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Search Results: 1 - 10 of 39302 matches for " Hans-Peter Duerr "
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The influenza pandemic preparedness planning tool InfluSim
Martin Eichner, Markus Schwehm, Hans-Peter Duerr, Stefan O Brockmann
BMC Infectious Diseases , 2007, DOI: 10.1186/1471-2334-7-17
Abstract: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers.InfluSim is an online available software http://www.influsim.info webcite which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability.Preparedness against pandemic influenza has become a high priority public health issue and many countries that have pandemic preparedness plans [1]. For the design of such plans, mathematical models and computer simulations play an essential role because they allow to predict and compare the effects of different intervention strategies [2]. The outstanding significance of the tools for purposes of intervention optimization is limited by the fact that they cannot maximize realism, generality and precision at the same time [3]. Public health planners, on the other hand, wish to have an optimal combination of these properties, because they need to formulate intervention strategies which can be generalized into recommendations, but are sufficiently realistic and precise to satisfy public health requirements.Published influenza models which came into application, are represented by two extremes: generalized but over-simplified models without dynamic structure which are publicly available (e.g. [4]), and complex comput
Treatment of Visceral Leishmaniasis: Model-Based Analyses on the Spread of Antimony-Resistant L. donovani in Bihar, India
Anette Stauch ,Hans-Peter Duerr,Jean-Claude Dujardin,Manu Vanaerschot,Shyam Sundar,Martin Eichner
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001973
Abstract: Background Pentavalent antimonials have been the mainstay of antileishmanial therapy for decades, but increasing failure rates under antimonial treatment have challenged further use of these drugs in the Indian subcontinent. Experimental evidence has suggested that parasites which are resistant against antimonials have superior survival skills than sensitive ones even in the absence of antimonial treatment. Methods and Findings We use simulation studies based on a mathematical L. donovani transmission model to identify parameters which can explain why treatment failure rates under antimonial treatment increased up to 65% in Bihar between 1980 and 1997. Model analyses suggest that resistance to treatment alone cannot explain the observed treatment failure rates. We explore two hypotheses referring to an increased fitness of antimony-resistant parasites: the additional fitness is (i) disease-related, by causing more clinical cases (higher pathogenicity) or more severe disease (higher virulence), or (ii) is transmission-related, by increasing the transmissibility from sand flies to humans or vice versa. Conclusions Both hypotheses can potentially explain the Bihar observations. However, increased transmissibility as an explanation appears more plausible because it can occur in the background of asymptomatically transmitted infection whereas disease-related factors would most probably be observable. Irrespective of the cause of fitness, parasites with a higher fitness will finally replace sensitive parasites, even if antimonials are replaced by another drug.
Antiviral prophylaxis during pandemic influenza may increase drug resistance
Martin Eichner, Markus Schwehm, Hans-Peter Duerr, Mark Witschi, Daniel Koch, Stefan O Brockmann, Beatriz Vidondo
BMC Infectious Diseases , 2009, DOI: 10.1186/1471-2334-9-4
Abstract: Using the freely available program InfluSim, the authors examine to what extent NI-treatment and prophylaxis promote the occurrence and transmission of a NI resistant strain.Under a basic reproduction number of R0 = 2.5, a NI resistant strain can only spread if its transmissibility (fitness) is at least 40% of the fitness of the drug-sensitive strain. Although NI drug resistance may emerge in treated patients in such a late state of their disease that passing on the newly developed resistant viruses is unlikely, resistant strains quickly become highly prevalent in the population if their fitness is high. Antiviral prophylaxis further increases the pressure on the drug-sensitive strain and favors the spread of resistant infections. The authors show scenarios where pre-exposure antiviral prophylaxis even increases the number of influenza cases and deaths.If the fitness of a NI resistant pandemic strain is high, any use of prophylaxis may increase the number of hospitalizations and deaths in the population. The use of neuraminidase inhibitors should be restricted to the treatment of cases whereas prophylaxis should be reduced to an absolute minimum in that case.Neglecting the possible emergence of NI resistance, modeling studies have suggested that an influenza pandemic may be contained if treatment and prophylaxis are introduced immediately [1-3]. Switzerland has stockpiled sufficient NI to treat 25% of the population and considers using some of the stockpile for prophylaxis in health care workers and essential services (fire brigade, police, etc). As influenza viruses mutate constantly, widespread use of antivirals in the case of a pandemic could cause selection pressure which could lead to the emergence and spread of NI resistant strains. De novo emergence of a resistant strain does not necessarily cause negative outcomes; it is the transmission fitness of the resistant strain which plays a major role [4-7]. Simulation studies on HIV [8] and HSV-2 [9] have also show
Modeling the effects of drug resistant influenza virus in a pandemic
Stefan O Brockmann, Markus Schwehm, Hans-Peter Duerr, Mark Witschi, Daniel Koch, Beatriz Vidondo, Martin Eichner
Virology Journal , 2008, DOI: 10.1186/1743-422x-5-133
Abstract: Neuraminidase inhibitors (NI) play an important role in plans to mitigate future influenza pandemics [1]. Modeling studies suggested that a pandemic may be contained at the source, if treatment and prophylaxis are applied in an early phase of the epidemic. Large amounts of NI (mainly oseltamivir) have been stockpiled in many countries to prepare for pandemic influenza, and many national preparedness plans rely on this. However, recently doubts have been raised whether this strategy is realistic. Timeliness of the intervention due to difficulties in early recognition and logistic challenges are some of the points considered. The development of NI resistance is of further concern.Influenza viruses undergo continuous genetic changes by means of mutation and recombination, promoting the emergence of drug resistant strains. Viral resistance may develop by modifications in the amino acid composition of the neuraminidase or in the affinity of haemagglutinin to the receptors of the cell surface [reviewed in [2]]. Prior to the 2007/8 influenza season, NI resistant strains were found in patients after treatment with oseltamivir and in patients not exposed to oseltamivir. Resistance to NI occurred at a low level: less then 1% of immuno-competent patients were found to be infected with resistant virus [3]. The emergence of a resistant strain may not necessarily be dangerous, as the "fitness" of the resistant strain determines its transmissibility [4,5]. Most resistant strains lacked "fitness" and were unlikely to spread, but early surveillance data from the 2007/8 influenza season on the northern hemisphere suggest that an oseltamivir resistant influenza virus type A(H1N1) circulates in several European countries and in the US [6,7]. The proportion of resistant infections ranges between 4% and 67% (mean 20%, approximately 1.700 tested isolates) and have been reported from 15 of 25 European countries under surveillance [8].To obtain a better understanding of the consequences ass
Genetic counselling for hypertrophic cardiomyopathy: are we ready for it?
Hans-Peter Vosberg
Trials , 2000, DOI: 10.1186/cvm-1-1-041
Abstract: A young boy of 13 collapsed while running after the schoolbus. He could be resuscitated, but at the price of crippling brain damage. Clinical and genetic analysis subsequently revealed that he and his father were predisposed to hypertrophic cardiomyopathy (HCM): they were carriers of a missense mutation in the α-tropomyosin gene. The boy had no symptoms before he collapsed, whereas his father (in his early forties) had borderline myocardial hypertrophy in the interventricular septum associated with mild symptoms of cardiac disease. A daughter, age 11, also carried the mutation, but she was entirely asymptomatic. On average, penetrance of the disease gene was incomplete in this family. The boy's collapse was presumably due to an episode of extreme ventricular tachycardia. Although the familial character of the disorder was suspected for some time prior to this event, genetic counselling had not been considered before the boy experienced cardiac arrest.In a second family the disease was associated with a high frequency of cardiac death. Three documented cases of premature sudden death in two generations, two of them in young adults, and numerous relatives being clinically affected imposed a heavy burden on the family. Early onset of the disease, syncopes, chest pain and progression to heart failure with no, or inconspicuous, hypertrophy were encountered. A few patients were only mildly affected. A mutation in the cardiac troponin T gene was identified by genetic analysis. All first-degree relatives of the patients were seeking counselling and asked for a DNA test. They were aware that this test offered a 50% chance of excluding the carrier status for those who were asymptomatic, in particular for children of parents at risk. Hence, parents also asked on behalf of their children.These are two different disease phenotypes randomly picked from numerous published or unpublished case reports of familial HCM. This is a heavily investigated disorder for which we have ample k
Bemerkungen zur deutschen Privatrechtswissenschaft zwischen 1925 und 1935 - dargestellt an der Debatte um die Behandlung der exceptio doli generalis
Hans-Peter Haferkamp
Forum Historiae Iuris , 1997,
Abstract:
Der Einfluss des Code civil auf das Bürgerliche Gesetzbuch - Wissenschaftsgeschichtliche Komplement rbetrachtungen zur Studie von Dieter Strauch
Hans-Peter Haferkamp
Forum Historiae Iuris , 2005,
Abstract:
Richterkulturen im 20. Jahrhundert – Eine Skizze über den Nutzen der DDR-Ziviljustizgeschichte
Hans-Peter Haferkamp
Forum Historiae Iuris , 2011,
Abstract:
Heinrich Schoppmeyer, Juristische Methode als Lebensaufgabe. Leben, Werk und Wirkungsgeschichte Philipp Hecks
Hans-Peter Haferkamp
Forum Historiae Iuris , 2004,
Abstract:
Recht als System bei Georg Friedrich Puchta
Hans-Peter Haferkamp
Forum Historiae Iuris , 2003,
Abstract: Hans-Peter Haferkamp -------------------------------------------------------------------------------- Recht als System bei Georg Friedrich Puchta / Georg Friedrich Puchta and his system of law - English Summary - To this day, Georg Friedrich Puchta, who was Savigny`s follower and, later, his successor in Berlin, is seen as the founder of the "Begriffsjurisprudenz". The present paper contradicts prejudices, which flow from this image. Focusing on a dispute about the formation of systems among Puchta and Friedrich Julius Stahl, a new picture is painted, regarding Puchta`s systematic thinking. Insights from more recent research on F. W. J. Schelling show that Puchta`s understanding of systems was based on ideas of Schelling rather than on those of Wolff, Kant or others. Thus, Puchta constructed a system that could be interpreted, with Schelling, as both necessary and free. It was free with regard to the origin of legal principles. For such principles did not derive from fixed concepts. Rather, concepts derived from principles. At the same time, it was necessary to connect legal principles with one another as comprehensively as possible. In this context, the academic had to find causal connections between single principles. According to both Schelling and Puchta, a systematic pattern like academic research was unthinkable without such connections. As a result, the common idea of Puchta being a "Begriffsjurist" turned out to be unsubstantiated.
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