OPTIMIZING A SHORT-END ELECTROPHORETICALLY MEDIATED MICRO-ANALYSIS (EMMA) ASSAY FOR CREATININE

In this work electrophoretically mediated micro-analysis (EMMA) is used in conjunction with short end injection to improve the in-capillary Jaffé assay for creatinine. Key advances over prior work include (i) using simulation to ensure intimate overlap of reagent plugs, (ii) using OH- to drive the reaction, (iii) using short-end injection to minimize analysis time and in-line product degradation. The potential-driven overlapping time with the EMMA approach, as well as the borate buffer background electrolyte (BGE) concentration and pH are optimized with the short end approach. The best conditions for short-end analyses would not have been predicted by the prior long end work, owing to a complex interplay of separation time and product degradation rates. Raw peak areas and flow-adjusted peak areas for the Jaffé reaction product (at 505 nm) are used to assess the sensitivity of the short-end EMMA approach. Optimal overlap conditions depend heavily on local conductivity differences within the reagent zone(s), as these differences cause dramatic voltage field differences, which effect reagent overlap dynamics. Simul 5.0, a dynamic simulation program for capillary electrophoresis (CE) systems, is used to understand the ionic boundaries and profiles that give rise to the experimentally obtained data for EMMA analysis. Overall, fast migration of hydroxide ions from the picrate zone makes difficult reagent overlap. In addition, the challenges associated with the simultaneous overlapping of three reagent zones are considered, and experimental results validate the predictions made by the simulation. With one set of “optimized” conditions including OH- (253 mM) as the third reagent zone the response was linear with creatinine concentration (R2 = 0.998) and reproducible over the clinically relevant range (0.08 to 0.1 mM) of standard creatinine concentrations. An LOD (S/N = 3) of 0.02 mM and LOQ (S/N=10) of 0.08 mM were determined. A significant improvement (43%) in assay sensitivity was obtained compared to prior work that considered only two reagents in the overlap.

The Ideology, Politics and Autonomous Art of Richard Weiner: (An Event in Discourse)"

The first aim of the project was to compile documentation on the life and work of Richard Weiner, a Czech journalist, writer and poet who spent the best part of his life as Paris correspondent for Lidove noviny. Langerova looked at the contexts and the growing independence of certain parts of his work, the distribution of thematic compositional elements into different parts of discourse and their position in the autonomous space of a work of art. Looking at the features of minority literature and the contemporary contexts of Weiner's life and work Langerova focuses on the situation of the Jewish community (Wiener came from an assimilated Jewish family). For this minorities, the function of language as a medium of communication which is able to create an autonomous world became increasingly important. Literature, which is based on this function of language, is a political matter par excellence before it begins forming as an autonomous, independent and divergent place. This means that everything private and intimate is closely connected to political and social responsibility, while supposedly objective genres contain subjective features. Another important characteristic is "nomadism", which asks the question of "Where do I belong". This was very important in Czechoslovakia after World War I , as in the issue of Zionism. Although Weiner rejected Zionism, he asks this question in his writing and it is reflected at a symbolic level in his work, which shows a fundamental thematic and compositional plan of a journey, cross-roads and wandering. These theses were reflected in Weiner's life, which was a series of continuous transfers and unplanned moves, often when he thought he had found his place. As well as tracing the course of his life, and his relations with and views of other writers, Langerova looks at his writings in various areas. Her major focus is the divergence of trivial and great events into different types of discourse in Richard Weiner's work, their transfer (small into great, trivial into mythical) and their historical context.

Molecular mechanisms of pathogenicity of Mycoplasma mycoides subsp. mycoides SC

Mycoplasma mycoides subsp. mycoides SC, the aetiological agent of contagious bovine pleuropneumonia (CBPP), is considered the most pathogenic of the Mycoplasma species. Its virulence is probably the result of a coordinated action of various components of an antigenically and functionally dynamic surface architecture. The different virulence attributes allow the pathogen to evade the host's immune defence, adhere tightly to the host cell surface, persist and disseminate in the host causing mycoplasmaemia, efficiently import energetically valuable nutrients present in the environment, and release and simultaneously translocate toxic metabolic pathway products to the host cell where they cause cytotoxic effects that are known to induce inflammatory processes and disease. This strategy enables the mycoplasma to exploit the minimal genetic information in its small genome, not only to fulfil the basic functions for its replication but also to damage host cells in intimate proximity thereby acquiring the necessary bio-molecules, such as amino acids and nucleic acid precursors, for its own biosynthesis and survival.

Evaluation of a novel biphasic calcium phosphate in standardized bone defects: a histologic and histomorphometric study in the mandibles of minipigs

OBJECTIVE: A novel biphasic calcium phosphate (CaP) granulate consisting of hydroxyapatite (HA) and beta-tricalciumphosphate (TCP) was compared with pure HA and pure TCP and with autograft as positive control. MATERIALS AND METHODS: Four standardized bone defects were prepared in both mandibular angles of 16 minipigs and grafted with autogenous bone chips, HA, HA/TCP (60% : 40%), or TCP. Histologic and histomorphometric analysis of bone formation and graft degradation followed healing periods of 2, 4, 8, and 24 weeks. RESULTS: 2 weeks: more bone formation in defects filled with autograft than with the three CaP materials (P<0.05). 4 weeks: bone formation differed significantly (P<0.05) between all four materials (autograft>TCP>HA/TCP>HA). 8 weeks: more bone formation in defects with autograft and TCP than with HA/TCP (P<0.05), and HA/TCP had more bone formation than HA (P<0.05). 24 weeks: no difference in bone formation between the groups. Autograft and TCP resorbed quickly and almost completely over 8 weeks, whereas HA/TCP and HA showed limited degradation over 24 weeks. CONCLUSION: All defects healed with mature lamellar bone and intimate contact between bone and the remaining graft material. The rate of bone formation corresponded to the content of TCP in the CaP materials.

Modulation of chemokine gene expression by Shiga-toxin producing Escherichia coli belonging to various origins and serotypes

Infection with Shiga-toxin producing Escherichia coli (STEC) may result in the development of the haemolytic-uremic syndrome (HUS), the main cause of acute renal failure in children. While O157:H7 STEC are associated with large outbreaks of HUS, it is difficult to predict whether a non-O157:H7 isolate can be pathogenic for humans. The mucosal innate immune response plays a central role in the pathogenesis of HUS; therefore, we compared the induction of IL-8 and CCL20 in human colon epithelial cells infected with strains belonging to different serotypes, isolated from cattle or from HUS patients. No correlation was observed between strain virulence and chemokine gene expression. Rather, the genetic background of the strains seems to determine the chemokine gene expression profile. Investigating the contribution of different bacterial factors in this process, we show that the type III secretion system of O157:H7 bacteria, but not the intimate adhesion, is required to stimulate the cells. In addition, H7, H10, and H21 flagellins are potent inducers of chemokine gene expression when synthesized in large amount.

Mental health and quality of life after genetic testing for Huntington disease: a long-term effect study in Germany

Predictive genetic testing for Huntington disease (HD) might cause severe short-term psychological reactions in patients with poor mental health. Very few studies exist on the long-term effects of genetic HD testing. The aim of this study was to assess mental health and quality of life in persons who were tested for HD mutation, to compare mental health depending on the result of the genetic test (non-carriers, gene carriers, and patients with HD) and to identify predictors of mental health and quality of life via linear regression. The data were collected by self-report questionnaires. In total, 121 individuals participated in this study: 52 were non-carriers, 54 were gene carriers, and 15 were gene carriers suffering from HD. Non-carriers and gene carriers showed better mental health and quality of life than HD-patients but did not differ from each other. In non-carriers four variables predicted increased depression and low mental quality of life: low perceived social support, no intimate relationship, female sex and younger age. For gene carriers three predictors were found: low perceived social support, the expectation of an unfavorable genetic test result before the testing procedure and being childless. To prevent detrimental effects of HD testing on mental health and mental quality of life, specific attention should be paid to persons with limited social networks during genetic counseling. Assessment of expectations related to the test result and mental health prior to a genetic testing procedure may help to identify gene carriers at risk of poor coping after an unfavorable test result.

General laboratory diagnostics of eosinophilic GI diseases

Eosinophils and gastrointestinal tract interact in an intimate and enigmatic relationship. Under inflammatory conditions, eosinophil infiltration in the gastrointestinal tract is a common feature of numerous eosinophilic gastrointestinal disorders (EGIDs). EGIDs are disorders, for which the diagnosis is relatively difficult. Nevertheless, some common laboratory techniques are currently used for their diagnosis and disease monitoring. Besides eosinophils, mast cells and T cells have also been suggested to play a role in the pathogenesis of these disorders. Here, we review the pathogenesis and common laboratory approaches applied for their diagnosis, in particular eosinophil and mast cell markers.

Bouddhisme et éthique: le cas de l'euthanasie

Cet article vise à présenter les principales pistes d’analyse éthique qui ont été proposées en matière d’euthanasie dans la tradition bouddhiste. Les nombreuses branches et cultures issues et influencées par le bouddhisme engendrent une importante hétérogénéité de vues face à de telles questions. Une interprétation prudente de leurs valeurs et enseignements fondamentaux permet, cependant, de discuter la vraisemblance des théories exprimées par la poignée d’auteurs s’étant penchés sur la question. Certains discutent de l’action homicide du professionnel de la santé, se demandant, en particulier, si l’incontesté principe du respect de la vie ne pourrait être relativisé par une compassion à l’égard du patient à l’agonie. D’autres raisonnent dans une perspective de refus de traitement de la part d’un malade, situant donc exclusivement l’enjeu du côté du patient. L’article conclut que l’euthanasie ne serait pas acceptée par le bouddhisme, la question de la cessation des soins ou du refus de traitement étant plus difficile à trancher. Notre revue de littérature n’a pas identifié d’écrits provenant des principaux pays concernés par les mouvements bouddhistes. Il est ainsi difficile d’apprécier la place réelle de l’euthanasie dans le questionnement des théoriciens et professionnels de la santé dont la culture est empreinte de cette tradition.

STATE-AND-TRANSITION MODELING AND ADAPTIVE MANAGEMENT: TOOLS FOR FUTURE CO-DEVELOPMENT OF MADAGASCAR’S NATURAL RESOURCES AND PEOPLE

Madagascar’s terrestrial and aquatic ecosystems have long supported a unique set of ecological communities, many of whom are endemic to the tropical island. Those same ecosystems have been a source of valuable natural resources to some of the poorest people in the world. Nevertheless, with pride, ingenuity and resourcefulness, the Malagasy people of the southwest coast, being of Vezo identity, subsist with low development fishing techniques aimed at an increasingly threatened host of aquatic seascapes. Mangroves, sea grass bed, and coral reefs of the region are under increased pressure from the general populace for both food provisions and support of economic opportunity. Besides purveyors and extractors, the coastal waters are also subject to a number of natural stressors, including cyclones and invasive, predator species of both flora and fauna. In addition, the aquatic ecosystems of the region are undergoing increased nutrient and sediment runoff due, in part, to Madagascar’s heavy reliance on land for agricultural purposes (Scales, 2011). Moreover, its coastal waters, like so many throughout the world, have been proven to be warming at an alarming rate over the past few decades. In recognizing the intimate interconnectedness of the both the social and ecological systems, conservation organizations have invoked a host of complimentary conservation and social development efforts with the dual aim of preserving or restoring the health of both the coastal ecosystems and the people of the region. This paper provides a way of thinking more holistically about the social-ecological system within a resiliency frame of understanding. Secondly, it applies a platform known as state-and-transition modeling to give form to the process. State-and-transition modeling is an iterative investigation into the physical makeup of a system of study as well as the boundaries and influences on that state, and has been used in restorative ecology for more than a decade. Lastly, that model is sited within an adaptive management scheme that provides a structured, cyclical, objective-oriented process for testing stakeholders cognitive understanding of the ecosystem through a pragmatic implementation and monitoring a host of small-scale interventions developed as part of the adaptive management process. Throughout, evidence of the application of the theories and frameworks are offered, with every effort made to retool conservation-minded development practitioners with a comprehensive strategy for addressing the increasingly fragile social-ecological systems of southwest Madagascar. It is offered, in conclusion, that the seascapes of the region would be an excellent case study worthy of future application of state-and-transition modeling and adaptive management as frameworks for conservation-minded development practitioners whose multiple projects, each with its own objective, have been implemented with a single goal in mind: preserve and protect the state of the supporting environment while providing for the basic needs of the local Malagasy people.

Production of interferon-gamma by activated T-cell receptor-alphabeta CD8alphabeta intestinal intraepithelial lymphocytes is required and sufficient for disruption of the intestinal barrier integrity

Maintenance of intestinal epithelial barrier function is of vital importance in preventing uncontrolled influx of antigens and the potentially ensuing inflammatory disorders. Intestinal intraepithelial lymphocytes (IEL) are in intimate contact with epithelial cells and may critically regulate the epithelial barrier integrity. While a preserving impact has been ascribed to the T-cell receptor (TCR)-gammadelta subset of IEL, IEL have also been shown to attenuate the barrier function. The present study sought to clarify the effects of IEL by specifically investigating the influence of the TCR-alphabeta CD8alphabeta and TCR-alphabeta CD8alphaalpha subsets of IEL on the intestinal epithelial barrier integrity. To this end, an in vitro coculture system of the murine intestinal crypt-derived cell-line mIC(cl2) and syngeneic ex vivo isolated IEL was employed. Epithelial integrity was assessed by analysis of transepithelial resistance (TER) and paracellular flux of fluorescein isothiocyanate-conjugated (FITC-) dextran. The TCR-alphabeta CD8alphaalpha IEL and resting TCR-alphabeta CD8alphabeta IEL did not affect TER of mIC(cl2) or flux of FITC-dextran. In contrast, activated TCR-alphabeta CD8alphabeta IEL clearly disrupted the integrity of the mIC(cl2) monolayer. No disrupting effect was seen with activated TCR-alphabeta CD8alphabeta IEL from interferon-gamma knockout mice. These findings demonstrate that secretion of interferon-gamma by activated TCR-alphabeta CD8alphabeta IEL is strictly required and also sufficient for disrupting the intestinal epithelial barrier function.

Explaining the Long-Term Trend in Violent Crime: A Heuristic Scheme and Some Methodological Considerations

There has been a discontinuous but fairly persistent long-term decline in homicide rates in core European countries since about 1500. Since the 1950s, however, we observe an upward trend in violent crime not only in Europe but in almost all of the economically advanced nations that combine democratic political structures with free-market economies. The paper presents an explanatory scheme designed to account for both, the long decline and its apparent reversal. The theoretical model draws heavily upon ideas taken from the sociological work of Emile Durkheim and Norbert Elias—with some modifications and extensions. It seeks to integrate sociological and historical perspectives and to give due weight to both, structural and developmental forces. A key hypothesis is that the pacifying effects of the erosion of traditional collectivism can only be maintained to the extent by which “cooperative individualism” dominates over against the forces of “disintegrative individualism.” Some suggestions are made concerning the selection of appropriate indicators and the handling of methodological problems related to causal attribution.

Modernity Strikes Back? A Historical Perspective on the Latest Increase in Interpersonal Violence (1960-1990)

There is a plethora of criminological explanations why criminal violence increased during the three decades between the early 1960s and the early 1990s. This paper argues that most available interpretations are lacking in three respects: they lack a historical perspective that anchors the three critical decades in a wider understanding of long-term trends; they take the nation-state as their unit of analysis and disregard important commonalities across the Western world; and they pay insufficient attention to different trends in broad categories of physical violence.This paper therefore takes a macro-level and long-term perspective on violent crime, focussing on European homicide during the past 160 years. It demonstrates that the period of increase was preceded by a long-term decline and convergence of homicide rates from the 1840s to the 1950s. Also, it shows that both the decline and the increase primarily resulted from temporal variation in the likelihood of physical aggression between men in public space. It argues that explanations of these common trends need to take into account broad long-term cultural change common to Western societies. In particular, the paper suggests that shifts in culturally transmitted and institutionally embedded ideals of the conduct of life may provide an explanation for long-term change in levels of interpersonal violence.

Want Amid Plenty: Developing and Testing a Cross-National Measure of Anomie

One of the biggest challenges facing researchers trying to empirically test structural or institutional anomie theories is the operationalization of the key concept of anomie. This challenge is heightened by the data constraints involved in cross-national research. As a result, researchers have been forced to rely on surrogate or proxy measures of anomie and indirect tests of the theories. The purpose of this study is to examine an innovative and more theoretically sound measure of anomie and to test its ability to make cross-national predictions of serious crime. Our results are supportive of the efficacy of this construct to explain cross-national variations in crime rates. Nations with the highest rates of structural anomie also have the highest predicted rates of homicide.

Domestic Violence

Since the 1960s, there has been growing awareness regarding the issue of domestic violence as a form of violence against women, which has been largely influenced by the work of feminist activist and scholars in North America and Europe (Dobash and Dobash 1992). Other terms have been used to describe the same phenomenon, including domestic abuse, spousal abuse, wife battering, marital violence, intimate partner violence. Though there is no doubt that this problem has existed for much more than five decades, the tendency to label it as ‘private matters’ or ‘marital disagreements’ has obscured the reality of women living with abuse in their home. At a general level, domestic violence can be defined as the means used by a man in order to assert his control and domination over his intimate partner, whether they are married or not (Mullender 1996). It can involve incidents of physical and sexual violence, as well as verbal, psychological and financial abuse. Though some of its manifestations may be associated with particular cultural or religious groups – e.g. forced marriage and honour killing in South-Asian communities – domestic violence affects women from all classes and backgrounds.

Action crisis and cost–benefit thinking: A cognitive analysis of a goal-disengagement phase

The present research is based on the notion that disengagement from goals is not a discrete event but a process (Klinger, 1975). A critical phase in this process is when difficulties and setbacks in striving for a goal accumulate. This critical phase is termed here as an action crisis. Given the profound effects that people's thoughts have on their self-regulatory efficiency, it is essential to understand the cognitive correlates of an action crisis. In two experimental lab and two correlational field studies, the hypothesis that goal-related costs and benefits become cognitively highly accessible during an action crisis was tested and supported. Participants who were experiencing an action crisis in such diverse goal areas as intimate relationships, sports, and university studies, thought about goal-related costs and benefits more intensively and frequently in comparison to participants who were not in an action crisis. In an incidental learning task they recognized more of cost–benefit-items and less of implementation-items than the control group. Results are interpreted in terms of action phase specific mindsets (Gollwitzer, 1990, 2012).