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Introduction: Patient-reported outcomes (PROs) provide an insightful method of assessing the subjective impact of therapies for those affected by multiple sclerosis (MS), a chronic neurologic disease notable for symptoms of fatigue and reduced physical function. The ongoing CLAWIR study aims to assess the effect of cladribine tablets (3.5 mg/kg cumulative dose over 2 years) in patients with highly active relapsing MS focusing on PROs of fatigue, physical function, treatment satisfaction, and work productivity. Here, we report on a pre-planned analysis at 12 months after treatment initiation with cladribine tablets. Methods: CLAWIR is a 2-year, multicenter, prospective, observational study of patients with relapsing MS newly initiating cladribine tablets. The following PROs were analyzed: PRO Measurement Information System (PROMIS®) Fatigue MS (v1.0) and Physical Function MS (v2.1), Treatment Satisfaction Questionnaire for Medication (TSQM, v1.4), and Work Productivity and Activity Impairment MS Questionnaire (WPAI-MS). Data were analyzed descriptively. Results: In total, 128 patients were eligible for analysis: 95 females (74.2%); median (range) age 34.5 (29, 44) years; 34 patients (26.6%) were treatment-naïve, and 89 (69.5%) were early switchers from platform therapies (the remaining 5 patients [3.9%] switched from a high-efficacy disease-modifying therapy). PROMIS® Fatigue MS mean (± standard deviation [SD]) T-scores decreased from 54.6 (± 9.59) at baseline to 51.8 (± 10.30) at 12 months, indicating an alleviation of fatigue, whereas PROMIS® Physical Function MS mean T-scores remained stable over time [baseline: 49.4 (± 10.69); 12 months: 50.3 (± 10.88)]. TSQM v1.4 mean scores indicated an improvement over time, increasing from 52.2 (± 27.79) at baseline to 81.4 (± 17.06) at 12 months for global satisfaction. WPAI-MS scores also showed an improvement across all four domains over 12 months. Conclusion: This real-world study demonstrates the effect of cladribine tablets over 12 months on PROs of fatigue, physical function, treatment satisfaction, and work productivity. Trial Registration: The CLAWIR study is registered at the German Federal Institute for Drugs and Medical Devices with the internal NIS number 7469. [ABSTRACT FROM AUTHOR]

Purpose: The transport behavior of human pharmaceuticals in groundwater depends on a multitude of factors such as the physico-chemical conditions in the aquifer and the organic carbon content of the sediment, and, in particular, on the redox conditions in the groundwater. This is of special interest at managed aquifer recharge sites where the occurrence of trace organics is important for drinking water production. The aim of this study was to evaluate the possibility of influencing the redox system of the aquifer in a way that optimizes the potential of managed aquifer recharge systems to reduce the amount of trace organics. Materials and methods: Column studies were performed using natural and thermally treated sediments from an infiltration basin of the Berlin area, Germany. Special emphasis was placed on thermal treatment of the sediments to influence the total organic carbon (TOC) content in the sediment. In one experiment, the sediment was thermally pretreated at 550 °C, in two experiments the sediment was pretreated at 200 °C, and in one the sediment was untreated. Furthermore, the influence of ozonation, a very common disinfectant used in drinking water production, was studied in the experiments. The retardation and degradation parameters for primidone (PMD), carbamazepine (CBZ), and sulfamethoxazole (SMX) under different redox conditions were evaluated. Results and discussion: Oxic conditions were obtained in the experiment with low TOC (0.06 wt%) in the sediment pre-treated at 550 °C. Anoxic conditions were predominant in two column experiments with a TOC content of 0.17 wt% in the sediment, irrespective of the mode of treatment (natural or 200 °C). All three pharmaceutical compounds show almost conservative transport behavior with retardation factors between 1.02 and 1.25 for PMD, between 1.06 and 1.37 for CBZ, and between 1.00 and 1.08 for SMX. Differences in the transport behavior were observed depending on the TOC content of the sediment. For CBZ, and to a minor extent for PMD, the higher retardation factors were observed in the sediment with a TOC content of 0.17 wt% under anoxic conditions. The ozonation of the influent water affects the influent concentrations of PMD, CBZ and SMX. However, it has no influence on the oxygen concentration of the column outflow. Conclusions: CBZ and PMD are retarded in the presence of organic matter in the aquifer. Variations of the TOC content of the sediment have a direct influence on the retardation of CBZ and PMD. The three human pharmaceuticals may be ranked in order of decreasing retardation: CBZ > PMD > SMX. The microbial activity in the experiments was not studied, although it can be assumed that the thermal pretreatment influences the microbial activity in the sediments. In particular, the microbial activity was severely inhibited at 550 °C, resulting in a shift of the redox conditions. [ABSTRACT FROM AUTHOR]

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In recent years, human pharmaceutical substances have been increasingly detected in the aquatic environment. Specific attention has been drawn to the occurrence of pharmaceutical substances at bank filtration sites which are used for drinking water production. In the course of the authorisation application for new pharmaceutical compounds, an environmental risk assessment is required. Currently, the expected concentration of the human pharmaceutical compound in groundwater at bank filtration sites is calculated following the guideline Pre-Authorisation Evaluation of Medicines for Human Use issued by the European Medicines Agency (EMEA ). A simple estimation is applied: The predicted environmental concentration (PEC) is the predicted environmental concentration in surface water (PEC) multiplied with 0.25. A new approach considering the hydraulic and hydrogeological characteristics of bank filtration sites as well as transport processes is presented in this study. First, a numerical groundwater flow model was developed to simulate the groundwater flow processes at bank filtration sites in general. Flow times were calculated as a function of the hydraulic and hydrogeological parameters: hydraulic conductivity, shore-well distance, screen depth and extraction rate. In a second step, the PEC was calculated based on the compound concentration in surface water and the modelled groundwater flow times considering linear sorption and first-order decay. Sorption and degradation can only be calculated based on the data provided by the pharmaceutical company in the course of the authorisation application. The current approach following the EMEA guideline invariably connects the PEC with the PEC without considering sorption and/or degradation processes. We introduce an approach that incorporates the hydraulic process bank filtration and the main transport processes sorption and degradation. The new approach is compound specific as well as aquifer, flow and transport specific resulting in a more realistic PEC value compared to the old approach. [ABSTRACT FROM AUTHOR]

In Kafka's "Penal Colony", censorship -- the control and manipulation of information -- is functionalized for an aesthetic and poetological discourse. Within the closed-off colony, social hierarchies and groups are formed on the basis of information and disinformation, such that the penal system itself relies on the ignorance of those to be punished. For in the process of his execution, the offender is supposed to decipher the inscription the machine administers to his body, and it is this eventual decoding which represents the torture's true purpose. Here, the dysfunctional quality of the machine, together with the artistic nature of the inscriptions, open up a poetological perspective which revolves around the motif of understanding. The object of these endeavours is the literary text, symbolized by the inscriptions. Taking the narrated world of the island colony as a frame of reference, the figures embody the narrative functions of author, fictional character and reader, engaged in creation and reception. But ultimately, the literary text acts as censor: It does not yield to the reader's knocking on the gate; complete understanding is impossible. [ABSTRACT FROM AUTHOR]

During growth on poly(3-hydroxyvaleric acid), P(3HV), or valerate Pseudomonas lemoignei secretes a P(3HV) depolymerase. This P(3HV) depolymerase was purified from the culture medium of valerate-grown cells by ammonium sulphate precipitation, chromatography on DEAe-sephacel and CM-Sepharose CL 6B. The relative molecular masses of the native as well as the sodium dodecyl sulphate (SDS)-treated enzyme were 53 000 or 54 000, respectively. In contrast to the poly(3-hydroxybutyric acid), P(3HB), depolymerase of Comamonas sp. and P(3HB) depolymerases A and B of P. lemoignei, which are specific for the hydrolysis of P(3HB), the purified P(3HV) depolymerase hydrolysed P(3HB), P(3HV) and co-polymers of 3-hydroxybutyric acid and 3-hydroxyvaleric acid at similar rates. Poly(hydroxyalkanoic acids), consisting of monomers with six and more carbon atoms or substrates characteristic for lipases such as Tween 80 or triolein were not hydrolysed. Maximum activities were measured in 50 mm TRIS-HCl buffer, pH 8.0, at 55° C. The apparent K values of the purified P(3HV) depolymerase for P(3HB) and P(3HV) were 77 and 65 μg polyester/ml, respectively. As the main product of enzymatic hydrolysis of P(3HV), 3-hydroxyvalerate was identified. The depolymerase was insensitive to p-hydroxymercuribenzoate but sensitive to dithioerythritol and phenylmethylsulphonyl fluoride, indicating the absence of active reduced sulphur groups and the presence of essential disulphide bonds and serine residues. [ABSTRACT FROM AUTHOR]

A correction to the article "Pharmaceuticals as indicators of sewage-influenced groundwater" that was published in the 2012 issue is presented.