Sulfamate in environmental waters.

Although sulfamate (the anion of sulfamic acid) has been in use for decades in various industrial and other applications, there is no previously published information about its occurrence and fate in environmental waters. In this study sulfamate was widely detected in environmental waters in Ontario, Canada, ranging up to 128,000ng/L. It was always detected (>100ng/L) in bulk precipitation samples and streams, it was usually detected in samples of lake water, and often detected in groundwater. Spatial and temporal variations suggest that both widespread atmospheric deposition and localized land-based anthropogenic sources of sulfamate may be important. Lower concentrations or non-detections of sulfamate in waters that had relatively low dissolved oxygen (e.g. some groundwaters) suggest that sulfamate may be degraded in the environment under suboxic or anoxic conditions. Given our findings of a wide distribution of sulfamate in environmental waters, including precipitation, it is not likely to be very useful as a wastewater tracer.

Estimating cumulative wastewater treatment plant discharge influences on acesulfame and Escherichia coli in a highly impacted watershed with a fully-integrated modelling approach.

Wastewater treatment plant (WWTP) discharge is often considered a principal source of surface water contamination. In this study, a three-dimensional fully-integrated groundwater-surface water model was used to simulate the transport characteristics and cumulative loading of an artificial sweetener (acesulfame) and fecal indicator bacteria (Escherichia coli) from WWTPs within a 6800 km2 mixed-use, highly impacted watershed in Ontario, Canada. The model, which employed 3.5 × 106 computational nodes and 15 layers, facilitated a comprehensive assessment of groundwater-surface water interactions under high and low flow conditions; processes typically not accounted for in WWTP cumulative effects models. Simulations demonstrate that the model had significant capacity in reproducing the average and transient multi-year groundwater and surface water flow conditions in the watershed. As a proxy human-specific conservative tracer, acesulfame was useful for model validation and to help inform the representation of watershed-scale transport processes. Using a uniform WWTP acesulfame loading rate of 7.14 mg person-1 day-1, the general spatial trends and magnitudes of the acesulfame concentration profile along the main river reach within the watershed were reproduced; however, model performance was improved by tuning individual WWTP loading rates. Although instream dilution and groundwater-surface water interactions were strongly dependent on flow conditions, the main reach primarily consisted of groundwater discharge zones. For this reason, hydrodynamic dispersion in the hyporheic zone is shown as the predominant mechanism driving acesulfame into near-stream shallow groundwater, while under high flow conditions, the simulations demonstrate the potential for advective flushing of the shallow groundwater. Regarding the cumulative impact of the WWTPs on E. coli concentrations in the surface flow system, simulated transient E. coli levels downstream of WWTPs in the watershed were significantly lower than observed values, thus highlighting the potential importance of other sources of E. coli in the watershed.

Use of an Artificial Sweetener to Identify Sources of Groundwater Nitrate Contamination.

The artificial sweetener acesulfame (ACE) is a potentially useful tracer of waste water contamination in groundwater. In this study, ACE concentrations were measured in waste water and impacted groundwater at 12 septic system sites in Ontario, Canada. All samples of septic tank effluent (n = 37) had ACE >6 µg/L, all samples of groundwater from the proximal plume zones (n = 93) had ACE >1 µg/L and, almost all samples from the distal plume zones had ACE >2 µg/L. Mean mass ratios of total inorganic nitrogen/ACE at the 12 sites ranged from 680 to 3500 for the tank and proximal plume samples. At five sites, decreasing ratio values in the distal zones indicated nitrogen attenuation. These ratios were applied to three aquifers in Canada that are nitrate-stressed and an urban stream where septic systems are present nearby to estimate the amount of waste water nitrate contamination. At the three aquifer locations that are agricultural, low ACE values (<0.02-0.15 µg/L) indicated that waste water contributed <15% of the nitrate in most samples. In groundwater discharging to the urban stream, much higher ACE values (0.2-11 µg/L) indicated that waste water was the likely source of >50% of the nitrate in most samples. This study confirms that ACE is a powerful tracer and demonstrates its use as a diagnostic tool for establishing whether waste water is a significant contributor to groundwater contamination or not.

Degradation of sucralose in groundwater and implications for age dating contaminated groundwater.

The artificial sweetener sucralose has been in use in Canada and the US since about 2000 and in the EU since 2003, and is now ubiquitous in sanitary wastewater in many parts of the world. It persists during sewage treatment and in surface water environments and as such, has been suggested as a powerful tracer of wastewater. In this study, longer-term persistence of sucralose was examined in groundwater by undertaking a series of three sampling snapshots of a well constrained wastewater plume in Canada (Long Point septic system) over a 6-year period from 2008 to 2014. A shrinking sucralose plume in 2014, compared to earlier sampling, during this period when sucralose use was likely increasing, provides clear evidence of degradation. However, depletion of sucralose from a mean of 40 µg/L in the proximal plume zone, occurred at a relatively slow rate over a period of several months to several years. Furthermore, examination of septic tank effluent and impacted groundwater at six other sites in Canada, revealed that sucralose was present in all samples of septic tank effluent (6-98 µg/L, n = 32) and in all groundwater samples (0.7-77 µg/L, n = 64). Even though sucralose degradation is noted in the Long Point plume, its ubiquitous presence in the groundwater plumes at all seven sites implies a relatively slow rate of decay in many groundwater septic plume environments. Thus, sucralose has the potential to be used as an indicator of 'recent' wastewater contamination. The presence of sucralose identifies groundwater that was recharged after 2000 in Canada and the US and after 2003 in the EU and many Asian countries.

Modelling the impact of HIV on the populations of South Africa and Botswana.

We develop and use mathematical models that describe changes in the South African population over the last decades, brought on by HIV and AIDS. We do not model all the phases in HIV progression but rather, we show that a relatively simple model is sufficient to represent the data and allows us to investigate important aspects of HIV infection: firstly, we are able to investigate the effect of awareness on the prevalence of HIV and secondly, it enables us to make a comparison between South Africa and Botswana. A comparison is made between two models: a model that does not reflect awareness of the devastating impact of HIV and AIDS, and a model with an added psychological awareness factor. Both models are fitted to data that reflects the incidence of HIV and AIDS within South Africa. This allows us to examine the impact of psychological awareness. We show that inclusion of the effect of awareness is absolutely necessary to arrive at a model description that satisfactorily fits the available HIV and AIDS data for South Africa. We also show that a relatively simple modelling of awareness (as opposed to more complex mathematical techniques that have been used in past studies) is sufficient to accurately describe the observed patterns in the data. Even though awareness alone is not sufficient to eradicate any disease and other control strategies should be explored and implemented concurrently with educational campaigns, we are able to conclude (through thorough model analyses procedures) that the current level of awareness in South Africa is far below the level that is effectively required to eradicate HIV from the South African population. The awareness model is also fitted to HIV-related data for Botswana and we compare the results with the South African case. Though the effect of awareness is currently estimated at a much higher level in Botswana, other factors such as poorer health care and cultural differences may play a role in limiting the ability of awareness to combat HIV in Botswana.

Sinks for nitrogen inputs in terrestrial ecosystems: a meta-analysis of 15N tracer field studies.

Effects of anthropogenic nitrogen (N) deposition and the ability of terrestrial ecosystems to store carbon (C) depend in part on the amount of N retained in the system and its partitioning among plant and soil pools. We conducted a meta-analysis of studies at 48 sites across four continents that used enriched 15N isotope tracers in order to synthesize information about total ecosystem N retention (i.e., total ecosystem 15N recovery in plant and soil pools) across natural systems and N partitioning among ecosystem pools. The greatest recoveries of ecosystem 15N tracer occurred in shrublands (mean, 89.5%) and wetlands (84.8%) followed by forests (74.9%) and grasslands (51.8%). In the short term (< 1 week after 15N tracer application), total ecosystem 15N recovery was negatively correlated with fine-root and soil 15N natural abundance, and organic soil C and N concentration but was positively correlated with mean annual temperature and mineral soil C:N. In the longer term (3-18 months after 15N tracer application), total ecosystem 15N retention was negatively correlated with foliar natural-abundance 15N but was positively correlated with mineral soil C and N concentration and C:N, showing that plant and soil natural-abundance 15N and soil C:N are good indicators of total ecosystem N retention. Foliar N concentration was not significantly related to ecosystem 15N tracer recovery, suggesting that plant N status is not a good predictor of total ecosystem N retention. Because the largest ecosystem sinks for 15N tracer were below ground in forests, shrublands, and grasslands, we conclude that growth enhancement and potential for increased C storage in aboveground biomass from atmospheric N deposition is likely to be modest in these ecosystems. Total ecosystem 15N recovery decreased with N fertilization, with an apparent threshold fertilization rate of 46 kg N x ha(-1) x yr(-1) above which most ecosystems showed net losses of applied 15N tracer in response to N fertilizer addition.

Natural attenuation of septic system nitrogen by anammox.

On-site disposal of sewage in septic systems can lead to groundwater plumes with NO(3)(-)-N concentrations exceeding the common drinking water limit of 10 mg/L. Currently, denitrification is considered as the principal natural attenuation process. However, at a large seasonal-use septic system in Ontario (256 campsites), a suboxic zone exists where nitrogen removal of up to 80% occurs including removal of NH(4)(+)-N. This zone has both NO(3)(-)-N and NH(4)(+)-N at >5 mg/L each. In the distal NH(4)(+)-rich zone, NH(4)(+)-N concentrations (8.1 ± 8.0 mg/L) are lower than in the proximal zone (48 ± 36 mg/L) and NH(4)(+)-N is isotopically enriched (concentration-weighted mean δ(15)N of +15.7‰) compared to the proximal zone (+7.8‰). Furthermore, δ(15)N-NH(4)(+) isotopic enrichment increases with depth in the distal zone, which is opposite to what would result if nitrification along the water table zone was the mechanism causing NH(4)(+) depletion. Bacterial community composition was assessed with molecular (DNA-based) analysis and demonstrated that groundwater bacterial populations were predominantly composed of bacteria from two Candidatus genera of the Planctomycetales (Brocadia and Jettenia). Together, these data provide strong evidence that anaerobic ammonium oxidation (anammox) plays an important role in nitrogen attenuation at this site.

Initiation of glucose-lowering therapy in Type 2 diabetes mellitus patients in general practice.

AIM: The purpose of this study was to investigate which factors determine the initiation of glucose-lowering therapy in patients with Type 2 diabetes mellitus in general practice and their future glycaemic control. METHODS: All incident Type 2 diabetic patients in the general practices in a Dutch middle-sized town from 1994 to 2000 were identified. Factors associated with initiation of glucose-lowering therapy were obtained from clinical files and examined by Cox's regression analyses. Using anova, the associations between clinical characteristics at diagnosis and future glycaemic control were investigated. RESULTS: In total, 603 newly diagnosed patients with Type 2 diabetes mellitus were included in the study. In the first month following diagnosis, 319 (53%) started with oral therapy. One, two and three years after diagnosis of diabetes, the cumulative incidences were 71% (95% CI 66-73%), 75% (71-79%) and 81% (77-84%), respectively. Age, gender, body weight, blood pressure, history of cardiovascular disease or total serum cholesterol values were not associated with time to start of drug therapy. An increased plasma glucose level at diagnosis was strongly related to faster initiation of drug therapy and worse future glycaemic control. Immediate initiation of glucose-lowering medication was not related to future glycaemic control. CONCLUSION: This study shows that the initial severity of diabetes, assessed by the degree of hyperglycaemia at time of diagnosis, is a major factor in determining the time to start of glucose-lowering drugs and the likelihood of achieving target levels of glycaemic control in the future, independent of glucose-lowering strategy. Therefore, patients with high glucose levels at diagnosis need close monitoring from the beginning of their disease.

Development of a teleconsultation system for communication between physiotherapists concerning children with complex movement and postural disorders.

We investigated whether a relatively low-cost, PC-based teleconsultation system could be used for interinstitutional communication about children with complex movement and postural disorders. Four paediatric physiotherapists in three different institutions participated. Both email and videoconferencing were tested. Videoconferencing was unsuccessful, as the low-bandwidth analogue lines, used by the majority of the therapists, made the quality of the realtime video-images very poor. However, email with attached video-recordings was successful and the therapists used the system to consult each other about 20 cases. The therapists regarded the system as effective in clinical practice. However, some improvements would be desirable, such as making the system quicker to use and reducing the number of technical errors. Nonetheless, structured communication between physicians about complex postural and movement disorders appears to be promising both for patient referral and for decisions concerning treatment.

Factors associated with switching from oral hypoglycaemic agents to insulin therapy.

BACKGROUND: The aim of our study was to determine which factors are associated with switching from oral hypoglycaemic agents to insulin therapy in patients with type 2 diabetes mellitus in general practice. METHODS: Longitudinal, observational study in a Dutch general healthcare centre. All pharmacologically treated patients with type 2 diabetes mellitus were included (n = 152). Comorbidity, laboratory results and medication use were obtained from the general practitioners' files. RESULTS: A total of 31 (20.4%) patients switched from oral hypoglycaemic agents to insulin therapy; they were significantly younger at the onset of diabetes, 50.5 versus 57.7 years. Fasting blood glucose levels and HbA(1c) values were significantly higher after the switch compared with patients on oral treatment, 10.0 mmol/l versus 8.4 mmol/l and 8.8% versus 7.9%, respectively. Concerning comorbidity, they suffered more frequently from acute myocardial infarction, lipid disorders, depression, retinopathy and atrial fibrillation. Cardiovascular disease in general was more often present in patients who switched over to insulin, 77.4% versus 52.9% (OR 3.1; CI 1.2-7.6). CONCLUSIONS: Patients who switch over to insulin therapy are younger at diagnosis, suffer from more health problems besides diabetes, especially cardiovascular disease, and have worse metabolic control, compared with users of oral hypoglycaemic agents.

Use of fluorquinolones is associated with a reduced risk of coronary heart disease in diabetes mellitus type 2 patients.

AIMS: The aim of the present study was to investigate whether use of specific antibiotic drugs decreases the risk of coronary heart disease in diabetes mellitus type 2 patients. METHODS AND RESULTS: Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and hospitalizations for all 450,000 residents of eight Dutch cities. In a nested case-control study among diabetes mellitus type 2 patients, 244 cases with a first hospitalization for coronary heart disease and 686 controls without coronary heart disease matched on age, sex, calendar time, and registration date in PHARMO RLS were selected. Use of antibiotic drugs among cases and controls was determined over 3 years prior to the event. Use of fluorquinolones for more than 14 days compared to no use of fluorquinolones was associated with a lower risk of coronary heart diseases (OR(adj)=0.30 (95%CI: 0.12-0.75)). No association between tetracycline, macrolide and lincosamide treatment, or other antibiotic drugs (penicillins, cephalosporines, sulphonamides and trimethoprim), and the risk of coronary heart disease was found. CONCLUSION: Our results suggest that treatment with fluorquinolones in doses commonly prescribed in routine clinical practice is associated with a reduction in the risk of coronary heart diseases among diabetes mellitus type 2 patients.

Cardiovascular drug use and hospitalizations attributable to type 2 diabetes.

OBJECTIVE: To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from 1 year before until 6 years after the start of oral antidiabetic therapy. RESEARCH DESIGN AND METHODS: In this cohort study, 2,584 patients with type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997. Nondiabetic subjects were 1:1-matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies. RESULTS: Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23-1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33-1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects. Differences between patients with type 2 diabetes and nondiabetic subjects lessened from 1 year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks for diuretics, beta-blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were approximately 50% in the years close to the start of oral antidiabetic treatment and decreased to approximately 33% in the following years. CONCLUSIONS: Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially beta-blockers, whereas cardiovascular hospitalizations first decreased and then stabilized.

Cerebellar learning of accurate predictive control for fast-reaching movements.

Long conduction delays in the nervous system prevent the accurate control of movements by feedback control alone. We present a new, biologically plausible cerebellar model to study how fast arm movements can be executed in spite of these delays. To provide a realistic test-bed of the cerebellar neural model, we embed the cerebellar network in a simulated biological motor system comprising a spinal cord model and a six-muscle two-dimensional arm model. We argue that if the trajectory errors are detected at the spinal cord level, memory traces in the cerebellum can solve the temporal mismatch problem between efferent motor commands and delayed error signals. Moreover, learning is made stable by the inclusion of the cerebello-nucleo-olivary loop in the model. It is shown that the cerebellar network implements a nonlinear predictive regulator by learning part of the inverse dynamics of the plant and spinal circuit. After learning, fast accurate reaching movements can be generated.

Role of the cerebellum in reaching movements in humans. II. A neural model of the intermediate cerebellum.

The cerebellum is essential for the control of multijoint movements; when the cerebellum is lesioned, the performance error is more than the summed errors produced by single joints. In the companion paper (Schweighofer et al., 1998), a functional anatomical model for visually guided arm movement was proposed. The model comprised a basic feedforward/feedback controller with realistic transmission delays and was connected to a two-link, six-muscle, planar arm. In the present study, we examined the role of the cerebellum in reaching movements by embedding a novel, detailed cerebellar neural network in this functional control model. We could derive realistic cerebellar inputs and the role of the cerebellum in learning to control the arm was assessed. This cerebellar network learned the part of the inverse dynamics of the arm not provided by the basic feedforward/feedback controller. Despite realistically low inferior olive firing rates and noisy mossy fibre inputs, the model could reduce the error between intended and planned movements. The responses of the different cell groups were comparable to those of biological cell groups. In particular, the modelled Purkinje cells exhibited directional tuning after learning and the parallel fibres, due to their length, provide Purkinje cells with the input required for this coordination task. The inferior olive responses contained two different components; the earlier response, locked to movement onset, was always present and the later response disappeared after learning. These results support the theory that the cerebellum is involved in motor learning.