Segmentation, Reconstruction, and Analysis of Blood Thrombus Formation in 3D 2-Photon Microscopy Images

We study the problem of segmenting, reconstructing, and analyzing the structure growth of thrombi (clots) in blood vessels in vivo based on 2-photon microscopic image data. First, we develop an algorithm for segmenting clots in 3D microscopic images based on density-based clustering and methods for dealing with imaging artifacts. Next, we apply the union-of-balls (or alpha-shape) algorithm to reconstruct the boundary of clots in 3D. Finally, we perform experimental studies and analysis on the reconstructed clots and obtain quantitative data of thrombus growth and structures. We conduct experiments on laser-induced injuries in vessels of two types of mice (the wild type and the type with low levels of coagulation factor VII) and analyze and compare the developing clot structures based on their reconstructed clots from image data. The results we obtain are of biomedical significance. Our quantitative analysis of the clot composition leads to better understanding of the thrombus development, and is valuable to the modeling and verification of computational simulation of thrombogenesis

Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease

BACKGROUND. Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals. METHODS. We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (= 30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period. RESULTS. Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1 beta plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1 beta plasma levels. CONCLUSION. We demonstrated that IL-1 beta inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1 beta plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1 beta inhibition is warranted

The Effect of Dimethyl Sulfoxide on Macromolecular Structures

poster abstractHemorrhagic and thrombotic disorders are a consequence of the body’s inability to form effective blood clots. A major component of the hemostatic clot is a polymerized fibrin network. The network is formed by polymerization of fibrin which is generated by the enzymatic processing of the precursor fibrinogen in blood by the coagulation enzyme thrombin. In our study we investigated how dimethyl sulfoxide (DMSO) effects the formation of the fibrin mesh. These networks were grown over micron-sized pores in polymer membranes with varying concentrations of DMSO. The samples were characterized optically using confocal and differential interference contrast microscopies. Image analysis was performed to determine the structural changes in the fibrin organization

Missing the forest (plot) for the trees? A critique of the systematic review in tobacco control

<p>Abstract</p> <p>Background</p> <p>The systematic review (SR) lies at the core of evidence-based medicine. While it may appear that the SR provides a reliable summary of existing evidence, standards of SR conduct differ. The objective of this research was to examine systematic review (SR) methods used by the Cochrane Collaboration ("<it>Cochrane</it>") and the Task Force on Community Preventive Services ("the <it>Guide</it>") for evaluation of effectiveness of tobacco control interventions.</p> <p>Methods</p> <p>We searched for all reviews of tobacco control interventions published by Cochrane (4^thquarter 2008) and the <it>Guide</it>. We recorded design rigor of included studies, data synthesis method, and setting.</p> <p>Results</p> <p>About a third of the Cochrane reviews and two thirds of the Guide reviews of interventions in the community setting included uncontrolled trials. Most (74%) Cochrane reviews in the clinical setting, but few (15%) in the community setting, provided pooled estimates from RCTs. Cochrane often presented the community results narratively. The Guide did not use inferential statistical approaches to assessment of effectiveness.</p> <p>Conclusions</p> <p>Policy makers should be aware that SR methods differ, even among leading producers of SRs and among settings studied. The traditional SR approach of using pooled estimates from RCTs is employed frequently for clinical but infrequently for community-based interventions. The common lack of effect size estimates and formal tests of significance limit the contribution of some reviews to evidence-based decision making. Careful exploration of data by subgroup, and appropriate use of random effects models, may assist researchers in overcoming obstacles to pooling data.</p

The Effect of Free Amino Acids on Fibrin Formation

poster abstractFibrinogen, a plasma protein, is a main component of blood clot formation. In the event of an injury, blood loss is hindered through a process that forms a thrombus by conversion of fibrinogen to fibrin induced by activation of the enzyme thrombin. The fibrin network structure depends on the concentration of thrombin, as expected, but is also highly influenced by its environment during formation. In particular, we find that fibrin formation is altered in the presence of zwitterions. Zwitterions are dipolar molecules, typically highly polarizable, exhibiting both a positive and a negative charge depending on the pH of the solution. Amino acids are highly abundant zwitterions in biological materials. In this study we measured by visible/UV-spectroscopy the effects of various types of amino acids on the rate of fibrin network formation. We show that the electrical charge and type of amino acid, such as lysine, glycine and arginine, inhibits or promotes formation of fibrin networks. Such an ability to decrease or increase the rate of coagulation can be valuable in the treatment of patients suffering from hemostatic and thrombotic disorders

Can We Reduce Eating Disorder Risk Factors in Female College Athletes? A Randomized Exploratory Investigation of Two Peer-Led Interventions

Female athletes are at least as at risk as other women for eating disorders (EDs) and at risk for the female athlete triad (i.e., inadequate energy availability, menstrual disorders, and osteoporosis). This study investigated whether two evidence-based programs appear promising for future study if modified to address the unique needs of female athletes. Athletes were randomly assigned to athlete-modified dissonance prevention or healthy weight intervention (AM-HWI). ED risk factors were assessed pre/post-treatment, and 6-week and 1-year follow-up. Results (analyzed sample, N = 157) indicated that both interventions reduced thin-ideal internalization, dietary restraint, bulimic pathology, shape and weight concern, and negative affect at 6 weeks, and bulimic pathology, shape concern, and negative affect at 1 year. Unexpectedly we observed an increase in students spontaneously seeking medical consultation for the triad. Qualitative results suggested that AM-HWI may be more preferred by athletes

An exploration of the factor structure of executive functioning in children

There has been considerable debate and interest in the factor structure of Executive Functioning. For children and young people, there is evidence for a progression from a single factor to a more differentiated structure, although the precise nature of these factors differs between investigations. The purpose of the current study was to look at this issue again with another sample, and try to understand possible reasons for previous differences between investigations. In addition, we examined the relationship between less central EF tasks, such as fluency and planning, to the more common tasks of updating/executive working memory, inhibition and switching/shifting. A final aim was to carry out analyses which are relevant to the debate about whether EF is influenced by language ability, or language ability is influenced by EF. We reasoned that if language ability affects EF, a factor analysis of verbal and non-verbal EF tasks might result in the identification of a factor which predominantly contains verbal tasks and a factor that predominately contains non-verbal tasks. Our investigation involved 128 typically developing participants (mean age 10:4) who were given EF assessments that included verbal and non-verbal versions of each task: executive working memory; switching; inhibition; fluency; and planning. Exploratory factor analyses on executive working memory, switching and inhibition produced a structure consisting of inhibition in one factor and the remaining tasks in another. It was decided to exclude verbal planning from the next analyses of all the ten tasks because of statistical considerations. Analysis of the remaining nine EF tasks produced two factors, one factor containing the two inhibition tasks, and another factor that contained all the other tasks (switching, executive working memory, fluency and non-verbal planning). There was little evidence that the verbal or non-verbal elements in these tasks affected the factor structure. Both these issues are considered in the discussion, where there is a general evaluation of findings about the factor structure of EF. Data availability. The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher