Predicted no effect concentration derivation as a significant source of variability in environmental hazard assessments of chemicals in aquatic systems: an international analysis.

Environmental hazard assessments for chemicals are carried out to define an environmentally "safe" level at which, theoretically, the chemical will not negatively affect any exposed biota. Despite this common goal, the methodologies in use are very diverse across different countries and jurisdictions. This becomes particularly obvious when international scientists work together on documents with global scope, e.g., in the World Health Organization (WHO) International Program on Chemical Safety. In this article, we present a study that describes the extent of such variability and analyze the reasons that lead to different outcomes in deriving a "safe level" (termed the predicted no effect concentration [PNEC] throughout this article). For this purpose, we chose 5 chemicals to represent well-known substances for which sufficient high-quality aquatic effects data were available: ethylene glycol, trichloroethylene, nonylphenol, hexachlorobenzene, and copper (Cu). From these data, 2 data sets for each chemical were compiled: the full data set, that contained all information from selected peer-review sources, and the base data set, a subsample of the full set simulating limited data. Scientists from the European Union (EU), United States, Canada, Japan, and Australia independently carried out hazard assessments for each of these chemicals using the same data sets. Their reasoning for key study selection, use of assessment factors, or use of probabilistic methods was comprehensively documented. The observed variation in the PNECs for all chemicals was up to 3 orders of magnitude, and this was not simply due to obvious factors such as the size of the data set or the methodology used. Rather, this was due to individual decisions of the assessors within the scope of the methodology used, especially key study selection, acute versus chronic definitions, and size of assessment factors. Awareness of these factors, together with transparency of the decision-making process, would be necessary to minimize confusion and uncertainty related to different hazard assessment outcomes, particularly in international documents. The development of a "guideline on transparency in decision-making" ensuring the decision-making process is science-based, understandable, and transparent, may therefore be a promising way forward.

Archetypes of famine and response.

Famines have long been characterised by rapidly shifting dynamics: sudden price spirals, sharp increases in mortality, the media frenzy that often accompanies such spikes, the swift scaling up of aid flows, and a subsequent decline in interest. In arguing that these aspects of famine have been largely ignored in recent years due to attention to the famine process', this paper attempts to make these dynamics more explicit by applying systems thinking. It uses standard archetypes of systems thinking to explain six situations--watch, price spiral, aid magnet, media frenzy, overshoot, and peaks--that are present in many famine contexts. It illustrates their application with examples from crises in Ethiopia, Malawi, Niger, and Sudan. The paper contends that the systems approach offers a tool for analysing the larger patterns in famines and for pinpointing the most appropriate responses to them, based on an awareness of the dynamics of the crises.

Protection of the environment from ionising radiation in a regulatory context (protect): proposed numerical benchmark values.

Criteria are needed to be able to judge the level of risk associated with dose rates estimated for non-human biota. In this paper, European guidance on the derivation of predicted no-effect chemical concentrations has been applied to appropriate radiation sensitivity data. A species sensitivity distribution fitted to the data for all species resulted in a generic predicted no-effect dose rate of 10 microGy h(-1).Currently, data are inadequate to derive screening values for separate organism groups. A second, higher, benchmark could aid in decision making by putting results into context on the scale of no effect to a risk of 'serious' effect. The need for, meaning and use of such a value needs to be debated by the wider community. This paper explores potential approaches of deriving scientific input to this debate. The concepts proposed in this paper are broadly consistent with the framework for human protection.

Famine intensity and magnitude scales: a proposal for an instrumental definition of famine.

Ambiguities in current usage of the term "famine" have had tragic implications for response and accountability in a number of recent food crises. This paper proposes a new approach to defining famine based on the use of intensity and magnitude scales, where "intensity" refers to the severity of the crisis at a given location and point in time, while "magnitude" describes the aggregate impact of a crisis. The scales perform three operations on "famine": first, moving from a binary conception of "famine/no famine" to a graduated, multi-level definition; second, disaggregating the dimensions of intensity and magnitude; and third, assigning harmonised "objective" criteria in place of subjective, case-by-case judgements. If adopted, the famine scales should contribute to more effective and proportionate responses, as well as greater accountability in future food crises.

Clinical and mycological responses to fluconazole and fluconazole MIC in oropharyngeal candidiasis in HIV-infected patients.

INTRODUCTION: OPC is a common opportunistic infection in HIV-infected patients. Although some patients are asymptomatic, progression of the disease may occur leading to esophageal candidiasis. Fluconazole resistant candidiasis has been reported in several international studies. OBJECTIVES: This study aimed to test the MICs (minimal inhibitory concentrations) to fluconazole of Candida species isolated from mouthwash specimens of 54 HIV positive patients with oral candidiasis. Clinical and mycological responses to fluconazole were also assessed in 16 patients. MATERIAL AND METHOD: This was a prospective study. Mouthwash specimens were cultured on sabouraud dextrose agar twice. Candida species identification was performed and MICs for fluconazole were obtained using NCCLS guidelines. Clinical and mycological responses were assessed on day 14 and 42 in 16 patients who received a 14-day course of fluconazole. RESULTS: 48/54 patients (88.89%) were found to carry pure C. albicans. The other 6 patients (11.11%) had mixed Candida species on cultures. Among these 6 patients, 5 patients had mixed C. albicans and C. glabrata, and 1 patient had C. albicans and C. krusei. Fluconazole MICs of C. albicans, C. glabrata, and C. krusei ranged from 0.125-32 (median=0.250), 4-64 (median=2), and 8 g/L respectively. This study showed that the MICs to fluconazole of oropharyngeal Candida was a good predictor of the therapeutic responses.

Development and evaluation of rapid urinary antigen detection tests for diagnosis of penicilliosis marneffei.

Penicilliosis, caused by the dimorphic fungus Penicillium marneffei, is an important opportunistic systemic fungal infection affecting immunocompromised individuals living in areas where penicilliosis is endemic. We have demonstrated previously that a urinary enzyme-linked immunosorbent assay (ELISA) with purified rabbit polyclonal antibody against killed whole-fission-form arthroconidia of P. marneffei was specific and highly sensitive for the diagnosis of penicilliosis. In this study, a dot blot ELISA and a latex agglutination (LA) test were developed with the same polyclonal antibody and compared with the ELISA for the detection of P. marneffei urinary antigen. Urine specimens from 37 patients with culture-proven penicilliosis and 300 controls (52 healthy subjects and 248 hospitalized patients without penicilliosis) were tested. Antigen was detected in urine from all 37 (100%) penicilliosis patients by the LA test, 35 (94.6%) penicilliosis patients by the dot blot ELISA, and 36 (97.3%) penicilliosis patients by the ELISA. False-positive results were found by the three assays for 2 (0.7%), 8 (2.7%), and 6 (2%) of 300 controls, respectively. The overall sensitivities of the diagnostic tests were as follows: dot blot ELISA, 94.6%; ELISA, 97.3%; and LA test, 100% (specificities, 97.3, 98, and 99.3%, respectively). The LA test is simple, robust, rapid, and convenient and should prove to be an important addition to the existing diagnostic tests for penicilliosis.