Automated clarity assessment of retinal images using regionally based structural and statistical measures

An automated image analysis system for application in mass medical screening must assess the clarity of the images before analysing their content. This is the case in grading for diabetic retinopathy screening where the failure to assess clarity could result in retinal images of people with retinopathy being erroneously classed as normal. This paper compares methods of clarity assessment based on the degradation of visible structures and based on the deviation of image properties outside expected norms caused by clarity loss. Vessel visibility measures and statistical measures were determined at locations in the image which have high saliency and these were used to obtain an image clarity assessment using supervised classification. The usefulness of the measures as indicators of image clarity was assessed. Tests were performed on 987 disc-centred and macula-centred retinal photographs (347 with inadequate clarity) obtained from the English National Screening Programme. Images with inadequate clarity were detected with 92.6% sensitivity at 90% specificity. In a set of 2000 macula-centred images (200 with inadequate clarity) from the Scottish Screening Programme, inadequate clarity was detected with 96.7% sensitivity at 90% specificity. This study has shown that structural and statistical measures are equally useful for retinal image clarity assessment.     

Humoral innate immune response and disease

The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathology. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies.     

Azacitidine favorably modulates PSA kinetics correlating with plasma DNA LINE-1 hypomethylation in men with chemonaïve castration-resistant prostate cancer

Background

Azacitidine is a hypomethylating agent that activates genes repressed by promoter methylation. Preclinically, demethylating agents reverse resistance of prostate cancer to androgen ablation. A phase II trial evaluated azacitidine for men with castration-resistant prostate cancer (CRPC) progressing on combined androgen blockade (CAB).

Methods

Chemonaïve patients with CRPC on CAB and PSA-doubling time (DT) < 3 months were eligible. The primary endpoint was prolongation of PSA-DT to ≥3 months. Correlation of biologic activity (fetal hemoglobin, plasma DNA LINE-1 methylation) with prolongation of PSA-DT was tested. CAB was continued and azacitidine 75 mg/m² was administered subcutaneously on days 1–5 of each 28-day cycle up to 12 cycles or until clinical progression/intolerable toxicities.

Results

Thirty-six patients were enrolled, 80.6% had metastatic disease, and 34 were evaluable. A PSA-DT ≥ 3 months was attained in 19 patients (55.8%). Overall median PSA-DT was significantly prolonged compared to baseline (2.8 vs. 1.5 months, P < 0.01). Fourteen patients had some PSA decline during therapy and 1 patient had a ≥30% decline compared with baseline. The median clinical progression-free survival was 12.4 weeks. Grade 3 toxicities included fatigue (12%), and neutropenia (6%), with 4 patients discontinuing due to toxicities. A trend in decreasing plasma DNA LINE-1 methylation was seen with longer treatment duration (P = 0.06), which significantly correlated with prolongation of PSA-DT (P = 0.02).

Conclusions

Azacitidine favorably modulates PSA kinetics in chemonaïve CRPC that correlates with decreasing plasma DNA LINE-1 methylation. Given the excellent tolerability, further development of azacitidine for CRPC may be warranted, with exploration of combination regimens.     

Identifying and aligning expectations in a mentoring relationship

The mentoring relationship between a scholar and their primary mentor is a core feature of research training. Anecdotal evidence suggests this relationship is adversely affected when scholar and mentor expectations are not aligned. We examined three questions: (1) What is the value in assuring that the expectations of scholars and mentors are mutually identified and aligned? (2) What types of programmatic interventions facilitate this process? (3) What types of expectations are important to identify and align? We addressed these questions through a systematic literature review, focus group interviews of mentors and scholars, a survey of Clinical and Translational Science Award (CTSA) KL2 program directors, and review of formal programmatic mechanisms used by KL2 programs. We found broad support for the importance of identifying and aligning the expectations of scholars and mentors and evidence that mentoring contracts, agreements, and training programs facilitate this process. These tools focus on aligning expectations with respect to the scholar's research, education, professional development and career advancement as well as support, communication, and personal conduct and interpersonal relations. Research is needed to assess test the efficacy of formal alignment activities.     

Mentoring K scholars: strategies to support research mentors

The goal of this paper is to present strategies utilized to support K scholar research mentors. K scholars are generally assistant professors who are close to developing independent research programs. Of all the various types of mentees, K scholars offer the greatest challenges, as well as the greatest rewards, for research mentors. To see one's mentee achieve independent PI status and become an established investigator is one of the great joys of being a research mentor. Research mentors for K scholars, however, may not directly benefit from their mentoring relationship, neither in terms of obtaining data to support their research program or laboratory, nor in assistance with grants or scientific papers. There is a pressing need for the research community to address the workload, institutional expectations, and reward system for research mentors. The dearth of research mentors and role models in clinical translational science parallels the decreasing number of physicians choosing careers in clinical research. While there is limited empirical information on the effectiveness of mentor support mechanisms, this white paper concludes that providing mentor support is critical to expanding the available pool of mentors, as well as providing training opportunities for K scholars.