacular retinal exposure sites were examined by ophthalmoscopic and histopathological techniques. Flat preparations of the pigmented epithelium and sensory layers of the retina were utilized in the confirmation of damage at low power levels. All data were statistically analyzed to establish trends, and results were compared for the wavelengths employed. Results indicate that retinal damage is primarily dependent on energy distribution as a function of image diameter and exposure duration.