Vander Lugt Research Articles

Automated segmentation of ophthalmological images by an optical based approach for early detection of eye tumor growing

PurposeIris neoplasm is a non-symptom cancer that causes a gradual loss of sight. The first purpose of this study was to present a novel and automatic method for segmenting the iris tumors and detecting the corresponding areas changing along time. The second aim of this work was to investigate several recently published methods after being applied for the iris tumors segmentation. MethodsOur approach consists firstly in segmenting the iris region by using the Vander Lugt correlator based active contour method. Secondly, by treating only the iris region, a K-means clustering model was used to assign the tumorous tissue to one pixel-cluster. This model is quite sensitive to the center initialization and to the choice of the distance measure. To solve these problems, a proportional probability based approach was introduced for the cluster center initialization, and the impact of several distance measure was investigated. The proposed method and the different comparative methods were evaluated on two databases: the Eye Cancer and the Miles Research. ResultsResults reported using several performance metrics reveal that the first step assures the detection of all iris tumors with an accuracy of 100%. Additionally, the proposed method yields better performance compared to the recently published methods.

One lens optical correlation: application to face recognition.

Despite its extensive use, the traditional 4f Vander Lugt Correlator optical setup can be further simplified. We propose a lightweight correlation scheme where the decision is taken in the Fourier plane. For this purpose, the Fourier plane is adapted and used as a decision plane. Then, the offline phase and the decision metric are re-examined in order to keep a reasonable recognition rate. The benefits of the proposed approach are numerous: (1)it overcomes the constraints related to the use of a second lens; (2)the optical correlation setup is simplified; (3)the multiplication with the correlation filter can be done digitally, which offers a higher adaptability according to the application. Moreover, the digital counterpart of the correlation scheme is lightened since with the proposed scheme we get rid of the inverse Fourier transform (IFT) calculation (i.e., decision directly in the Fourier domain without resorting to IFT). To assess the performance of the proposed approach, an insight into digital hardware resources saving is provided. The proposed method involves nearly 100 times fewer arithmetic operators. Moreover, from experimental results in the context of face verification-based correlation, we demonstrate that the proposed scheme provides comparable or better accuracy than the traditional method. One interesting feature of the proposed scheme is that it could greatly outperform the traditional scheme for face identification application in terms of sensitivity to face orientation. The proposed method is found to be digital/optical implementation-friendly, which facilitates its integration on a very broad range of scenarios.

Misalignment influence of components on the performance of an integrated zigzag Vander Lugt correlator

The idea of integrating a zigzag Vander Lugt correlator with spatial light modulators (IZVLC) is rather flexible as a means of applying the parallelism of optics and rapid processing speed to a wider range of applications. The alignment of components poses an important impact on the performance of hybrid-optical architecture IZVLC. Based on planar optical and transfer function theory, we establish a simulation model of IZVLC system, systematically analyze the impact of components misalignment on the system performance, and demonstrate that the system is more sensitive to transversal misalignment of components than longitudinal misalignment of those. This analysis method of components misalignment can be important and useful for the designers, manufacturers and users of the IZVLC system to improve the robustness.

Leibniz et Bayle: Confrontation et dialogue ed. by Christian Leduc, Paul Rateau, and Jean-Luc Solère

Reviewed by: Leibniz et Bayle: Confrontation et dialogue ed. by Christian Leduc, Paul Rateau, and Jean-Luc Solère Mara van der Lugt Christian Leduc, Paul Rateau, and Jean-Luc Solère, editors. Leibniz et Bayle: Confrontation et dialogue. Studia Leibnitiana 43. Stuttgart: Franz Steiner, 2015. Pp. 452 €64.00. Central to this volume are two philosophical powerhouses of the early modern period: Gottfried Wilhelm Leibniz and Pierre Bayle. Born in, respectively, 1646 and 1647, both made for an astonishing career in a variety of scholarly disciplines and reached, if not equal, then certainly comparable fame in the course of their lives. Nowadays, Bayle's reputation is eclipsed by that of Leibniz, who is the focus of yearly conferences and libraries of scholarship, while Bayle had to await the later twentieth century to be rediscovered. He has since been at the center of a quickly expanding body of scholarship, which continues to be sharply divided over the vexed question how to interpret his religious stance. This imbalance in the amount of scholarship devoted to the two thinkers partly has to do with their respective modes of philosophizing. Though it is an exaggeration to say that Leibniz was systematic where Bayle was critical, it is the case that Leibniz was more intent on building his own systems, Bayle on exposing the inherent weaknesses of others'. Leibniz left a corpus of philosophical treatises, monographs and essays, while Bayle left his arguments scattered in a variety of textual curiosity cabinets, combining philosophical argument with generous helpings of historical and literary digressions. But if this diverse treatment of Leibniz and Bayle seems warranted by the character of their philosophical oeuvres, it becomes questionable when one takes into account their intellectual itineraries, which crossed in various debates. As intellectual sparring partners, they engaged with each other's arguments with the highest degree of dedication, to such an extent that Leibniz's philosophical legacy would be unthinkable without Bayle. One of the major strengths of this collection of articles is to bring out Leibniz and Bayle in "confrontation and dialogue" and emphasize the dialectical and interactive component of their philosophical sparring sessions, which spanned decades and a wide variety of texts. The twenty-one articles collected in this bilingual volume (French-English) are grouped thematically into four categories. The articles in the first section, "Methods, Hypotheses and Truth," discuss both philosophers' views on epistemology, skepticism, truth and belief, and trace the evolution of their debate in these areas; a valuable contribution by Michael Hickson questions the common dichotomy that associates Leibniz with rationalism, Bayle with skepticism. The second section, "Pre-established Harmony and Plastic Natures," is oriented more towards the various stages within the development of Leibniz's system, and the role played by Bayle's criticism throughout this process. A crucial part in this is the debate on animal sensation and Bayle's attempt to disprove the logic of Leibniz's pre-established harmony via the thought-experiment of a dog that suddenly passes from a state of pleasure to a state of pain; and Bayle and Leibniz's differing views on Ralph Cudworth and plastic natures, which Bayle connects to the philosophical specter of Stratonism. [End Page 353] The third section, "Faith and Reason," focuses on Bayle and Leibniz's views on religion, theology, rationalism and fideism, sometimes questioning the assumption that Leibniz and Bayle were diametrically opposed with regard to reason and religious belief (Kristen Irwin). Other articles examine their respective views on quietism (Thomas Lennon) and the apocalypse (Hartmut Rudolph): this last article contains some unfortunate inaccuracies (e.g. the misattribution of Bayle's Critique Générale to Louis Maimbourg, 337). An especially insightful contribution by Paul Rateau discusses the figure of the virtuous atheist in Leibniz and Bayle. The fourth section, "Evil and Theodicy," is centered on one of the most influential interactions between Bayle and Leibniz, which would leave a huge impact on the eighteenth century: their debate on the problem of evil, various aspects of which are discussed by the articles in this section. Especially noteworthy is Gianni Paganini's contribution, which raises an important question with regard to the eclipse of the Book of Job from the...

Vander Lugt Correlator based active contours for iris segmentation and tracking

Iris segmentation using active contours approaches is receiving increasing attention. In this paper, a self-ruling active contour approach based on the optical correlation algorithm is proposed. The novelty of this research effort is to apply the Optical Correlation based Active Contours (OCAC) on iris segmentation and tracking and highlight the advantages of its small computation time and better accuracy performance. Optical correlation computed with a numerical simulation of the Vander Lugt correlator is used to detect iris and pupil areas which used as an initial contours. As a result, these initial contours assists the method to calculate terms in an energy expression. In the proposed method, several references images called filters of iris and pupil have been introduced. Images from four iris datasets as CASIA v4, WVU non-ideal, MMU2, UBIRIS v2, and a motion video were used in the experiments phase. To present an aggregate overview of the proposed method advantages, we computed several parameters as iris and pupil centers localization errors, iris and pupil rays errors, three performance metrics (as Jaccard coefficient, Dice coefficient, Hausdroff distance), average segmentation error, and average execution time. We compare these segmentation performance parameters with several leading techniques demonstrating significantly improved results with the proposed OCAC technique.

Correction.

HomeStrokeVol. 47, No. 7Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published1 Jul 2016https://doi.org/10.1161/STR.0000000000000104Stroke. 2016;47:e201This article corrects the followingCarotid Atherosclerotic Plaque Characteristics on Magnetic Resonance Imaging Relate With History of Stroke and Coronary Heart DiseaseIn the article by Selwaness et al (Selwaness M, Bos D, van den Bouwhuijsen Q, Portegies MLP, Ikram MA, Hofman A, Franco OH, van der Lugt A, Wentzel JJ, Vernooij MW. Carotid atherosclerotic plaque characteristics on magnetic resonance imaging relate with history of stroke and coronary heart disease. Stroke. 2016;47:1542–1547. DOI: 10.1161/STROKEAHA.116.012923.), which published online on May 10, 2016, and appeared in the June 2016 issue of the journal, a correction was needed.On page 1545, Table 2, column Women Model 1 P value, row Wall thickness, “0.04,” has been changed to read “0.4.”This correction has been made to the online version of the article, which is available at http://stroke.ahajournals.org/content/47/6/1542. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesCarotid Atherosclerotic Plaque Characteristics on Magnetic Resonance Imaging Relate With History of Stroke and Coronary Heart DiseaseMariana Selwaness, et al. Stroke. 2016;47:1542-1547 July 2016Vol 47, Issue 7 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/STR.0000000000000104PMID: 27354664 Originally publishedJuly 1, 2016 PDF download Advertisement

Advanced driver assistance system: Road sign identification using VIAPIX system and a correlation technique

We present a three-step approach based on the commercial VIAPIX® module for road traffic sign recognition and identification. Firstly, detection in a scene of all objects having characteristics of traffic signs is performed. This is followed by a first-level recognition based on correlation which consists in making a comparison between each detected object with a set of reference images of a database. Finally, a second level of identification allows us to confirm or correct the previous identification. In this study, we perform a correlation-based analysis by combining and adapting the Vander Lugt correlator with the nonlinear joint transformation correlator (JTC). Of particular significance, this approach permits to make a reliable decision on road traffic sign identification. We further discuss a robust scheme allowing us to track a detected road traffic sign in a video sequence for the purpose of increasing the decision performance of our system. This approach can have broad practical applications in the maintenance and rehabilitation of transportation infrastructure, or for drive assistance.

IL-33/ST2 Triggering of IL-9-Secreting T Cells Alters the Balance of Fatal Immunity and Tumor Immunity

Treatment of acute myeloid leukemia (AML) has changed little over the last several decades and prognosis remains very poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is one potentially curative option for relapsed or high-risk AML. The immunotherapeutic activity of allo-HCT is known as the graft-vs-leukemia (GVL) activity. However, GVL activity is often accompanied by T-cell reactivity to allo-antigens in normal host tissues, which leads to graft-versus-host disease (GVHD), another major cause of death after HCT with relapse. Therefore, there is a great unmet need to improve the current process of allo-HCT through increasing the GVL activity and decreasing GVHD. We have shown that an elevated plasma level of soluble (s)ST2 in HCT patients is a risk factor for severe GVHD (Vander Lugt et al, N Engl J Med, 2013) and that ST2 blockade reduces sST2-producing T cells while maintaining protective membrane (m)ST2-expressing T cells during GVHD (Zhang et al, Sci Transl Med, 2015). In addition, the interleukin (IL)-9-producing CD4 T helper (Th)9 and CD8 cytotoxic T (Tc)9 cell subsets (together T9 cells) have higher antitumor activity than Th1 and Tc1 cells in melanoma models (Lu et al, J Clin Invest, 2012 and Lu et al, ProcNatl Acad Sci, 2014). We hypothesized that activation of the ST2/IL-33 pathway in T9 cells will both alleviate GVHD and increase GVL. In our laboratory, we have shown that T9 cells express a high level of mST2 and that differentiation of total T cells into T9 cells in the presence of IL-33 (T9IL-33 cells) increases expression of mST2 (Figure 1A) and PU.1 (Figure 1B), a transcription factor that promotes IL-9 production on both CD4 and CD8 T cells. Adoptive transfer of T9IL-33 cells with bone marrow cells in a murine model of HCT resulted in less severe GVHD compared to transfer of T9IL33 cells generated from ST2-/- or IL-9-/- T cells (Figure 1C). Ex-vivo analysis of target organs such as gut showed a decrease in T9IL-33 interferon (IFN)g-producing T cells that was abolished in mice receiving T9IL-33 cells derived from ST2-/- or IL-9-/- T cells (not shown). Furthermore, T9IL-33 cells revealed higher anti-leukemic activity in vitro when cultured with a B cell lymphoma line (A20) or retrovirally transduced MLL-AF9 leukemic cells in cytolytic assays (not shown). In vivo GVL experiments with MLL-AF9 induced leukemia, and adoptive transfer of T9IL-33 cells resulted in increased survival compared to transfer of T9IL-33 cells generated from ST2-/- or IL-9-/- T cells (Figure 1D). Human T9 cells are poorly explored. We demonstrated that differentiation of human T9 cells in the presence of IL-33 enhanced IL-9 production by CD4 and CD8 T cells (Figure 2A). T9IL-33 cells also upregulated the expression of the cytolytic molecules granzymes A and B compared to T9 cells (Th9IL-33: 33.6%±4%, vs. Th9: 15.69%±2.53% p=0.021), (Tc9IL-33: 57.6%±4.7%, vs. Tc9: 34.61%±3.4% p=0.018), as well as demonstrated higher in vitro anti- leukemic cytolytic activity when incubated with MOLM14, an aggressive AML tumor cell line expressing FLT3/ITD mutations (Figure 2B). Transcriptome analysis of T9IL-33 cells from wild-type and ST2-/- T cells showed upregulation of molecules implicated in anti-leukemic activity (granzymes A and B, CD8α, IL-15, IL-15rα, IFNα, and IL-1α) on both CD4 and CD8 T cells (Figure 2C), and such upregulation was confirmed at the protein level (Figure 2D). Furthermore,investigations into the possible mechanism of activation using transwell assays revealed that both soluble factors and cell contact between Th9IL-33 and Tc9IL-33 T cells were required for maximum killing (not shown). We next investigated the possible mechanism of action and hypothesized that CD8α might be the contact-dependent component. CD8α blockade with neutralizing antibody during human T9IL-33 differentiation reduced the cytotoxicity of both murine T9IL-33 and human T9IL-33 cells (Figure 2E). Altogether, our observations suggest that adoptive transfer of T9IL-33 cells represents a promising cellular therapy following HCT. [Display omitted] [Display omitted] DisclosuresPaczesny:Viracor laboratories: Patents & Royalties: "Methods of detection of graft-versus-host disease" (US- 13/573,766).

MaRBLe uncensored: An experience report of the MaRBLe adventure

Marble: Maastricht Research-Based Learning, program for excellence. It sounds interesting, intriguing and challenging. Well, it really is all of that and more. Overall it is lots of fun! In the present article I will provide you with an overview of what Marble is. I will describe the different steps of the program, from ups to (occasional) downs. Furthermore, I will briefly explain my Marble study and results. When I first heard of Marble I did not quite know what it entailed. It did, however, sound tempting enough for me to find out more about it. Marble offers highly motivated and excellent students with research affinity the chance to improve their skills during an intensive research program. In a nutshell, you set up a study under supervision of an expert in the field, exchange and discuss ideas with fellow students, learn in depth about research skills and develop these skills yourself. If you want to apply, there are some requirements you should take into consideration. First, you need a grade point average of 7.0 and you have to write a letter of motivation. Please do not be discouraged if your GPA is slightly under 7.0. Strong motivation can squeeze you in anyway. I believe motivation and enthusiasm might be equally, if not more important than GPA. However, I am not the one deciding whether you may enroll. Secondly, you should be interested in research. If you are planning a career in research, or maybe strive for a PhD, Marble would be a great opportunity to develop and elaborate your research skills. Considering my ignorance when it comes to statistics I thought I would never be admitted when I applied. Our Marble coordinator Arie van der Lugt's enthusiasm was contagious, though, and eventually I went home with an overload of motivation and self-esteem. Arie appeared to be an excellent captain of the Marble ship; committed and inspiring with a bunch of humour. Now that I was officially admitted, the next step was to think of a topic and to contact a supervisor.

Regulation of Immune Responses during Acute GvHD Via the IL-33/ST2 Axis

The IL-1 superfamily member IL-33 is produced in barrier tissues. IL-33 binds to the receptor suppression of tumorigenicity 2 (ST2), expressed on stromal cells, regulatory T cells (Tregs), myeloid derived suppressor cells (MDSCs), and macrophages. IL-33 has both anti-inflammatory and pro-inflammatory properties. It is not known if IL-33 plays a role in acute GvHD, and if so what properties it exerts. By immunohistochemistry staining of gut tissues, IL-33 production by non-hematopoietic cells was increased in mice post-conditioning and in patients during GvHD. To determine whether IL-33 could augment GvHD via a host signaling mechanism, we compared st2-/- to wildtype (wt) hosts and observed decreased GvHD lethality (Figure 1A). Additionally, IL-33-/- versus wt hosts had a marked decrease in GvHD lethality and reduced TNFα production. Conversely, IL-33 administration during the peak inflammatory response worsened GvHD. Previous studies have shown increased levels of the soluble form of ST2 (sST2) are a biomarker for steroid-refractory GvHD (Vander Lugt, NEJM, 2013). We hypothesized that sST2 acted not only as an indicator of tissue injury and biomarker of GvHD but also as an immune modulator during GvHD. In rodents, we found that ST2 was upregulated on alloreactive T cells and sST2 increased as GvHD progressed. St2-/- versus wt donor T cells had a marked reduction in GvHD lethality (Figure 1B) without compromise of graft-vs-leukemia responses. Comparable data was seen in 2 different strain combinations. Alloantigen-induced IL-18 receptor upregulation was significantly lower in the absence of ST2, which was linked to significantly reduced IFNγ production by st2-/- vs wt CD4 and CD8 T cells during GvHD. Similarly, sST2 transgenic hosts and wt recipients given exogenous sST2-Fc fusion protein infusions (Figure 1C) to block ST2/IL-33 interaction each had significantly reduced GVHD lethality, establishing the functional role of ST2 as a decoy receptor modulating GVHD. During the peak of the GvHD inflammatory response, IL-33 signalling of either donor or host cells promoted activation of donor T cells, while the use of exogenous sST2-Fc protein to prevent IL33/ST2 engagement ameliorates disease. Together, these studies point to targeting of the IL-33/ST2 axis as a novel and potent target for GvHD therapy. [Display omitted] DisclosuresWarncke:Novartis Pharma AG: Employment. Junt:Novartis Pharma AG: Employment.

Generic histories of German cinema: genre and its deviations

Over the last few decades, the field of film studies has seen a rise in approaches oriented toward genre: studies that look at thematic, narrative, and stylistic similarities between films, contextualizing them within culture and society. Although there now exists a large body of genre-based scholarship on international film, German film studies has largely ignored the importance of genre. Even as the last several years have witnessed increasing scholarly interest in popular cinema from Germany, very few works have substantively engaged with genre theory. Generic Histories offers a fresh approach, tracing a series of key genres -- including horror, science fiction, the thriller, Heimat films, and war films -- over the course of German cinema history. It also addresses detective films, comedies, policiers, and romances that deliberately localize global genres within Germany - a form of transnationalism frequently neglected. This focus on genre and history encourages rethinking of the traditional opposition (and hierarchy) between art and popular cinema that has informed German film studies. In these ways, the volume foregrounds genre theory's potential for rethinking film history as well as cultural history more broadly. CONTRIBUTORS: Marco Abel, Nora M. Alter, Antje Ascheid, Hester Baer, Steve Choe, Paul Cooke, Jaimey Fisher, Gerd Gemunden, Sascha Gerhards, Lutz Koepnick, Eric Rentschler, Kris Vander Lugt. JAIMEY FISHER is Associate Professor of German and Cinema and Technocultural Studies, and Director of Cinema and Technocultural Studies, at the University of California, Davis.

A Biomarker-Based Grading System At Onset Of GvHD Predicts NRM Better Than The Modified Glucksberg Grading System

▪Maximum grades of the commonly used modified Glucksberg staging system for acute graft versus host disease (GVHD) correlate with non-relapse mortality (NRM), but cannot guide treatment at diagnosis. All patients with GVHD grade II-IV are standardly treated with high dose steroids, and no further treatment decisions are based on GVHD severity at onset. In contrast, treatment for GVHD grade I varies so that some patients receive systemic steroid therapy while others are observed. We wished to devise a grading system that predicted eventual mortality and that could therefore guide treatment at diagnosis. We have previously shown that plasma concentrations of GVHD biomarkers (TNFR1, IL2Rα, elafin, REG3α, ST2) have prognostic significance (Paczesny, Blood, 2009, Paczesny, Sci Trans Med, 2010, Ferrara Blood, 2011, Vander Lugt, NEJM, 2013). We identified 360 University of Michigan allogeneic hematopoietic cell recipients with acute GVHD (median age 48y, range 0-70y) who had plasma samples taken at the time of diagnosis [median day 28, range: 5-174] and stored in our repository: grade I (n =130, 36%), grade II (n = 151, 42%), or grade III/IV (n = 79, 22%). Biopsy confirmation was available for >80% of cases. Progression from Glucksberg I to Glucksberg ≥ II occurred in 84 (64%) patients at a median of 6 days from onset, whether systemic therapy for grade I was initiated (N=80; 70%) or not (N=50; 56%, p=0.12). We chose 6 month NRM as the key endpoint as it encompasses treatment failures due to nonresponse, loss of treatment response, and complications of treatment; 93% of 6 m NRM was due to GVHD. The 6 m NRM for patients presenting with Glucksberg I (15%) and Glucksberg II (24%) was not significantly different [as also shown by others: MacMillan, Blood, 2010]; their combined NRM was 20% (n=281, Panel A). Patients who presented with Glucksberg III/IV had significantly worse 6 m NRM than Glucksberg I/II (56%, N=79, p<0.001, Panel C). We measured the plasma concentrations of the 5 prognostic biomarkers above and used logistic regression to develop Ann Arbor GVHD grades such that 6 m NRM for Ann Arbor I would be ∼10% (as in patients with Glucksberg I whose GVHD never progressed) and >50% for Ann Arbor III (similar to the 6 m NRM for Glucksberg III/IV). We treated relapse after development of GVHD as a competing risk and developed separate regression models according to the clinical severity at presentation, i.e. Glucksberg I/II and III/IV. Panel B shows the 6 m NRM of patients who presented with Glucksberg I/II according to Ann Arbor I (thin), II (medium), and III (thick). Patients with Ann Arbor III (n=29/281, 10%) experienced far worse 6 m NRM (59%) than either Ann Arbor I (11%) or Ann Arbor II (17%) [p<0.001 for each]. Likewise, Panel D shows that biomarkers reclassify significant numbers of patients with Glucksberg III/IV at onset to Ann Arbor I and II (n=21/79, 27%). These reclassified patients experienced much lower NRM (0% and 21%, respectively) than patients with Ann Arbor III (71%, p<0.001). Results are summarized in Panels E (combined Glucksberg NRM) and F (combined Ann Arbor NRM). NRM for Ann Arbor grade III remained significantly worse compared to Ann Arbor grade I and II (p<0.001 for both comparisons). Of note, the difference between Ann Arbor grade I and II (10% vs 18%, p=0.08) approaches statistical significance. Comparison of the models by the Akaike Information Criterion indicated that Ann Arbor grades predict NRM better than Glucksberg grades. Patients with Ann Arbor grade III GVHD experienced worse NRM (67%) than those with Glucksberg III/IV (56%), while patients with Ann Arbor grade I (10%) have better NRM than those with Glucksberg I/II (20%). As expected, patients with Ann Arbor grade I were most likely to respond to treatment by day 28 and those with Ann Arbor III GVHD were least likely (p=0.01 and p=0.03, respectively). In conclusion, we have developed a new acute GVHD grading system using biomarkers at onset of disease that reclassifies significant numbers of patients and produces more accurate risk groups than Glucksberg grades. If validated in patients from other centers, this system may be able to guide therapy: patients with Ann Arbor Grade III who experience high rates of treatment failure with standard approaches would benefit from experimental therapies as primary treatment. Likewise, patients with Ann Arbor grade I might require low dose/no systemic steroids. [Display omitted] Disclosures:Levine:University of Michigan: Patent for GVHD biomarkers, Patent for GVHD biomarkers Patents & Royalties. Braun:University of Michigan: Patent for GVHD Biomarkers, Patent for GVHD Biomarkers Patents & Royalties. Ferrara:University of Michigan: Patent for GVHD Biomarkers, Patent for GVHD Biomarkers Patents & Royalties.

High Day 28 ST2 Biomarker Levels Predict Severe Day 100 Acute Graft-Versus-Host Disease and Day 180 Transplant-Related Mortality After Double-Unit Cord Blood Transplantation

BackgroundCord blood transplantation (CBT) is a proven therapy for high-risk hematologic malignancies. However, severe grade III-IV acute graft-versus-host disease (aGVHD) has emerged as a significant source of morbidity and mortality and most commonly targets the gastrointestinal (GI) tract after CBT. Plasma biomarkers have been found to predict aGVHD onset, aGVHD therapy response, and transplant-related mortality (TRM) after adult donor hematopoietic stem cell transplantation. However, whether plasma biomarkers are informative in CBT recipients has not been investigated. MethodsPlasma biomarkers were measured 28 days after unrelated donor double-unit CBT in 113 consenting patients (median age 41 years, range 1.7-69) transplanted at a single center between 5/2006 and 5/2012 for the treatment of high-risk hematologic malignancies. Conditioning was myeloablative (n = 37), reduced intensity (n = 47), or non-myeloablative (n = 29), and CB units were 4-6/6 HLA-A, -B antigen, -DRB1 allele matched to the recipient. The median follow-up was 44 months (range 14-84). Batched samples blinded to transplant outcomes were analyzed by enzyme-linked immunosorbent assay for levels of suppressor of tumorigenicity 2 (ST2), IL-2 receptor-α (IL-2Rα), tumor necrosis factor receptor-1 (TNFR1), hepatocyte growth factor (HGF), IL-8, elafin, and regenerating islet-derived protein 3-α (REG3α). Patients were grouped according to being above or below the median day 28 value for each biomarker. The cumulative incidence of aGVHD and TRM from day 28 landmark was estimated for each biomarker and significance was assessed using Gray's test. Patients who had aGVHD onset prior to day 28 (n = 7) were excluded from aGVHD evaluation. ResultsWe found significant associations between day 28 plasma biomarkers and grade II-IV aGVHD and/or 6-month TRM, which are shown in Table. IL2Rα, elafin, and HGF were not significant for either outcome (data not shown). ST2 was the only biomarker associated with day 100 grade II-IV aGVHD with high ST2 patients having a median aGVHD onset of 42 days (range 28-93). Notably, patients with high day 28 ST2 had significantly increased day 100 grade III-IV aGVHD of 27% (95%CI:16-40) versus 11% (95%CI:4-20) in patients with low ST2 levels, p = 0.025. High ST2 was also associated with substantially increased 6-month TRM, and GVHD was the most common cause of transplant-related death [11/19 (58%) of deaths] with a median time to GVHD death of 170 days (range 70-400). High concentrations of TNFR1, IL-8, and REG3a were also significantly associated with 6-month TRM. Notably, aGVHD and organ failure due to lung toxicity were the most common causes of TRM in patients with high TNFR1, IL8, and REG3α levels.TableBiomarker (ng/ml)Day 100 Grade II-IV aGVHD (95%CI)p-value6-month TRM (95% CI)p-valueST2 ≤ 33.9 ST2 > 33.948% (35-61) 64% (49-76)0.0455% (1-13) 23% (13-35)0.001TNFR1 ≤ 4792 TNFR1 > 479257% (42-69) 54% (40-67)0.6605% (1-13) 23% (13-35)0.005IL8 ≤ 51 IL8 > 5156% (41-68)56% (41-68)0.6525% (1-13) 23% (13-35)0.005REG3α ≤ 42 REG3α > 4257% (42-69) 55% (40-67)0.9385% (1-13) 24% (13-36)0.032 ConclusionsThis is the first biomarker analysis conducted in CBT recipients. We demonstrate that a high day 28 ST2 level is associated with a subsequent increased risk of grade II-IV and III-IV aGVHD, as well as 6-month TRM. These findings are consistent with those recently reported in adult unmodified (T-replete) allograft recipients (Vander Lugt et al, NEJM, 2013). GVHD is the predominant mechanism of death in high ST2 patients and the day of onset is after day 28 in the majority which would permit time for therapeutic intervention. Thus, our findings have significant practical implications. Whether the other biomarkers offer additional prognostic information remains to be determined. They were not associated with the overall grade II-IV aGVHD incidence, but where associated with mortality from GVHD and organ failure. Overall, our promising results warrant further prospective evaluation in a large patient cohort with the ultimate aim of future interventions to ameliorate severe aGVHD and improve survival after CBT. Disclosures:No relevant conflicts of interest to declare.

Integrated zigzag Vander Lugt correlators incorporating an optimal trade-off synthetic discriminant filter for invariant pattern recognition

Optical correlators (OCs) have a wide range of applications in the field of pattern recognition. We present a type of integrated zigzag Vander Lugt correlator (IZVLC). The IZVLC incorporates two Fourier transform lenses and one spatial light modulator (SLM) as a programmable filter, which can effectively miniaturize the volume of OCs and hence achieve better optical pattern recognition. In order to precisely recognize distortion targets, an optimal trade-off synthetic discriminant filter (OTSDF) is programmed on the SLM of the IZVLC. Both the simulative and experimental results have shown that the IZVLC can effectively identify distortion targets within a rotation angle of ±π/3 and a scaling range of 0.6–1.6.

E-056 MR CLEAN - Multicentre Randomised Clinical trial of endovascular treatment for acute ischaemic stroke in the Netherlands (NTR1804)

RationaleIschaemic stroke is often caused by embolic occlusion of proximal intracranial arteries. The effect of intravenous alteplase is limited in these patients. Endovascular treatment increases the likelihood of recanalisation, but...

Method of synthesized phase objects for pattern recognition: matched filtering

To solve the pattern recognition problem, a method of synthesized phase objects is suggested. The essence of the suggested method is that synthesized phase objects are used instead of real amplitude objects. The former is object-dependent phase distributions calculated using the iterative Fourier-transform (IFT) algorithm. The method is experimentally studied with a Vander Lugt optical-digital 4F-correlator. We present the comparative analysis of recognition results using conventional and proposed methods, estimate the sensitivity of the latter to distortions of the structure of objects, and determine the applicability limits. It is demonstrated that the proposed method allows one: (а) to simplify the procedure of choice of recognition signs (criteria); (b) to obtain one-type δ-like recognition signals irrespective of the type of objects; (с) to improve signal-to-noise ratio (SNR) for correlation signals by 20 - 30 dB on average. The spatial separation of the Fourier-spectra of objects and optical noises of the correlator by means of the superposition of the phase grating on recognition objects at the recording of holographic filters and at the matched filtering has additionally improved SNR (>10 dB) for correlation signals. To introduce recognition objects in the correlator, we use a SLM LC-R 2500 device. Matched filters are recorded on a self-developing photopolymer.

Advanced Magnetic Resonance Neuroimaging of Language Function Recovery After Aphasic Stroke: A Technical Review

Smits M, Visch-Brink EG, van de Sandt-Koenderman ME, van der Lugt A. Advanced magnetic resonance neuroimaging of language function recovery after aphasic stroke: a technical review. Arch Phys Med Rehabil 2012;93(1 Suppl 1):S4-14. Two advanced magnetic resonance neuroimaging techniques, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), have recently made their way into clinically oriented research and hold great promise to study the brain's adaptive changes of function and structure after aphasic stroke, respectively. Such functional and structural neuroplasticity is thought to underlie the recovery of language function, occurring spontaneously and/or in the context of therapeutic intervention. With fMRI, brain activity can be visualized. Spontaneous brain activity, present in multiple brain networks, is measured with resting-state fMRI and language-related brain activity by having the subject perform a language task during scanning (task-based fMRI). With DTI the major white matter tracts, such as the dorsal and ventral language pathways and the commissural fibers, can be visualized and quantified. Both techniques are entirely noninvasive and thus offer the unique opportunity to perform multiple assessments within the same subject. To gain more insight in functional and structural neuroplasticity after aphasic stroke, advanced magnetic resonance neuroimaging studies in specific patient populations, at several stages after stroke and in the course of language recovery, are needed. Such studies will help to clarify the influence of the many factors that play a role in the recovery of language function and are thus vital to further the development of aphasia therapy. Application of these techniques in aphasic stroke patients, however, is not without challenge. The purpose of this article is to discuss the methodologic challenges of fMRI and DTI in the assessment of language recovery after aphasic stroke.

Arterial calcifications as a marker of vascular brain disease

Poster: ECR 2011 / C-0359 / Arterial calcifications as a marker of vascular brain disease by: D. Bos, M. A. Ikram, A. van der Lugt, G. P. Krestin, J. C. M. Witteman, M. W. Vernooij; Rotterdam/NL

Maaike van der Lugt and Charles de Miramon (eds), L’hérédité entre Moyen Âge et Époque Moderne: Perspectives Historiques, Micrologus’ Library, 27 (Florence: Sismel – Edizioni del Galluzzo, 2008), pp. vii + 416, €58.00, ISBN: 978-88-8450-309-1.

This book is a collection of essays on the place of heredity in the thought of the Middle Ages. Its core is the clear demonstration by Maaike van der Lugt that the notion of hereditary disease emerged in the thirteenth century, and found a clear expression in the fourteenth. Its roots were in the writings of Arab philosophers and doctors, but what was revolutionary was the metaphoric transfer of the expression ‘hereditary’, previously used to designate goods and properties transmitted through generations, to the domain of medicine. This book challenges the view that the Renaissance was a revolutionary time for medical and biological thought. The opposite is true: the notion of hereditary disease emerged in the thirteenth century, was not deeply transformed during the Renaissance, and took on increasing importance at the end of the eighteenth century, finally leading to the birth of a scientific theory of heredity in the middle of the nineteenth century. But this book also challenges the alternative hypothesis: heredity was a central question for thinkers of the Middle Ages. The justification of the power of the nobility by the existence of a ‘noble blood’, the rise of anti-semitism supporting a differentiation between human beings, the efforts made to breed animals of higher quality, the progressive interpretation of original sin in biological terms, the rules established by the Church against consanguinity: all would have contributed to the emergence of an hereditarian vision. The different contributors show that the situation was much more complex. There was a sharp contrast between the hereditarian functioning of society, with a strict hereditarian transmission of power and charges, and the numerous factors which opposed this hereditarian vision: the conviction, based on the Bible, of the uniqueness of human nature, the emphasis placed on the conditions surrounding conception and pregnancy to explain human characteristics, the importance of the notion of complexion in medicine, a product of nature and local environment, opposed the emergence of a science of heredity. The widely accepted belief in an heredity of acquired characters made the picture even more fuzzy. The rules preventing consanguinity were not justified by a ‘eugenic’ project. The existence of ‘noble’ blood was a popular conception, disconnected from the writings of doctors. The improvement in animal breeding only concerned animals of the nobility, falcons and dogs. The interpretations of original sin were numerous and contradictory. The consequence was that the list of hereditary diseases included leprosy and gout, but none of the diseases that today would be found in a similar list. Two interesting lessons emerge from reading this book. The first is the role of interdisciplinarity considered in an extensive way. The emergence of the notion of hereditary disease in the Middle Ages required borrowing the notion of heredity from its use in law. The concept of latency, necessary to explain the transmission of hereditary diseases, has its roots in theology. The second lesson comes from the comparison with what happened in the nineteenth century. The rise of a science of heredity was made possible by the coalescence, the conjunction of different social, scientific, and epistemic transformations. In particular, the disconnection between the characteristics of organisms, humans included, and the place in which they were living, due to the increasing circulation of plants, animals and humans, as well as the classifications of human beings following colonisation, had very important roles in the rise of a science of heredity. It explains the limits of the hereditarian vision in the Middle Ages. All the contributions collected in this book are rich in information and offer acute critical perspectives. This book will be of interest not only to those involved in the history of medicine in the Middle Ages, but also to all historians working on the interaction between sociocultural conditions and the growth of scientific knowledge.

L'h�r�dit� entre Moyen �ge et �poque moderne: Perspectives historiques (review)

Reviewed by: L'hérédité entre Moyen Âge et Époque moderne: Perspectives historiques Silvia De Renzi Maaike van der Lugt and Charles de Miramon, eds. L'hérédité entre Moyen Âge et Époque moderne: Perspectives historiques. Micrologus' Library 27. Florence: Sismel-Edizioni del Galluzzo, 2008. vi + 412 pp. Ill. €58.00 (978-88-8450-309-1). With a programmatically broad scope, this volume investigates whether and how heredity was conceptualized centuries before the scientific view with which we are familiar emerged in the nineteenth century. The focus is on the late Middle Ages, and in the three sections "Heredity, Law and Religion," "Heredity and Nobility," and "Heredity and Nature," the contributors' wide-ranging expertise brings to life the variety of languages, concepts, and discourses within which the question was articulated. No tight definition of heredity is provided, but at the core of most chapters is the issue of the transmission of traits, moral and physical, from one generation to the next. So explorations of theological debates—here the exceptionally interesting issue was the transmission of original sin—are followed by chapters on the law—the definition of marriage in the canon law brought blood kinship into unprecedented relief—and on politics—in medieval Italian cities and in fifteenth-century France alike controversies over the sources of nobility hinged on the opposition between lineage and individual virtue. Nonmedievalists may be tested by the details of some of the chapters, but they will be rewarded with evidence of the richness and political importance of the intellectual conflicts. For example, fifteenth-century controversies over the conversion of the Jews drew on broader assumptions about the nature of humankind—either fundamentally one, [End Page 680] making the Jews' complete conversion possible, or rather based on unalterable racial differences. Far from being the outcome of the encounter with the New World, the volume argues, a vigorous anthropological debate was already taking place in the late Middle Ages; in this framework, the editors claim, a "tournant héréditaire" (p. 13) should rather be located in the fourteenth century. The relations between the domains in which heredity was discussed could have received more sustained attention, but historians of medicine will be interested in the consensus that overall theories of generation had little impact on legal and political discourse. However rich in itself, natural and medical knowledge did not provide a unifying and coherent resource for thinking about transmission, not even when the nature of noble blood was at stake. Yet medicine has an important place in the volume. The final section includes a chapter on physiognomy and two on hereditary diseases. It was only within scholastic medicine that a specific language and interest in them emerged, including a rich, if not dominant, debate about their definition. But just as age could change complexions—for some the result of mixing semens—so environmental factors, including during pregnancy, made the transmission of diseases from parents to children much less inexorable than their twentieth-century equivalent. The last chapter of the volume takes the history of these diseases up to the eighteenth century, when physicians became key actors in the development of a modern notion of heredity. Such an extended chronology is applied only to medical knowledge, and the implication seems to be that, despite crucial changes, it is here that we should find one of the strongest threads connecting the Middle Ages to recent times. Projects recapturing the remote history of concepts that have come to define modern science raise questions about continuity and breaks. The editors and some of the contributors look at the Middle Ages as a creative intellectual workshop where key ideas and practices were forged for the first time. But they have also commissioned an epilogue by two historians of science whose own cultural history of heredity argues for a very different periodization. In their powerful survey, Staffan Müller-Wille and Hans-Jörg Rheinberger identify a cluster of innovations between 1500 and 1850, including a greater mobility of people, plants, and animals, as providing the conditions for the slow and fragmented emergence of a notion of heredity linked to reproduction. While arguing for fundamental epistemological shifts in approaches to the...