Treatment of patients with Parkinson's disease in specialized units is quite common in Germany. Data on the benefit of this hospitalization of patients with Parkinson's disease on motor and non-motor symptoms in conjunction with standardized tests are rare. Objective was to determine the efficacy of this therapeutic setting. We scored disease severity and performed clinical tests, respectively, instrumental procedures under standardized conditions in consecutively referred in-patients initially and at the end of their hospital stay. There was a decrease of motor and non-motor symptoms. The extent of improvement of non-motor and motor symptoms correlated to each other. Performance of complex movement sequences became better, whereas execution of simple movement series did not ameliorate. The interval for the timed up and go test went down. We demonstrate the effectiveness of an in-patient stay in a specialized unit for Parkinson's disease. Objective standardized testing supplements subjective clinical scoring with established rating scales.
bWe previously reported the development of a prototype antibiotic sensitivity assay to detect drug-resistant Mycobacterium tuberculosis using infection by mycobacteriophage to create a novel nucleic acid transcript, a surrogate marker of mycobacterial viability, detected by reverse transcriptase PCR (M. C. Mulvey et al., mBio 3:e00312-11, 2012). This assay detects antibiotic resistance to all drugs, even drugs for which the resistance mechanism is unknown or complex: it is a phenotypic readout using nucleic acid detection. In this report, we describe development and characteristics of an optimized reporter system that directed expression of the RNA cyclase ribozyme, which generated circular RNA through an intramolecular splicing reaction and led to accumulation of a new nucleic acid sequence in phage-infected bacteria. These modifications simplified the assay, increased the limit of detection from 10 4 to <10 2 M. tuberculosis cells, and correctly identified the susceptibility profile of M. tuberculosis strains exposed for 16 h to either first-line or second-line antitubercular drugs. In addition to phenotypic drug resistance or susceptibility, the assay reported streptomycin MICs and clearly detected 10% drug-resistant cells in an otherwise drug-susceptible population. Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis strains resistant to at least two of the drugs, isoniazid (INH) and rifampin (RIF), in the recommended four-drug TB treatment regimen (1). The World Health Organization (WHO) estimates the prevalence of MDR-TB to be approximately 50 million people worldwide (2), expanding by nearly 500,000 new cases each year (3). A more disquieting development is the increase in and global distribution of extremely drug-resistant TB (XDR-TB) (M. tuberculosis resistant to INH, RIF, and key second-line drugs) (4). Early recognition of M/XDR-TB through the use of an accurate and sensitive antibiotic susceptibility test (AST) promises to improve patient outcomes and assist in TB control efforts.Due to the notoriously slow doubling time of M. tuberculosis, a standard AST using culture takes several weeks to months. Culture-based assays are the gold standard for AST, however, because they measure every type of drug susceptibility and do not require knowledge of the genetics underlying resistance. However, they are slow or too insensitive to interrogate effects of antibiotics on small numbers of M. tuberculosis present in most clinical samples. Rapid molecular diagnostic tests such as Xpert MTB/RIF (Cepheid) and GenoType MTBDR (Hain Lifescience) are the emerging standard for rapid INH-or RIF-resistant M. tuberculosis detection, markers of MDR-TB, because their detection thresholds from patient specimens are comparable to culture (5, 6). These tests identify M. tuberculosis DNA in a patient sample and detect common mutations that confer resistance to INH (GenoType MTBDR) and/or RIF (GenoType MTBDR and Xpert MTB/RIF) in 2 h (Xpert MTB/RIF) or 2 days (GenoType MTBDR) from the initiation of t...
In the present review paper by members of the collaborative research center “Register: Language Users' Knowledge of Situational-Functional Variation” (CRC 1412), we assess the pervasiveness of register phenomena across different time periods, languages, modalities, and cultures. We define “register” as recurring variation in language use depending on the function of language and on the social situation. Informed by rich data, we aim to better understand and model the knowledge involved in situation- and function-based use of language register. In order to achieve this goal, we are using complementary methods and measures. In the review, we start by clarifying the concept of “register”, by reviewing the state of the art, and by setting out our methods and modeling goals. Against this background, we discuss three key challenges, two at the methodological level and one at the theoretical level: (1) To better uncover registers in text and spoken corpora, we propose changes to established analytical approaches. (2) To tease apart between-subject variability from the linguistic variability at issue (intra-individual situation-based register variability), we use within-subject designs and the modeling of individuals' social, language, and educational background. (3) We highlight a gap in cognitive modeling, viz. modeling the mental representations of register (processing), and present our first attempts at filling this gap. We argue that the targeted use of multiple complementary methods and measures supports investigating the pervasiveness of register phenomena and yields comprehensive insights into the cross-methodological robustness of register-related language variability. These comprehensive insights in turn provide a solid foundation for associated cognitive modeling.
The concept of bias is familiar to linguists primarily from the literature on questions. Following the work of Giannakidou and Mari (Truth and Veridicality in Grammar and Thought: Modality, Mood, and Propositional Attitudes, University of Chicago Press, Chicago, 2021), we assume “nonveridical equilibrium” (implying that p and ¬p as equal possibilities) to be the default for epistemic modals, questions and conditionals. The equilibrium of conditionals, as that of questions, can be manipulated to produce bias (i.e., reduced or higher speaker commitment). In this paper, we focus on three kinds of modal elements in German that create bias in conditionals and questions: the adverb wirklich ‘really’, the modal verb sollte ‘should’, and conditional connectives such as falls ‘if/in case’. We conducted two experiments collecting participants’ inference about speaker commitment in different manipulations, Experiment 1 on sollte/wirklich in ob-questions and wenn-conditionals, and Experiment 2 on sollte/wirklich in wenn/falls/V1-conditionals. Our findings are that both ob-questions and falls-conditionals express reduced speaker commitment about the modified (antecedent) proposition in comparison to wenn-conditionals, which did not differ from V1-conditionals. In addition, sollte/wirklich in the antecedent of conditionals both create negative bias about the antecedent proposition. Our studies are among the first that deal with bias in conditionals (in comparison to questions) and contribute to furthering our understanding of bias.
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