Nanoparticular iron complex drugs for parenteral administration - physicochemical characterization, biological distribution and pharmacological safety

Iron deficiency is the most common deficiency disease worldwide with many patients who require intravenous iron. Within the last years new kind of parenteral iron complexes as well as generic preparations entered the market. There is a high demand for methods clarifying benefit to risk profiles of old and new iron complexes. It is also necessary to disclose interchangeability between originator and intended copies to avoid severe anaphylactic and anaphylactoid side reaction and assure equivalence of therapeutic effect.rnrnThe investigations presented in this work include physicochemical characterization of nine different parenteral iron containing non-biological complex drugs. rnWe developed an in-vitro assay, which allows the quantification of labile iron in the different complexes and thus it is a useful tool to estimate the pharmaclogical safety regarding iron related adverse drug events. This assay additionally allowed the estimation of complex stability by evaluation of degradation kinetics at the applied conditions.rnrnAn in-ovo study was performed to additionally compare different complexes in respect to body distribution. This in combination with complex stability information allowed the risk estimation of potential local acute and chronic reactions to iron overload.rnrnInformation obtained by the combination of the methods within this work are helpful to estimate the safety and efficacy profile of different iron containing non-biological complex drugs. rnrnPhysicochemical differences between the complexes were demonstrated in respect to size of the inorganic fraction, size and size distribution of the complete particles, structure of the inorganic iron fraction, morphology of the complexes and charge of the complexes. And furthermore significant differences in the biological behavior of different complexes were demonstrated. rnrnThe combination of complex stability and biodistribution as well as the combination of structure, size and stability represent helpful tools for the physicochemical characterization of iron containing non-biological complex drugs and for the estimation of pharmacological safety. This work thus represents an up to date summary of some relevant methods for the characterization of intravenous iron complex drugs in respect to pharmaceutical quality, pharmacological safety and aspects of efficacy. rnrnProspectively, it is worthwhile that the methods within this work will contribute to the development and/or characterization of iron containing nanoparticular formulations with beneficial efficacy and safety profiles.rn

Panel Discussion - Finns in the United States

“Book Notes with Four Authors from Finns in the United States: A History of Settlement, Dissent, and Integration” This panel presentation will highlight chapters in the newly released book, Finns in the United States, published by Michigan State University Press. Authors will discuss their contribution to the book, and highlight key aspects of their work. Finns in the United States has been touted as a fresh and up-to-date analysis of Finnish Americans, an insightful volume that lays the groundwork for exploring this unique culture through a historical context, followed by an overview of the overall composition and settlement patterns of these newcomers.

Histo-blood group antigens as allo- and autoantigens

The science of blood groups has made giant steps forward during the last decade. Blood-group typing of red blood cells (RBCs) is performed on more than 15 million samples per year in Europe, today much less often for forensic reasons than for clinical purposes such as transfusion and organ transplantation. Specific monoclonal antibodies are used with interpretation on the basis of RBC agglutination patterns, and mass genotyping may well be on its way to becoming a routine procedure. The discovery that most blood group systems, whose antigens are by definition found on RBCs, are also expressed in multiple other tissues has sparked the interest of transplantation medicine in immunohematology beyond the HLA system. The one and only "histo-blood group" (HBG) system that is routinely considered in transplantation medicine is ABO, because ABO antigen-incompatible donor/recipient constellations are preferably avoided. However, other HBG systems may also play a role, thus far underestimated. This paper is an up-to-date analysis of the importance of HBG systems in the alloimmunity of transplantation and autoimmune events, such as hemolytic anemia.

St. Louis, Missouri, 1895 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: The Matthews-Northrup up-to-date map of St. Louis MO. It was published by Matthews-Northrup Co in 1895. Scale [ca. 1:95,040]. Covers also a portion of East Saint Louis, Stites, and Madison, Illinois. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Missouri East State Plane Coordinate System NAD83 (in Feet) (Fipszone 2401). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, street car lines, drainage, selected public buildings, parks, cemeteries, and more. Includes index to hotels, prominent buildings and institutions, churches, and places of amusement. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Vaccin RRO et autisme : la désinformation à l'œuvre

L'objectif de ce texte est de faire le point sur la controverse soulevée par Wakefield et ses collaborateurs concernant l'effet du vaccin RRO à titre de déclencheur éventuel d'une forme d'autisme. Après avoir présenté les travaux de Wakefield et al., les auteurs montrent que les recherches effectuées dans plusieurs pays mettent en évidence que l'hypothèse du lien entre le vaccin RRO et l'autisme n'est nullement fondée. La présentation de l'ensemble des résultats débouche sur une discussion comprenant trois volets: la nature de l'augmentation du nombre de cas d'autisme au cours des dernières années, la méthodologie utilisée pour vérifier l'hypothèse du lien vaccin RRO et autisme et les enjeux éthiques d'une telle controverse.

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In several pathogens, this process triggers the production of virulence factors and/or a switch in bacterial lifestyle that is a major determining factor in the outcome and severity of the infection. Understanding how bacteria control these signaling systems is crucial to the development of novel antimicrobial agents capable of reducing virulence while allowing the immune system of the host to clear bacterial infection, an approach likely to reduce the selective pressures for development of resistance. We provide here an up-to-date overview of the molecular basis and physiological implications of cell-to-cell signaling systems in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas aeruginosa. All of the known cell-to-cell signaling systems in this bacterium are described, from the most-studied systems, i.e., N-acyl homoserine lactones (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), to less-well-studied signaling molecules, including diketopiperazines, fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and pyocyanin. This overview clearly illustrates that bacterial communication is far more complex than initially thought and delivers a clear distinction between signals that are quorum sensing dependent and those relying on alternative factors for their production.

Vaccin RRO et autisme : la désinformation à l'œuvre.

L'objectif de ce texte est de faire le point sur la controverse soulevée par Wakefield et ses collaborateurs concernant l'effet du vaccin RRO à titre de déclencheur éventuel d'une forme d'autisme. Après avoir présenté les travaux de Wakefield et al., les auteurs montrent que les recherches effectuées dans plusieurs pays mettent en évidence que l'hypothèse du lien entre le vaccin RRO et l'autisme n'est nullement fondée. La présentation de l'ensemble des résultats débouche sur une discussion comprenant trois volets: la nature de l'augmentation du nombre de cas d'autisme au cours des dernières années, la méthodologie utilisée pour vérifier l'hypothèse du lien vaccin RRO et autisme et les enjeux éthiques d'une telle controverse.

Green operations initiatives in the automotive industry:an environmental reports analysis and benchmarking study

Purpose: The purpose of this paper is to focus on investigating and benchmarking green operations initiatives in the automotive industry documented in the environmental reports of selected companies. The investigation roadmaps the main environmental initiatives taken by the world's three major car manufacturers and benchmarks them against each other. The categorisation of green operations initiatives that is provided in the paper can also help companies in other sectors to evaluate their green practices. Design/methodology/approach: The first part of the paper is based on existing literature on the topic of green and sustainable operations and the "unsustainable" context of automotive production. The second part relates to the roadmap and benchmarking of green operations initiatives based on an analysis of secondary data from the automotive industry. Findings: The findings show that the world's three major car manufacturers are pursuing various environmental initiatives involving the following green operations practices: green buildings, eco-design, green supply chains, green manufacturing, reverse logistics and innovation. Research limitations/implications: The limitations of this paper start from its selection of the companies, which was made using production volume and country of origin as the principal criteria. There is ample evidence that other, smaller, companies are pursuing more sophisticated and original environmental initiatives. Also, there might be a gap between what companies say they do in their environmental reports and what they actually do. Practical implications: This paper helps practitioners in the automotive industry to benchmark themselves against the major volume manufacturers in three different continents. Practitioners from other industries will also find it valuable to discover how the automotive industry is pursuing environmental initiatives beyond manufacturing, apart from the green operations practices covering broadly all the activities of operations function. Originality/value: The originality of the paper is in its up-to-date analysis of environmental reports of automotive companies. The paper offers value for researchers and practitioners due to its contribution to the green operations literature. For instance, the inclusion of green buildings as part of green operations practices has so far been neglected by most researchers and authors in the field of green and sustainable operations. © Emerald Group Publishing Limited.

VLSI Watermark Implementations and Applications

This paper presents an up to date review of digital watermarking (WM) from a VLSI designer point of view. The reader is introduced to basic principles and terms in the field of image watermarking. It goes through a brief survey on WM theory, laying out common classification criterions and discussing important design considerations and trade-offs. Elementary WM properties such as robustness, computational complexity and their influence on image quality are discussed. Common attacks and testing benchmarks are also briefly mentioned. It is shown that WM design must take the intended application into account. The difference between software and hardware implementations is explained through the introduction of a general scheme of a WM system and two examples from previous works. A versatile methodology to aid in a reliable and modular design process is suggested. Relating to mixed-signal VLSI design and testing, the proposed methodology allows an efficient development of a CMOS image sensor with WM capabilities.

Alcohol consumption and related harm among university students in Ireland

Aim: Alcohol consumption is a leading cause of global suffering. The harms caused by alcohol to the individual, their peers and the society in which they live provokes public health concern. Elevated levels of consumption and consequences have been noted in those aged 18-29 years. University students represent a unique subsection of society within this age group. University authorities have attempted to tackle this issue throughout the past decade. However, the issue persists. Thus, the aim of this study is to contribute to the evidence base for policy and practice in relation to alcohol harm reduction among third-level students in Ireland. Methods: A mixed methods approach was employed. A systematic review of the prevalence of hazardous alcohol consumption among university students in Ireland and the United Kingdom from 2002 to 2014 was conducted. In addition, a narrative synthesis of studies of drinking types evidenced among youths in western societies was undertaken. A cross-sectional study focused on university students’ health and lifestyle behaviours with particular reference to alcohol consumption was undertaken using previously validated instruments. Undergraduate students registered to one university in Ireland were recruited using two separate modes; classroom and online. Studies investigated the impact of mode of data collection, the prevalence of hazardous alcohol consumption and resultant adverse consequences for mental health and wellbeing. In addition a study using a Q-methodology approach was undertaken to gain a deeper understanding of the cultural factors influencing current patterns of alcohol consumption. Data were analysed using IBM SPPS statistics 20, Stata 12, MPLUS and PQ Method. Results: The literature review focusing on students’ alcohol consumption found that there has been both an increase in hazardous alcohol consumption among university students and a convergence of male and female drinking patterns throughout the past decade. Updating this research, the thesis found that two-thirds of university students consume alcohol at a hazardous level, detailing the range of adverse consequences reported by university students in Ireland. Finally, the heterogeneous nature of this drinking was described in a narrative synthesis exposing six types of consumption. The succeeding chapters develop this review further by describing three typologies of consumption, two quantitative and one quali-quantilogical. The quantitative typology describes three types of drinking for men (realistic hedonist, responsible conformer and guarded drinker) and four types for women (realistic hedonist, peer-influenced, responsible conformer and guarded drinker). The quali-quantilogical approach describes four types of consumption. These are defined as the ‘guarded drinker’, the ‘calculated hedonist’, the ‘peer-influenced drinker’ and the ‘inevitable binger’. Discussion: The findings of this thesis highlight the scale of the issue and provide up-to-date estimates of alcohol consumption among university students in Ireland. Hazardous alcohol consumption is associated with a range of harms to self and harms to others in proximity to the alcohol consumer. The classification of drinkers into types signal the necessity for university management, health promotion practitioners and public health policy makers to tackle this issue using a multi-faceted approach.

Cancer and fertility preservation: International recommendations from an expert meeting

In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians. In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of "cancer and fertility preservation". A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation. Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations.

Mise en oeuvre de la surveillance pour la Directive Cadre Européenne sur l’Eau dans les départements d’Outre-Mer - Volet littoral

The implementation of the WFD in the French overseas takes into account local, morphological, climatic and socioeconomic peculiarities, as well as specificities of their ecosystems. This document provide an up-to-date assessment of the state of characteristics of the coastal water bodies, of development of indicators and of WFD monitoring programs in each of the French overseas departments: Martinique, Guadeloupe, French Guyana, Reunion Island and Mayotte.

Edible and poisonous fungi. (With 25 coloured plates.)

"The Board of agriculture published in 1910 a small handbook containing 25 coloured plates. This ... has been for some years out of print, and the Ministry ... has decided to republish. In the present edition the nomenclature and text-matter have been brought up-to-date. Some of the old plates have been omitted ... In their place seven new plates have been inserted."--Foreword.

Structure of polyamidoamide dendrimers up to limiting generations: A mesoscale description

The polyamidoamide (PAMAM) class of dendrimers was one of the first dendrimers synthesized by Tomalia and co-workers at Dow. Since its discovery the PAMAMs have stimulated many discussions on the structure and dynamics of such hyperbranched polymers. Many questions remain open because the huge conformation disorder combined with very similar local symmetries have made it difficult to characterize experimentally at the atomistic level the structure and dynamics of PAMAM dendrimers. The higher generation dendrimers have also been difficult to characterize computationally because of the large size (294852 atoms for generation 11) and the huge number of conformations. To help provide a practical means of atomistic computational studies, we have developed an atomistically informed coarse-grained description for the PAMAM dendrimer. We find that a two-bead per monomer representation retains the accuracy of atomistic simulations for predicting size and conformational complexity, while reducing the degrees of freedom by tenfold. This mesoscale description has allowed us to study the structural properties of PAMAM dendrimer up to generation 11 for time scale of up to several nanoseconds. The gross properties such as the radius of gyration compare very well with those from full atomistic simulation and with available small angle x-ray experiment and small angle neutron scattering data. The radial monomer density shows very similar behavior with those obtained from the fully atomistic simulation. Our approach to deriving the coarse-grain model is general and straightforward to apply to other classes of dendrimers.