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The human immunodeficiency virus (HIV) can be suppressed by highly active anti-retroviral therapy (HAART) in the majority of infected patients. Nevertheless, treatment interruptions inevitably result in viral rebounds from persistent, latently infected cells, necessitating lifelong treatment. Virological failure due to resistance development is a frequent event and the major threat to treatment success. Currently, it is recommended to change treatment after the confirmation of virological failure. However, at the moment virological failure is detected, drug resistant mutants already replicate in great numbers. They infect numerous cells, many of which will turn into latently infected cells. This pool of cells represents an archive of resistance, which has the potential of limiting future treatment options. The objective of this study was to design a treatment strategy for treatment-naive patients that decreases the likelihood of early treatment failure and preserves future treatment options. We propose to apply a single, pro-active treatment switch, following a period of treatment with an induction regimen. The main goal of the induction regimen is to decrease the abundance of randomly generated mutants that confer resistance to the maintenance regimen, thereby increasing subsequent treatment success. Treatment is switched before the overgrowth and archiving of mutant strains that carry resistance against the induction regimen and would limit its future re-use. In silico modelling shows that an optimal trade-off is achieved by switching treatment at & 80 days after the initiation of antiviral therapy. Evaluation of the proposed treatment strategy demonstrated significant improvements in terms of resistance archiving and virological response, as compared to conventional HAART. While continuous pro-active treatment alternation improved the clinical outcome in a randomized trial, our results indicate that a similar improvement might also be reached after a single pro-active treatment switch. The clinical validity of this finding, however, remains to be shown by a corresponding trial.
Zenralamerika
(2011)
Zentralamerika
(2011)
Which repair strategy does the language system deploy when it gets garden-pathed, and what can regressive eye movements in reading tell us about reanalysis strategies? Several influential eye-tracking studies on syntactic reanalysis (Frazier & Rayner, 1982; Meseguer, Carreiras, & Clifton, 2002; Mitchell, Shen, Green, & Hodgson, 2008) have addressed this question by examining scanpaths, i.e., sequential patterns of eye fixations. However, in the absence of a suitable method for analyzing scanpaths, these studies relied on simplified dependent measures that are arguably ambiguous and hard to interpret. We address the theoretical question of repair strategy by developing a new method that quantifies scanpath similarity. Our method reveals several distinct fixation strategies associated with reanalysis that went undetected in a previously published data set (Meseguer et al., 2002). One prevalent pattern suggests re-parsing of the sentence, a strategy that has been discussed in the literature (Frazier & Rayner, 1982); however, readers differed tremendously in how they orchestrated the various fixation strategies. Our results suggest that the human parsing system non-deterministically adopts different strategies when confronted with the disambiguating material in garden-path sentences.
The late mediaeval prose epic Loher und Muller constantly challenges a naive interpretation of what constitutes justice by confronting it over and over again with extreme cases. Generally speaking, 'poetic justice' succeeds in establishing coherence and propel the narrative forward. The constituents of societal norms and of laws are nevertheless relentlessly questioned - to such an extent that the narrative inquiry occasionally departs from the common understanding of justice. With its focus on morality, especially the presence or absence of faith, Loher und Muller is primarily concerned with the potential for conflict inherent in medieval constructions of legality and justice. In doing so, the epic opens up a narrative playground unencumbered by legal constraints as - after all - literature need not comply with medieval jurisdiction and its claims to the validity and scope of its writings. It is literature's privilege to facilitate unfamiliar ways of looking. The playful - but by no means inconsequential - casuistry played out in Loher und Maller gives rise to a 'probable' world tangential to historical reality and its understanding of justice and the law.
Work-related behavior and experience patterns of entrepreneurs compared to teachers and physicians
(2011)
Purpose This study examined the status of health-related behavior and experience patterns of entrepreneurs in comparison with teachers and physicians to identify specific health risks and resources.
Methods Entrepreneurs (n = 632), teachers (n = 5,196), and physicians (n = 549) were surveyed in a cross-sectional design. The questionnaire Work-related Behavior and Experience Patterns (AVEM) was used for all professions and, in addition, two scales (health prevention and self-confidence) from the Checklist for Entrepreneurs in the sample of entrepreneurs.
Results The largest proportion of the entrepreneurs (45%) presented with a healthy pattern (compared with 18.4% teachers and 18.3% physicians). Thirty-eight percent of entrepreneurs showed a risk pattern of overexertion and stress, followed by teachers (28.9%) and physicians (20.6%). Unambitious or burnout patterns were seen in only 9.3/8.2% of entrepreneurs, respectively, and 25.3/27.3% of teachers, and 39.6/21.5% of physicians. While the distribution of patterns in teachers and physicians differed significantly between genders, a gender difference was not found among entrepreneurs. Entrepreneurs with the risk pattern of overexertion scored significantly (P < 0.01) lower in self-confidence and health care than those with the healthy pattern.
Conclusions The development of a successful enterprise depends, in part, on the health of the entrepreneur. The large proportion of entrepreneurs with the healthy pattern irrespective of gender may support the notion that self-selection effects of healthy individuals in this special career might be important. At the same time, a large proportion was at risk for overexertion and might benefit from measures to cope with professional demands and stress and promote a healthy behavior pattern.
Vorwort
(2011)