Nederlandse kerkarchitectuur in de twintigste eeuw : functie en betekenis van het kerkgebouw in een veranderende samenleving

This doctoral thesis describes the cultural history of Dutch church architecture in the twentieth century, a period in which more than 5,000 churches were built in the Netherlands. The majority of these houses of worship are not listed buildings and suffer from a lack of maintenance. Because of the country’s overwhelming secularization, more and more churches are vacant, for sale or slated for demolition. The absence of any general study of the function and significance of modern churches in the Netherlands complicates the discussion in religious, cultural and political circles about the future of this vulnerable group of buildings. One major factor in the design, decoration and organization of these churches was the liturgical renewal within the Roman Catholic Church and two Protestant religious communities, the Nederlandse Hervormde Kerk and the Gereformeerde Kerken in Nederland. The democratic impulse to foster greater participation in services by the congregation had an aesthetic dimension. At the same time, demographic and urban developments put pressure on congregations to construct new churches at a rapid pace. Priests and pastors looked to architects to accommodate their liturgical and pastoral preferences by designing distinctively modern churches. In the late 1960s, both Catholic and Protestant churches became functional houses of worship, drained of their traditional sacred character.LEI Universiteit LeidenPolitical Culture and National Identit

Pharmacodynamics and differential activity of nitrofurantoin against ESBL-positive pathogens involved in urinary tract infections.

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Genus- and species-specific identification of mycoplasmas by 16S rRNA amplification.

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Pharmacodynamics of Cefepime Combined with Tazobactam against Clinically Relevant Enterobacteriaceae in a Neutropenic Mouse Thigh Model

The lack of new antibiotics has prompted investigation of the combination of two existing agents-cefepime, a broad-spectrum cephalosporin, and tazobactam-to broaden their efficacy against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae We determined the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the combination in a murine neutropenic thigh model in order to establish its exposure-response relationships (ERRs). The PK of cefepime were determined for five doses; that of tazobactam was determined in earlier studies (Melchers et al., Antimicrob Agents Chemother 59:3373-3376, 2015, https://doi.org/10.1128/AAC.04402-14). The PK were linear for both compounds. The estimated mean (standard deviation [SD]) half-life of cefepime was 0.33 (0.12) h, and that of tazobactam was 0.176 (0.026) h; the volumes of distribution (V) were 0.73 liters/kg and 1.14 liters/kg, respectively. PD studies of cefepime administered every 2 h (q2h) with or without tazobactam, including dose fractionation studies of tazobactam, were performed against six ESBL-producing isolates. A sigmoidal maximum-effect (Emax) model was fitted to the data. In the dose fractionation study, the q2h regimen was more efficacious than the q4h and q6h regimens, indicating time-dependent activity of tazobactam. The threshold concentration (CT ) best correlating with tazobactam efficacy was 0.25 mg/liter, as evidenced by the best fit of the percentage of time above the threshold concentration (%fT>CT ) and response. A mean %fT>CT of 24.6% (range, 11.4 to 36.3%) for a CT of 0.25 mg/liter was required to obtain a bacteriostatic effect. We conclude that tazobactam enhanced the effect of cefepime in otherwise resistant isolates of Enterobacteriaceae and that the %fT>CT of 0.25 mg/liter best correlated with efficacy. These studies provide the basis for the development of human dosing regimens for this combination

Evaluation of the post-antibiotic effect in vivo for the combination of a beta-lactam antibiotic and a beta-lactamase inhibitor: ceftazidime-avibactam in neutropenic mouse thigh and lung infections

The post-antibiotic effect (PAE) of ceftazidime-avibactam in vivo was evaluated using models of thigh- and lung-infection with Pseudomonas aeruginosa in neutropenic mice. In thigh-infected mice, the PAE was negative (–2.18 to −0.11 h) for three of four strains: caused by a ‘burst’ of rapid bacterial growth after the drug concentrations had fallen below their pre-specified target values. With lung infection, PAE was positive, and longer for target drug concentrations in ELF (>2 h) than plasma (1.69–1.88 h). The time to the start of regrowth was quantified as a new parameter, PAER, which was positive (0.35–1.00 h) in both thigh- and lung-infected mice. In the context that measurements of the PAE of β-lactam/β-lactamase inhibitor combinations in vivo have not previously been reported, it is noted that the negative values were consistent with previous measurements of the PAE of ceftazidime-avibactam in vitro and of ceftazidime alone in vivo