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An inadvertent consequence of pesticide use is aquatic pesticide pollution, which has prompted the implementation of mitigation measures in many countries. Water quality monitoring programs are an important tool to evaluate the efficacy of these mitigation measures. However, large interannual variability of pesticide losses makes it challenging to detect significant improvements in water quality and to attribute these improvements to the application of specific mitigation measures. Thus, there is a gap in the literature that informs researchers and authorities regarding the number of years of aquatic pesticide monitoring or the effect size (e.g., loss reduction) that is required to detect significant trends in water quality. Our research addresses this issue by combining two exceptional empirical data sets with modelling to explore the relationships between the achieved pesticide reduction levels due to mitigation measures and the length of the observation period for establishing statistically significant trends. Our study includes both a large (Rhine at Basel, ∼36,300 km 2 ) and small catchment (Eschibach, 1.2 km 2 ), which represent spatial scales at either end of the spectrum that would be realistic for monitoring programs designed to assess water quality. Our results highlight several requirements in a monitoring program to allow for trend detection. Firstly, sufficient baseline monitoring is required before implementing mitigation measures. Secondly, the availability of pesticide use data helps account for the interannual variability and temporal trends, but such data are usually lacking. Finally, the timing and magnitude of hydrological events relative to pesticide application can obscure the observable effects of mitigation measures (especially in small catchments). Our results indicate that a strong reduction (i.e., 70-90 %) is needed to detect a change within 10 years of monitoring data. The trade-off in applying a more sensitive method for change detection is that it may be more prone to false-positives. Our results suggest that it is important to consider the trade-off between the sensitivity of trend detection and the risk of false positives when selecting an appropriate method and that applying more than one method can provide more confidence in trend detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aquatic pesticide pollution is an important issue worldwide. Countries rely on monitoring programs to observe water bodies quality and on models to evaluate pesticide risks for entire stream networks. Measurements are typically sparse and discontinuous which lead to issues in quantifying pesticide transport at the catchment scale. Therefore, it is essential to assess the performance of extrapolation approaches and provide guidance on how to extend monitoring programs to improve predictions. Here we present a feasibility study to predict pesticide levels in a spatially explicit manner in the Swiss stream network based on the national monitoring program quantifying organic micropollutants at 33 sites and spatially distributed explanatory variables. Firstly, we focused on a limited set of herbicides used on corn crops. We observed a significant relationship between herbicide concentrations and the areal fraction of hydrologically connected cornfields. Neglecting connectivity revealed no influence of areal corn coverage on the herbicide levels. Considering chemical properties of the compounds slightly improved the correlation. Secondly, we analysed a set of 18 pesticides widely used on different crops and monitored across the country. In this case, the areal fractions of arable or crop lands showed significant correlations with average pesticide concentrations. Similar results were found with average annual discharge or precipitation if two outlier sites were neglected. The correlations found in this paper explained only about 30 % of the observed variance leaving most of the variability unexplained. Accordingly, extrapolating the results from the existing monitoring sites to the Swiss river network comes with substantial uncertainty. Our study highlights possible reasons for weak matches, such as missing pesticide application data, limited set of compounds in the monitoring program, or a limited understanding of factors differentiating the loss rates from different catchments. Improving the data on pesticide applications will be essential to progress in this regard., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Artisanal and small-scale mining (ASM) is an important livelihood activity in many low- and middle-income countries. It is widely acknowledged that there are a myriad of health risk and opportunities associated with ASM. However, little is known with regard to which aspects of health have been studied in ASM settings. We conducted a scoping review of peer-reviewed publications, using readily available electronic databases (i.e., PubMed, Scopus, and Web of Science) from inception to 14 July 2020. Relevant information was synthesized with an emphasis on human and environmental exposures and health effects in a context of ASM. Our search yielded 2764 records. After systematic screening, 176 health studies from 38 countries were retained for final analysis. Most of the studies ( n = 155) focused on health in ASM extracting gold. While many of the studies included the collection of environmental and human samples ( n = 154), only few ( n = 30) investigated infectious diseases. Little attention was given to vulnerable groups, such as women of reproductive age and children. Our scoping review provides a detailed characterisation of health studies in ASM contexts. Future research in ASM settings should address health more comprehensively, including the potential spread of infectious diseases, and effects on mental health and well-being.

Aquatic pesticide pollution from both agricultural and urban pest control is a concern in many parts of the world. Making an accurate assessment of pesticide exposure is the starting point to protecting aquatic ecosystems. This in turn requires the design of an effective monitoring program. Monitoring is also essential to evaluate the efficacy of mitigation measures aimed to curb pesticide pollution. However, empirical evidence for their efficacy can be confounded by additional influencing factors, most prominently variable weather conditions. This review summarizes the experiences gained from long-term (>5 years) pesticide monitoring studies for detecting trends and provides recommendations for their improvement. We reviewed articles published in the scientific literature, with a few complements from selected grey literature, for a total of 20 studies which fulfill our search criteria. Overall, temporal trends of pesticide use and hydrological conditions were the two most common factors influencing aquatic pesticide pollution. Eighteen studies demonstrated observable effects to surface water concentrations from changes in pesticide application rates (e.g., use restriction) and sixteen studies from interannual variability in hydrological conditions during the application period. Accounting for seasonal- and streamflow-related variability in trend analysis is important because the two factors can obscure trends caused by changes in pesticide use or management practices. Other mitigation measures (e.g., buffer strips) were only detectable in four studies where concentrations or loads were reduced by > 45%. Collecting additional agricultural (e.g., pesticide use, mitigation measures) and environmental (e.g., precipitation, stream flow) data, as well as establishing a baseline before the implementation of mitigation measures have been consistently reported as prerequisites to interpret water quality trends from long-term monitoring studies, but have rarely been implemented in the past., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Swiss Federal Institute of Aquatic Science and Technology (Eawag).)

Introduction: The increasing professionalization and the cost pressure on farms combined with a decreasing availability of veterinary expertise procures the demand for treatments and interventions performed by non-veterinarians. A current survey resulting in 56 responses of food animal practitioners showed that a majority delivered pour-on anthelmintics, drugs for oral application and ointments after respective instruction to farmers. Udder injectors, antimicrobials and vaccines were handled more restrictively, but even hormones were committed by more than half of the veterinarians to livestock owners. In respect to interventions, most practitioners supported that farmers perform functional foot trimming, administration of boli, inseminations, dehorning and castrations of calves. By contrast, many veterinarians refused that farmers apply intravenous injections, insert a trocar or treat sole ulcers. In respect to the future development, implications of non-veterinarian interventions on animal welfare, consumer protection and drug safety have to be considered. Indispensable are qualification and skills of the person performing interventions which can be acquired by certificated training courses. Moreover, a basic conception and taking responsibility in particular for application of veterinary drugs is mandatory - in this respect, at present marked deficits exist among many farmers. Based on the current legal situation, several interventions can be delegated to non-veterinarians, but the technical responsibility for the proper implementation is due to the veterinarian. This includes an evaluation of interventions and treatments on a regular basis together with the farmer. On this basis, the assessment of clinical symptoms as well as the initial treatment can be useful and appropriate to ensure a rapid therapy especially in animals suffering from factorial diseases. Having in mind profound differences in respect to the competence of non-veterinarians, general procedures to deliver drugs and to delegate interventions have to be rejected. Advanced diagnostic procedures and the prescription of veterinary drugs remain an exclusive mission of the veterinarian.

The EU falsified Medicines Directive 2011/62/EU will be applied in Switzerland as well. It mandates unique identifiers on medication packages and a process to ensure that these identifiers are decommissioned when the medication package is handed to the patient. While this is not a major problem for Swiss community pharmacies, it is yet unclear how decommissioning shall be managed within hospitals. This paper analyses the drug supply chain in 5 Swiss hospitals and drafts a system architecture to support a decommissioning process upon arrival of new drug deliveries at the hospital pharmacy.

Objective: The aim of this systematic review was to provide a comprehensive synthesis of available evidence evaluating the effect of dietary loading on temporomandibular joint/condyle, condylar cartilage, alveolar bone of the mandible and the periodontal ligament in healthy mice and rats., Design: Medline via PubMed, EMBASE and Open Grey databases were searched for published and unpublished literature. Search terms included "mandiblular condyle", "alveolar bone", "temporomandibular joint", "condylar cartilage", "periodontal ligament", "rat", "mice". After data extraction, risk of bias (SYRCLE) and reporting quality (ARRIVE) were assessed. Random effects meta-analyses were performed for the outcomes of interest where applicable., Results: A total of 33 relevant articles were considered in the systematic review, while only 6 studies were included in the quantitative synthesis. Risk of Bias in all studies was judged to be unclear to high overall, while reporting quality was suboptimal. Comparing soft to hard diet animals, significantly reduced anteroposterior condylar length (4 studies, weighted mean difference: -0.40 mm; 95% CI: -0.47, -0.32; p < 0.001) and width (4 studies, weighted mean difference: -0.043 mm; 95% CI: -0.51, -0.36; p < 0.001) were found in rats. Decreased anteroposterior condylar dimensions were detected for mice as well (2 studies, weighted mean difference: -0.049; 95% CI: -0.56, -0.43; p < 0.001)., Conclusions: Overall, there was strong evidence to suggest a significant effect of soft diet on reduced condylar dimensions in rodents; however, there is need for further high quality experimental studies to inform current knowledge on condylar cartilage, alveolar bone and periodontal ligament related outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Adequate sanitation, wastewater treatment and irrigation infrastructure often lacks in urban areas of developing countries. While treated, nutrient-rich reuse water is a precious resource for crop production in dry regions, excessive salinity might harm the crops. The aim of this study was to quantify, from a system perspective, the nutrient and salt flows a new infrastructure connecting water supply, sanitation, wastewater treatment and nutrient-rich water reuse for the irrigation of agriculture, from a system perspective. For this, we developed and applied a quantitative assessment method to understand the benefits and to support the management of the new water infrastructure in an urban area in semi-arid Namibia. The nutrient and salt flows, as affected by sanitation user behavior, were quantified by mathematical material flow analysis that accounts for the low availability of suitable and certain data in developing countries, by including data ranges and by assessing the effects of different assumptions in cases. Also the nutrient and leaching requirements of a crop scheme were calculated. We found that, with ideal sanitation use, 100% of nutrients and salts are reclaimed and the slightly saline reuse water is sufficient to fertigate 10 m(2)/cap/yr (90% uncertainty interval 7-12 m(2)/cap/yr). However, only 50% of the P contained in human excreta could be finally used for crop nutrition. During the pilot phase fewer sanitation users than expected used slightly more water per capita, used the toilets less frequently and practiced open defecation more frequently. Therefore, it was only possible to reclaim about 85% of nutrients from human excreta, the reuse water was non-saline and contained less nutrient so that the P was the limiting factor for crop fertigation. To reclaim all nutrients from human excreta and fertigate a larger agricultural area, sanitation user behavior needs to be improved. The results and the methodology of this study can be generalized and used worldwide in other semi-arid regions requiring irrigation for agriculture as well as urban areas in developing countries with inadequate sanitation infrastructure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to investigate spontaneous low-frequency signal fluctuations across brain resting state networks. However, BOLD only provides relative measures of signal fluctuations. Arterial Spin Labeling (ASL) MRI holds great potential for quantitative measurements of resting state network fluctuations. This study systematically quantified signal fluctuations of the large-scale resting state networks using ASL data from 20 healthy volunteers by separating them from global signal fluctuations and fluctuations caused by residual noise. Global ASL signal fluctuation was 7.59% ± 1.47% relative to the ASL baseline perfusion. Fluctuations of seven detected resting state networks vary from 2.96% ± 0.93% to 6.71% ± 2.35%. Fluctuations of networks and residual noise were 6.05% ± 1.18% and 6.78% ± 1.16% using 4-mm resolution ASL data applied with Gaussian smoothing kernel of 6mm. However, network fluctuations were reduced by 7.77% ± 1.56% while residual noise fluctuation was markedly reduced by 39.75% ± 2.90% when smoothing kernel of 12 mm was applied to the ASL data. Therefore, global and network fluctuations are the dominant structured noise sources in ASL data. Quantitative measurements of resting state networks may enable improved noise reduction and provide insights into the function of healthy and diseased brain., (© The Author(s) 2015.)

Rivers in developing and emerging countries often lack good water quality. Tools to assess the water quality in rivers, including identification of possible sources of pollution, are therefore of increasing importance. The aim of this study is to apply mathematical material flow and spatial land use analyses to identify and geographically locate the main nitrogen and phosphorus sources and processes in Bang Pakong Basin (BPB). Potential measures to mitigate the nitrogen and phosphorus loads to the water system can then be efficiently evaluated. The combination of these two methods reveals the overall nutrient load as well as local "hot spots." This allows possible mitigation measures to be discussed with regard to their spatial location. This approach goes beyond previous work in which mathematical material flow analysis was shown to be a useful tool to investigate sources of nutrients regardless of their location. The results show that the main sources contributing nutrients to waterways are aquaculture, such as shrimp, tilapia, catfish, and sea bass farming, as well as rice paddies along the main river. Additional sources contributing nutrients to this basin are field crops, livestock, aquaculture, households, and industry. High levels of nutrient inflows come from feeds and fertilizers through aquaculture and rice cultivation. The excess nutrients run into the waterways by direct discharge from aquaculture and runoff processes from rice paddies. Scenario analysis shows that management practices for aquaculture, rice, pig, and poultry farming are key drivers for reducing nutrients in the BPB.

Off-resonance saturation transfer images have shown intriguing differences in intensity in glioma compared to normal brain tissues. Interpretation of these differences is complicated, however, by the presence of multiple sources of exchanging magnetization including amide, amine, and hydroxyl protons, asymmetric magnetization transfer contrast (MTC) from macromolecules, and various protons with resonances in the aliphatic spectral region. We report a study targeted at separating these components and identifying their relative contributions to contrast in glioma. Off-resonance z-spectra at several saturation powers and durations were obtained from 6 healthy controls and 8 patients with high grade glioma. Results indicate that broad macromolecular MTC in normal brain tissue is responsible for the majority of contrast with glioma. Amide exchange could be detected with lower saturation power than has previously been reported in glioma, but it was a weak signal source with no detectable contrast from normal brain tissue. At higher saturation powers, amine proton exchange was a major contributor to the observed signal but showed no significant difference from normal brain. Robust acquisition strategies that effectively isolate the contributions of broad macromolecular MTC asymmetry from amine exchange were demonstrated that may provide improved contrast between glioma and normal tissue., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Pharmaceuticals constitute an important environmental issue for receiving waters. A holistic approach, taking into consideration the sources of these compounds (hospitals, domestic use), discharges (wastewater effluent, combined sewer overflows) and related risks to the environment, is therefore needed to develop the best protection strategy. The substance flow analysis (SFA) approach, applied, for example, to the city of Lausanne, Switzerland, is an ideal tool to tackle these issues. Four substances were considered: one antibiotic (ciprofloxacin), an analgesic (diclofenac), and two anti-epileptics (carbamazepine and gabapentin). Consumption data for the main hospital of the city (916 beds) and for the population were available. Micropollutant concentrations were measured at different points of the system: wastewater inlet and outlet (WWTP), combined sewer overflows (CSO) and in the receiving waters (Vidy Bay, Lake Geneva). Measured and predicted concentrations were in agreement, except for diclofenac, for which analytical uncertainties were expected. Seven different scenarios were considered (supplementary treatment at the WWTP, at the hospital or at both places, etc.). Based on the results obtained, the supplementary treatment at the WWTP decreases the load of pharmaceuticals reaching surface water by a factor between 2 and 27, depending on the compound and on the technique. The treatment at the hospitals only influences the amount of ciprofloxacin reaching the environment and decreases the release by one third. The contribution of CSO to surface water pollution is low compared to that of the WWTP for the selected compounds. Regarding the risk for the receiving waters, ciprofloxacin was found to be the most problematic compound, with a risk quotient far above 1. In this particular case, a treatment at the WWTP is not sufficient to reduce the risk, and additional measures at the CSO or at the hospital should be considered. SFA is an ideal tool for developing the best strategy for pharmaceutical elimination, but its application depends on data availability and local conditions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf-β/Bmp activity.

Amide proton transfer (APT) imaging has shown promise as an indicator of tissue pH and as a marker for brain tumors. Sources of error in APT measurements include direct water saturation, and magnetization transfer (MT) from membranes and macromolecules. These are typically suppressed by postprocessing asymmetry analysis. However, this approach is strongly dependent on B(0) homogeneity and can introduce additional errors due to intrinsic MT asymmetry, aliphatic proton features opposite the amide peak and radiation damping-induced asymmetry. Although several methods exist to correct for B(0) inhomogeneity, they tremendously increase scan times and do not address errors induced by asymmetry of the z-spectrum. In this article, a novel saturation scheme-saturation with frequency alternating RF irradiation (SAFARI)-is proposed in combination with a new magnetization transfer ratio (MTR) parameter designed to generate APT images insensitive to direct water saturation and MT, even in the presence of B(0) inhomogeneity. The feasibility of the SAFARI technique is demonstrated in phantoms and in the human brain. Experimental results show that SAFARI successfully removes direct water saturation and MT contamination from APT images. It is insensitive to B(0) offsets up to 180 Hz without using additional B(0) correction, thereby dramatically reducing scanning time., (Copyright © 2011 Wiley Periodicals, Inc.)

Biocides leach from facades during rain events and subsequently enter the aquatic environment with storm water. Little is known about the losses of an entire settlement, since most studies referred to wash-off experiments conducted under laboratory conditions. Their results show a fast decrease of concentrations in the beginning, which subsequently slows down. The aim of this study is to develop a simple model to understand the mechanisms leading to these losses as well as to simulate losses under various rainfall and application conditions. We developed a four-box model based on the knowledge gained from fits of an exponential function to an existing experimental data set of a wash-off experiment. The model consists of two mobile stocks from which biocides are washed off during a rain event. These mobile stocks are supplied with biocides from storage stocks by diffusion-type processes. The model accurately reproduced the measured data of wash-off during single cycles as well as peak wash-offs over all cycles. Our model results for diuron losses showed that a large proportion (∼ 70%) of the applied biocides are still in the stocks even after a rain volume corresponding to several years (1100 mm y(-1), Swiss Plateau). Applications to realistic outdoor conditions showed that losses can not be neglected for urban environments and that knowledge about the amount of rainfall turned into runoff and the decay constants of the biocides in the facades are crucial. The model increased our understanding of the processes leading to the observed dynamic in laboratory experiments and was used to simulate losses for various rainfall and application conditions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Context: Dental and skeletal fluorosis is endemic in the Ethiopian Rift Valley. Children are especially vulnerable to excessive fluoride intake because their permanent teeth are still being formed. Strategies to reduce the total fluoride intake by children are thus warranted., Case Presentation: By combining the results of field studies in Ethiopia, the relevant pathways for fluoride intake have been identified in 28 children 2-5 years of age living in two villages on the Wonji Shoa Sugar Estate in the Ethiopian Rift Valley. The focus of the present study was to simulate the fluoride intake of the children using the methods of material flow analysis (MFA) and substance flow analysis., Discussion: With a model based on MFA, we quantified the potential reduction in total fluoride intake given different scenarios-for example, by reducing the fluoride intake from drinking water and cooking water. The results show clearly that only by removing fluoride completely from both drinking and cooking water does the probability of remaining below the daily tolerable upper intake level exceed 50%. Both prepared food and food ingredients must be taken into consideration when assessing the total fluoride intake by children living in high-fluoride areas., Relevance: This knowledge will help health personnel, the government, and the food authorities to give scientifically based advice on strategies for reducing the total fluoride intake by children living in high-fluoride areas in the Ethiopian Rift Valley.

Biocides and pesticides are used to control unwanted organisms in urban and agricultural areas. After application, they can be lost to surface waters and impair water quality. Several national consumption studies have shown that urban and agricultural use may be in the same range. It is difficult to judge whether this results in similar loadings of surface waters because there is a lack of sound, comparative studies addressing urban and agricultural losses simultaneously. The aim of this study is thus to relate the biocide and pesticide loads found in surface waters to their respective urban and agricultural usage (loss rates). To simultaneously assess the loss rates, we conducted a comprehensive field study in a catchment of mixed land use on the Swiss Plateau. The study area was divided into four sub-catchments with different degrees of urban and agricultural land use. In addition, we studied the only wastewater treatment plant, a combined sewer overflow and a storm sewer within the area. Rain events were sampled at high temporal resolution from March to November, 2007. Information on agricultural applications was gained from local farmers. For urban uses, consumption estimations were conducted based on statistical and product information. Despite substantially lower amounts used, the measured loads of urban biocides were in the same range as the most widely-used agricultural pesticides. The lower usage was compensated by urban loss rates that were up to ten times higher than agricultural ones (0.6 to 15% for urban, 0.4 to 0.9% for agricultural compounds). For most biocides and pesticides, the loads were controlled by rain events. Besides the rain-controlled losses, some urban-used biocides (e.g. diazinon) showed a continuous load independent of rain events and season. This study demonstrates that in catchments with mixed land use, mitigation strategies have to pay sufficient attention to the urban sources., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Human activity results in the production of a wide range of pollutants that can enter the water cycle through stormwater or wastewater. Among others, heavy metals are still detected in high concentrations around urban areas and their impact on aquatic organisms is of major concern. In this study, we propose to use a substance flow analysis as a tool for heavy metals management in urban areas. We illustrate the approach with the case of copper in Lausanne, Switzerland. The results show that around 1,500 kg of copper enter the aquatic compartment yearly. This amount contributes to sediment enrichment, which may pose a long-term risk for benthic organisms. The major sources of copper in receiving surface water are roofs and catenaries of trolleybuses. They represent 75% of the total input of copper into the urban water system. Actions to reduce copper pollution should therefore focus on these sources. Substance flow analysis also highlights that copper enters surface water mainly during rain events, i.e., without passing through any treatment procedure. A reduction in pollution could also be achieved by improving stormwater management. In conclusion, the study showed that substance flow analysis is a very effective tool for sustainable urban water management.

The objective of this study was to evaluate if cartilage fixed charge density is the only factor determining the distribution of the measured delayed gadolinium-enhanced magnetic resonance imaging of cartilage index, T(1) (Gd-DTPA(2-) ), across cartilage in the clinical delayed gadolinium-enhanced magnetic resonance imaging of cartilage protocol. Nineteen subjects with osteoarthritis and 14 controls were included. Cartilage T(1) (Gd) was measured following administration of 0.2 mmol kg(-1) of nonionic (Gd-DTPA-BMA) and, at a different date, anionic (Gd-DTPA(2-). T(1) (Gd-DTPA-BMA) was plotted against T(1) (Gd-DTPA(2-); a slope of 0 would indicate domination by charge effects; a nonzero slope would suggest that other factors influence T(1) (Gd-DTPA-BMA), and hence potentially T(1) (Gd-DTPA(2-). The low slope of the curve found in osteoarthritis subjects (0.31) indicates that Gd-DTPA-BMA penetrated most osteoarthritis cartilage to the same extent, and T(1) (Gd-DTPA-BMA) did not differentiate cartilages, which were differentiated by T(1) (Gd-DTPA(2-). The higher slopes in control subjects (0.88) are possibly due to inhibited transport of contrast agent into healthier cartilage, potentially exaggerated by the fast body clearance of the nonionic contrast agent. Overall, the use of anionic Gd-DTPA(2-) for delayed gadolinium-enhanced magnetic resonance imaging of cartilage is indicated for better discrimination of the health status of cartilage. Future studies could be designed to use contrast-enhanced dynamics to understand the transport properties of tissues in the joint and to evaluate the concentration of tissue constituents., (Copyright © 2010 Wiley-Liss, Inc.)

This paper explores the potential of combining substance-flow modelling with water and wastewater sampling to trace consumption-related substances emitted through the urban wastewater. The method is exemplified on sucralose. Sucralose is a chemical sweetener that is 600 times sweeter than sucrose and has been on the European market since 2004. As a food additive, sucralose has recently increased in usage in a number of foods, such as soft drinks, dairy products, candy and several dietary products. In a field campaign, sucralose concentrations were measured in the inflow and outflow of the local wastewater treatment plant in Linköping, Sweden, as well as upstream and downstream of the receiving stream and in Lake Roxen. This allows the loads emitted from the city to be estimated. A method consisting of solid-phase extraction followed by liquid chromatography and high resolution mass spectrometry was used to quantify the sucralose in the collected surface and wastewater samples. To identify and quantify the sucralose sources, a consumption analysis of households including small business enterprises was conducted as well as an estimation of the emissions from the local food industry. The application of a simple model including uncertainty and sensitivity analysis indicates that at present not one large source but rather several small sources contribute to the load coming from households, small business enterprises and industry. This is in contrast to the consumption pattern seen two years earlier, which was dominated by one product. The inflow to the wastewater treatment plant decreased significantly from other measurements made two years earlier. The study shows that the combination of substance-flow modelling with the analysis of the loads to the receiving waters helps us to understand consumption-related emissions., (Copyright 2010 Elsevier B.V. All rights reserved.)

Biocides and pesticides are designed to control the occurrence of unwanted organisms. From their point of application, these substances can be mobilized and transported to surface waters posing a threat to the aquatic environment. Historically, agricultural pesticides have received substantially more attention than biocidal compounds from urban use, despite being used in similar quantities. This study aims at improving our understanding of the influence of mixed urban and agricultural land use on the overall concentration dynamics of biocides and pesticides during rain events throughout the year. A comprehensive field study was conducted in a catchment within the Swiss plateau (25 km(2)). Four surface water sampling sites represented varying combinations of urban and agricultural sources. Additionally, the urban drainage system was studied by sampling the only wastewater treatment plant (WWTP) in the catchment, a combined sewer overflow (CSO), and a storm sewer (SS). High temporal resolution sampling was carried out during rain events from March to November 2007. The results, based on more than 600 samples analyzed for 23 substances, revealed distinct and complex concentration patterns for different compounds and sources. Five types of concentration patterns can be distinguished: a) compounds that showed elevated background concentrations throughout the year (e.g. diazinon >50 ng L(-1)), indicating a constant household source; b) compounds that showed elevated concentrations driven by rain events throughout the year (e.g. diuron 100-300 ng L(-1)), indicating a constant urban outdoor source such as facades; c) compounds with seasonal peak concentrations driven by rain events from urban and agricultural areas (e.g. mecoprop 1600 ng L(-1) and atrazine 2500 ng L(-1) respectively); d) compounds that showed unpredictably sharp peaks (e.g. atrazine 10,000 ng L(-1), diazinon 2500 ng L(-1)), which were most probably due to improper handling or even disposal of products; and finally, e) compounds that were used in high amounts but were not detected in surface waters (e.g. isothiazolinones). It can be safely concluded that in catchments of mixed land use, the contributions of biocide and pesticide inputs into surface waters from urban areas are at least as important as those from agricultural areas., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate circulating cytokines and chemokines as correlates of the degree of brain injury in individuals with advanced human immunodeficiency virus (HIV) infection., Experimental Design: Study participants included ten well-characterized subjects in advanced stage HIV infection. High-throughput multiplexed analysis was used to quantify markers of interest at baseline and 3 years later in the clinical course. Objective measurements of the brain were derived in vivo with quantitative magnetic resonance segmentation algorithms and with diffusion tensor imaging., Results: Of the markers examined, monocyte chemoattractant protein-1 (MCP-1 or CCL-2) was the most prominent correlate of brain injury. Elevated MCP-1 levels correlated with brain white matter alterations at the initial assessment. The relationship to injury was more extensive 3 years later; elevated MCP-1 was significantly correlated with measures of brain microstructural alterations and of abject atrophy., Conclusions and Clinical Relevance: The findings build on our prior observations that elevated MCP-1 levels may be a useful predictive marker for HIV-associated neurocognitive disorder. As a potent chemoattractant, MCP-1 may mediate injury through participation in self-reinforcing cycles of chronic immune activation and cytokine/chemokine-mediated neurotoxicity., (Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Major rivers in developing and emerging countries suffer increasingly of severe degradation of water quality. The current study uses a mathematical Material Flow Analysis (MMFA) as a complementary approach to address the degradation of river water quality due to nutrient pollution in the Thachin River Basin in Central Thailand. This paper gives an overview of the origins and flow paths of the various point- and non-point pollution sources in the Thachin River Basin (in terms of nitrogen and phosphorus) and quantifies their relative importance within the system. The key parameters influencing the main nutrient flows are determined and possible mitigation measures discussed. The results show that aquaculture (as a point source) and rice farming (as a non-point source) are the key nutrient sources in the Thachin River Basin. Other point sources such as pig farms, households and industries, which were previously cited as the most relevant pollution sources in terms of organic pollution, play less significant roles in comparison. This order of importance shifts when considering the model results for the provincial level. Crosschecks with secondary data and field studies confirm the plausibility of our simulations. Specific nutrient loads for the pollution sources are derived; these can be used for a first broad quantification of nutrient pollution in comparable river basins. Based on an identification of the sensitive model parameters, possible mitigation scenarios are determined and their potential to reduce the nutrient load evaluated. A comparison of simulated nutrient loads with measured nutrient concentrations shows that nutrient retention in the river system may be significant. Sedimentation in the slow flowing surface water network as well as nitrogen emission to the air from the warm oxygen deficient waters are certainly partly responsible, but also wetlands along the river banks could play an important role as nutrient sinks.

Circulating levels of specific matrix metalloproteinases (MMPs; 1 and 7) were evaluated as correlates of brain injury in eight individuals in advanced human immunodeficiency virus (HIV) infection. Neurological status was quantified in vivo with automated segmentation algorithms and with diffusion tensor imaging. Both metalloproteinases correlated with microstructural brain alterations and the degree of atrophy. MMPs may influence neurological outcome through involvement in neuroimmune response, blood-brain barrier permeability, leukocyte migration, and MMP-mediated neurotoxicity.

Purpose: To evaluate if the difference between pre- and post-Gd-DTPA(2-) relaxation rate (DeltaR(1)) provides better differentiation of osteoarthritic patients (OA) from healthy subjects (HS) with dGEMRIC, as compared to post-Gd-DTPA(2-) spin-lattice relaxation time (T(1Gd))., Materials and Methods: Seventeen OA and 14 HS underwent pre- and 90 minutes postcontrast (Gd-DTPA(2-)) magnetic resonance imaging (MRI) of the knee, using inversion recovery fast spin-echo and/or Lock-Locker sequences for T(1) mapping. Effect sizes for T(1pre), T(1Gd), and DeltaR(1) were calculated, and receiver operating characteristic (ROC) curve and regression analysis were also performed to assess the effectiveness of each parameter in the separation of OA and HS., Results: T(1Gd) and DeltaR(1) were almost identical in terms of areas under ROC curves (0.903 and 0.914, respectively), and effect sizes (1.34 and 1.31, respectively). These were significantly higher than T(1pre). In addition, a high inverse correlation was observed between DeltaR(1) vs. T(1Gd) (R = 0.96)., Conclusion: Either T(1Gd) or DeltaR(1) could be used as an index in the evaluation of native cartilage. However, considering the practical logistical cost involved in terms of time and effort to acquire precontrast T(1) measurements, our data further support the continued use of T(1Gd) as the dGEMRIC index in the evaluation of native cartilage.

Phosphorus is an important substance for agricultural production of food. Being a limited resource, it is of great interest for regional, as well as global food security. At the same time it presents a pollution problem for the aquatic environment in Sweden since it contributes to eutrophication of surface waters and the Baltic Sea. This study analyses the flow of phosphorus based on consumption and production of food for an average inhabitant of a Swedish city, Linköping, from 1870 until 2000. The study shows the changes in flows within the system of production and consumption of food, as well as between the different processes in this system, such as agriculture, food processing, consumption and waste handling, and output flows to the environment. The main changes in this system over time are a) the increasing flow of phosphorus reaching the consumer and hence the waste handling system, b) the increase in the flow of products from animal production, which mainly causes the increase in (a), and most notably c) the increased input of chemical fertilizer.

Purpose: To validate the accuracy of T1 measurement by three-dimensional Look-Locker method (3D LL) for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of human subjects with and without osteoarthritis (OA), as compared with two-dimensional inversion recovery fast spin-echo (2D IR-FSE) technique., Materials and Methods: MR sagittal images of the knees were acquired for T1 mapping in 29 subjects with standard 2D IR-FSE and 3D LL sequences 90-135 min following administration of 0.2 mmol/kg Gd-DTPA(2-). T1 maps of femoral and tibial cartilage were generated using custom software. Comparisons in T1 values between the two techniques were performed using regression analysis., Results: Good agreement in T1 values between 2D IR-FSE and 3D LL was observed (R values of 0.90, and 0.85, and 0.86 for all, OA, and control subjects, respectively) when acquired within 15 min., Conclusion: The 3D LL sequence provides accurate T1 estimates of articular cartilage with advantages of entire joint coverage, shorter acquisition time, and a wide range of inversion times sampled within a single acquisition.

Despite continuous investment and various efforts to control pollution, urban water environments are worsening in large parts of the developing world. In order to reveal potential constraints and limitations of current practices of urban water management and to stimulate proactive intervention, we conducted a material flow analysis of the urban water system in Kunming City. The results demonstrate that the current efficiency of wastewater treatment is only around 25% and the emission of total phosphorous from the city into its receiving water, Dianchi Lake, is more than 25 times higher than its estimated tolerance. With regard to the crisis of water quantity and quality, the goal of a sustainable urban water environment cannot be attained with the current problem-solving approach in the region due to the technical limitations of the conventional urban drainage and treatment systems. A set of strategies is therefore proposed. The urban drainage system in Zurich is used as a reference for a potential best-available technology for conventional urban water management (BAT) scenario in terms of its low combined frequency of sewer overflow.

In the present study the water movement in a bottom ash landfill from a municipal solid waste incinerator (MSWI) was investigated. The pore regime of such landfills consists of macropores (with diameter > 50 microm), which make up about two-thirds of the total porosity and micropores. The program MACRO, which describes flow through porous media and takes both macro- and micropore flows into account, was applied. The model was calibrated with a time series from the landfill Riet, near Winterthur in Switzerland. In the present study the model was recalibrated at a time series for 1 year. With this scenario the influence of an expected reduction or increase of the porosity on leachate behaviour of such landfills over a long time (> 100 years) was studied ('long-term behaviour'). It has been shown that reliable information about water percolation can only be provided by obtaining more information about the hydraulic structure of such landfills. In particular, the number of macropores and the porosity exert great influence on the water movement.

The objective of the study was to identify risk factors for reintroduction of Actinobacillus pleuopneumoniae and Mycoplasma hyopneumoniae (enzootic pneumonia) onto pig farms in areas in Switzerland that were involved in an eradication programme from 1996 to 1999 and to assess the role of dealers in relation to these reinfections. The study was based on the comparison of pig farms that were reinfected in the year 2000 (cases) and pig farms that remained uninfected in the same area (controls). Additionally, data were collected from Swiss pig dealers and transport companies. Out of a total of 3983 farms, 107 farms were reinfected in the year 2000. The incidences were 0.1% for Actinobacillus pleuopneumoniae and 2.6% for Mycoplasma hyopneumoniae (enzootic pneumonia). Compared to reinfection rates prior to the eradication programme, this is a considerable reduction. Statistically significant risk factors for the reinfection were 'finishing farm', 'large mixed breeding-finishing farm', 'reinfected neighbour' and 'parking site for pig transport vehicles close to the farm'. Pig farmers that purchased pigs from only one supplier per batch had a lower risk of reintroducing infection (protective factor). As long as infected and uninfected regions co-exist in Switzerland, direct and indirect contact between farms, pig herds and slaughter sites via transport vehicles are a major pathway of disease spread. Risk management measures linked to these contacts are therefore of key importance. The survey of dealers indicated various areas for improvement such as strategic planning of pick-up routes or cleaning and disinfecting of trucks.

The oxygenated carotenoids zeaxanthin and lutein, found in the macular area of the retina, may offer protection against or repair of oxidative damage associated with the degenerative diseases of aging. Since both superoxide and nitrogen monoxide, which react to form peroxynitrite, are found in the retina, we studied the reaction of peroxynitrite with zeaxanthin in liposomes. Zeaxanthin was easily incorporated into liposomes constructed from the fully saturated lipid L-alpha-dimyristoyl-phosphatidylcholine (C14:0) and from egg lecithin, and its absorbance spectrum in liposomes strongly resembles in shape and amplitude that of zeaxanthin dissolved in methanol. The reaction between peroxynitrite and zeaxanthin is first-order in both substrates. The pH profile indicates that the reaction with zeaxanthin involves peroxynitrous acid and not the conjugate anion. We hypothesize that zeaxanthin plays a major role in protection of macular tissue from oxidative damage.