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Toward the use of a standardized assessment for young children with autism: current assessment practices in the UK.

Little is known about the progress of autistic children following specific interventions in England. Nor do we know how frequently standardized assessments are used to monitor progress or to evaluate specific educational interventions. The reports of 75 children with autism, for whom special educational provision had been determined by a local education authority, were reviewed. Parents were interviewed and educational psychologists were contacted for details of any norm-referenced assessments. Of these children, 39 percent had no standardized assessments before education authorities determined their provision, and only 9 percent had follow-up assessments that could be used to evaluate progress. Children with autism in the UK rarely have sufficient assessments to allow an objective evaluation of their progress. There is currently no standardized assessment protocol to prescribe a specific educational intervention, to evaluate the progress of children or to make comparisons between interventions. We recommend the development of such a protocol.

Autistic Disorder↗

The usefulness of cytogenetic parameters, level of p53 protein and endogenous glutathione as intermediate end-points in raw betel-nut genotoxicity.

Betel-nut (BN) chewing related oral mucosal lesions are potential hazards to a large population worldwide. Genotoxicity of betel alkaloids, polyphenol and tannin fractions have been reported. It has been shown earlier that BN ingredients altered the level of endogenous glutathione (GSH) which could modulate the host susceptibility to the action of other chemical carcinogens. The north-east Indian variety of BN, locally known as 'kwai', is raw, wet and consumed unprocessed with betel-leaf and slaked lime and contains higher alkaloids, polyphenol and tannins as compared to the dried one. Therefore, the purpose of this study was to investigate the extent of DNA damage, pattern of cell kinetics, the level of p53-protein and endogenous GSH in kwai chewers in the tribal population of Meghalaya state in the northeastern region of India with an aim to see whether these end-points could serve as biomarkers of genetic damage of relevance for genotoxic/carcinogenic process. The present data show higher DNA damage, delay in cell kinetics, p53 expression and lower GSH-level in heavy chewers (HC) than nonchewers (NC). The influence of bleomycin (BLM) on chromatid break induction in G2-phase of peripheral blood lymphocytes in NC and HC has been analysed to determine individual susceptibility to carcinogenic assaults. HC showed higher induction of chromatid breaks than NC. Risk assessment in this study suggests an interaction between carcinogen exposure and mutagen sensitivity measures, risk estimates being higher in those individuals who both consume kwai and express sensitivity to free radical oxygen damage in vitro. From this study it seems that besides cytogenetical parameters, the level of endogenous GSH and the level of p53 protein could act as effective biomarkers for kwai chewers.

Adult↗

Sunscreens prevent local and systemic immunosuppression of contact hypersensitivity in mice exposed to solar-simulated ultraviolet radiation.

Ultraviolet (UV) irradiation causes the immunosuppression of contact hypersensitivity (CH) responses in animals and humans. There are conflicting reports regarding the effectiveness of sunscreens in preventing UV-induced suppression of both local-type CH (induced by the application of the contact sensitizer directly to UV-exposed skin) and systemic-type CH (induced by the application of the contact sensitizer to an unirradiated skin site 3 days after UV exposure). The purposes of this study were as follows: 1. to derive solar simulator UV dose-response curves for the induction of local and systemic CH suppression in C3H mice; 2. to establish minimum immune suppression doses (MISDs) for local and systemic CH; 3. to determine the local and systemic immune protection capacity of two commercial sunscreen lotions with labeled sun protection factors (SPFs) of 4 and 8. Dose-response curves for the induction of local and systemic CH suppression were derived by exposing groups of mice to a range of full-spectrum UV doses (0.37-21.4 kJ m-2) on two consecutive days delivered from a filtered 1000 W xenon arc lamp solar simulator. The MISDs, defined as the lowest dose tested to cause approximately 50% suppression of the normal CH response, were obtained from the dose-response curves. Although the local and systemic immunosuppression dose-response curves were not statistically different, the MISD for local suppression of CH (1.35 kJ m-2) was about fivefold lower than that for systemic CH suppression (6.76 kJ m-2). The MISD was used as the endpoint to determine sunscreen immune protection levels. Both sunscreens, applied at 2 mg cm-2, provided immune protection against the induction of local and systemic CH suppression in mice exposed to an effective UV dose of 1 MISD given through the sunscreen, i.e. 4 MISD to SPF 4 sunscreen-protected mice and 8 MISD to SPF 8 sunscreen-protected mice mounted CH responses that were significantly greater than those elicited in unprotected mice exposed to 1 MISD of solar-simulated UV radiation. The calculated immune protection factors for these sunscreens exceeded the level of protection predicted by their labeled SPFs, i.e. the local immune protection factor of both sunscreens was 15 and the systemic immune protection factors were 8 for the SPF 4 sunscreen and 15 for the SPF 8 sunscreen. Our data show that these two sunscreens provide levels of immune protection which exceed the levels predicted by their labeled SPFs in immunoprotection tests conducted in mice exposed to a relevant MISD of UV radiation from a source emitting a UV power spectrum similar to that of sunlight.

Animals↗

Differences between endocarditis with true negative blood cultures and those with previous antibiotic treatment.

BACKGROUND AND AIM OF THE STUDY: High morbidity and mortality are attributed to patients with culture-negative endocarditis. The main reason for negative blood culture in infectious endocarditis (IE) is administration of antibiotics before sample withdrawal. The study aim was to determine any difference in prognosis between patients with 'aborted' culture-negative endocarditis (A-CNE) and those with true culture-negative endocarditis (T-CNE). METHODS: A total of 107 patients with a diagnosis of IE was studied retrospectively. Diagnosis was confirmed pathologically during surgery, at post-mortem examination, or by fulfillment of Duke's criteria. Twenty patients (18.7%) had negative-culture endocarditis and comprised the study population. Of these patients, 14 (70%) had received previous antibiotic therapy (A-CNE), and six (30%) were considered T-CNE cases. In-hospital outcome and clinical characteristics were compared between both patient groups. The main end-point was death or need for surgical repair of the heart valves during hospitalization. RESULTS: There were no significant inter-group differences with respect to mean age, gender distribution, and other clinical characteristics. The composite endpoint of death or surgical repair occurred more frequently in T-CNE patients (100% versus 64%, p = 0.0394). Anatomic complications also occurred more frequently in T-CNE patients, but the difference was statistically not significant. CONCLUSION: Among patients with IE and a negative blood culture, those without previous antibiotic therapy (T-CNE) have the worse prognosis.

Antibiotic Prophylaxis↗

Mechanisms of spontaneous mutagenesis: an analysis of the spectrum of spontaneous mutation in the Escherichia coli lacI gene.

We have obtained via DNA sequence analysis a spectrum of 174 spontaneous mutations occurring in the lac I gene of Escherichia coli. The spectrum comprised base substitution, frameshift, deletion, duplication and insertion mutations, of which the relative contributions to spontaneous mutation could be estimated. Two thirds of all lacI mutations occurred in the frameshift hotspot site. An analysis of the local DNA sequence suggested that the intensity of this hotspot may depend on structural features of the DNA that extend beyond those permitted by the repeated tetramer at this site. Deletions comprised the largest non-hotspot class (37%). They could be divided into two subclasses, depending on whether they included the lac operator sequence; the latter was found to be a preferred site for deletion endpoints. Most of the deletions internal to the lacI gene were associated with the presence of directly or invertedly repeated sequences capable of accounting for their endpoints. Base substitutions comprised 34% of the non-hotspot events. Unlike the base substitution spectrum obtained via nonsense mutations, G . C----A . T transitions do not predominate. A new base substitution hotspot was discovered at position +6 in the lac operator; its intensity may reflect specific features of the operator DNA. IS1 insertion mutations contributed 12% of the non-hotspot mutations and occurred dispersed throughout the gene in both orientations. Since the lacI gene is not A + T-rich, the contribution of IS1 insertion to spontaneous mutation in general might be underestimated. Single-base frameshift mutations were found only infrequently. In general, they did not occur in runs of a common base. Instead, their occurrence seemed based on the "perfection" of direct or inverted repeats in the local DNA sequence. Three (tandem) duplication events were recovered. No repeated sequences were found that might have determined their endpoints.

Base Sequence↗

Development of classification and response criteria for rheumatic diseases.

RELEVANCE TO THE CLINICIAN: Clinicians already know that not all patients who are diagnosed with rheumatic diseases really have them. Moreover, determining which patients have improved and by how much is also difficult. Classification criteria allow clinical researchers to recruit patients with similar diseases (e.g., rheumatoid arthritis or systemic lupus erythematosus) into studies. Response criteria help to determine whether treatments really work, i.e., whether they actually produce clinically important improvement. As the science of clinical research advances, we must update our standards for considering classification and response criteria. In this editorial, members of the American College of Rheumatology (ACR) Subcommittee on Classification and Response Criteria describe the purpose of criteria sets, their development and validation, and the role of the ACR in adopting them.

Americas↗

Pitfalls in the design of clinical trials for prevention or treatment of acute graft-versus-host disease.

This review addresses pitfalls of clinical trials to evaluate new approaches for prevention or treatment of graft-versus-host disease. Determination of end points poses a difficult challenge in the design of clinical trials, and examples from previous studies are used to illustrate some of the pitfalls. Also discussed is the need for a new conceptual approach for evaluation of graft-versus-host disease after non-myeloablative conditioning regimens, because the donor anti-recipient alloimmune reaction is the primary mechanism of benefit with this type of treatment. Finally, investigators should be aware of regulatory and socioeconomic pitfalls that apply to all clinical trials.

Acute Disease↗

Assessment of resistance towards biocides following the attachment of micro-organisms to, and growth on, surfaces.

AIMS: To develop a rapid method for the assessment of biocidal activity directed towards intact biofilms. METHODS AND RESULTS: Escherichia coli and Staphylococcus epidermidis were cultured for up to 48 h within 96-well microtitre plates. The planktonic phase was removed and the wells rinsed. Residual biofilms were exposed to various concentrations of chloroxylenol, peracetic acid, polyhexamethylene biguanide (PHMB), cetrimide or phenoxyethanol for 1 h. At 15-min intervals, biocide was removed, and the wells washed in neutraliser and filled with volumes of fresh medium. Re-growth of the cultures was monitored during incubation at 35 degrees C in the plate reader. Times taken for the treated wells to re-grow to fixed endpoints were determined and related to numbers of surviving cells. Time--survival curves were constructed and the survival of the attached bacteria, following exposure to the agents for 30 min, interpolated for each biocide concentration. Log--log plots of these survival data and biocide concentration were constructed, and linear regression analysis performed in order to (i) calculate concentration exponents and (ii) compare the effectiveness of the biocides between variously aged biofilm and planktonic cells. From such analyses iso-effective concentrations of biocide (95% kill in 30 min) were calculated and expressed as planktonic : biofilm indices (PBI). CONCLUSION: PBI varied between 1.02 and 0.02, were relatively unaffected by age of the biofilms but differed significantly between organism and biocide. Notably those compounds with the higher activity against planktonic bacteria (PHMB and peracetic acid) were most prone to a biofilm effect but remained the most effective of the agents selected. SIGNIFICANCE AND IMPACT OF THE STUDY: The endpoint method proved robust, enabled the bactericidal effects of the biocides to be assessed against in-situ biofilms, and was suitable for routine screening applications.

Bacterial Adhesion↗

Epidermal-skin-test 1,000 (EST-1,000)--a new reconstructed epidermis for in vitro skin corrosivity testing.

The determination of a possible corrosive or irritative potential of certain products and ingredients is necessary for their classification and labeling requirements. Reconstructed skin as a model system provides fundamental advantages to single cell culture testing and leads to promising results as shown by different validation studies (for review: Fentem, J.H., Botham, P.A., 2002. ECVAM's activities in validating alternative tests for skin corrosion and irritation. ATLA 30(Suppl. 2), 61-67). In this study we introduce our new reconstructed epidermis "Epidermal-Skin-Test" (EST-1,000). This fully grown epidermis consists of proliferating as well as differentiating keratinocytes. EST-1,000 shows a high comparability to normal human skin as shown by histological and immunohistochemical data. Characteristic markers (KI-67, CK 1/10/5/14, transglutaminase, collagen IV, involucrin, beta 1 integrin) can be identified easily. The main focus of this work was to characterize EST-1,000 especially with respect to its barrier function by testing several substances of known corrosive potential. Skin corrosion was detected by the cytotoxic effect of the substances on a reconstructed epidermis after short-term application to the stratum corneum. The effect was determined by standard MTT assay and accompanying histological analysis. Hence EST-1,000 shows a very high predictive potential and closes the gap between animal testing and the established full-thickness model Advanced-Skin-Test 2,000 (AST-2,000) (Noll, M., Merkle, M.-L., Kandsberger, M., Matthes, T., Fuchs, H., Graeve, T., 1999. Reconstructed human skin (AST-2,000) as a tool for pharmaco-toxicology. ATLA 27, 302).

Acrylates↗

Validation of a single-patient drug trial methodology for personalized management of gastroesophageal reflux disease.

BACKGROUND: Single-patient trials (SPTs) are randomized, often multiple-crossover trials where patients serve as their own control to determine their appropriate treatment. Historically, SPTs have been individually customized, requiring significant time and cost for execution. The patient.s progress is tracked and evaluated in a blinded, multiple-crossover design comparing different therapies. Standardized, cost-efficient SPTs could help avoid (a) inappropriate extrapolation of the average-group outcomes from parallel, clinical trials to community-practice patients and (b) wasteful prescribing of high-cost drugs. Aggregate SPT results can also provide new data on appropriate drug prescribing in subpopulations. OBJECTIVE: To validate a standardized, commercially useful SPT method for comparing drugs/doses in patients with gastroesophageal reflux disease (GERD) requiring maintenance therapy. METHODS: A double-blind, single-dummy, randomized, 3 paired-period (28 days per period, 14 days per leg), multiple-crossover, SPT comparing omeprazole 20 mg daily and ranitidine hydrochloride (ranitidine) 150 mg twice daily was employed for 32 patients with GERD taking acid-suppressing medications chronically. Endpoints to determine effectiveness were selected from a recently approved new-drug application. Heartburn, regurgitation, difficulty swallowing, epigastric pain, and nausea were evaluated daily. Use of rescue medications was also measured. Quality of life was measured weekly by the patient.s global evaluation. Observations for days 1 to 4 were excluded by using aggregate database sensitivity analyses to define appropriate surrogate washout periods. Frequently reported adverse events found in labeling for acid-suppressing drugs were directly solicited and compared between treatments. Unsolicited events were recorded. Patients completed a test-kit-acceptability questionnaire. RESULTS: Fourteen of 27 evaluable SPTs (52%) showed significant superiority for omeprazole over ranitidine and 7 of 27 (26%) for ranitidine over omeprazole. Four of 27 (15%) showed parity performance. Neither agent could be recommended in 2 of 27 (7%) of SPTs due to significant adverse events experienced with both drugs. For those patients taking proton pump inhibitors (PPIs) prior to enrollment, the estimated step-down substitution rate from omeprazole to ranitidine, combined with the drug therapy discontinuation rate, was 40% (90% confidence interval: 22% to 68%). The majority of patients rated the test kits as appropriate and desirable. CONCLUSION: Omeprazole was the appropriate treatment in only 52% of these chronic users of acid-suppressing drugs. Eleven of 27 trials (41%) indicated that ranitidine was the preferred treatment. The SPT method proved acceptable to patients, feasible to administer, and reproducible. It can statistically discriminate effectiveness and adverse events and serve as a useful, prognostic tool in community practice by determining the least costly, evidence-based, appropriate treatment.

Clinical Trial↗

Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.

PURPOSE: This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2-overexpressing solid malignancies. PATIENTS AND METHODS: Heavily pretreated patients with metastatic cancers overexpressing ErbB2 and/or expressing ErbB1 were randomly assigned to one of five dose cohorts of lapatinib (GW572016) administered orally once daily continuously. The biologic effects of lapatinib on tumor growth and survival pathways were assessed in tumor biopsies obtained before and after 21 days of therapy. Clinical response was determined at 8 weeks. RESULTS: Sequential tumor biopsies from 33 patients were examined. Partial responses occurred in four patients with breast cancer, and disease stabilization occurred in 11 others with various malignancies. Responders exhibited variable levels of inhibition of p-ErbB1, p-ErbB2, p-Erk1/2, p-Akt, cyclin D1, and transforming growth factor alpha. Even some nonresponders demonstrated varying degrees of biomarker inhibition. Increased tumor cell apoptosis (TUNEL) occurred in patients with evidence of tumor regression but not in nonresponders (progressive disease). Clinical response was associated with a pretreatment TUNEL score > 0 and increased pretreatment expression of ErbB2, p-ErbB2, Erk1/2, p-Erk1/2, insulin-like growth factor receptor-1, p70 S6 kinase, and transforming growth factor alpha compared with nonresponders. CONCLUSION: Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB1 and/or ErbB2-overexpressing tumors. However, the limited sample size of this study and the variability of the biologic endpoints suggest that further work is needed to prioritize biomarkers for disease-directed studies, and underscores the need for improved trial design strategies in early clinical studies of targeted agents.

Adult↗

Biomarker responses in Macoma nasuta (Bivalvia) exposed to sediments from northern San Francisco Bay.

Our study investigates biomarker responses and survival of Macoma nasuta exposed to sediments collected from six locations in northern San Francisco Bay. Biomarkers analyzed were stress proteins (hsp70) in gill, mantle and digestive gland, lysosomal membrane damage and histopathologic lesions. Sediments and clam tissues were analyzed for a comprehensive suite of heavy metals and trace organic pollutants. Sediment grain size and organic carbon content were determined. Clams accumulated metals, polyaromatic hydrocarbons (PAHs) and organochlorine pesticides (aldrin and p,p(')-DDT and its metabolites p,p(')-DDD and p,p(')-DDE). Pearson and Spearman correlation analysis revealed that mortality, hsp70 in gill and histopathologic lesion scores in gonads, and lysosomal membrane damage were significantly correlated with tissue concentrations of DDT and/or its metabolites. Tissue concentrations of metals, in particular nickel, chromium, and copper, were associated with macrophage aggregates in digestive gland and germ cell necrosis. Cadmium was linked to mortality and lysosomal membrane damage.

Animals↗

Remission versus response: the new gold standard of antidepressant care.

As descriptors for the clinical course and treatment of depressive illness, terms such as response, remission, and recovery have evolved with our understanding of the disease, yet have been inconsistently applied as measures of outcome in clinical trials. Indeed, a wide variety of definitions may be found in contemporary study reports. This article reviews the breadth of definitions, the ways in which they affect interpretation of clinical study data, and their relationship to clinical practice. Therapeutic experience over the past decade indicates that remission is the optimal outcome of treatment, and patients said to have remitted generally are considered to be well. By some standards, however, patients may be considered in remission despite harboring one or two minor symptoms. The presence of residual symptoms, like continued functional or social impairment, is considered a strong predictor of relapse or recurrence. Wellness thus must be determined by symptom level, functional status, and increasingly (as our understanding of brain neurophysiology grows), the nature of pathophysiologic changes. The various factors that may predispose patients toward or away from a state of sustained recovery also are reviewed, helping to inform a concept of remission more consistent with true wellness. Defining such a target can serve to sharpen the focus of therapeutic intervention in the clinical environment. This dynamic is reinforced via the integration of current best therapeutic thinking in research settings, leading to clinical trials that more closely approximate an ideal, remission-focused treatment regimen.

Antidepressive Agents↗

Scoring alternatives for FIM in neurological disorders applying Rasch analysis.

OBJECTIVE: The Functional Independence Measure (FIM) is an internationally widely used outcome measure. The aim of this study was to evaluate the structural properties of FIM using the Rasch model, with regard to scoring within rehabilitation centres in Scandinavia. MATERIALS AND METHODS: FIM data from 1660 patients with stroke, traumatic brain injury and spinal cord injury were analysed. The best models with respect to person separation were determined, together with person reliability, item separation, disordered categories, distance of more than 1.4 logits between categories and item fit to the model. RESULTS: Analysis showed disordering using seven categories in all three diagnoses. After collapsing of categories a four-category scale was the best solution. CONCLUSIONS: Decreasing the categories from seven to four may be one way of dealing with problems of disordered thresholds. Further studies are also needed in order to try the suggested scale in clinical settings and to compare it with the original FIM scale.

Activities of Daily Living↗

Tests for inter-subject and total variabilities under crossover designs.

In this paper, we consider statistical tests for inter-subject and total variabilities between treatments under crossover designs. Since estimators of variance components for inter-subject variability and total variability in crossover design are not independent, the usual F-test cannot be applied. Alternatively, we propose a test based on the concept of the extension of the modified large sample method to compare inter-subject variability and total variability between treatments under a 2 x 2 m replicated crossover design. An asymptotic power of the proposed test is derived. A sensitivity analysis is performed based on the asymptotic power to determine how the power changes with respect to various parameters such as inter-subject correlation and intra-class correlation. Also the two methods for sample size calculation for testing total variability under 2 x 4 crossover design are discussed. The method based on the Fisher-Cornish inversion shows better performance than the method based on the normal approximation. Several simulation studies were conducted to investigate the finite sample performance of the proposed test. Our simulation results show that the proposed test can control type I error satisfactorily.

Analysis of Variance↗

Dose-response curves and tolerance doses for late functional changes in the normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance imaging: influence of end points and follow-up time.

Late reaction of normal tissue is still a limiting factor in radiotherapy and radiosurgery of patients with brain tumors. Few quantitative data in terms of dose-response curves are available. In the present study, 99 animals were irradiated stereotactically at the right frontal lobe using a linear accelerator and single doses between 26 and 50 Gy. The diameter of the spherical dose distribution was 4.7 mm (80% isodose). Dose-response curves for late changes in the normal brain at 20 months were measured using T1- and T2-weighted magnetic resonance imaging (MRI). The dependence of the dose-response curves on the follow-up time and the definition of the biological end point were determined. Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were found to be dependent on dose and progressive in time. At 20 months, the tolerance doses at a 50% effect probability level were 39.6 +/- 1.0 Gy and 42.4 +/- 1.4 Gy for changes in T1- and T2-weighted images, respectively. These dose-response curves can be used for further quantitative investigations on the influence of various treatment parameters, such as the application of charged particles, radiopharmaceuticals or the variation of tissue oxygenation.

Animals↗

Evaluation of the susceptibility of the cultured shrimp Litopenaeus vannamei to vibriosis when orally exposed to the insecticide methyl parathion.

The causes of disease in cultured shrimp are difficult to ascertain but there is evidence that disease is correlated with environmental factors. Crustaceans are particularly sensitive to insecticides due to their close phylogenetic relationship with insects. The objective of this study was to investigate whether there was an increased susceptibility of the shrimp Litopenaeus vannamei to Vibrio parahaemolyticus, when exposed to methyl parathion. The outline of the study was the following: An LC50 96 h was determined to methyl parathion orally offered to juvenile shrimp. Further experiments were carried out in order to determine a concentration that affected the shrimp (verified by measuring the acethylcholinesterase activity) while producing minimal mortalities. This sublethal concentration was used in a susceptibility experiment where methyl parathion was offered to shrimp which were later injected with V. parahaemolyticus in a dose expected to kill less than 15%. Probit analysis estimated a 96 h median lethal concentration (LC50) of 1.56 microg g(-1). Mortality and AChE activity showed a concentration-response relationship in the exposure treatments. The median inhibitory concentration (IC50) determined was 0.029 microg g(-1). These results suggested that a concentration of 0.1 microg g(-1) was appropriate for the bacteria-pesticide interaction test as it was able to elicit 11.1% mortality after 10 days of exposure, while producing an AChE inhibition of 57.12%. Cumulative mortalities were significantly increased (P<0.01) in the treatment that combined exposure to methyl parathion and V. parahaemolyticus (35.19%) in comparison with methyl parathion or V. parahaemolyticus alone (9.26% and 7.41%, respectively).

Acetylcholinesterase↗

Optimal eradication: when to stop looking for an invasive plant.

The notion of being sure that you have completely eradicated an invasive species is fanciful because of imperfect detection and persistent seed banks. Eradication is commonly declared either on an ad hoc basis, on notions of seed bank longevity, or on setting arbitrary thresholds of 1% or 5% confidence that the species is not present. Rather than declaring eradication at some arbitrary level of confidence, we take an economic approach in which we stop looking when the expected costs outweigh the expected benefits. We develop theory that determines the number of years of absent surveys required to minimize the net expected cost. Given detection of a species is imperfect, the optimal stopping time is a trade-off between the cost of continued surveying and the cost of escape and damage if eradication is declared too soon. A simple rule of thumb compares well to the exact optimal solution using stochastic dynamic programming. Application of the approach to the eradication programme of Helenium amarum reveals that the actual stopping time was a precautionary one given the ranges for each parameter.

Conservation of Natural Resources↗