Label-free classification of cultured cells through diffraction imaging

Automated classification of biological cells according to their 3D morphology is highly desired in a flow cytometer setting. We have investigated this possibility experimentally and numerically using a diffraction imaging approach. A fast image analysis software based on the gray level co-occurrence matrix (GLCM) algorithm has been developed to extract feature parameters from measured diffraction images. The results of GLCM analysis and subsequent classification demonstrate the potential for rapid classification among six types of cultured cells. Combined with numerical results we show that the method of diffraction imaging flow cytometry has the capacity as a platform for high-throughput and label-free classification of biological cells

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Defending Diversity: Affirmative Action and Medical Education

Affirmative action programs of all types are under attack legally and politically. Although medical schools have not been specifically targeted their affirmative action programs like others in higher education are potentially in danger. This article examines the current legal status of affirmative action in medical education and concludes that a refurbished defense of such programs is essential if they are to survive impending judicial and political scrutiny. An analysis of existing case law and available evidence suggests that a carefully reinvigorated diversity argument is the tactic most likely to pass constitutional muster as well as the justification most likely to blunt growing public and political opposition to admissions policies that take race and ethnicity into consideration. Originally published American Journal of Public Health Vol. 89 No. 8 Aug 199

Improving the System for Protecting Human Subjects: Counteracting IRB "Mission Creep" Unit Contributors College of Law College of Liberal Arts and Sciences Offi ce of the Vice Chancellor for Research The Center for Advanced Study Project Steering Committe

1 Our system of research self-regulation, designed to provide internal checks and balances for those who participate in research involving human subjects, is under considerable stress. Study after study recently has reported that this is a system "in crisis," "in jeopardy," and in need of thoughtful re-examination. Much of this crisis has been caused by what we call mission creep, in which the workload of IRBs has expanded beyond their ability to handle effectively. Mission creep is caused by rewarding wrong behaviors, such as focusing more on procedures and documentation than diffi cult ethical questions; unclear defi nitions, which lead to unclear responsibilities; efforts to comply with unwieldy federal requirements even when research is not federally funded; exaggerated precautions to protect against program shutdowns; and efforts to protect against lawsuits. Honest IRB specialists admit that they operate under constant concern about the one case in a thousand that might slip through review -with the consequence that the other 999 receive exaggerated reviews and risk rejection in an effort to err on the side of caution. As a consequence, mission creep is causing IRBs to lose the respect and "buy-in" of the very people they are meant to regulate; they are misdirecting their energies, threatening both academic and fi rst amendment freedoms; and most importantly, mission creep is taking needed resources from the most risky research, which truly does need IRB oversight. Following an invitational, national, interdisciplinary conference held at the University of Illinois, recommendations were formulated to strengthen and reinvigorate the functioning of the internal review boards (Institutional Review Boards or IRBs) at universities and research centers and to gather accurate data on the scope of the problem. Our recommendations focus on fi elds and methodologies of coverage, and they apply primarily to research outside the biomedical arena. We recommend collecting data. The greatest irony of the entire IRB debate is how little of it is informed by actual, reliable research about the facts of the problem. Experts from across the nation have identifi ed very few studies that could even provide accurate descriptive national data (numbers of cases reviewed; numbers of serious abuses; etc.), let alone a more systematic examination of effort and effectiveness of the IRB system. We propose gathering information, both examples of good practices and examples of poor practices. We suggest the latter because the rumors and stories that make their way through the academic or national grapevine are, of course, the most sensationalistic or outrageous -cases where abuses have been most egregious and the punishments or censure have been particularly severe. Such a clearing house of information will ensure that the examples of practices that reduce bureaucratic overhead in ways that still comply with ethical and regulatory mandates are shared and will provide information helpful to other institutions seeking to improve procedures as well as substantive ethical oversight. We also call for refi nements to our regulatory system that will provide a set of regulations designed for non-biomedical research. This will enable IRBs to direct attention to the areas of greatest risk, while intentionally scaling back oversight in areas of lesser risk. IRBs need examples of methodologies that have warranted IRB oversight and those that are exempt. These examples will enable IRBs to determine such things as what is meant by risk and harm, how practice differs from research, and when a subject needs to be kept anonymous and when that is not required. These refi ned regulations would provide appeal procedures, guidelines specifi c to social sciences and humanities proposals, and lists of approved exemptions, among other things. Universities might develop different tracks and methods by which to review research proposals, tailoring the review process depending on such criteria as the fi eld and methods of research, as well as the vulnerability of the subjects. This process would allow us to discard the current "one-size-fi ts-all" approach that relies so heavily on criteria and procedures developed for biomedical research. We recommend removing some kinds of activity from IRB review altogether. We recommend focusing on those areas of research that pose the greatest risk, such as biomedical research, while removing or reducing scrutiny of many fi elds within the social sciences and humanities that pose minimal risk. Some fi elds, such as journalism and ethnography, and methods, such as oral history, have their own, well-established sets of ethical guidelines and appeal procedures. In addition, they pose virtually no risk to the subjects. In the case of journalism, where a subject might be harmed with the exposure of their activities, as in the case of President Nixon and Watergate, the goal is to benefi t the greater good, not the individual. This is another argument for removing journalism and similar fi elds from IRB oversight. In conclusion, members of the invited conference and others affected by the IRB system recognize that the system, if not broken, is seriously straining at the seams. It is imperative that we have a respected and effective system in place to protect human research subjects, so that much-needed research into the causes and prevention of disease and other research expanding the boundaries of knowledge can proceed. We hope that this White Paper will further the discussion about what reasonable procedures can be instituted to help get IRBs back on track and do what they were originally meant to do -protect the rights and welfare of human subjects, while allowing the research enterprise to progress and its benefi ts to society to accrue

The American Association for the Surgery of Trauma Severity Grade is valid and generalizable in adhesive small bowel obstruction

BACKGROUND The American Association for the Surgery of Trauma (AAST) anatomic severity grading system for adhesive small bowel obstruction (ASBO) was validated at a single institution. We aimed to externally validate the AAST ASBO grading system using the Eastern Association for the Surgery of Trauma multi-institutional small bowel obstruction prospective observational study. METHODS Adults (age 18) with (ASBO) were included. Baseline demographics, physiologic parameters (heart rate, blood pressure, respiratory rate), laboratory tests (lactate, hemoglobin, creatinine, leukocytosis), imaging findings, operative details, length of stay, and Clavien-Dindo complications were collected. The AAST ASBO grades were assigned by two independent reviewers based on imaging findings. Kappa statistic, univariate, and multivariable analyses were performed. RESULTS There were 635 patients with a mean (SD) age of 61 17.8 years, 51% female, and mean body mass index was 27.5 +/- 8.1. The AAST ASBO grades were: grade I (n = 386, 60.5%), grade II (n = 135, 21.2%), grade III (n = 59, 9.2%), grade IV (n = 55, 8.6%). Initial management included: nonoperative (n = 385; 61%), laparotomy (n = 200, 31.3%), laparoscopy (n = 13, 2.0%), and laparoscopy converted to laparotomy (n = 37, 5.8%). An increased median [IQR] AAST ASBO grade was associated with need for conversion to an open procedure (2 [1-3] vs. 3 [2-4], p = 0.008), small bowel resection (2 [2-2] vs. 3 [2-4], p < 0.0001), postoperative temporary abdominal closure (2 [2-3] vs. 3 [3-4], p < 0.0001), and stoma creation (2 [2-3] vs. 3 [2-4], p < 0.0001). Increasing AAST grade was associated with increased anatomic severity noted on imaging findings, longer duration of stay, need for intensive care, increased rate of complication, and higher Clavien-Dindo complication grade. CONCLUSION The AAST ASBO severity grading system has predictive validity for important clinical outcomes and allows for standardization across institutions, providers, and future research focused on optimizing preoperative diagnosis and management algorithms. LEVEL OF EVIDENCE Prognostic, level III

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.Peer reviewe