De Jonge Research Articles

A plant effector-triggered immunity signaling sector is inhibited by pattern-triggered immunity.

Since signaling machineries for two modes of plant-induced immunity, pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), extensively overlap, PTI and ETI signaling likely interact. In an Arabidopsis quadruple mutant, in which four major sectors of the signaling network, jasmonate, ethylene, PAD4, and salicylate, are disabled, the hypersensitive response (HR) typical of ETI is abolished when the Pseudomonas syringae effector AvrRpt2 is bacterially delivered but is intact when AvrRpt2 is directly expressed in planta These observations led us to discovery of a network-buffered signaling mechanism that mediates HR signaling and is strongly inhibited by PTI signaling. We named this mechanism the ETI-Mediating and PTI-Inhibited Sector (EMPIS). The signaling kinetics of EMPIS explain apparently different plant genetic requirements for ETI triggered by different effectors without postulating different signaling machineries. The properties of EMPIS suggest that information about efficacy of the early immune response is fed back to the immune signaling network, modulating its activity and limiting the fitness cost of unnecessary immune responses.

Exploring the Value of Interprofessional Collaboration between Occupational Therapy and Design: A Pilot Survey Study

Background: Consistent with the American Occupational Therapy Association’s Vision 2025, interprofessional partnerships between occupational therapy and designers is necessary to “maximize health, well-being, and quality of life for all people . . . through effective solutions that facilitate participation in everyday living” (2016, para 1). Occupational therapy’s knowledge of the person-environment-occupation fit appears to make us well suited to collaborate with design teams to create environments that facilitate optimal function and promote health and well-being (Ainsworth & de Jonge, 2014).

Evidence appraisal of de Jonge SW, Atema JJ, Solomkin JS, Boermeester MA. Meta-analysis and trial sequential analysis of triclosan-coated sutures for the prevention of surgical-site infection.: Br J Surg. 2017;104(2):e118-e133.

AORN JournalVolume 106, Issue 1 p. 77-82 Column Evidence appraisal of de Jonge SW, Atema JJ, Solomkin JS, Boermeester MA. Meta-analysis and trial sequential analysis of triclosan-coated sutures for the prevention of surgical-site infection. Br J Surg. 2017;104(2):e118-e133. George Allen PhD, MS, BSN, RN, CNOR, CIC, FAPIC, George Allen PhD, MS, BSN, RN, CNOR, CIC, FAPICSearch for more papers by this author George Allen PhD, MS, BSN, RN, CNOR, CIC, FAPIC, George Allen PhD, MS, BSN, RN, CNOR, CIC, FAPICSearch for more papers by this author First published: 26 June 2017 https://doi.org/10.1016/j.aorn.2017.05.009 Editor's notes:MEDLINE is a registered trademark of the US National Library of Medicine's Medical Literature Analysis and Retrieval System, Bethesda, MD. EMBASE is a registered trademark of Elsevier BV, Amsterdam, The Netherlands. PubMed is a registered trademark of the US National Library of Medicine, Bethesda, MD. Vicryl and PDS are registered trademarks of Johnson & Johnson, New Brunswick, NJ. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume106, Issue1July 2017Pages 77-82 RelatedInformation

Southeast Asia. Journal, memorials and letters of Cornelis Matelieff de Jonge: Security, diplomacy and commerce in 17th-century Southeast Asia Edited by Peter Borschberg Singapore: NUS Press, 2015. Pp. 688. Illustrations, Maps, Glossary, Notes, Bibliography, Index.

Southeast Asia. Journal, memorials and letters of Cornelis Matelieff de Jonge: Security, diplomacy and commerce in 17th-century Southeast Asia Edited by Peter Borschberg Singapore: NUS Press, 2015. Pp. 688. Illustrations, Maps, Glossary, Notes, Bibliography, Index. - Volume 48 Issue 2

An Expert Review on Corporate Real Estate Strategies for Hotel Industry in Sri Lanka

Corporate Real Estate (CRE) is the fifth corporate resource after the capital, people, technology, and information. As per the views of the industry experts CRE is identified as the second most expensive cost after labor in many occurrences. The contribution of CRE for overall business activities cannot be restricted to one specific business function where inter-functional use is evident in the overall business setting. To this end, CRE is identified as a diversified resource. The academic discussion on CRE began with scholarly works of Zeckhauser and Silverman (1983) and later CRE developed as a strategic business discipline with the pioneering erudite work on strategic CRE of Nourse and Roulac (1993), De Jonge, (1996) and Lindholm and Levainen (2006). However, all these CRE strategies were tested and reviewed in the European context ignoring the diversity of Asian business practices, nature of the industry and the level of CRE holding. Thus, adopted CRE strategies are required for contemporary management applications in the Asian region. In this context, the aim of this study is to review expert opinion on CRE strategies for hotel industry in Sri Lanka. The expert opinion used to evaluate possible CRE strategies and its dimensions for Sri Lankan hotel industry. The expert panel includes senior and middle-level managers of hotels, senior academics specializing in the hotel industry, representatives of Sri Lanka Tourist Development Authority and retired veterans of the hotel industry. The Analytic Hierarchical Model (AHP) was used as the main analytical tool to identify criteria weights of identified CRE strategies for hotel industry in Sri Lanka. The finding contributes CRE literature of hotel industry in Sri Lanka and makes empirical validation of CRE strategies for hotels in real world scenario.

TFIID or not TFIID, a continuing transcriptional SAGA.

Eukaryotic protein‐coding genes are typically classified into two groups: those with expression regulated by specific signals versus the relatively constant “housekeeping” genes. Although these differences are associated with alternative modes of RNA polymerase II (RNAP II) pre‐initiation complex (PIC) assembly, a role for gene‐specific activators in controlling “regulatability” has been difficult to rule out. To address this question, de Jonge et al () studied a group of genes controlled by a common activator but dependent on either TFIID or SAGA and found that the magnitude of regulation strongly correlates with the mechanism of PIC assembly.

Admiral Matelieff’s Singapore and Johor (1606–1616) ed. by Peter Borschberg

Reviewed by: Admiral Matelieff’s Singapore and Johor (1606–1616) ed. by Peter Borschberg Dhiravat Na Pombejra Admiral Matelieff’s Singapore and Johor (1606–1616) Peter Borschberg (ed.) Singapore: NUS Press, 2016. ISBN: 978-981-4722-18-6. 260pp. This attractive paperback, with a generous number of beautiful and apposite illustrations, is designed for use by students as well as advanced researchers. It contains a long introduction of over 80 pages by the editor, Peter Borschberg, lucidly outlining the issues covered by the contents of the book. This is followed by a selection of documents and document extracts around and about the voyage of Admiral Cornelis Matelieff (or Matelief) de Jonge to Johor or, as the title insists, ‘Singapore and Johor’. Many of the texts come from the former working papers of Hugo Grotius. At the end of the book are a glossary and list of place names, both extremely useful tools in helping the reader make sense of the documents. Peter Borschberg has assembled a collection of rarely studied sources, notably Matelieff’s ‘memorials’ concerning the Singapore-Johor region and the state of Dutch trade in the East Indies. This is a continuation of his scholarly, detailed and often revelatory studies on the area’s geo-political and historical significance [End Page 144] during the early seventeenth century. Borschberg has previously published a monograph on the Singapore and Melaka Straits region, as well as edited the writings of the Flemish trader Jacques de Coutre, some of which concerns the Singapore-Johor-Melaka area.1 Two of the longest documents in this volume are the excerpts from Admiral Matelieff’s Journal of his voyage to Asia (1605–1608), and excerpt from Matelieff’s Memorial of June 1607, both of which contain astute observations on Johor, on the conclusion of the Dutch–Johor treaties of May and September 1606 as well as other related matters. Other fascinating documents include the letters written by King Ala’udin of Johor and Raja Bongsu to Prince Maurits (the stadhouder or Stadholder of the Dutch Republic). Although translated from the original Malay into Dutch (and now into English), they still reflect a Malay perception of diplomacy and international relations. The study of diplomatic correspondence between Asian potentates and European rulers or governors-general continues to be essential to a deeper understanding of how the rulers of indigenous states dealt with Western diplomatic and commercial norms. The archives of the Dutch United East India Company (VOC) are especially rich in this genre of correspondence, for instance the diplomatic letters from Asian rulers to the Governors-General and Council in Batavia included in the daily journals of Batavia Castle (Daghregister Batavia).2 A key issue analysed in this volume (and the analysis may be found both in Borschberg’s own introduction and the sources themselves) is the VOC’s search for a suitable spot to serve as a ‘rendezvous’ or ‘central warehouse’ for its ships, cargoes and merchants in Southeast Asia. The Matelieff documents reveal that around 1606 Jayakerta (the future Batavia) was far from being the only possible candidate as the VOC’s headquarters in the Indies. The Singapore-Johor area, especially the site of present-day Singapore, was also seriously considered, as were Aceh, Melaka (then still in Portuguese hands), Palembang, Banten, and even Pulau Condor and the Spice Islands. That the Dutch eventually opted for a location near the Sunda Straits (rather than Singapore or Melaka Straits) was because of a perception (espoused by Matelieff) that those seas were navigable all year round, unaffected by monsoons. Such an advantage would enable Dutch vessels to travel without costly delays. Other factors which weakened Johor’s case were the apparent instability of Johorese court politics and the lure of Malukan spices. Though the book’s major emphasis is on Dutch perceptions and decision-making, the Malay element is never neglected by Borschberg. Indeed, he manfully grapples with the complex nomenclature as well as the convoluted intrigues of the leading personalities at the Johor court. However much focus is concentrated on the figure of Matelieff and, to a lesser extent, on his fellow-admiral Pieter Willemsz Verhoeff, the royal house and orang kaya of Johor also feature...

Michael P.De Jonge: Bonhoeffer's Theological Formation: Berlin, Barth and Protestant Theology. Oxford: Oxford University Press, 2012; pp. xiv + 158.

Journal of Religious HistoryVolume 40, Issue 4 p. 620-621 BOOK REVIEW Michael P. De Jonge: Bonhoeffer's Theological Formation: Berlin, Barth and Protestant Theology. Oxford: Oxford University Press, 2012; pp. xiv + 158. John A. Moses, John A. Moses St Mark's National Theological CentreSearch for more papers by this author John A. Moses, John A. Moses St Mark's National Theological CentreSearch for more papers by this author First published: 02 December 2016 https://doi.org/10.1111/1467-9809.12393Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume40, Issue4December 2016Pages 620-621 RelatedInformation

Book Review: Journal, Memorials and Letters of Cornelis Matelieff de Jonge: Security, Diplomacy and Commerce in 17th-century Southeast Asia

Book Review: Journal, Memorials and Letters of Cornelis Matelieff de Jonge: Security, Diplomacy and Commerce in 17th-century Southeast Asia

Improving Research into Models of Maternity Care to Inform Decision Making.

In a Perspective, Ank de Jonge and Jane Sandall discuss research on models of maternity care led by midwives.

Comments on Bozzatello et al. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data. J. Clin. Med. 2016, 5, 67.

Paola Bozzatello et al. [1] have done a comprehensive qualitative review of the potential use of long-chain polyunsaturated fatty acids in the prevention and treatment of mental disorders.[...].

Are we misinforming our low-risk mothers regarding birthplace outcomes: is it time for formal consent?: AGAINST: Formal consent is not necessary for home births.

Every woman with a planned pregnancy wants to have a good birth and a healthy baby. Low-risk expectant mothers, especially, are very likely nowadays to have the desired outcome. In Western countries births predominantly take place in hospital. In some countries, such as the Netherlands and the UK, home birth is still a viable option for low risk pregnant women. The debate about the safety of home birth is often heated and it is frequently suggested that women should wisely ‘choose to be on the safe side’ and opt for a hospital birth, since complications cannot always be predicted in advance. If it is true that the hospital is always the safest choice, the question may arise whether women who prefer to give birth at home should formally be advised of the risks and asked to give formal consent. We want to argue against formal consent in planned home birth situations, unless the system is such that formal consent is also being asked in case a low-risk woman chooses to have a hospital birth. Women should always be informed of the pros and cons of different places of birth and asked to consider carefully where they want to give birth. Placing the burden on home birth situations only, is misleading. In recent years a number of studies have looked at the safety of planned home births compared to planned hospital births in low risk pregnant women. The highest quality data and largest studies are from Dutch and UK studies (de Jonge A et al. BJOG 2015;122:720–728. BMJ 2011; 343:d7400 doi: 10.1136/bmj.d7400; BMJ 2013; 346:f3263 doi: 10.1136/bmj.f3263). Adverse perinatal outcomes were uncommon irrespective of birth setting. The largest study included 743 070 low-risk planned home and hospital births in the Netherlands. It showed no increase in adverse perinatal outcomes in home births (de Jonge A et al. BJOG 2015;122:720–728.). The UK Birthplace study showed an increase in adverse outcomes (not deaths) in home births, only in the subgroup of primiparous women (Open Access. BMJ 2011; 343:d7400 doi: 10.1136/bmj.d7400). A large Dutch study that looked at maternal outcomes, showed no increase in morbidity in planned home births (BMJ 2013; 346:f3263 doi: 10.1136/bmj.f3263). Low-risk women who have a planned birth in an obstetric unit are far more likely to receive medical interventions such as epidural anaesthesia, augmentation, instrumental delivery or caesarean section (Open Access. BMJ 2011; 343:d7400 doi: 10.1136/bmj.d7400). Those interventions carry risks for the mother and baby and in the case of caesarean sections also for the baby in a subsequent pregnancy (Kok N et al. BJOG 2014;121:216–223). In a system with good midwifery care, good transportation possibilities to hospital and good collaboration between midwives and obstetricians, such as in the Netherlands, the risks for the baby of a home birth are not larger than those of a hospital birth. The risks of interventions that can have major side effects, however, is far larger in a hospital than in a home setting. Pregnant women should receive ample information on the risks and benefits of place of delivery. Formal informed consent for home births only, denies low-risk pregnant women the opportunity to carefully consider the risks of a hospital delivery. Full disclosure of interests available to view online as supporting information. ■ Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract CT113: The time to progression ratio: a new individualized volumetric parameter for early detection of clinical benefit of targeted therapies

Abstract Introduction: Early signs of clinical activity are an important factor in the decision to advance development of novel targeted drugs. Response Evaluation Criteria In Solid Tumors (RECIST) has limited value however, as many patients with relatively slowly growing tumors will end up in the Stable Disease (SD) group, obscuring the distinction between a slow natural course of disease or treatment effect. Furthermore, when determining therapeutic efficacy across tumor types using progression free survival, there is also no correction for the individual tumor's natural growth rate. To address this, we developed the Time To Progression (TTP) ratio, a novel clinical trial efficacy endpoint that is based on volumetrics and an intra-patient control. Methods: A prospective multicenter biomarker discovery study (CPCT-03, NCT01566279) was designed. Unselected cancer patients, without regular treatment options, were included and received treatment with the mTOR inhibitor everolimus. Treatment response was determined using both RECIST and the volumetric TTP ratio. The TTP ratio was defined as TTP1/TTP2, i.e. the quotient of the time to a prospectively determined ?30% volumetric increase in target lesions or occurrence of new lesions before treatment (TTP1) and on-treatment (TTP2). Response was classified as a TTP ratio of <0.7. Volumetric measurements were performed by two observers, independent from each other, using EncoreUnFoie v5.0. TTP ratio was correlated with Overall Survival (OS). Results: Seventy-three patients were included, of whom 59 patients started treatment with everolimus. A TTP ratio could be determined in 43 of these patients (73%). According to RECIST, 35 patients (59%) had SD and one patient demonstrated a partial response (PR), while only 21 patients (36%) met the pre-specified criteria for treatment success according to our volumetric TTP ratio. Whereas RECIST (SD+PR) and TTP ratio were both correlated with OS (p<0.001, log- rank test), TTP ratio also differentiated which patients had a longer median OS within the SD RECIST group (n = 28). TTP ratio responders had a median OS of 11 months (95% CI 4.4-17.6), compared to 5 months (95%CI 3.2-6.8) for non-responders (p = 0.0496, log-rank test). The inter-observer agreement (Krippendorff's alpha) for volumetric measurements was 0.78 (95%CI 0.70-0.87) for a total of 199 evaluated scans. Conclusion: These results suggest that volumetric TTP ratio is a reliable method to determine response, with a high inter-observer agreement. The TTP ratio correlates to OS and distinguishes which patients within the RECIST SD group had longer survival, which could be interpreted as a sign of clinical benefit. The TTP ratio may be an important tool to guide early clinical drug development and deserves further investigation. Citation Format: Fleur Weeber, Geert A. Cirkel, Christa G.M. Gadellaa - van Hooijdonk, Sander Bins, Marlous Hoogstraat, Erik van Werkhoven, Stefan M. Willems, Marijn van Stralen, Wouter B. Veldhuis, Nicolle J.M. Besselink, Neeltje Steeghs, Maja J. de Jonge, Marlies H.G. Langenberg, Edwin Cuppen, Jan H. Schellens, Stefan Sleijfer, Martijn P.J.K. Lolkema, Emile E. Voest. The time to progression ratio: a new individualized volumetric parameter for early detection of clinical benefit of targeted therapies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT113.

Abstract 3193: Development of a colon cancer model system reveals epithelial contribution to poor-prognosis gene signatures

Abstract Background: Recent consensus on molecular classification categorizes colorectal cancer (CRC) into 4 robust subtypes: CMS1 (epithelial-MSI), CMS2 (epithelial-canonical), CMS3 (epithelial-metabolic) and CMS4 (mesenchymal)1. CMS4 is linked to poor cancer prognosis and characterized by mesenchymal and epithelial-to-mesenchymal transition (EMT) gene expression2,3. Recent attempts to deconvolute the transcriptome from CRC tumors have suggested that the mesenchymal gene expression results from a large stromal compartment and is not due to epithelial cells with EMT-like features4,5. This challenges the classic notion that tumor cells activate the EMT program to undergo trans-differentiation into mesenchymal cells as observed in a number of in vitro and in vivo studies6. To resolve these conflicting views a detailed investigation of the tumor or stromal cell contributions to the mesenchymal signature is important. Material & methods: We developed patient-derived xenografts (PDX) from multiple subtypes of CRCs. Transcriptome analysis was performed to assign each tumor and PDX to a CMS subtype, and further dissect the contribution of both epithelial and stromal gene expression to the overall expression phenotype. Additionally, we established multiple cultures from primary human CRCs to further assess subtypes-differences. Results: We developed a panel of human CRC PDXs from all subtypes (CMS1-4). The expression profiles of the patient's tumor and PDXs remain stable for multiple serial passages in vivo. Evaluating the gene expression in the PDXs, which are free of human stroma, our analyses identified tumor specific expression markers that were differentially expressed in the mesenchymal subtype (CMS4). This finding suggests the presence of an epithelial tumor derived signal in mesenchymal tumors which contributes to CMS4 specific gene expression. This set of epithelial specific CMS4 tumor markers has been validated in other CRC expression datasets and associated with disease relapse. Our panel of primary cell lines representing various subtypes showed differential sensitivity to certain therapeutic agents thus indicating a subtype-specific drug response. Conclusions: The identification of diverse subtypes in our panel of CRCs and corresponding PDXs, shows the presence of distinct tumor specific gene expression in mesenchymal CMS4 tumors. Furthermore, the primary CRC cell line panel comprising all subtypes, provides great insight into CRC heterogeneity and serves as a valuable model system to accelerate the development of effective treatment.

Editorial Comment

Semen analyses remain the foundation of andrological work-up in the evaluation of male fertility and infertility. It is highly quantitative based on visual parameters and does not usually take into consideration the functionality of the sperm itself as measured by certain other parameters such as reactive oxygen species (ROS) and/or DNA fragmentation. 1 Lamb D. Semen analysis in 21st century medicine: the need for sperm function testing. Asian J Androl. 2010; 12: 64-70 Crossref PubMed Scopus (48) Google Scholar These have been shown to potentially affect pregnancy outcomes along with quantitative parameters. Semen parameters rely on the physiological and pathophysiological mechanisms of spermato genesis in the seminiferous tubules; the cycle of production; issues of processing and transportation through the reproductive tract; storage in the reproductive tract; and the natural degradation process of the sperm if not ejaculated. All these factors influence clinical management. As such, one of the simplest ways to consider this process and the quality of semen parameters is the abstinence period since last ejaculation, but the exact time frame is not completely defined in the literature. 2 Amann R.P. Considerations in evaluating human spermatogenesis on the basis of total sperm per ejaculate. J Androl. 2009; 30: 626-641 Crossref PubMed Scopus (34) Google Scholar How frequent is too frequent for ejaculation to deplete the sperm stored or produced or time to “restock” between ejaculations? How long is too long before sperm is broken down or become ‘stagnant”? 3 Mortimer D. Templeton A.A. Lenton E.A. Coleman R.A. Influence of abstinence and ejaculation-to-analysis delay on semen analysis parameters of suspected infertile men. Arch Androl. 1982; 8: 251-256 Crossref PubMed Scopus (45) Google Scholar , 4 Correa-Pérez J.R. Fernández-Pelegrina R. Aslanis P. Zavos P.M. Clinical management of men producing ejaculates characterized by high levels of dead sperm and altered seminal plasma factors consistent with epididymal necrospermia. Fertil Steril. 2004; 8: 1148-1150 Abstract Full Text Full Text PDF Scopus (20) Google Scholar The World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen (5th Edition) 2010, which is viewed as the authoritative text on the matter, states, “The sample should be collected after a minimum of 2 days and a maximum of 7 days of sexual abstinence. If additional samples are required, the number of days of sexual abstinence should be as constant as possible at each visit.” 5 Cooper T.G. Keck C. Oberdieck U. Nieschlag E. Effects of multiple ejaculations after extended periods of sexual abstinence on total, motile and normal sperm numbers, as well as accessory gland secretions, from healthy normal and oligozoospermic men. Hum Reprod. 1993; 8: 1251-1258 PubMed Google Scholar , 6 Tyler J.P. Crockett N.G. Driscoll G.L. Studies of human seminal parameters with frequent ejaculation. I. Clinical characteristics. Clin Reprod Fertil. 1982; 1: 273-285 Google Scholar , 7 De Jonge C. LaFromboise M. Bosmans E. Ombelet W. Cox A. Nijs M. Influence of the abstinence period on human sperm quality. Fertil Steril. 2004; 82: 57-65 Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Amann and Chapman performed an eloquent study in 2009 that showed that to obtain meaningful values for diagnosis and distinguishing men with high or low sperm production and that the best abstinence period was more in the 42-54 hour time frame to an upper limit of 64 hours. 8 Amann R.P. Chapman P.L. Total sperm per ejaculate of men: obtaining a meaningful value or a mean value with appropriate precision. J Androl. 2009; 30: 642-649 Crossref PubMed Scopus (20) Google Scholar For men producing few sperm, up to 7 days was recommended. 8 Amann R.P. Chapman P.L. Total sperm per ejaculate of men: obtaining a meaningful value or a mean value with appropriate precision. J Androl. 2009; 30: 642-649 Crossref PubMed Scopus (20) Google Scholar

Journal, Memorials and Letters of Cornelis Matelieff de Jonge — Security, Diplomacy and Commerce in 17 th-century Southeast Asia, Peter Borschberg, éd.

Journal, Memorials and Letters of Cornelis Matelieff de Jonge — Security, Diplomacy and Commerce in 17 th-century Southeast Asia, Peter Borschberg, éd.

Permissive hypoxemia/conservative oxygenation strategy: Dr. Jekyll or Mr. Hyde?

Oxygen is one of the essentials required for sustaining life, which plays an important role in human medical history. It has become a routine therapy for critically ill patients, and the assessment and administration of oxygen in the ICU gained more and more attention (1,2). Both hypoxia and hyperoxia is related to adverse outcome. de Jonge et al. demonstrated that there was a U-shaped relationship between PaO 2 and in-hospital mortality, the lowest of the mortality being at PaO 2 values of 110–150 mmHg; mortality sharply increased both at PaO 2 values 225 mmHg (3). Nowadays, the “double-edged sword” character of oxygen is well established. On one hand, the hypoxia result in the imbalance between O 2 supply and requirements, which could induce tissue hypoxia and cell death. On the other hand, the presence of hyperoxia enhances reactive oxygen species (ROS) and oxidative stress, which cause alveolar and cell damage. The benefit/harm ratio of oxygen therapy is determined by the O 2 dose, exposure duration, and underlying diseases. To reduce the potential risks of hyperoxia, a lower oxygenation targets may be acceptable in critically ill patients. A tolerable low SaO 2 also termed as permissive hypoxemia/conservative oxygenation strategy. Generally, the permissive hypoxemia strategy aims for an SaO 2 between approximately 85% and 95%, which always use in the ARDS patients and preterm infants (4,5).

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

De Jonge, Ross, and Wang to receive MRS Innovation in Materials Characterization Award

De Jonge, Ross, and Wang to receive MRS Innovation in Materials Characterization Award

Abstract P2-05-17: ARGX-111 depletes MET-expressing circulating tumor cells via enhanced ADCC, resulting in inhibition of metastasis

Abstract Several lines of experimental evidence suggest that Hepatocyte Growth Factor (HGF) and its receptor MET play an important role in breast cancer progression and drug resistance. To date, targeted MET inhibitors in clinical development have primarily shown cytostatic rather than cytotoxic effects. Development of a cytotoxic MET inhibitor would serve to complement standard breast cancer therapy, especially when administered in the adjuvant/neo-adjuvant setting. We have developed ARGX-111, a human antibody antagonist of MET function. ARGX-111 blocks both HGF-dependent and -independent signaling, down-regulates tumor cell surface expression of MET and kills MET-overexpressing cells by enhanced antibody-dependent cellular cytotoxicity (ADCC). ARGX-111 was shown to be more efficacious than an ADCC-inactive control antibody in both HGF-dependent and -independent tumor xenograft models. ADCC reporter assays confirmed the cytotoxic effects of ARGX-111 in patient-derived primary tumor specimens, including MET-expressing breast cancer stem-like cells. In an orthotopic mouse model of metastatic mammary carcinoma (MDA-MB-231), adjuvant or neo-adjuvant treatment with ARGX-111 was significantly more effective in depleting circulating tumor cells (CTCs) and suppressing the development of bone and lung metastases than the ADCC-inactive control. Taken together, these results provide a rationale for clinical investigation of ARGX-111 in the early breast cancer setting. An ongoing Phase 1 study (NCT02055066) is examining the effects of ARGX-111 on CTCs, alongside the assessment of its safety and efficacy. Citation Format: Morello V, Hultberg A, De Jonge N, Huyghe L, Hanssens V, Brouckaert P, Saunders M, Dreier T, Thibault A, Rolfo C, Aftimos P, Awada A, Michieli P, de Haard H. ARGX-111 depletes MET-expressing circulating tumor cells via enhanced ADCC, resulting in inhibition of metastasis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-17.