Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology.

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs.

Diabetes or war? Incidence of and indications for limb amputation in Lebanon, 2007.

Chronic diseases such as diabetes and vascular disease are a major public health problem in Lebanon, where primary care is not well developed. This study aimed to describe the incidence and indications for limb amputation in Lebanon and identify associated factors (age, sex, level of surgery, length of hospital stay). There were 1.6 amputations per 10 000 persons. The rate of amputation was highest in southern Lebanon at 3.8 per 10 000. The most important indication for surgery was diabetes (59%). Diabetic patients were older (mean age 73 years versus 30 years), more likely to have major surgery (OR = 7.87; 95% CI: 2.83-21.9) and stay in hospital longer (RR = 4.56, 95% CI: 2.41-8.64) than patients with trauma-related amputation. Diabetes prevention, detection and management should be prioritized in any attempt to reduce the current incidence of amputation in Lebanon.

Diabetes or war? Incidence of and indications for limb amputation in Lebanon, 2007

Chronic diseases such as diabetes and vascular disease are a major public health problem in Lebanon, where primary care is not well developed. This study aimed to describe the incidence and indications for limb amputation in Lebanon and identify associated factors [age, sex, level of surgery, length of hospital stay]. There were 1.6 amputations per 10 000 persons. The rate of amputation was highest in southern Lebanon at 3.8 per 10 000. The most important indication for surgery was diabetes [59%]. Diabetic patients were older [mean age 73 years versus 30 years], more likely to have major surgery [OR = 7.87; 95% CI: 2.83-21.9] and stay in hospital longer [RR = 4.56, 95% CI: 2.41-8.64] than patients with trauma-related amputation. Diabetes prevention, detection and management should be prioritized in any attempt to reduce the current incidence of amputation in Lebanon

Interocular transfer of the movement aftereffect in central and peripheral vision of people with strabismus.

PURPOSE: To compare binocularity in central and peripheral vision of people with early-onset strabismus and people with normal binocular vision. METHODS: Ten subjects with early-onset strabismus, and nine subjects with normal binocular vision were tested. To assess binocularity, interocular transfer (IOT) of a rotary movement aftereffect (MAE) was measured. The MAE stimuli were either confined to the central 2.8 degrees of the visual field or were presented 10 degrees into peripheral vision. RESULTS: In peripheral vision, there was no significant difference in IOT for the two groups of subjects. In central vision, there was a significant decrease of IOT in subjects with early-onset strabismus. Their IOT was, however, significantly greater than zero. CONCLUSIONS: Early-onset strabismus appears to spare binocularity in peripheral vision but reduces it in central vision. It does not abolish binocularity assessed by IOT of MAE, suggesting that some binocular connections survive early-onset strabismus, even in central vision.