Hydraulic system analysis by the method of characteristics.

SIGLEAvailable from British Library Document Supply Centre- DSC:D38814/82 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Anarchy, Groups, and Conflict: An Experiment on the Emergence of Protective Associations

In this paper, we investigate the implications of the philosophical considerations presented in Nozick’s Anarchy, State, and Utopia, by examining group formation in a laboratory setting where subjects engage in both cooperative and conflictual interactions. We endow participants with a commodity used to generate earnings, plunder others, or protect against plunder. In our primary treatment, we allow participants to form groups to pool their resources. We conduct a baseline comparison treatment that does not allow group formation. We find that allowing subjects to organize themselves into groups does not lead to more cooperation and may in fact exacerbate tendencies for conflict.Nozickian protective associations, Conflict, Anarchy, Experimental economics

Anarchy, Groups, and Conflict: An Experiment on the Emergence of Protective Associations

In this paper, we investigate the implications of the philosophical considerations presented in Nozick’s Anarchy, State, and Utopia, by examining group formation in a laboratory setting where subjects engage in both cooperative and conflictual interactions. We endow participants with a commodity used to generate earnings, plunder others, or protect against plunder. In our primary treatment, we allow participants to form groups to pool their resources. We conduct a baseline comparison treatment that does not allow group formation. We find that allowing subjects to organize themselves into groups does not lead to more cooperation and may in fact exacerbate tendencies for conflict

Formulation and evaluation of new oxazaphosphorine prodrugs-loaded lipid nanocapsules for cancer treatment

Oxazaphosphorines (cyclophosphamide (CPA) and ifosfamide (IFO)) represent an important group of therapeutic molecules due to their substantial antitumor and immunomodulating activities. Unfortunately, despite the benefits brought by these molecules, their clinical use shows limitations, notably in chemotherapy, due to the development of resistance, interpatients variation and toxicities (urinary toxicity, neurotoxicity and nephrotoxicity). To circumvent these problems, new oxazaphosphorine analogs have been synthetized and present an interesting anti-tumor activity alone with reduced toxicity [1]. Pentanoxy moiety has been grafted on C4 position of ifosfamide (P-IFO). Nevertheless, these new analogs are lipophilic and unstable in aqueous medium. To administer it, this paper proposes to formulate this analog into nanocarriers. Lipid nanocapsules form a new generation of nanovector that can encapsulate a number of anticancer agents [2]. In the present research, P-IFO-loaded LNCs were formulated and characterized. A new formulation based on glycerol monooleate (Peceol®) was developed, optimized and then characterized. Batches of P-IFO-LNCs were obtained with a size of 47.2±0.7nm with a narrow size distribution and a drug payload of 8.42±1.05mg/g. The suspension remained stable at 4°C for 14 days in terms of mean particle size, polydispersity index and pH. The drug payload decreased after 7 days but a high rate was still found (5.88±1.01mg/g) up to 14 days. The stealth properties of these nanoparticles were examined in vitro using the complement activation (CH50) test. This test revealed a low consumption of plasma protein in the presence of such P-IFO-LNCs. In vitro cytotoxicity of P-IFO-LNCs was determined in two human cell lines; i.e. rhabdomyosarcoma (RMS-1) and Ewing sarcoma (A673) and showed a similar activity compared to the free form. Finally, in vivo activity testing of P-IFO-LNCs is in progress in a murine model bearing a RMS-1 xenograft after intravenous administration. References [1] Skarbek C, et al., Preactivated Oxazaphosphorines Designed for Isophosphoramide Mustard Delivery as Bulk Form or Nanoassemblies: Synthesis and Proof of Concept. Journal of Medicinal Chemistry. 22;58(2):105-17, 2015. [2] Huynh NT, et al., Lipid nanocapsules: A new platform for nanomedicine. International Journal of Pharmaceutics. 379(2):201–9, 2009. Acknowledgments: The authors are very grateful to the Ligue contre le Cancer, Comité du Maine et Loire and Comité d’Ille et Vilaine which founded this work

A potential library for primary MFL pedagogy: the case of Young Pathfinders

As readers of this journal will know very well, 2010 will see all KS2 (ages 7-11) pupils in England entitled to learn a modern foreign language in normal curriculum time. This development of the commitment to primary language learning should provide an excellent opportunity and experience for pupils, whilst at the same time requiring some radical changes for many teachers, schools and much of the wider language learning community. Recent research has indicated general trends suggesting an increase in primary languages already, in anticipation of this development and even beforehand. One of the most recent studies indicates that 43% of primary children currently learn a foreign language at KS2, either in class or as an extra-curricular activity, although the extent of this learning varies considerably (Driscoll, Jones and Macrory, 2004). It has also been suggested (Muijs et al, 2005) that there are certain aspects of the process that will be particularly demanding if the challenge of providing this entitlement are to be met

Combined strategy based on pre-activated analogs of oxazaphosphorines for increased therapeutic index and immune modulation

Oxazaphosphorines (Oxaza) represented by cyclophosphamide (CPA) and ifosfamide (IFO) are still the corner stone of several polychemotherapy protocols as they are widely indicated in the treatment of numerous cancer from soft tissue sarcomas to lymphomas and immune-related diseases. However, Oxaza are prodrugs requiring cytochrome (CYP) P450 bioactivation responsible of limiting adverse effects. In the case of IFO, bioactivation leads to a low release of 4-OH-IFO (10%), which generates the active nitrogen mustard displaying DNA cross-links. Associated toxicities of IFO due to acrolein, (urotoxicity) and to chloroacetaldehyde (neuro and nephrotoxicity) have been described. Thus, increasing IFO therapeutic index could be of major interest. To circumvent these toxicities, our team has designed new pre-activated IFO analogs to avoid CYP bioactivation (Skarbek et al J Med Chem 2015). Among these analogues some have the ability to self-assemble as nanoassemblies (NAs), the others can be encapsulated within nano-lipid capsules (NLCs). These new drug delivery systems (DDS) can take advantage of passive targeting, as stealthiness of these DDS can be provided by PEGylation by using Cholesterol-polyethylene glycol or the use of surfactant. These DDS can also be functionalized by appropriate monoclonal antibodies leading to multi stage DDS with active targeting properties. Regarding CPA, it has been shown and described in literature that low doses of CPA enhance the immunity by promoting differentiation of CD4⁺ cell toward Th1. As IFO is isomeric form of CPA, it was assumed that IFO could also have such properties. Studies on immunocompetent MCA205 mouse model, an immunogenic fibrosarcoma mouse model, demonstrate a dose-dependent immunomodulation of IFO towards a modulation of the secretion of IFNy, IL-17A and IL-6 cytokines. The ongoing experiments on mouse model depleted in CD4⁺ T cells and CD8⁺ T cells show the antitumor efficacy of IFO 150mg/kg on these immune cells in tumor regression. Both strategies could lead to the design of nano-immuno-conjugates (NICs) which could benefit of the immunomodulatory effects of X-Oxaza combined to their antiproliferative properties targeted through immune checkpoint antibodies. These new functionalized DDS may provide a useful strategy to give specificity to active drugs used for many years in clinical practice. Both DDS could be grafted with mAbs which could lead to a new family of DDS aiming to combine antiproliferative and immunomodulatory properties for a dual antitumoral action Citation Format: Julia Delahousse, Charles Skarbek, Valentine Gauthier, M Desbois, Emilie Roger, C. Pioche-Durieu, M. Rivard, D. Desmaële, T. Martens, E. LeCam, Jean-Pierre Benoit, P. Couvreur, Nathalie Chaput-Gras, Angelo Paci. Combined strategy based on pre-activated analogs of oxazaphosphorines for increased therapeutic index and immune modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2195. doi:10.1158/1538-7445.AM2017-219

Changes in disease burden in Poland between 1990–2017 in comparison with other Central European countries: A systematic analysis for the Global Burden of Disease Study 2017

Background Systematic collection of mortality/morbidity data over time is crucial for monitoring trends in population health, developing health policies, assessing the impact of health programs. In Poland, a comprehensive analysis describing trends in disease burden for major conditions has never been published. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides data on the burden of over 300 diseases in 195 countries since 1990. We used the GBD database to undertake an assessment of disease burden in Poland, evaluate changes in population health between 1990–2017, and compare Poland with other Central European (CE) countries

Analysis of density based and fuzzy c-means clustering methods on lesion border extraction in dermoscopy images

<p>Abstract</p> <p>Background</p> <p>Computer-aided segmentation and border detection in dermoscopic images is one of the core components of diagnostic procedures and therapeutic interventions for skin cancer. Automated assessment tools for dermoscopy images have become an important research field mainly because of inter- and intra-observer variations in human interpretation. In this study, we compare two approaches for automatic border detection in dermoscopy images: density based clustering (DBSCAN) and Fuzzy C-Means (FCM) clustering algorithms. In the first approach, if there exists enough density –greater than certain number of points- around a point, then either a new cluster is formed around the point or an existing cluster grows by including the point and its neighbors. In the second approach FCM clustering is used. This approach has the ability to assign one data point into more than one cluster.</p> <p>Results</p> <p>Each approach is examined on a set of 100 dermoscopy images whose manually drawn borders by a dermatologist are used as the ground truth. Error rates; false positives and false negatives along with true positives and true negatives are quantified by comparing results with manually determined borders from a dermatologist. The assessments obtained from both methods are quantitatively analyzed over three accuracy measures: border error, precision, and recall. </p> <p>Conclusion</p> <p>As well as low border error, high precision and recall, visual outcome showed that the DBSCAN effectively delineated targeted lesion, and has bright future; however, the FCM had poor performance especially in border error metric.</p