Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment.

OBJECTIVES: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively. RESULTS: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Identifying research priorities for public health research to address health inequalities: use of Delphi-like survey methods.

BACKGROUND: In the funding of health research and public health research it is vital that research questions posed are important and that funded research meets a research need or a gap in evidence. Many methods are used in the identification of research priorities, however, these can be resource intensive, costly and logistically challenging. Identifying such research priorities can be particularly challenging for complex public health problems as there is a need to consult a number of experts across disciplines and with a range of expertise. This study investigated the use of Delphi-like survey methods in identifying important research priorities relating to health inequalities and framing tractable research questions for topic areas identified. METHODS: The study was conducted in two phases, both using Delphi-like survey methods. Firstly, public health professionals with an interest in health inequalities were asked to identify research priorities. Secondly academic researchers were asked to frame tractable research questions relating to the priorities identified. These research priorities identified using Delphi-like survey methods were subsequently compared to those identified using different methods. RESULTS: A total of 52 public health professionals and 21 academics across the United Kingdom agreed to take part. The response rates were high, from public health professionals across three survey rounds (69%, 50% and 40%) and from academics across one round (52%), indicating that participants were receptive to the method and motivated to respond. The themes identified as encompassing the most important research priorities were mental health, healthy environment and health behaviours. Within these themes, the topic areas that emerged most strongly included community interventions for prevention of mental health problems and the food and alcohol environment. Some responses received from academic researchers were (as requested) in the form of tractable research questions, whereas others contributed further potential topic areas instead. CONCLUSIONS: Delphi-like survey methods are practical and productive as a means of obtaining opinions from a wide number of relevant experts identifying potential priority topic areas for research; however, this method is less appropriate for framing tractable research questions.

SERVAL: a new framework for the evaluation of animal health surveillance.

Animal health surveillance programmes may change in response to altering requirements or perceived weaknesses but are seldom subjected to any formal evaluation to ensure that they provide valuable information in an efficient manner. The literature on the evaluation of animal health surveillance systems is sparse, and those that are published may be unstructured and therefore incomplete. To address this gap, we have developed SERVAL, a SuRveillance EVALuation framework, which is novel and aims to be generic and therefore suitable for the evaluation of any animal health surveillance system. The inclusion of socio-economic criteria ensures that economic evaluation is an integral part of this framework. SERVAL was developed with input from a technical workshop of international experts followed by a consultation process involving providers and users of surveillance and evaluation data. It has been applied to a range of case studies encompassing different surveillance and evaluation objectives. Here, we describe the development, structure and application of the SERVAL framework. We discuss users' experiences in applying SERVAL to evaluate animal health surveillance systems in Great Britain.

Impact of Schmallenberg virus on British sheep farms during the 2011/2012 lambing season.

British sheep farmers were invited to complete a questionnaire about the impact of Schmallenberg virus (SBV) on animal health, welfare and their own emotional wellbeing during the 2011-2012 lambing season, through Defra and Farming Industry websites, letters to farmers who had requested SBV laboratory tests and advertisement at Sheep 2012. The 494 responders included SBV confirmed (positive by RT-PCR) (n=76), SBV suspected by farmer (n=140) or SBV not suspected (n=278). Percentage of barren ewes was similar across SBV groups, however, lamb and ewe losses were higher on responder farms where SBV was confirmed or suspected. The median percentages of all lambs born (and lambs born deformed ) that died within one week of birth was 10.4 per cent (5.5 per cent), 7.0 per cent (2.9 per cent) and 5.3 per cent (0 per cent), respectively, on SBV confirmed, suspected and not suspected farms (P<0.001). Eight to 16 per cent of SBV confirmed or suspected farms reported lamb mortality of ≥40 per cent. Farmer perceived impact was greater where SBV was confirmed or suspected (P<0.001): 25 per cent reported a high impact on emotional wellbeing (4 per cent of SBV not suspected), 13 per cent reported a high impact on flock welfare and financial performance and 6 per cent were less likely to farm sheep next year because of SBV (<2 per cent in SBV not suspected). Overall, SBV impact has been large relative to reported sheep loss.

Quantifying the natural history of breast cancer.

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.

Publication rate for funded studies from a major UK health research funder: a cohort study.

OBJECTIVES: This study aimed to investigate what percentage of National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme-funded projects have published their final reports in the programme's journal HTA and to explore reasons for non-publication. DESIGN: Retrospective cohort study. SETTING: Failure to publish findings from research is a significant area of research waste. It has previously been suggested that potentially over 50% of studies funded are never published. PARTICIPANTS: All NIHR HTA projects with a planned submission date for their final report for publication in the journal series on or before 9 December 2011 were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The projects were classified according to the type of research, whether they had been published or not; if not yet published, whether they would be published in the future or not. The reasons for non-publication were investigated. RESULTS: 628 projects were included: 582 (92.7%) had published a monograph; 19 (3%) were expected to publish a monograph; 13 (2.1%) were discontinued studies and would not publish; 12 (1.9%) submitted a report which did not lead to a publication as a monograph; and two (0.3%) did not submit a report. Overall, 95.7% of HTA studies either have published or will publish a monograph: 94% for those commissioned in 2002 or before and 98% for those commissioned after 2002. Of the 27 projects for which there will be no report, the majority (21) were commissioned in 2002 or before. Reasons why projects failed to complete included failure to recruit; issues concerning the organisation where the research was taking place; drug licensing issues; staffing issues; and access to data. CONCLUSIONS: The percentage of HTA projects for which a monograph is published is high. The advantages of funding organisations requiring publication in their own journal include avoidance of publication bias and research waste.

An economic evaluation of screening 60- to 70-year-old adults for hearing loss.

BACKGROUND: Hearing loss is common among older adults and has consequences for sufferers, families and society, but there is substantial unmet need for intervention. Screening could expedite intervention and improve outcomes. METHODS: We use Markov models to estimate the incremental cost-effectiveness ratio (ICER) of potential screening programmes compared with current provision (GP-referral), from a health service perspective. Alternative options are investigated through scenario analysis. One-way and probabilistic sensitivity analyses are undertaken. RESULTS: All modelled screens are cost-effective and reduce unmet need for hearing aids. The most cost-effective option identified is a one-stage audiometric screen for bilateral hearing loss ≥30 dB hearing level (HL) at age 60, repeated at ages 65 and 70. This option has an ICER of £1461 compared to GP-referral and would mean an additional 15 437 adults benefiting from hearing intervention per 100 000 population aged 60. The cost-effectiveness acceptability curve shows that screening is more cost-effective than GP-referral provided a Quality Adjusted Life Year is valued at £2000 or more. CONCLUSIONS: Adult hearing screening would provide a cost-effective way to improve quality of life for older adults. We recommend piloting an audiometric screen offered to all adults age 60, 65 and 70 years to identify bilateral hearing loss of at least 30 dB HL.

Evaluation of animal and public health surveillance systems: a systematic review.

Disease surveillance programmes ought to be evaluated regularly to ensure they provide valuable information in an efficient manner. Evaluation of human and animal health surveillance programmes around the world is currently not standardized and therefore inconsistent. The aim of this systematic review was to review surveillance system attributes and the methods used for their assessment, together with the strengths and weaknesses of existing frameworks for evaluating surveillance in animal health, public health and allied disciplines. Information from 99 articles describing the evaluation of 101 surveillance systems was examined. A wide range of approaches for assessing 23 different system attributes was identified although most evaluations addressed only one or two attributes and comprehensive evaluations were uncommon. Surveillance objectives were often not stated in the articles reviewed and so the reasons for choosing certain attributes for assessment were not always apparent. This has the potential to introduce misleading results in surveillance evaluation. Due to the wide range of system attributes that may be assessed, methods should be explored which collapse these down into a small number of grouped characteristics by focusing on the relationships between attributes and their links to the objectives of the surveillance system and the evaluation. A generic and comprehensive evaluation framework could then be developed consisting of a limited number of common attributes together with several sets of secondary attributes which could be selected depending on the disease or range of diseases under surveillance and the purpose of the surveillance. Economic evaluation should be an integral part of the surveillance evaluation process. This would provide a significant benefit to decision-makers who often need to make choices based on limited or diminishing resources.

Does diet cost mediate the relation between socioeconomic position and diet quality?

BACKGROUND/OBJECTIVES: Socioeconomic disparities in diet quality are well established. This study tested the hypothesis that such disparities are mediated, in part, by diet cost. SUBJECTS/METHODS: The Seattle Obesity Study (S.O.S) was a cross-sectional study based on a representative sample of 1266 adults of King County, WA, conducted in 2008-09. Demographic and socioeconomic variables were obtained through telephone survey. Income and education were used as indicators of socioeconomic position. Dietary intake data were obtained using a food frequency questionnaire (FFQ). Diet cost was calculated based on retail prices for FFQ component foods. Energy density (KJ/g) and mean adequacy ratio (MAR) were used as two indices of overall diet quality. RESULTS: Higher income and education were each associated with lower energy density and higher MAR scores, adjusting for covariates. Higher income and education were also associated with higher energy adjusted diet cost. Higher quality diets were in turn associated with higher diet costs. All these associations were significant (P<0.0001). In formal mediation analyses, diet cost significantly mediated the pathway between income and diet quality measures, adjusting for covariates (P<0.05 each). Further, income-diet cost-diet quality pathway was found to be moderated by education level. CONCLUSIONS: The social gradient in diet quality may be explained by diet cost. Strategies to improve diet quality among lower socioeconomic strata may need to take food prices and diet cost along with nutrition education into account.

Towards a standardised surveillance for Trichinella in the European Union.

Each year, more than 167 million pigs in the European Union (EU) are tested for Trichinella spp. under the current meat hygiene regulations. This imposes large economic costs on countries, yet the vast majority of these pigs test negative and the public health risk in many countries is therefore considered very low. This work reviewed the current Trichinella status across the EU as well as the national level of monitoring and reporting. It also reviewed which animal species were affected by Trichinella and in which species it should be surveyed. This information was used to design a cost-effective surveillance programme that enables a standardised monitoring approach within the EU. The proposed surveillance programme relies on identifying sub-populations of animals with a distinct risk. Low-risk pigs are finisher pigs that originate from so-called controlled housing. All other pigs are considered high-risk pigs. Controlled housing is identified by the application of a specific list of management and husbandry practices. We suggest that member states (MS) be categorised into three classes based on the confidence that Trichinella can be considered absent, in the specified sub-population of pigs above a specified design prevalence which we set to 1 per million pigs. A simple and transparent method is proposed to estimate this confidence, based on the sensitivity of the surveillance system, taking into account the sensitivity of testing and the design prevalence. The probability of detecting a positive case, if present, must be high (>95 or >99%) to ensure that there is a low or negligible risk of transmission to humans through the food chain. In MS where the probability of a positive pig is demonstrated to be negligible, testing of fattening pigs from a sub-population consisting of pigs from controlled housing can be considered unnecessary. Furthermore, reduced testing of finishers from the sub-population consisting of pigs from non-controlled housing might even be considered, if conducted in conjunction with a proportionate sampling scheme and a risk-based wildlife surveillance programme where applicable. The proposed surveillance programme specifies the required number of samples to be taken and found negative, in a MS. A MS with no data or positive findings will initially be allocated to class 1, in which all pigs should be tested. When a MS is able to demonstrate a 95% or 99% confidence that Trichinella is absent, the MS will be allocated to class 2 or 3, in which the testing requirement is lower than in class 1.

Salmonella Typhimurium and Salmonella Enteritidis in England: costs to patients, their families, and primary and community health services of the NHS.

This is the first study comparing societal costs of acute illness with Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE) in the UK. It included the cost and severity of the illness and explored the impact of each Salmonella serovar on the patients, their families, the NHS, and the wider economy. The study ascertained confirmed cases of ST and SE between July and November 2008. The mean costs per case were £1282 (ST) and £993 (SE). The indirect costs associated with the work-time lost by the case, parents, or carers were £409 (ST) and £228 (SE); this difference was statistically significant. The aggregate cost of ST and SE identified using laboratory test results for the UK as a whole was estimated as £6.5 million. Work-time lost and caring activities are cost categories that are not frequently investigated within the infectious intestinal disease literature, although they represent an important societal cost.

Reducing Campylobacter and Salmonella infection: two studies of the economic cost and attitude to adoption of on-farm biosecurity measures.

To date there has been little research in the UK on farmer adoption of biosecurity measures to control food-borne zoonoses that have little or no impact on animal health or production but which threaten public health. Campylobacteriosis and salmonellosis are the two most common causes of food-borne infectious intestinal disease in people in Great Britain, causing approximately 57,000 and 13,000 reported cases in 2007 respectively (Anon 2008a) with an important cost to society. Poultry are an important source of both infections, while pigs may also contribute to human salmonellosis. However, these infections in poultry and pigs seldom cause disease. Research has shown that improved farm biosecurity may reduce the prevalence of these infections in livestock and if the majority of farmers were prepared to enhance biosecurity then there could be an important impact on public health. This article reports on the findings of two studies of farmer attitudes to and cost of the adoption of on-farm biosecurity measures to reduce the risk of animal diseases and therefore enhance food safety. One study, of Campylobacter infection among broiler flocks, is based on a survey of farmers faced with a hypothetical biosecurity intervention, while the other study, of Salmonella infection among pigs, is based on the participation of a group of farmers in an intervention study. In both cases, the results show a clear inverse relationship between the willingness of farmers to adopt a biosecurity measure and its estimated cost. This finding has implications for the success of on-farm biosecurity-enhancement policies based on voluntary adoption by farmers. In particular, financial inducements or penalties to farmers could be necessary to facilitate adoption of these measures.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment.

OBJECTIVES: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. METHODS: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. RESULTS: Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. CONCLUSIONS: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.

Evaluation of a surveillance programme for women with a family history of breast cancer.

AIM: To establish health related costs and benefits of clinical services for women at increased familial risk of breast cancer. METHODS: Analysis of costs and outcomes for one UK regional service, supplemented with data from a multinational collaborative study. Main outcome measures were aggregate costs for regular clinical examination, mammographic screening and further investigations; breast cancer incidence; proportion of cancers detected at "early" or "late" stage, compared with corresponding data for unscreened women of comparable age; survival in relation to stage at diagnosis; itemised and aggregate costs of management for "early" and "late" stage breast cancer; hence direct health care costs per quality adjusted life-year (QALY) gained. RESULTS: The surveillance programme costs pound1500 (euro1600, US$2100) per woman (over 15 years). Breast cancer incidence is close to 6 per thousand examinations; 75% of tumours are detected through screening and 77% are "early" (path stage 1 or 2). Corresponding figures for unscreened women (including relatives of those attending the breast cancer family clinic) indicate that surveillance achieves a beneficial "stage shift", with reduction in treatment costs and improvement in survival, in about 22% of cases. CONCLUSIONS: The current clinical service for women at familial risk of breast cancer costs about pound4800 (euro5200, US$6800) per QALY gained. That figure is sensitive to the rate of detection of breast cancer and the degree of beneficial stage shift achieved. Within the realistic range of estimates for these two parameters, the cost per QALY may be as high as pound14,000 (euro15,300, US$20,000) or as low as pound1000 (euro1100, US$1400).

Comparison of Assessment of Citrus Canker Foliar Symptoms by Experienced and Inexperienced Raters.

Citrus canker (Xanthomonas citri subsp. citri) is destructive in many citrus production regions in tropical and subtropical parts of the world. Assessment of canker symptoms is required for diverse reasons, including monitoring epidemics, evaluating the efficacy of control strategies, and disease response in breeding material. The objectives were to compare the ability of experienced and inexperienced raters at assessing citrus canker, to identify factors that affect the quality of the assessment, to determine common sources of error, and to discern how error is related to actual disease magnitude. Two-hundred digital leaf images (0 to 37% area infected) were assessed once by 28 raters, five of whom were experienced plant pathologists (PPs), and 23 who had no experience in disease severity assessment (NPPs). True disease (lesion number [LN], % necrotic area [%N], and % chlorotic+necrotic area [%CN]) was measured using image analysis on a leaf-by-leaf basis, and each parameter was estimated by the 28 raters. LN was neither severely over- nor underestimated, while %N was greatly overestimated, with a lesser tendency to overestimate %CN over the true severity range of these two symptom types. A linear relationship existed between estimate of the disease and true disease for all measures of severity. Data were heteroscedastic and error was not constant with increasing true disease. Agreement between rater estimates and true disease was measured with Lin's concordance correlation coefficient (ρc). LN showed greatest agreement (ρc = 0.88 to 0.99), followed by %CN (ρc = 0.80 to 0.95) and %N (ρc = 0.19 to 0.84). Greater lesion number resulted in overestimation of area infected for both %N and %CN. Overestimation was particularly noticeable at low disease severities. There was a linear relationship between log variance and log true disease for LN (r2 = 0.71), %N (r2 = 0.85), and %CN (r2 = 0.88), and raters tended to estimate disease above 10% to the nearest 5 or 10%. GLM analysis showed differences between PP and NPP groups in assessing disease. For LN, precision of assessment for both groups was similar (r2 > 0.92 and 0.94, respectively), but for estimates of %N and %CN, the PPs were more precise (%N and %CN, r2 = 0.61 and 0.73, respectively) compared to NPPs (%N and %CN, r2 = 0.45 and 0.58, respectively). Absolute error for mean LN was low. The absolute error of %N and %CN showed overestimation to approximately 8% area infected. Above 8%, absolute error increased, but comprised both over- and underestimation. For %N and %CN, relative error was almost exclusively positive and dramatic at severity <8% (up to approximately 600%), but at severity >10% it was relatively small. Error in rater estimates of canker severity is ubiquitous. Understanding these sources of error will aid in the development of both appropriate training and relevant rating aids.

Constructing the effect of alternative intervention strategies on historic epidemics.

Data from historical epidemics provide a vital and sometimes under-used resource from which to devise strategies for future control of disease. Previous methods for retrospective analysis of epidemics, in which alternative interventions are compared, do not make full use of the information; by using only partial information on the historical trajectory, augmentation of control may lead to predictions of a paradoxical increase in disease. Here we introduce a novel statistical approach that takes full account of the available information in constructing the effect of alternative intervention strategies in historic epidemics. The key to the method lies in identifying a suitable mapping between the historic and notional outbreaks, under alternative control strategies. We do this by using the Sellke construction as a latent process linking epidemics. We illustrate the application of the method with two examples. First, using temporal data for the common human cold, we show the improvement under the new method in the precision of predictions for different control strategies. Second, we show the generality of the method for retrospective analysis of epidemics by applying it to a spatially extended arboreal epidemic in which we demonstrate the relative effectiveness of host culling strategies that differ in frequency and spatial extent. Some of the inferential and philosophical issues that arise are discussed along with the scope of potential application of the new method.

Screening health risk assessment of micropullutants for indirect potable reuse schemes: a three-tiered approach.

Indirect potable reuse schemes are an important consideration in the sustainable management of scarce water resources. However, communities still hold real concerns about the potential health risks of micropullutants in recycled water entering their potable water supply. Microfiltration or ultrafiltration followed by reverse osmosis is currently the standard treatment technology for potable use of recycled water. Nevertheless, membranes are not 100% efficient in the removal of trace organic contaminants and the potential health risks of these micropullutants need to be assessed. The aim of this paper is to present a three-tiered approach for the preliminary assessment of micropullutants in recycled water. A risk quotient is calculated by comparing measured concentrations against benchmark values. Tier 1 corresponds to regulated chemicals; the maximum contaminant level in drinking water is used as benchmark value. Tier 2 corresponds to unregulated chemicals with toxicity information; slope factors or risk specific doses are used to calculate benchmark values. Tier 3 corresponds to unregulated chemicals without toxicity information. The "Threshold of Toxicological Concern" concept is used to calculate benchmark values. The characterization of chemicals of concern following reverse osmosis in a water reclamation plant and the application of the three-tiered approach for the evaluation of the potential health risks is presented.

Measuring bidirectional mutation.

The estimation of mutation rates is usually based on a model in which mutations are rare independent Poisson events. Back-mutation of mutants, an even rarer event, is ignored. In the hypermutating B cells of the immune system, mutation between phenotypes exhibiting, vs. not exhibiting, surface immunoglobulin is common in both directions. We develop three strategies for the estimation of mutation rates under circumstances such as these, where mutation rates in both directions are estimated simultaneously. Our model for the growth of a cell culture departs from the classical assumption of cell division as a memoryless (Poisson) event; we model cell division as giving rise to sequential generations of cells. On this basis, a Monte-Carlo simulation is developed. We develop also a numerical approach to calculating the probability distribution for the proportion of mutants in each culture as a function of forward- and backward-mutation rates. Although both approaches are too computationally intensive for routine laboratory use, they provide the insight necessary to develop and evaluate a third, 'hand-calculator' approach to extracting mutation rate estimators from experiments of this type.

An assessment of exposure indices in computed radiography for the posterior-anterior chest and the lateral lumbar spine.

Studies have indicated that computed radiography (CR) can increase radiation dose to the patient, leading to potential biological effects. Although manufacturers have set parameters to safeguard against overexposure, it is unclear whether these are being used by radiographers or if their recommended values are consistent with the ALARA principle. The research aims are to investigate (i) whether radiographers are producing images with exposure indices within the manufacturers recommended range (MRR); (ii) the phenomenon of exposure creep, and (iii) the relationship between exposure indices (EIs) and radiation dose. A retrospective analysis of exposure indices over an 18-month period for the posteroanterior (PA) chest and lateral (LAT) lumbar spine at two centres using Kodak 800 and 850 CR systems was conducted. A phantom study was performed to assess the relationship between EI and entrance surface dose (ESD) for fixed and varying tube potentials. Kodak recommends that images have EIs between 1700 and 1900. Thirty percent of LAT lumbar spine examinations at hospital B and 38% of PA chest examinations at hospital A were produced with EIs below 1700. In the phantom study, when using a varied tube potential (70-125 kVp) and maintaining a constant EI of 1550, ESD was reduced by 56%. All clinical and phantom images were assessed to be of a diagnostic quality. The retrospective results indicate that there is a potential to reduce the MRR and optimize patient dose. There is also evidence to suggest that EI is not a reliable indicator of patient dose. The authors recommend that staff training is essential on these newer systems.

Assessment of fitness for purpose of an insect bioassay using the desert locust (Schistocerca gregaria L.) for the detection of paralytic shellfish toxins in shellfish flesh.

We have developed a bioassay using 5th instar desert locusts (Schistocerca gregaria L.) for the detection of saxitoxin-the paralytic shellfish poison in shellfish flesh. The bioassay procedure is to inject 10 locusts with a shellfish extract, and assess their conditions at time points up to 2h post injection, looking for an endpoint of paralysis. From the proportion responding, the equivalent dose of pure saxitoxin could be estimated. Performance characteristics of the bioassay were assessed using shellfish samples spiked with saxitoxin, and we found the bioassay could detect and quantify toxin levels in the range of regulatory relevance. Relative toxicities of selected saxitoxin analogues differed from those reported in mammalian systems. Variation for repeatability conditions was acceptable but variation was higher under reproducibility conditions. This was related to (a) batches of insects from different suppliers, (b) different operators, and (c) different observers assessing the endpoint. We also noted adverse reactions with some shellfish species. These problems may be resolved by further refinement of the method and operator training, before formal validation. Nevertheless, we suggest the method potentially offers a simple, ethically acceptable, broad-specificity functional bioassay, which is desirable in any toxin-monitoring programme.