Assessing nitrate groundwater hotspots in Europe reveals an inadequate designation of Nitrate Vulnerable Zones.

Monitoring networks show that the European Union Nitrates Directive (ND) has had mixed success in reducing nitrate concentrations in groundwater. By combining machine learning and monitored nitrate concentrations (1992-2019), we estimate the total area of nitrate hotspots in Europe to be 401,000 km2, with 47% occurring outside of Nitrate Vulnerable Zones (NVZs). We also found contrasting increasing or decreasing trends, varying per country and time periods. We estimate that only 5% of the 122,000 km2 of hotspots in 2019 will meet nitrate quality standards by 2040 and that these may be offset by the appearance of new hotspots. Our results reveal that the effectiveness of the ND is limited by both time-lags between the implementation of good practices and pollution reduction and an inadequate designation of NVZs. Substantial improvements in the designation and regulation of NVZs are necessary, as well as in the quality of monitoring stations in terms of spatial density and information available concerning sampling depth, if the objectives of EU legislation to protect groundwater are to be achieved.

Biomechanics of wheelchair turning manoeuvres: novel insights into wheelchair propulsion.

Introduction: Wheelchair turning biomechanics is an under researched area despite its obvious relevance to functional mobility of wheelchair users. Wheelchair turns might be linked to a higher risk of upper limb injuries due to the increased forces and torques potentially associated with asymmetric movement. Our aim was to obtain a better theoretical understanding of wheelchair turning by biomechanically analyzing turns compared to steady-state straightforward propulsion (SSSFP). Methods: Ten able-bodied men received 12-min familiarization and 10 trials (in a random order) of SSSFP and multiple left and right turns around a rectangular course. A Smartwheel was mounted at the right wheel of a standard wheelchair to measure kinetic parameters during SSSFP and of the inner hand during right turns and the outer hand during left turns. A repeated measures ANOVA was used to detect differences across tasks. Results: Two strategies were identified: 3% demonstrated roll turns and 97% spin turns. Spin turns consisted of three phases: approach, turning and depart phase. The turning phase was accomplished by increasing peak force (72.9 ± 25.1 N vs. 43.38 ± 15.9 N in SSSFP) of the inner hand, while maintaining high push frequency of the outer hand (1.09 ± 0.20 push/s vs. 0.95 ± 0.13 push/s in SSSFP). Peak negative force and force impulse during the turning phase were much higher than SSSFP, 15.3 ± 15.7 and 4.5 ± 1.7 times higher, respectively. Conclusion: The spin turn strategy might carry an increased risk of upper limb injuries due to higher braking force and requires particular attention by rehabilitation professionals to preserve upper limb function of long-term wheelchair users.

From planetary to regional boundaries for agricultural nitrogen pollution.

Excessive agricultural nitrogen use causes environmental problems globally1, to an extent that it has been suggested that a safe planetary boundary has been exceeded2. Earlier estimates for the planetary nitrogen boundary3,4, however, did not account for the spatial variability in both ecosystems' sensitivity to nitrogen pollution and agricultural nitrogen losses. Here we use a spatially explicit model to establish regional boundaries for agricultural nitrogen surplus from thresholds for eutrophication of terrestrial and aquatic ecosystems and nitrate in groundwater. We estimate regional boundaries for agricultural nitrogen pollution and find both overuse and room for intensification of agricultural nitrogen. The aggregated global surplus boundary with respect to all thresholds is 43 megatonnes of nitrogen per year, which is 64 per cent lower than the current (2010) nitrogen surplus (119 megatonnes of nitrogen per year). Allowing the nitrogen surplus to increase to close yield gaps in regions where environmental thresholds are not exceeded lifts the planetary nitrogen boundary to 57 megatonnes of nitrogen per year. Feeding the world without trespassing regional and planetary nitrogen boundaries requires large increases in nitrogen use efficiencies accompanied by mitigation of non-agricultural nitrogen sources such as sewage water. This asks for coordinated action that recognizes the heterogeneity of agricultural systems, non-agricultural nitrogen losses and environmental vulnerabilities.

Large variations between NICU nurses in predicting nasogastric tube insertion length in a mannequin study.

Aim: To evaluate the inter- and intraindividual variation of predicted nasogastric tube insertion lengths by nurses working in two neonatal intensive care units in the Netherlands, using a mannequin model. Methods: A total of 110 nurses (55 nurses from Center A and 55 from Center B) were asked to predict the nasogastric tube insertion length on a neonatal mannequin. We evaluated the length and prediction method used by the nurses. We also estimated the number of tubes that would have correctly been placed in the stomach of a neonate according to the seize of the mannequin. Results: The mean predicted insertion length of the nasogastric tube was 30.0 cm with an interindividual variation of 12 cm (range 24-36 cm). The mean intraindividual variation was 0.75 cm. The two centers used two different prediction methods in their local guidelines, but overall at least 6 different methods were used by the nurses. We estimated that 77% (85/110) of the tubes would have ended in the body of the mannequins stomach, while 10% (11/110) would have ended in the esophagus and 13% (14/110) would have ended against the stomach lining or in the duodenum. Conclusion: Nurses in two neonatal intensive care units used many different methods which lead to a large interindividual variation in predicted insertion lengths of the nasogastric tubes. Regular evaluations using this mannequin model could lead to more uniformity and reduce the risk of tube misplacement in neonates.

Towards a global-scale soil climate mitigation strategy.

Sustainable soil carbon sequestration practices need to be rapidly scaled up and implemented to contribute to climate change mitigation. We highlight that the major potential for carbon sequestration is in cropland soils, especially those with large yield gaps and/or large historic soil organic carbon losses. The implementation of soil carbon sequestration measures requires a diverse set of options, each adapted to local soil conditions and management opportunities, and accounting for site-specific trade-offs. We propose the establishment of a soil information system containing localised information on soil group, degradation status, crop yield gap, and the associated carbon-sequestration potentials, as well as the provision of incentives and policies to translate management options into region- and soil-specific practices.

Prediction of plant species occurrence as affected by nitrogen deposition and climate change on a European scale.

Plant species occurrence in Europe is affected by changes in nitrogen deposition and climate. Insight into potential future effects of those changes can be derived by a model approach based on field-based empirical evidence on a continental scale. In this paper, we present a newly developed empirical model PROPS, predicting the occurrence probabilities of plant species in response to a combination of climatic factors, nitrogen deposition and soil properties. Parameters included were temperature, precipitation, nitrogen deposition, soil pH and soil C/N ratio. The PROPS model was fitted to plant species occurrence data of about 800,000 European relevés with estimated values for pH and soil C/N ratio and interpolated climate and modelled N deposition data obtained from the Ensemble meteo data set and EMEP model results, respectively. The model was validated on an independent data set. The test of ten species against field data gave an average Pearson's r-value of 0.79. PROPS was applied to a grassland and a heathland site to evaluate the effect of scenarios for nitrogen deposition and climate change on the Habitat Suitability Index (HSI), being the average of the relative probabilities, compared to the maximum probability, of all target species in a habitat. Results for the period 1930-2050 showed that an initial increase and later decrease in nitrogen deposition led to a pronounced decrease in HSI, and with dropping nitrogen deposition to an increase of the HSI. The effect of climate change appeared to be limited, resulting in a slight increase in HSI.

M-CSF and IL-34 expression as indicators for growth in sporadic vestibular schwannoma.

Macrophage colony stimulating factor and IL-34 are associated with clinical vestibular schwannoma progression. Investigating the biology behind vestibular schwannoma progression helps understanding tumor growth. Inflammation is important in the microenvironment of neoplasms. Macrophages are major players in the intratumoral infiltrate. These tumor-associated macrophages are known to stimulate angiogenesis and cell growth. M-CSF and IL-34 are cytokines that can regulate tumor-infiltrating macrophages. They are expressed by tumors and form potential targets for therapy. The goal of this study was to investigate these cytokines in vestibular schwannomas and to see if their expression is related to angiogenesis, macrophage numbers, cystic degeneration, and volumetric tumor progression. Immunohistochemical expression of M-CSF and IL-34 was analyzed in ten fast-growing vestibular schwannomas and in ten slow-growing vestibular schwannomas. Expression M-CSF and IL-34 were compared between fast- versus slow-growing and cystic versus non-cystic tumors. Data on macrophage numbers and microvessel density, known from earlier research, was also included. All tumors expressed M-CSF and its expression was higher in fast-growing tumors (p = 0.003) and in cystic tumors (p = 0.035). CD163 expression was higher in tumors with strong M-CSF expression (p = 0.003). All tumors expressed IL-34 as well, but no significant differences were found in relation to clinicopathological characteristics. This study demonstrated the expression of M-CSF and IL-34 in vestibular schwannomas. The results suggest that M-CSF is related to macrophage activity and tumor progression, making it a potential target for therapy. If a similar assumption can be made for IL-34 remains unclear.

Topically used corticosteroids: What is the big picture of drug product degradation?

Corticosteroids are widely used in topical formulations such as creams (aqueous) and ointments (non-aqueous). The generally used corticosteroids show large molecular resemblance, where especially the 20-keto-21-hydroxyl group bound to the 17 carbon is important for their chemical stability. Oxidation in both aqueous and non-aqueous environment occurs for triamcinolone acetonide (TCA), hydrocortisone (HC) and desoximethasone (DS). Besides the 20-keto-21-hydroxyl group, TCA, HC and DS have different other moieties attached to the same C17. These moieties are shown to influence not only the type of degradation product formed but also the degradation kinetics. Seven degradation products are found in total and a degradation mechanism is proposed. Furthermore the transesterfication of betamethasone-17-valerate to betamethasone-21-valerate is shown to occur both in aqueous and non-aqueous environment. Finally, a comprehensive scheme of degradation pathways is presented that is applicable for both aqueous and non-aqueous formulations.

Development and validation of a stability-indicating HPLC-UV method for the determination of triamcinolone acetonide and its degradation products in an ointment formulation.

A stability indicating high performance liquid chromatography method has been developed for the determination of triamcinolone acetonide (TCA) and its main degradation products in ointment formulations. The method, based on extensive stress testing using metal salts, azobisisobutyronitrile, acid, base and peroxide, showed that TCA undergoes oxidative degradation. All degradation products were identified using HPLC mass spectrometry. Separation and quantification was achieved using an Altima C18 RP18 HP column (250×4.6mm2, with 5µm particles) using a mobile phase consisting of acetonitrile and water buffered at pH 7 using 10mM phosphate buffer. A gradient mode was operated at a flow rate of 1.5ml/min and detection was at 241nm. The method showed linearity for TCA and Impurity C in 0.02-125% of the workload, both square roots of the correlation coefficients were larger than 0.9999. Repeatability and intermediate precision were performed by six consecutive injections of both 1.25% and 125% of the work load for both TCA and Impurity C divided equally over two days. RSD were 0.6% and 0.7% for TCA and 0.5% and 0.1% for Impurity C respectively. Accuracy was determined as well, the average recoveries were 99.5% (±0.1%, n=3) for TCA and 96.9% (±1.3%, n=3) for impurity C respectively from spiked ointment samples. The robustness was also evaluated by variations of column (old vs new), mobile phase pH and filter retention. The applicability of the method was evaluated by analysis of a commercial ointment formulation. Interestingly, the extensive stress tests were able to predict all degradation products of TCA in a long term stability ointment sample.

Medical students and physical education students as CPR instructors: an appropriate solution to the CPR-instructor shortage in secondary schools?

BACKGROUND: Integrating cardiopulmonary resuscitation (CPR) training in secondary schools will increase the number of potential CPR providers. However, currently too few certified instructors are available for this purpose. Training medical students and physical education student teachers to become CPR instructors could decrease this shortage. AIM: Examine whether medical students and physical education student teachers can provide CPR training for secondary school pupils as well as (i. e., non-inferior to) registered nurses. METHODS: A total of 144 secondary school pupils were randomly assigned to CPR training by a registered nurse (n = 12), a  medical student (n = 17) or a physical education student teacher (n = 15). CPR performance was assessed after training and after eight weeks in a simulated cardiac arrest scenario on a resuscitation manikin, using manikin software and video recordings. RESULTS: No significant differences were found between the groups on the overall Cardiff Test scores and the correctness of the CPR techniques during the post-training and retention test. All pupils showed sufficient CPR competence, even after eight weeks. CONCLUSION: Training by medical students or physical education student teachers is non-inferior to training by a registered nurse, suggesting that school teachers, student teachers and medical students can be recruited for CPR training in secondary schools.

Can shoulder joint reaction forces be estimated by neural networks?

To facilitate the development of future shoulder endoprostheses, a long term load profile of the shoulder joint is desired. A musculoskeletal model using 3D kinematics and external forces as input can estimate the mechanical load on the glenohumeral joint, in terms of joint reaction forces. For long term ambulatory measurements, these 3D kinematics can be measured by means of Inertial Magnetic Measurement Systems. Recording of external forces under daily conditions is not feasible; estimations of joint loading should preferably be independent of this input. EMG signals reflect the musculoskeletal response and can easily be measured under daily conditions. This study presents the use of a neural network for the prediction of glenohumeral joint reaction forces based upon arm kinematics and shoulder muscle EMG. Several setups were examined for NN training, with varying combinations of type of input, type of motion, and handled weights. When joint reaction forces are predicted by a trained NN, for motion data independent of the training data, results show a high intraclass correlation (ICC up to 0.98) and relative SEM as low as 3%, compared to similar output of a musculoskeletal model. A convenient setup in which kinematics and only one channel of EMG were used as input for the NN׳s showed comparable predictive power as more complex setups. These results are promising and enable long term estimation of shoulder joint reaction forces outside the motion lab, independent of external forces.

Environmental impacts of innovative dairy farming systems aiming at improved internal nutrient cycling: A multi-scale assessment.

Several dairy farms in the Netherlands aim at reducing environmental impacts by improving the internal nutrient cycle (INC) on their farm by optimizing the use of available on-farm resources. This study evaluates the environmental performance of selected INC farms in the Northern Friesian Woodlands in comparison to regular benchmark farms using a Life Cycle Assessment. Regular farms were selected on the basis of comparability in terms of milk production per farm and per hectare, soil type and drainage conditions. In addition, the environmental impacts of INC farming at landscape level were evaluated with the integrated modelling system INITIATOR, using spatially explicit input data on animal numbers, land use, agricultural management, meteorology and soil, assuming that all farms practised the principle of INC farming. Impact categories used at both farm and landscape levels were global warming potential, acidification potential and eutrophication potential. Additional farm level indicators were land occupation and non-renewable energy use, and furthermore all farm level indicators were also expressed per kg fat and protein corrected milk. Results showed that both on-farm and off-farm non-renewable energy use was significantly lower at INC farms as compared with regular farms. Although nearly all other environmental impacts were numerically lower, both on-farm and off-farm, differences were not statistically significant. Nitrogen losses to air and water decreased by on average 5 to 10% when INC farming would be implemented for the whole region. The impact of INC farming on the global warming potential and eutrophication potential was, however, almost negligible (<2%) at regional level. This was due to a negligible impact on the methane emissions and on the surplus and thereby on the soil accumulation and losses of phosphorus to water at INC farms, illustrating the focus of these farms on closing the nitrogen cycle.

Spatial boundary of urban 'acid islands' in southern China.

Elevated emissions of sulfur dioxide, nitrogen oxides and ammonia in China have resulted in high levels of sulfur and nitrogen deposition, being contributors to soil acidification, especially in and near large cities. However, knowledge gaps still exist in the way that large cities shape spatial patterns of acid deposition. Here, we assessed the patterns of pH, sulfate, nitrate and ammonium in bulk precipitation and throughfall in southern China's forests by synthesizing data from published literature. Concentrations and fluxes of sulfate, nitrate and ammonium in bulk precipitation and throughfall exhibited a power-law increase with a closer distance to the nearest large cities, and accordingly pH showed a logarithmic decline. Our findings indicate the occurrence of urban 'acid islands' with a critical radius of approximately 70 km in southern China, receiving potential acid loads of more than 2 keq ha(-1) yr(-1). These urban acid islands covered an area of 0.70 million km(2), accounting for nearly 30% of the land area in southern China. Despite a significant capacity to neutralize acids in precipitation, our analysis highlights a substantial contribution of ammonium to potential acid load. Our results suggest a joint control on emissions of multiple acid precursors from urban areas in southern China.

Modeling the cadmium balance in Australian agricultural systems in view of potential impacts on food and water quality.

The historical build up and future cadmium (Cd) concentrations in top soils and in crops of four Australian agricultural systems are predicted with a mass balance model, focusing on the period 1900-2100. The systems include a rotation of dryland cereals, a rotation of sugarcane and peanuts/soybean, intensive dairy production and intensive horticulture. The input of Cd to soil is calculated from fertilizer application and atmospheric deposition and also examines options including biosolid and animal manure application in the sugarcane rotation and dryland cereal production systems. Cadmium output from the soil is calculated from leaching to deeper horizons and removal with the harvested crop or with livestock products. Parameter values for all Cd fluxes were based on a number of measurements on Australian soil-plant systems. In the period 1900-2000, soil Cd concentrations were predicted to increase on average between 0.21 mg kg(-1) in dryland cereals, 0.42 mg kg(-1) in intensive agriculture and 0.68 mg kg(-1) in dairy production, which are within the range of measured increases in soils in these systems. Predicted soil concentrations exceed critical soil Cd concentrations, based on food quality criteria for Cd in crops during the simulation period in clay-rich soils under dairy production and intensive horticulture. Predicted dissolved Cd concentrations in soil pore water exceed a ground water quality criterion of 2 µg l(-1) in light textured soils, except for the sugarcane rotation due to large water leaching fluxes. Results suggest that the present fertilizer Cd inputs in Australia are in excess of the long-term critical loads in heavy-textured soils for dryland cereals and that all other systems are at low risk. Calculated critical Cd/P ratios in P fertilizers vary from <50 to >1000 mg Cd kg P(-1) for the different soil, crop and environmental conditions applied.

Cardiac biomarkers as indicators of hemodynamic adaptation during postasphyxial hypothermia treatment.

BACKGROUND: Little is known about the effects of hypothermia on the cardiovascular system in term newborns with neonatal encephalopathy. OBJECTIVES: To evaluate whether mild hypothermia for neonatal encephalopathy is cardioprotective as indicated by the cardiac biomarkers cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP). METHODS: This was an observational cohort study of infants treated for perinatal asphyxia. In infants, mild total body hypothermia treatment of 33.5°C during 72 h was initiated (n = 20). Samples of cTnI and BNP were collected before the start of hypothermia, at 24 and 48 h after birth, and after rewarming (84 h). BNP and cTnI values were then compared with BNP and cTnI values of asphyxiated infants not treated with hypothermia (n = 28). RESULTS: No differences were found between the groups in clinical patient characteristics or inotropic support. The hypothermia-treated patients seemed to be clinically more affected (5-min Apgar score, p < 0.05; umbilical artery pH, p = 0.08), but showed similar encephalopathy scores. Significantly lower values for BNP were found in hypothermia- compared to nonhypothermia-treated infants at 48 h and at normothermia after rewarming [144 pmol/l (95-286) vs. 75 pmol/l (45-143), 182 pmol/l (73-341) vs. 43 pmol/l (24-163)]. No differences were found for cTnI concentrations between both groups. CONCLUSIONS: The raised, but similar, cTnI values between hypothermia- and nonhypothermia-treated infants indicate similar myocardial damage in both groups. The lower BNP levels during hypothermia treatment suggest that hypothermia after perinatal asphyxia exerts a beneficial effect on cardiac function.

Course of life into adulthood of patients with biliary atresia: the achievement of developmental milestones in a nationwide cohort.

PURPOSE: To investigate the course of life of young adults diagnosed with biliary atresia (BA) in infancy by comparing patients who did and did not underwent transplantation with an age-matched Dutch reference group. METHODS: All patients from the Dutch BA registry, aged >18 years, were invited to complete the course of life questionnaire. RESULTS: Forty patients participated (response = 74%). Twenty-five had not undergone transplantation; 15 had undergone orthotopic liver transplantation. One significant between-group difference was found, namely in substance use and gambling. BA patients who underwent transplantation reported less use than the reference group (p = .01, moderate effect size). Additional moderate effect sizes were found for differences in psychosexual and social development and antisocial behavior. Patients who underwent transplantation had lower scores than one or both other groups. CONCLUSIONS: Development of BA survivors who did not undergo transplantation seems not delayed, whereas that of transplanted patients does seem somewhat delayed. However, patients who underwent transplantation display less risk behavior. Larger samples are necessary to confirm these findings.

Assessment of N and P status at the landscape scale using environmental models and measurements.

We assessed the compliance of a Dutch landscape, dominated by dairy farming, with environmental quality standards using a combination of model calculations and measurements. The total ammonia emission of 2.4 kton NH(3) yr(-1) does not exceed the environmental quality standard (2.6 kton NH(3) yr(-1)). Nevertheless, the total N deposition (on average 24.4 kg N ha(-1) yr(-1)) is such that critical N loads are exceeded at 53% of the nature areas. The deposited N mainly results from non-agricultural sources and agricultural sources outside the area (72%). The calculated average NO(3)(-) concentration in the upper groundwater does not exceed the 50 mg l(-1) threshold. Calculated annual average N-total and P-total concentrations in discharge water are relatively high but these cannot be directly compared with thresholds for surface water. The results suggest that compliance monitoring at the landscape scale needs to include source indicators and cannot be based on state indicators alone.

Determining a long term ambulatory load profile of the shoulder joint: neural networks predicting input for a musculoskeletal model.

To gain more insight in the development of joint damage, a long term load profile of the shoulder joint under daily living conditions is desirable. Standard musculoskeletal models estimate joint load using kinematics and exerted force. However, the latter cannot be measured continuously in ambulatory settings, hampering the use of these models. This paper describes a method for obtaining such a load profile, by training a Neural Network (NN), using kinematics and EMG. A small data set of specified movements with known exerted forces is used in two ways. First, the model calculates several variables of joint load, and a set of Generalized Forces and Net Moments (GFNM) around the model's degrees of freedom. Second, using kinematics and EMG, an NN is trained to predict these GFNM, which can concurrently be used as input for the model, resulting in full model output independent of exerted force. The method is validated with an independent trial. The NN could predict GFNM within 10% relative RMS, compared to output of the model. The NN-model combination estimated joint reaction forces with relative RMS values of 7 to 17%, enabling the estimation of a detailed load profile of the shoulder under daily conditions.

Forests under climate change and air pollution: gaps in understanding and future directions for research.

Forests in Europe face significant changes in climate, which in interaction with air quality changes, may significantly affect forest productivity, stand composition and carbon sequestration in both vegetation and soils. Identified knowledge gaps and research needs include: (i) interaction between changes in air quality (trace gas concentrations), climate and other site factors on forest ecosystem response, (ii) significance of biotic processes in system response, (iii) tools for mechanistic and diagnostic understanding and upscaling, and (iv) the need for unifying modelling and empirical research for synthesis. This position paper highlights the above focuses, including the global dimension of air pollution as part of climate change and the need for knowledge transfer to enable reliable risk assessment. A new type of research site in forest ecosystems ("supersites") will be conducive to addressing these gaps by enabling integration of experimentation and modelling within the soil-plant-atmosphere interface, as well as further model development.

Transfer functions for solid-solution partitioning of cadmium for Australian soils.

To assess transport and ecotoxicological risks of metals, such as cadmium (Cd) in soils, models are needed for partitioning and speciation. We derived regression-based "partition-relations" based on adsorption and desorption experiments for main Australian soil types. First, batch adsorption experiments were carried out over a realistic range of dissolved Cd concentrations in agricultural soils in Australia. Results showed linear sorption relationships, implying the adequacy of using Kd values to describe partitioning. Desorption measurements were then carried out to assess in-situ Kd values and relate these to soil properties The best transfer functions for solid-solution partitioning were found for Kd values relating total dissolved Cd concentration to total soil Cd concentrations, accounting for the variation in pH, SOM contents and DOC concentrations. Model predictions compared well with measurements of an independent data set, but there was a tendency to underestimate dissolved Cd concentrations of highly polluted soils.