Evaluating the role of point source discharges informs statewide nutrient control policy in Utah.

An evaluation of costs, rate, and environmental impacts of upgrading publically owned treatment works (POTWs) in the State of Utah to four levels of nutrient control allowed a variety of nutrient control policies to be assessed. Upgrade costs and rate impacts indicated that costs would be within a defined range for many POTWs, especially with design capacities greater than 40,000 m3/day (-10 mgd). However, costs were significantly higher for some POTWs with lower design capacities, and nutrient upgrades to the most stringent levels would not be affordable for these communities, representing about 15 percent of the service population. The resulting equity issues can be addressed through hardship grants program and/or regulations based on a trading scheme. Analysis demonstrated that trading offers advantages, including cost efficiency and flexibility to accommodate further nutrient reductions and population growth, and greater ability to interface with urban and rural nonpoint nutrient control. Currently, the State of Utah is establishing technology-based nutrient limits that can be affordably implemented at all POTWs in phases. Additionally, a multi-faceted approach is being evaluated that will consider prioritized watershed-scale strategies, point and nonpoint sources of pollution, ecological and socioeconomic implications, and stakeholder participation in nutrient reduction programs.

Restricted sleep and negative affective states in commercial pilots during short haul operations.

This study aims to investigate (1) the relationship between restricted sleep and Heightened Emotional Activity (HEA) during normal flight operations, and (2) whether sleep patterns influence the strength of the HEA as a response to threats. Accident investigation reports continue to highlight the relationship between restricted sleep and poor safety outcomes. However, to date we have a limited understanding of how sleep and HEA interact. A total of 302 sectors of normal airline flight operations were observed by trained observers, and instances of heightened emotional activity were recorded. During the cruise phase of each of these sectors, crew members were asked to calculate the amount of sleep they had obtained in previous 24 and 48 h. In the 302 sectors of normal flight operations, 535 instances of HEA were observed. Descriptive analyses of instances of HEA and sleep in the prior 24 and 48 h showed a significant relationship between the occurrence of HEA and recent sleep. The relationship between restricted sleep and HEA suggests that there may well be further implications with respect to operational safety.

An unusual barrier to gene flow: perpetually immature larvae from inter-population crosses in the flour beetle, Tribolium castaneum.

We genetically characterize an unusual hybrid incompatibility phenotype manifest in F(1) offspring of crosses between two populations of Tribolium castaneum. Hybrid larvae cease development at the third larval instar, persisting as 'perpetually immature larvae' thereafter. Although unable to produce viable adult hybrid offspring with one another, each population produces abundant, fertile hybrids with other populations, indicating a recent origin of the incompatibility and facilitating genetic studies. We mapped the paternal component of the hybrid phenotype to a single region, which exhibits two characteristics common to hybrid incompatibility: marker transmission ratio distortion within crosses and elevated genetic divergence between populations. The incompatible variation and an elevation in between-population genetic divergence is associated with a region containing the T. castaneum ecdysone receptor homologue, a major regulatory switch, controlling larval moults, pupation and metamorphosis. This contributes to understanding the genetics of speciation in the Coleoptera, one of the most speciose of all arthropod taxa.

Genetic variation and co-variation for fitness between intra-population and inter-population backgrounds in the red flour beetle, Tribolium castaneum.

Hybrids from crosses between populations of the flour beetle, Tribolium castaneum, express varying degrees of inviability and morphological abnormalities. The proportion of allopatric population hybrids exhibiting these negative hybrid phenotypes varies widely, from 3% to 100%, depending upon the pair of populations crossed. We crossed three populations and measured two fitness components, fertility and adult offspring numbers from successful crosses, to determine how genes segregating within populations interact in inter-population hybrids to cause the negative phenotypes. With data from crosses of 40 sires from each of three populations to groups of five dams from their own and two divergent populations, we estimated the genetic variance and covariance for breeding value of fitness between the intra- and inter-population backgrounds and the sire × dam population interaction variance. The latter component of the variance in breeding values estimates the change in genic effects between backgrounds owing to epistasis. Interacting genes with a positive effect, prior to fixation, in the sympatric background but a negative effect in the hybrid background cause reproductive incompatibility in the Dobzhansky-Muller speciation model. Thus, the sire × dam population interaction provides a way to measure the progress towards speciation of genetically differentiating populations on a trait by trait basis using inter-population hybrids.

The microbiological quality of seven large commercial private water supplies in the United Kingdom.

Some 1% of the UK population derives their potable water from 140,000 private water supplies (PWSs) regulated by Local Authorities. The overwhelming majority of these are very small domestic supplies serving a single property or a small number of properties. Treatment for such supplies is rudimentary or non-existent and their microbiological quality has been shown to be poor in every published study to date. Private water supplies serving commercial enterprises such as hotels, restaurants, food production premises and factories are more frequently treated and subject to closer regulation in the United Kingdom. As a result, it has been assumed that these larger commercial supplies are less likely to experience elevated faecal indicator and pathogen concentrations at the consumer tap which have been observed at small domestic supplies.This paper reports on intensive monitoring at seven commercial private water supplies (six of which were treated) spread throughout the UK serving hotels, holiday parks and food production enterprises. Daily sampling of 'potable' water, both at the consumer tap and using large volume filtration for Giardia and Cryptosporidium spp. was conducted over two six week periods in the spring and autumn of 2000. This allowed the effects of short term episodic peaks in faecal indicator and pathogen concentration to be quantified. All the supplies experienced intermittent pathogen presence and only one, a chlorinated deep borehole supply, fully complied with UK water quality regulations during both periods of sampling.Poor microbiological water quality typically followed periods of heavy rainfall. This suggests that the design and installation of such systems should be undertaken only after the likely range of raw water quality has been characterised, which requires a thorough understanding of the effects of flow and seasonality on raw water quality. There is no reason to suspect that the monitored sites are uncharacteristic of other commercial supplies and the results reinforce public health concerns related to domestic supplies. Furthermore, the pattern of contamination is highly episodic, commonly lasting only a few days. Thus, the relatively infrequent regulatory monitoring of such supplies would be unlikely to identify the poor water quality episodes and does not provide the data necessary for public health protection. Although some statistical relationship was found between faecal indicator organisms and the presence of pathogens, the use of FIOs in assessments of regulatory compliance may not always provide a reliable measure of public health risk, i.e. indicator absence does not preclude pathogen presence. The results of this study suggest that a risk assessment system similar to the WHO 'Water Safety Planning' approach might offer a more appropriate regulatory paradigm for private water supplies.

Estimating pollutant removal requirements for landfills in the UK: III. Policy analysis and operational implications.

The policy analysis and management implications for achieving landfill equilibrium status within a sustainable timescale (decades rather than centuries) are presented based on modelled results reported previously. Until relatively recently, timescale estimates suggested that equilibrium or landfill completion could be achieved within 40-60 years i.e. the same order of magnitude as financial provision for aftercare. However results of modelling in this study (reported in previous paper) suggest that timescales may be considerably longer (many centuries in some instances) suggesting that financial provision may be inadequate. The role of the most promising and available waste treatment technologies and strategic waste management options in contributing towards achieving equilibrium status are discussed. Results suggest that a re-examination of techniques for accelerating landfill stabilisation, including aerobic and bioreactor landfill, is warranted.

Estimating pollutant removal requirements for landfills in the UK: I. Benchmark study and characteristics of waste treatment technologies.

Introduction of the EU Landfill Directive is having a significant impact on waste management in the UK and in other member states that have relied on landfilling. This paper considers the length of the aftercare period required by the municipal solid waste streams that the UK will most probably generate following implementation of the Landfill Directive. Data were derived from literature to identify properties of residues from the most likely treatment processes and the probable management times these residues will require within the landfill environment were then modelled. Results suggest that for chloride the relevant water quality standard (250 mg l(-1)) will be achieved with a management period of 40 years and for lead (0.1 mg I(-1)), 240 years. This has considerable implications for the sustainability of landfill and suggests that current timescales for aftercare of landfills may be inadequate.

Estimating pollutant removal requirements for landfills in the UK: II. Model development.

A modelling methodology using a leachate source term has been produced for estimating the timescales for achieving environmental equilibrium status for landfilled waste. Results are reported as the period of active management required for modelled scenarios of non-flushed and flushed sites for a range of pre-filling treatments. The base scenario against which results were evaluated was raw municipal solid waste (MSW) for which only cadmium failed to reach equilibrium. Flushed raw MSW met our criteria for stabilisation with active leachate management for 40 years, subject to each of the leachate species being present at or below their average UK concentrations. Stable non-reactive wastes, meeting EU waste acceptance criteria, fared badly in the non-flushed scenario, with only two species stabilising after a management period within 1000 years and the majority requiring > 2000 years of active leachate management. The flushing scenarios showed only a marginal improvement, with arsenic still persisting beyond 2000 years management even with an additional 500 mm y(-1) of infiltration. The stabilisation time for mechanically sorted organic residues (without flushing) was high, and even with flushing, arsenic and chromium appeared to remain a problem. Two mechanical biological treatment (MBT) scenarios were examined, with medium and high intensity composting. Both were subjected to the non-flushing and flushing scenarios. The non-flushing case of both options fell short of the basic requirements of achieving equilibrium within decades. The intense composting option with minimal flushing appeared to create a scenario where equilibrium could be achieved. For incinerator bottom ash (raw and subjected to various treatments), antimony, copper, chloride and sulphate were the main controls on achieving equilibrium, irrespective of treatment type. Flushing at higher flushing rates (500 mm y(-1)) failed to demonstrate a significant reduction in the management period required.

Systematic review of recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysm.

BACKGROUND: Conventional management of abdominal aortic aneurysm (AAA) is by open repair and is associated with a mortality rate of 2-6 per cent. Endovascular aneurysm repair (EVAR) is an alternative technique first introduced in 1991. A systematic review was undertaken of the evidence for the safety and efficacy of elective EVAR in the management of asymptomatic infrarenal AAA. METHODS: Thirteen electronic bibliographical databases were searched, covering biomedical, health-related, science and social science literature. Outcomes were assessed with respect to efficacy (successful deployment, technical success, conversion rates and secondary intervention rates) and safety (30-day mortality rate, procedure morbidity rates and technical issues-endoleaks, graft thrombosis, stenosis and migration). RESULTS: Of 606 reports identified, 61 met the inclusion criteria (three randomized and 15 non-randomized controlled trials, and 43 uncontrolled studies). There were 29 059 participants in total; 19,804 underwent EVAR. Deployment was successful in 97.6 per cent of cases. Technical success (complete aneurysm exclusion) was 81.9 per cent at discharge and 88.8 per cent at 30 days. Secondary intervention to treat endoleak or maintain graft patency was required in 16.2 per cent of patients. Mean stay in the intensive care unit and mean hospital stay were significantly shorter following EVAR. The 30-day mortality rate for EVAR was 1.6 per cent (randomized controlled trials) and 2.0 per cent in nonrandomized trials and case series. Technical complications comprised stent migration (4.0 per cent), graft limb thrombosis (3.9 per cent), endoleak (type I, 6.8 per cent; type II, 10.3 per cent; type III, 4.2 per cent) and access artery injury (4.8 per cent). DISCUSSION: EVAR is technically effective and safe, with lower short-term morbidity and mortality rates than open surgery. However, there is a need for extended follow-up as the long-term success of EVAR in preventing aneurysm-related deaths is not yet known.

Cost-effectiveness of endovascular abdominal aortic aneurysm repair.

BACKGROUND: The rapid introduction of endovascular abdominal aortic aneurysm repair (EVAR) has considerable implications for the management of abdominal aortic aneurysm (AAA). This study was undertaken to determine an optimal strategy for the use of EVAR based on the best currently available evidence. METHODS: Economic modelling and probabilistic sensitivity analysis considered reference cases representing a fit 70-year-old with a 5.5-cm diameter AAA (RC1) and an 80-year-old with a 6.5-cm AAA unfit for open surgery (RC2). Results were assessed as incremental cost-effectiveness ratio (ICER) compared with open repair (RC1) or conservative management (RC2). RESULTS: In RC1 EVAR produced a gain of 0.10 quality-adjusted life years (QALYs) for an estimated cost of 11,449 pound, giving an ICER of 110,000 pound per QALY. EVAR consistently had an ICER above 30,000 pound per QALY over a range of sensitivity analyses and alternative scenarios. In RC2 EVAR produced an estimated benefit of 1.64 QALYs for an incremental cost of 14,077 pound giving an incremental cost per QALY of 8579 pound. CONCLUSION: : It is unlikely that EVAR for fit patients suitable for open repair is within the commonly accepted range of cost-effectiveness for a new technology. For those unfit for conventional open repair it is likely to be a cost-effective alternative to non-operative management. Sensitivity analysis suggests that research efforts should concentrate on determining accurate rates for late complications and reintervention, particularly in patients with high operative risks.

Continuous monitoring for Cryptosporidium--a novel approach to public health protection.

Regulations requiring water utilities in England and Wales to carry out continuous monitoring for Cryptosporidium in treated water were introduced in June 1999. The rationale of the Regulations and the technical basis for the sampling and analysis are reviewed. The results of the first nine months of monitoring are summarised and compared with other equivalent data sets. The impact of the Regulations on water utilities operational practices and the implications for public health protection are discussed.

Monitoring of 25-OH vitamin D levels in children with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are at risk for malabsorption of fat-soluble vitamins, and those with low 25-OH vitamin D levels have a higher risk of low bone mineral density and long-term skeletal complications. It is currently recommended that vitamins A and E be monitored yearly; however, no recommendations exist for 25-OH vitamin D. Because all three vitamins are fat-soluble, the hypothesis in the current study was that low levels of vitamins A and E could identify patients at risk for low 25-OH vitamin D, so that 25-OH vitamin D measurements could be obtained in only selected circumstances. METHODS: Forty (21 girls) patients with CF, age 10.5 +/- 3.9 (SD) years, were assessed in a cross-sectional survey for ideal weight for height (percentage of predicted), spirometry (percentage of predicted FEV1, 33/40 patients), and serum levels of vitamins A, E, 25-OH vitamin D, and cholesterol (37/40 patients). RESULTS: Nine (22.5%) of 40 patients were malnourished (percentage of predicted ideal weight for height <85%), 7 (21.2%) of 33 had moderate to severe lung disease (FEV1 <60%), 4 (10%) of 40 had low levels of vitamin A, 3 (7.5%) of 40 had low vitamin E levels, 4 (10.8%) of 37 low vitamin E/cholesterol levels, and 4 (10%) of 40 had marginal or low levels of 25-OH vitamin D (<40 mmol/l). The patients with low 25-OH vitamin D were older, with no child < 12 years of age having a 25-OH vitamin D level less than 40 mmol/l. They also had lower vitamin E and vitamin E/cholesterol levels than those with normal 25-OH vitamin D levels. The groups did not differ in percentage of predicted ideal weight for height, lung function, or vitamin A levels. The best positive predictor for 25-OH vitamin D less than 40 mmol/l was low vitamin E (66.7%), with a negative predictive value of 94.6%. 25-OH vitamin D levels correlated with vitamin E/cholesterol levels (r = 0.41, P < 0.01) and weakly with vitamin E levels (r = 0.28, P < 0.08), but not with vitamin A levels. CONCLUSIONS: These results suggest that children aged less than 12 years and older children with normal vitamin E levels are especially unlikely to have low 25-OH vitamin D levels, and this measure can therefore be omitted. In contrast, those children with low vitamin E levels may warrant monitoring.

The effect of submaximal exercise on recovery hemodynamics and thermoregulation in men and women.

Five women and 5 men were studied to examine the effects of submaximal exercise on thermoregulatory and hemodynamic variables during recovery in two environments: (a) control (C), 22 degrees C, 33% rh; and (b) hot humid (H), 32 degrees C. The participants exercised on a cycle ergometer at 60% of peak oxygen consumption for 35 min prior to 90 min of seated recovery. Sessions were identical, except for environment. Variables evaluated (p < .05) were: core temperature (TR), mean skin temperature (Ts), sweat rate (SR), heart rate (HR), stroke index (SI), cardiac index (CI), forearm blood flow (FBF), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Men and women exhibited similar patterns of TR, Ts, and SR in both environments. Ts and SR (collapsed means for gender) were higher in the H than in the C. DBP was higher in men than in women throughout recovery in both environments. With combined means for gender, HR was higher in the H than in the C. CI, SI, FBF, and SBP were similar in both environments and returned to baseline within 15 min into recovery. These data suggest that heat dissipation during extended recovery was accomplished with similar contributions of cutaneous vasodilation and sweating in M and F. Furthermore, the moderate exercise level did not influence hemodynamics beyond 15 min of recovery in either environment.

Influence of receptor reserve on beta-adrenoceptor-mediated responses in human lung mast cells.

1. The effects of the beta-adrenoceptor agonists isoprenaline and salbutamol on IgE-mediated histamine release from human lung mast cells (HLMC) were evaluated. Both agonists (10(-10)-10(-5) M) inhibited histamine release in a dose-dependent manner and isoprenaline (pD2, 8.3+/-0.1, mean+/-s.e.mean) was more potent than salbutamol (7.3+/-0.1). Moreover, the mean data indicated that salbutamol was a partial agonist when compared with isoprenaline. However, there was a large degree of interexperimental variability because, in 11 of 32 experiments, salbutamol was a full agonist and, in 21 of 32 experiments, a partial agonist relative to isoprenaline. These data suggest that different HLMC preparations possess variable receptor reserves. 2. The effect of the irreversible beta-adrenoceptor antagonist, bromoacetylalprenolol menthane (BAAM), on the inhibition of IgE-mediated histamine release by both isoprenaline and prostaglandin E2 (PGE2) was assessed. Whereas BAAM (100 nM) antagonized the isoprenaline inhibition of histamine release from activated HLMC, BAAM had no effect on the PGE2 inhibition. Pretreatment of HLMC with the beta2-selective competitive antagonist, ICI 118551 (100 nM), protected against the loss in responsiveness to isoprenaline following treatment with BAAM. 3. Concentrations of 1, 10 and 100 nM of BAAM caused dose-dependent rightward shifts in the dose-response curve for the isoprenaline inhibition of histamine release. Furthermore, there was a dose-dependent reduction in the maximal inhibitory response obtained with isoprenaline following treatments with increasing concentrations of BAAM. Although the rightward shifts in the isoprenaline dose-response curves, with a given concentration of BAAM, were similar in all experiments, there was some variability in the depression of the maximal response in individual experiments. Thus, in 6 of 16 experiments, BAAM (1 nM) did not depress the maximal response to isoprenaline, whereas in 10 of 16 experiments there was a depression (7 to 49% reduction) in the maximal response. These data suggest that different HLMC preparations possess variable receptor reserves. 4. Isoprenaline was more potent as an inhibitor in those HLMC preparations in which there was a larger receptor reserve (i.e. preparations in which the maximal inhibitory response to isoprenaline was unaffected by pretreatment with 1 nM BAAM). 5. The influence of receptor reserve on the inhibition by salbutamol of histamine release from HLMC was evaluated. There was a good correlation (r=0.77) between receptor reserve and the maximal response (relative to isoprenaline) obtained with salbutamol. Thus, HLMC preparations with larger receptor reserves were more responsive to salbutamol. 6. Receptor reserve influenced the desensitization of beta-adrenoceptor-mediated responses in HLMC. Cells were incubated (24 h) with isoprenaline (1 microM), washed and then the ability of a second isoprenaline (10(-10)-10(-5) M) exposure to inhibit histamine release was assessed. The pretreatment caused a reduction in the isoprenaline inhibition of histamine release although the extent of desensitization was highly variable, ranging from essentially negligible levels in some preparations to substantial reductions (93% desensitization) in the ability of isoprenaline to inhibit histamine release. There was a reasonable correlation (r=0.59) between receptor reserve and desensitization. Preparations that possessed a larger receptor reserve were more resistant to desensitization. 7. Collectively, these data suggest that a receptor reserve exists for the beta-adrenoceptor-mediated inhibition of histamine release from HLMC but that the size of this reserve varies between HLMC preparations. Moreover, the size of this receptor reserve may influence the sensitivity of HLMC to beta-adrenoceptor agonists and the susceptibility of individual HLMC preparations to desensitization.

Protection by dexamethasone of the functional desensitization to beta 2-adrenoceptor-mediated responses in human lung mast cells.

1. The beta-adrenoceptor agonist, isoprenaline, inhibited the IgE-mediated release of histamine from human lung mast cells (HLMC) in a dose-dependent manner. Maximal inhibitory effects were obtained with 0.1 microM isoprenaline. However, the inhibition of histamine release from HLMC by isoprenaline (0.1 microM) was highly variable ranging from 33 to 97% inhibition (mean, 59 +/- 3%, n = 27). 2. Long-term (24 h) incubation of HLMC with isoprenaline led to a subsequent reduction in the ability of a second exposure of isoprenaline to inhibit IgE-mediated histamine release from HLMC. The impairment in the ability of isoprenaline (0.1 microM) to inhibit histamine release following desensitizing conditions (1 microM isoprenaline for 24 h) was highly variable amongst HLMC preparations ranging from essentially negligible levels of desensitization in some preparations to complete abrogation of the inhibitory response in others (mean, 65 +/- 6% desensitization, n = 27). 3. The ability of HLMC to recover from desensitization was investigated. Following desensitizing conditions (1 microM isoprenaline for 24 h), HLMC were washed and incubated for 24 h in buffer and the effectiveness of isoprenaline (0.1 microM) to inhibit IgE-mediated histamine release from HLMC was assessed. The extent of recovery was highly variable with some HLMC preparations failing to recover and others displaying a complete restoration of responsiveness to isoprenaline (mean, 40 +/- 6% recovery, n = 23). 4. The effects of the glucocorticoid, dexamethasone, were also investigated. Long-term (24-72 h) treatments with dexamethasone (0.1 microM) had no effect on IgE-mediated histamine release from HLMC. Additionally, long-term (24-72 h) treatments with dexamethasone (0.1 microM) had no effect on the effectiveness of isoprenaline to inhibit histamine release. However, long-term (24-72 h) treatments with dexamethasone (0.1 microM) protected against the functional desensitization induced by incubation (24 h) of HLMC with isoprenaline (1 microM). The protective effect was time-dependent and pretreatment of HLMC with dexamethasone for either 24, 48 or 72 h prevented desensitization by either 15 +/- 7, 19 +/- 5 or 51 +/- 10%, respectively (n = 5-7). 5. HLMC preparations which were relatively refractory to isoprenaline even after withdrawal (24 h) from desensitizing conditions responded more effectively to isoprenaline (0.1 microM) if dexamethasone (0.1 microM) was also included during the recovery period (19 +/- 9% recovery after 24 h in buffer; 50 +/- 8% recovery after 24 h with dexamethasone, n = 5). 6. These data indicate that the responses of different HLMC preparations to isoprenaline, the susceptibility of HLMC to desensitization and the ability of HLMC to recover from desensitizing conditions varies markedly. Dexamethasone, which itself has no direct effects on IgE-mediated histamine release from HLMC, protected HLMC from the functional desensitization to beta-adrenoceptor agonists. Because beta 2-adrenoceptor agonists and glucocorticoids are important in the therapeutic management of asthma and as the HLMC is probably important in certain types of asthma, these findings may have wider clinical implications.