Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease

In Switzerland, the first course of intravenous steroids for treatment of episodes of demyelinating CNS disease is usually administered in an inpatient setting. We prospectively evaluated short term tolerance of treatment with special emphasis on sleep quality.

Tolerance and Critical Thinking

Post-soviet countries are in the process of transformation from a totalitarian order to a democratic one, a transformation which is impossible without a profound shift in people's way of thinking. The group set themselves the task of determining the essence of this shift. Using a multidisciplinary approach, they looked at concrete ways of overcoming the totalitarian mentality and forming that necessary for an open democratic society. They studied the contemporary conceptions of tolerance and critical thinking and looked for new foundations of criticism, especially in hermeneutics. They then sought to substantiate the complementary relation between tolerance and criticism in the democratic way of thinking and to prepare a a syllabus for teaching on the subject in Ukrainian higher education. In a philosophical exploration of tolerance they began with relgious tolerance as its first and most important form. Political and social interests often lay at the foundations of religious intolerance and this implicitly comprised the transition to religious tolerance when conditions changed. Early polytheism was more or less indifferent to dogmatic deviations but monotheism is intolerant of heresies. The damage wrought by the religious wars of the Reformations transformed tolerance into a value. They did not create religious tolerance but forced its recognition as a positive phenomenon. With the weakening of religious institutions in the modern era, the purely political nature of many conflicts became evident and this stimulated the extrapolation of tolerance into secular life. Each historical era has certain acts and operations which may be interpreted as tolerant and these can be classified as to whether or not they are based on the conscious following of the principle of tolerance. This criterion requires the separation of the phenomenon of tolerance from its concept and from tolerance as a value. Only the conjunction of a concept of tolerance with a recognition of its value can transform it into a principle dictating a norm of conscious behaviour. The analysis of the contemporary conception of tolerance focused on the diversity of the concept and concluded that the notions used cannot be combined in the framework of a single more or less simple classification, as the distinctions between them are stimulated by the complexity of the realty considered and the variety of its manifestations. Notions considered in relation to tolerance included pluralism, respect and particular-universal. The rationale of tolerance was also investigated and the group felt that any substantiation of the principle of tolerance must take into account human beings' desire for knowledge. Before respecting or being tolerant of another person different from myself, I should first know where the difference lies, so knowledge is a necessary condition of tolerance.The traditional division of truth into scientific (objective and unique) and religious, moral, political (subjective and so multiple) intensifies the problem of the relationship between truth and tolerance. Science was long seen as a field of "natural" intolerance whereas the validity of tolerance was accepted in other intellectual fields. As tolerance eemrges when there is difference and opposition, it is essentially linked with rivaly and there is a a growing recognition today that unlimited rivalry is neither able to direct the process of development nor to act as creative matter. Social and economic reality has led to rivalry being regulated by the state and a natural requirement of this is to associate tolerance with a special "purified" form of rivalry, an acceptance of the actiivity of different subjects and a specification of the norms of their competition. Tolerance and rivalry should therefore be subordinate to a degree of discipline and the group point out that discipline, including self-discipline, is a regulator of the balance between them. Two problematic aspects of tolerance were identified: why something traditionally supposed to have no positive content has become a human activity today, and whether tolerance has full-scale cultural significance. The resolution of these questions requires a revision of the phenomenon and conception of tolerance to clarify its immanent positive content. This involved an investigation of the contemporary concept of tolerance and of the epistemological foundations of a negative solution of tolerance in Greek thought. An original soution to the problem of the extrapolation of tolerance to scientific knowledge was proposed based on the Duhem-Quine theses and conceptiion of background knowledge. In this way tolerance as a principle of mutual relations between different scientific positions gains an essential epistemological rationale and so an important argument for its own universal status. The group then went on to consider the ontological foundations for a positive solution of this problem, beginning with the work of Poincare and Reichenbach. The next aspect considered was the conceptual foundations of critical thinking, looking at the ideas of Karl Popper and St. Augustine and at the problem of the demarcation line between reasonable criticism and apologetic reasoning. Dogmatic and critical thinking in a political context were also considered, before an investigation of critical thinking's foundations. As logic is essential to critical thinking, the state of this discipline in Ukrainian and Russian higher education was assessed, together with the limits of formal-logical grounds for criticism, the role of informal logical as a basis for critical thinking today, dialectical logic as a foundation for critical thinking and the universality of the contemporary demand for criticism. The search for new foundations of critical thinking covered deconstructivism and critical hermeneutics, including the problem of the author. The relationship between tolerance and criticism was traced from the ancient world, both eastern and Greek, through the transitional community of the Renaissance to the industrial community (Locke and Mill) and the evolution of this relationship today when these are viewed not as moral virtues but as ordinary norms. Tolerance and criticism were discussed as complementary manifestations of human freedom. If the completeness of freedom were accepted it would be impossible to avoid recognition of the natural and legal nature of these manifestations and the group argue that critical tolerance is able to avoid dismissing such negative phenomena as the degradation of taste and manner, pornography, etc. On the basis of their work, the group drew up the syllabus of a course in "Logic with Elements of Critical Thinking, and of a special course on the "Problem of Tolerance".

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

[Stress tolerance and quality of life--effect of a comprehensive ambulatory rehabilitation program for patients with chronic heart failure]

Chronic heart failure (CHF) impairs quality of life (QoL) much stronger than other chronic diseases. The objective of this evaluation was to assess the effect of a new integrated comprehensive outpatients rehabilitation program on somatic parameters and quality of life in 51 patients with stable CHF. After rehabilitation, left ventricular ejection fraction, NYHA class, and parameters of sub-maximum and maximum exercise capacity improved significantly between 11 and 20%, and 6-minute walking distance by 58% on average (p < 0.0001). Non-disease specific QoL (Short Form-36 questionnaire) improved in only 2 of 8 subscales (physical functioning [effect size 0.38, p < 0.001], and role functioning [effect size 0.17, p < 0.05]), and a mental component score [effect size 0.47, p < 0.0001]. Disease-specific QoL (Minnesota Living with Heart Failure questionnaire) improved in terms of sum score [effect size 0.24, p < 0.0001], and physical component score [effect size 0.35, p < 0.0001]. Improvement in exercise capacity correlated significantly with improvements in parameters of disease-specific QoL.

The tolerance of ambiguity in late cochlear-implanted pre-lingually deaf juveniles

OBJECTIVES: To examine the ambiguity tolerance, i.e. the ability to perceive new, contradictory and complex situations as positive challenges, of pre-lingually deafened adolescents who received a cochlear implant after their eighth birthday and to identify those dimensions of ambiguity tolerance which correlate significantly with specific variables of their oral communication. DESIGN AND SETTING: Clinical survey at an academic tertiary referral center. Participants and main outcome measures: A questionnaire concerning communication and subjectively perceived changes compared to the pre-cochlear implant situation was completed by 13 pre-lingually deafened patients aged between 13 and 23 years, who received their cochlear implants between the ages of 8 and 17 years. The results were correlated with the 'Inventory for Measuring Ambiguity Tolerance'. RESULTS: The patients showed a lower ambiguity tolerance with a total score of 134.5 than the normative group with a score of 143.1. There was a positive correlation between the total score for ambiguity tolerance and the frequency of 'use of oral speech', as well as between the subscale 'ambiguity tolerance towards apparently insoluble problems' and all five areas of oral communication that were investigated. Comparison of two variables of oral communication, which shows a significant difference pre- and postoperatively, yields a positive correlation with the subscale 'ambiguity tolerance towards the parental image'. CONCLUSIONS: Pre-lingually deafened juveniles with cochlear implant who increasingly use oral communication seem to regard the limits of a cochlear implant as an interesting challenge rather than an insoluble problem.

Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion

In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the artificial reperfusion, may lead to an improvement of the ex vivo perfusion technique.

Early season ozone uptake is important for determining ozone tolerance in two trembling aspen clones

There is substantial genetic variability in response to ozone amongst and within tree species. Aspen is a highly variable species with a wide range of responses to ozone. Aspen response to elevated O3 levels is being investigated at the Aspen FACE site near Rhinelander, WI where five aspen clones of varying O3 tolerance have been fumigated with elevated O3 over the past decade. In this study, we examined the physiological differences in two of the aspen clones that differed significantly in their O3 tolerance with 8L being tolerant and 42E being sensitive. Throughout the 2007 and 2008 growing seasons we periodically estimated instantaneous photosynthetic rates, ACi responses and light response curves. The results of our study suggest that aspen clone 8L’s tolerance is due in part to decreased stomatal conductance early in the season, which lowered ozone uptake. Later during the season O3 uptake was comparable for the two clones. Our results also suggest the response of Vcmax, TPU, Rd, Gm, light compensation point and quantum flux to elevated O3 did not differ significantly between the two clones. Ozone uptake is important for ozone tolerance in clone 8L early in the season but cannot explain late season tolerance. Photosynthetic parameters for the two clones were similar, so clone 8L’s ozone tolerance is not due to a more efficient photosynthetic system.

Effect of Manganese and Arsenic upon Current Efficiency in the Deposition of Zinc from Zinc Sulphate Solution

Throughout the entire experiment the electrolysis were conducted in an eight-hundred cubic centimeter beaker. An excellent circulation of the solution was assured by means of an electric stirrer, vigorous gas evolution from the anodes, and by means of a regulated feed-discharge system. By means of this balance, solution of the same impurity concentration as that of the electrolyte was fed in the cell just as fast as the discharge was syphoned out.

Exploring the MHC-peptide matrix of central tolerance in the human thymus

Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune- and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.

Biovolatilisation: a poorly studied pathway of the arsenic biogeochemical cycle

It has been known for over a hundred years that microorganisms can produce volatile arsenic (As) species, termed “arsines”. However, this topic has received relatively little attention compared to As behaviour in soils and biotransformation through the trophic level in the marine and terrestrial environment. We believe this is due to long-standing misconceptions regarding volatile As stability and transport as well as an absence, until recently, of appropriate sampling methods. First and foremost, an attempt is made to unify arsines' designations, notations and formulas, taking into account all the different terms used in the literature. Then, the stability of As volatile species is discussed and new analytical developments are explored. Further, the special cases of diffuse low-level emissions (e.g. soil and sediment biovolatilisation), and point sources with high-level emissions (geothermal environments, landfills, and natural gas) are comprehensively reviewed. In each case, future possible areas of research and unknown mechanisms are identified and their importance towards the global As biogeochemical cycle is explored. This review gathers new information regarding mechanisms, stability, transport and sampling of the very elusive arsines and shows that more research should be conducted on this important process.