Penicillin acylase (PA) from Escherichia coli can catalyze the coupling of an acyl group to penicillin- and cephalosporin-derived beta-lactam nuclei, a conversion that can be used for the industrial synthesis of beta-lactam antibiotics. The modest synthetic properties of the wild-type enzyme make it desirable to engineer improved mutants. Analysis of the crystal structure of PA has shown that residues alphaR145 and alphaF146 undergo extensive repositioning upon binding of large ligands to the active site, suggesting that these residues may be good targets for mutagenesis aimed at improving the catalytic performance of PA. Therefore, site-saturation mutagenesis was performed on both positions and a complete set of all 38 variants was subjected to rapid HPLC screening for improved ampicillin synthesis. Not less than 33 mutants showed improved synthesis, indicating the importance of the mutated residues in PA-catalyzed acyl transfer kinetics. In several mutants at low substrate concentrations, the maximum level of ampicillin production was increased up to 1.5-fold, and the ratio of the synthetic rate over the hydrolytic rate was increased 5-15-fold. Moreover, due to increased tendency of the acyl-enzyme intermediate to react with beta-lactam nucleophile instead of water, mutants alphaR145G, alphaR145S and alphaR145L demonstrated an enhanced synthetic yield over wild-type PA at high substrate concentrations. This was accompanied by an increased conversion of 6-APA to ampicillin as well as a decreased undesirable hydrolysis of the acyl donor. Therefore, these mutants are interesting candidates for the enzymatic production of semi-synthetic beta-lactam antibiotics.
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Free newspapers may offer different news contents to different audiences, when compared with traditional, paid-for newspapers, but they, nevertheless, concentrate on news, and thereby provide society with information on current affairs. These papers have seen circulation rise until 2008; after that, a decline set in, leading to closures and often a monopoly situation in the mature European newspaper markets covered in our research. Free newspapers seem to follow a typical life cycle pattern, moving from growth to maturity, and to saturation and decline. Diversification strategies – home-delivery, weekend, sports, afternoon, and financial – have been disappointing so far. There is no evidence, however, of total extinction, indicating that there is room for at least one title – possibly two – in every market. The situation in the surveyed markets also suggests that a free newspaper may be a ‘natural’ monopoly.
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In clinical practice, formal elements of art products are regularly used in art therapy observation to obtain insight into clients’ mental health and provide directions for further treatment. Due to the diversity of formal elements used in existing studies and the inconsistency in the interpretation, it is unclear which formal elements contribute to insight into clients’ mental health. In this qualitative study using Constructivist Grounded Theory, eight art therapists were interviewed in-depth to identify which formal elements they observe, how they describe mental health and how they associate formal elements with mental health. Findings of this study show that art therapists in this study observe the combination of movement, dynamic, contour and repetition (i.e., primary formal elements) with mixture of color, figuration and color saturation (i.e., secondary formal elements). Primary and secondary elements interacting together construct the structure and variation of the art product. Art therapists rarely interpret these formal elements in terms of symptoms or diagnosis. Instead, they use concepts such as balance and adaptability (i.e., self-management, openness, flexibility, and creativity). They associate balance, specifically being out of balance, with the severity of the clients’ problem and adaptability with clients’ strengths and resources. In the conclusion of the article we discuss the findings’ implications for practice and further research.
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From an evidence-based perspective, cardiopulmonary exercise testing (CPX) is a well-supported assessment technique in both the United States (US) and Europe. The combination of standard exercise testing (ET) [i.e. progressive exercise provocation in association with serial electrocardiograms (ECGs), haemodynamics, oxygen saturation, and subjective symptoms] and measurement of ventilatory gas exchange amounts to a superior method to: (i) accurately quantify cardiorespiratory fitness (CRF), (ii) delineate the physiologic system(s) underlying exercise responses, which can be applied as a means to identify the exercise-limiting pathophysiological mechanism(s) and/or performance differences, and (iii) formulate function-based prognostic stratification. Cardiopulmonary ET certainly carries an additional cost as well as competency requirements and is not an essential component of evaluation in all patient populations. However, there are several conditions of confirmed, suspected, or unknown aetiology where the data gained from this form of ET is highly valuable in terms of clinical decision making.1
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From an evidence-based perspective, cardiopulmonary exercise testing (CPX) is a well-supported assessment technique in both the United States (US) and Europe. The combination of standard exercise testing (ET) (ie, progressive exercise provocation in association with serial electrocardiograms [ECG], hemodynamics, oxygen saturation, and subjective symptoms) and measurement of ventilatory gas exchange amounts to a superior method to: 1) accurately quantify cardiorespiratory fitness (CRF), 2) delineate the physiologic system(s) underlying exercise responses, which can be applied as a means to identify the exercise-limiting pathophysiologic mechanism(s) and/or performance differences, and 3) formulate function-based prognostic stratification. Cardiopulmonary ET certainly carries an additional cost as well as competency requirements and is not an essential component of evaluation in all patient populations. However, there are several conditions of confirmed, suspected, or unknown etiology where the data gained from this form of ET is highly valuable in terms of clinical decision making
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Introduction: Retrospective studies suggest that a rapid initiation of treatment results in a better prognosis for patients in the emergency department. There could be a difference between the actual medication administration time and the documented time in the electronic health record. In this study, the difference between the observed medication administration time and documentation time was investigated. Patient and nurse characteristics were also tested for associations with observed time differences. Methods: In this prospective study, emergency nurses were followed by observers for a total of 3 months. Patient inclusion was divided over 2 time periods. The difference in the observed medication administration time and the corresponding electronic health record documentation time was measured. The association between patient/nurse characteristics and the difference in medication administration and documentation time was tested with a Spearman correlation or biserial correlation test. Results: In 34 observed patients, the median difference in administration and documentation time was 6.0 minutes (interquartile range 2.0-16.0). In 9 (26.5%) patients, the actual time of medication administration differed more than 15 minutes with the electronic health record documentation time. High temperature, lower saturation, oxygen-dependency, and high Modified Early Warning Score were all correlated with an increasing difference between administration and documentation times. Discussion: A difference between administration and documentation times of medication in the emergency department may be common, especially for more acute patients. This could bias, in part, previously reported time-to-treatment measurements from retrospective research designs, which should be kept in mind when outcomes of retrospective time-to-treatment studies are evaluated.
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Evaluation of the hydrological performance of grassed swales usually needs long-term monitoring data. At present, suitable techniques for simulating the hydrological performance using limited monitoring data are not available. Therefore, current study aims to investigate the relationship between saturated hydraulic conductivity (Ks) fitting results and rainfall characteristics of various events series length. Data from a full-scale grassed swale (Enschede, the Netherlands) were utilized as long-term rainfall event series length (95 rainfall events) on the fitting outcomes. Short-term rainfall event series were extracted from these long-term series and used as input in fitting into a multivariate nonlinear model between Ks and its influencing rainfall indicators (antecedent dry days, temperature, rainfall, rainfall duration, total rainfall, and seasonal factor (spring, summer, autumn, and winter, herein refer as 1, 2, 3, and 4). Comparison of short-term and long-term rainfall event series fitting results allowed to obtain a representative short-term series that leads to similar results with those using long-term series. A cluster analysis was conducted based on the fitting results of the representative rainfall event series with their rainfall event characteristics using average values of influencing rainfall indicators. The seasonal index (average value of seasonal factors) was found to be the most representative short rainfall event series indicator. Furthermore, a Bayesian network was proposed in the current study to predict if a given short-term rainfall event series is representative. It was validated by a data series (58 rainfall events) from another full-scale grassed swale located in Utrecht, the Netherlands. Results revealed that it is quite promising and useful to evaluate the representativeness of short-term rainfall event series used for long-term hydrological performance evaluation of grassed swales.
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OBJECTIVE: To assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of a twenty-week power-assisted exercise intervention in people with profound intellectual and multiple disabilities and to evaluate the potential beneficial effects of this intervention.DESIGN: Pilot randomised controlled trial.SETTING: A large-scale twenty-four-hour residential facility in the Netherlands.SUBJECTS: Thirty-seven persons with profound intellectual and multiple disabilities.INTERVENTION: Participants in the intervention group received a power-assisted exercise intervention three times a week for thirty minutes over a twenty-week period. Participants in the control group received care as usual.MAIN MEASURES: Trial feasibility by recruitment process and outcomes completion rates; intervention feasibility by programme compliance rates; potential outcomes by functional abilities, alertness, body composition, muscle tone, oxygen saturation, cardiovascular fitness and quality of life.RESULTS: Thirty-seven participants were recruited ( M age = 32.1, SD = 14.6) and were randomly allocated to intervention ( n = 19) and control ( n = 18) groups. Programme compliance rates ranged from 54.2% to 97.7% with a mean (SD) of 81.5% (13.4). Oxygen saturation significantly increased in the intervention group. Standardised effect sizes on the difference between groups in outcome varied between 0.02 and 0.62.CONCLUSIONS: The power-assisted exercise intervention and the trial design were feasible and acceptable to people with profound intellectual and multiple disabilities living in a residential facility. This pilot study suggests that the intervention improves oxygen saturation, but further implementation with the aim of improving other outcomes should be considered with caution.
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