Circulation of Campylobacter spp. in rhesus monkeys (Macaca mulatta) held in captivity: a longitudinal study

Campylobacteriosis is an extremely important zoonosis, circulating freely in the environment. In nonhuman primates kept in open facilities and bred for experimental purposes, the presence of Campylobacter spp. could cause severe damage to the production and interfere with the results of scientific research. In this paper, we assessed the circulation of Campylobacter spp. in a colony of clinically healthy rhesus monkeys (Macaca mulatta) destined to research. The analysis was carried out during seven non-consecutive years. Data showed that despite several changes made in animal management along the studied years in order to control this zoonosis, reduction of bacterial charge did not occur. Significant differences among the age groups and sex were observed. Infants showed higher susceptibility than adult animals. In general males were more infected than females. Modifications adopted in the handling techniques need to be reviewed with the intent of improving the production, reducing bacterial infection of the stock and avoiding undesirable cross reactions in the research carried out with these animals. Therefore, this paper alerts professionals that work directly with captive rhesus monkeys about the risks of Campylobacter spp. infection and possible interference on the experimental procedures.

Swiss adolescents' and adults' perceptions of cannabis use: a qualitative study.

Few studies have attempted to investigate the nature of adolescents' and adults' conceptions and perceptions of cannabis use. Our objectives were to explore adolescent and adult perception of use and misuse of cannabis, and their opinions and beliefs about the current legal context and preventive strategies. We used focus group discussions with four categories of stakeholders: younger (12-15 year old) adolescents, older (16-19 year old) adolescents, parents of teenagers and professionals working with young people. In some areas (legal framework, role of the media, importance of early preventive interventions), we found consensual attitudes and beliefs across the four groups of participants. In all four groups, participants did not have any consensual vision of the risks of cannabis use or the definition of misuse. In the area of the prevention of cannabis use/misuse, while parents focused on the potential role of professionals and the media, thus minimizing their own educational and preventive role, professionals stressed the importance of parental control and education. Within the Swiss context, we conclude there exists an urgent need for information and clarification of the issues linked with cannabis use and misuse directed at parents and professionals.

Analysis of GPCR properties of Frizzled receptors and establishment of the "in vitro" platform for screening of Frizzled agonists/antagonists as potential therapeutic agents

Morphogens of the Wnt protein family are the secreted lipoglycoprotein ligands which initiate several pathways heavily involved in the coordination of various developmental stages of organisms in the majority of animal species. Deregulation of these pathways in the adult leads to formation and sustaining of multiple types of cancer. The latter notion is reinforced by the fact that the very discovery of the first Wnt ligand was due to its role as the causative factor of carcinogenic transformation (Nusse and Varmus, 1982). Nowadays our knowledge on Wnt signaling has "moved with the times" and these pathways were identified to be often crucial for tumor formation, its interactions with the microenvironment, and promotion of the metastases (Huang and Du, 2008; Zerlin et al., 2008; Jessen, 2009). Thus the relevance of the pathway as the target for drug development has further increased in the light of modern paradigms of the complex cancer treatments which target also spreading and growth- promoting factors of tumors by specific and highly efficient substances (Pavet et al., 2010). Presently the field of the Wnt-targeting drug research is almost solely dominated by assays based on transcriptional activation induced by the signaling. This approach resulted in development of a number of promising substances (Lee et al., 2011). Despite its effectiveness, the method nevertheless suffers from several drawbacks. Among the major ones is the fact that this approach is prone to identify compounds targeting rather downstream effectors of the pathway, which are indiscriminately used by all the subtypes of the Wnt signaling. Additionally, proteins which are involved in several signaling cascades and not just the Wnt pathway turn out as targets of the new compounds. These issues increase risks of side effects due to off-target interactions and blockade of the pathway in healthy cells. In the present work we put forward a novel biochemical approach for drug development on the Wnt pathway. It targets Frizzleds (Fzs) - a family of 7-transmbembrane proteins which serve as receptors for Wnt ligands. They offer unique properties for the development of highly specific and effective drugs as they control all branches of the Wnt signaling. Recent advances in the understanding of the roles of heterotrimeric G proteins downstream from Fzs (Katanaev et al., 2005; Liu et al., 2005; Jernigan et al., 2010) suggest application of enzymatic properties of these effectors to monitor the receptor-mediated events. We have applied this knowledge in practice and established a specific and efficient method based on utilization of a novel high-throughput format of the GTP-binding assay to follow the activation of Fzs. This type of assay is a robust and well-established technology for the research and screenings on the GPCRs (Harrison and Traynor, 2003). The conventional method of detection involves the radioactively labeled non-hydrolysable GTP analog [35S]GTPyS. Its application in the large-scale screenings is however problematic which promoted development of the novel non-radioactive GTP analog GTP-Eu. The new molecule employs phenomenon of the time-resolved fluorescence to provide sensitivity comparable to the conventional radioactive substance. Initially GTP-Eu was tested only in one of many possible types of GTP-binding assays (Frang et al., 2003). In the present work we expand these limits by demonstrating the general comparability of the novel label with the radioactive method in various types of assays. We provide a biochemical characterization of GTP-Eu interactions with heterotrimeric and small GTPases and a comparative analysis of the behavior of the new label in the assays involving heterotrimeric G protein effectors. These developments in the GTP-binding assay were then applied to monitor G protein activation by the Fz receptors. The data obtained in mammalian cultured cell lines provides for the first time an unambiguous biochemical proof for direct coupling of Fzs with G proteins. The specificity of this interaction has been confirmed by the experiments with the antagonists of Fz and by the pertussis toxin-mediated deactivation. Additionally we have identified the specificity of Wnt3a towards several members of the Fz family and analyzed the properties of human Fz-1 which was found to be the receptor coupled to the Gi/o family of G proteins. Another process playing significant role in the functioning of every GPCR is endocytosis. This phenomenon can also be employed for drug screenings on GPCRs (Bickle, 2010). In the present work we have demonstrated that Drosophila Fz receptors are involved in an unusual for many GPCRs manifestation of the receptor-mediated internalization. Through combination of biochemical approaches and studies on Drosophila as the model organism we have shown that direct interactions of the Fzs and the α-subunit of the heterotrimeric G protein Go with the small GTPase Rab5 regulate internalization of the receptor in early endosomes. We provide data uncovering the decisive role of this self-promoted endocytosis in formation of a proper signaling output in the canonical as well as planar cell polarity (PCP) pathways regulated by Fz. The results of this work thus establish a platform for the high-throughput screening to identify substances active in the cancer-related Wnt pathways. This methodology has been adjusted and applied to provide the important insights in Fz functioning and will be instrumental for further investigations on the Wnt-mediated pathways.

Swiss adolescents' and adults' perceptions of cannabis use : a qualitative study

Abstract Few studies have attempted to investigate the nature of adolescents' and adults' conceptions and perceptions of cannabis use. Our objectives were to explore adolescent and adult perception of use and misuse of cannabis, and their opinions and beliefs about the current legal context and preventive strategies. We used focus group dis¬cussions with four categories of stakeholders: younger (12-15 year old) adolescents, older (16-19 year old) adolescents, parents of teen¬agers and professionals working with young people. In some areas (legal framework, role of the media, importance of early preventive inter¬ventions), we found consensual attitudes and beliefs across the four groups of participants. In all four groups, participants did not have any consensual vision of the risks of cannabis use or the definition of misuse. In the area of the prevention of cannabis use/misuse, while parents focused on the potential role of professionals and the media, thus minimizing their own educa¬tional and preventive role, professionals stressed the importance of parental control and educa¬tion. Within the Swiss context, we conclude there exists an urgent need for information and clari¬fication of the issues linked with cannabis use and misuse directed at parents and professionals.

Subclinical hypothyroidism and the risk of coronary heart disease and mortality.

CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE: To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS: Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.

Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.

BACKGROUND: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. METHODS: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P < .001, log-rank test). CONCLUSIONS: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value.

Trends in socioeconomic inequalities in preventable mortality in urban areas of 33 Spanish cities, 1996-2007 (MEDEA project).

Abstract Background: Preventable mortality is a good indicator of possible problems to be investigated in the primary prevention chain, making it also a useful tool with which to evaluate health policies particularly public health policies. This study describes inequalities in preventable avoidable mortality in relation to socioeconomic status in small urban areas of thirty three Spanish cities, and analyses their evolution over the course of the periods 1996–2001 and 2002–2007. Methods: We analysed census tracts and all deaths occurring in the population residing in these cities from 1996 to 2007 were taken into account. The causes included in the study were lung cancer, cirrhosis, AIDS/HIV, motor vehicle traffic accidents injuries, suicide and homicide. The census tracts were classified into three groups, according their socioeconomic level. To analyse inequalities in mortality risks between the highest and lowest socioeconomic levels and over different periods, for each city and separating by sex, Poisson regression were used. Results: Preventable avoidable mortality made a significant contribution to general mortality (around 7.5%, higher among men), having decreased over time in men (12.7 in 1996–2001 and 10.9 in 2002–2007), though not so clearly among women (3.3% in 1996–2001 and 2.9% in 2002–2007). It has been observed in men that the risks of death are higher in areas of greater deprivation, and that these excesses have not modified over time. The result in women is different and differences in mortality risks by socioeconomic level could not be established in many cities. Conclusions: Preventable mortality decreased between the 1996–2001 and 2002–2007 periods, more markedly in men than in women. There were socioeconomic inequalities in mortality in most cities analysed, associating a higher risk of death with higher levels of deprivation. Inequalities have remained over the two periods analysed. This study makes it possible to identify those areas where excess preventable mortality was associated with more deprived zones. It is in these deprived zones where actions to reduce and monitor health inequalities should be put into place. Primary healthcare may play an important role in this process. Keywords: Preventable avoidable mortality, Causes of death, Inequalities in health, Small area analysis

Effectiveness of intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy on placental malaria, maternal anaemia and birthweight in areas with high and low malaria transmission intensity in Tanzania.

OBJECTIVE: To assess the effectiveness of IPTp in two areas with different malaria transmission intensities. METHODS: Prospective observational study recruiting pregnant women in two health facilities in areas with high and low malaria transmission intensities. A structured questionnaire was used for interview. Maternal clinic cards and medical logs were assessed to determine drug intake. Placental parasitaemia was screened using both light microscopy and real-time quantitative PCR. RESULTS: Of 350 pregnant women were recruited and screened for placental parasitaemia, 175 from each area. Prevalence of placental parasitaemia was 16.6% (CI 11.4-22.9) in the high transmission area and 2.3% (CI 0.6-5.7) in the low transmission area. Being primigravida and residing in a high transmission area were significant risk factors for placental malaria (OR 2.4; CI 1.1-5.0; P = 0.025) and (OR 9.4; CI 3.2-27.7; P < 0.001), respectively. IPTp was associated with a lower risk of placental malaria (OR 0.3; CI 0.1-1.0; P = 0.044); the effect was more pronounced in the high transmission area (OR 0.2; CI 0.06-0.7; P = 0.015) than in the low transmission area (OR 0.4; CI 0.04-4.5; P = 0.478). IPTp use was not associated with reduced risk of maternal anaemia or low birthweight, regardless of transmission intensity. The number needed to treat (NNT) was four (CI 2-6) women in the high transmission area and 33 (20-50) in the low transmission area to prevent one case of placental malaria. CONCLUSION: IPTp may have an effect on lowering the risk of placental malaria in areas of high transmission, but this effect did not translate into a benefit on risks of maternal anaemia or low birthweight. The NNT needs to be considered, and weighted against that of other protective measures, eventually targeting areas which are above a certain threshold of malaria transmission to maximise the benefit.

Endocarditis prophylaxis revisited: experimental evidence of efficacy and new Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis.

Because of its severity, it is agreed that infectious endocarditis should be prevented whenever possible. Determining adequate prophylactic measures involves establishing (a) the patients at risk, (b) the procedures that might provoke bacteraemia, (c) the most effective prophylactic regimen, and (d) a balance between the risks of side effects from prophylaxis and of developing infectious endocarditis. Patients at risk and procedures inducing bacteraemia have been identified by clinical studies. On the other hand, the efficacy of prophylactic antibiotics has been based on animal studies. Randomised, placebo-controlled studies do not exist in humans because they would require large patient numbers and would raise ethical issues due to the severity of the disease. Case-control studies have indicated that infectious endocarditis prophylaxis is effective, but prevents only a limited number of cases. Animal experiments have revealed several key issues for human application. First, antibiotics do not prevent the early stages of valve colonisation, but rather kill the microorganisms after their attachment to the cardiac lesions. Second, the duration of antibiotic presence in the serum is critical. Under experimental conditions, the drugs must remain above their minimal inhibitory concentration for the organisms for > or = 10 h, to allow time for bacterial clearance from the valves. Third, antibiotic-induced killing is not the only mechanism allowing bacterial clearance. Other factors, such as platelet microbicidal proteins, may act in concert with the drugs to sterilise the lesions. Recommendations for prophylaxis have recently been revised in Europe and the USA. New information has improved the definition of groups at risk. Since most cases of infectious endocarditis are not preceded by medical procedures, primary prevention of infectious endocarditis should target infected foci responsible for spontaneous bacteraemia (e.g. poor dental hygiene). The purpose of this article is to update the existing recommendations in Switzerland, under the perspective of changing epidemiology, the availability of new drugs, and harmonisation with recommendations in other countries.

Overweight And Obesity Repercussion In The Postoperative Of Myocardial Revascularization Surgery

This is a descriptive, retrospective study with cross-sectional quantitative approach, which aimed to relate the body mass index with events in the postoperative period of the myocardial revascularization surgery with use of extracorporeal circulation. The data collection period was between April and June/2012. Patients were divided according to the body mass index and classified as without excess of weight, overweight or obese. The data analysis was based on the descriptive statistics. The patients without excess of weight had more complications, especially those related to the lungs. Among overweight and obese individuals, the cardiovascular complications stood out. The obese subjects had the worse prognostic. Obesity and overweight did not have statistically significant association with a higher frequency of postoperative complications, in spite of the occurrence of cardiovascular complications in this group. The patients without excess of weight had higher risks of developing neurological events.


Causes développementales dans la variabilité de l'efficacité et de la toxicité des antalgiques en pédiatrie [Developmental causes in variability of efficacy and toxicity of analgesics in pediatrics]

The intensity of pain perception and its sensibility to analgesic drugs is highly variable and unpredictable between individuals. Drug disposition varies during development due to the physiological maturation of enzymatic systems and physiological processes responsible for the absorption, distribution, elimination and effect at the site of action. Many of those developmental variables are not yet clearly defined, but their consideration is important for avoiding potential risks of ineffective or toxic treatment. Implications of those developmental changes for day-to-day clinical practice depend on the age of the child, on the type of drug, on the underlying disease and on the potential co-administration of other chemicals.

Insurance and safety after September 11, 2001: Coming to grips with the costs and threats of terrorism

This chapter, originally written as a consequence of the terrorist attacksof September 11, 2001, provides an elementary, everyday introduction tothe concepts of risk and insurance. Conceptually, risk has two dimensions:a potential loss, and the chance of that loss being realized. People can,however, transfer risk to insurance companies against the payment ofso-called premiums. In practice, however, one needs accurate assessmentsof both losses and probabilities to judge whether premiums are appropriate.For many risks, this poses little problem (e.g., life insurance); however,it is difficult to assess risks of many other kinds of events such as actsof terrorism. It is emphasized, that through evolution and learning, peopleare able to handle many of the common risks that they face in life. Butwhen people lack experience (e.g., new technologies, threats of terrorism),risk can only be assessed through imagination. Not surprisingly, insurancecompanies demand high prices when risks are poorly understood. In particular,the cost of insurance against possible acts of terrorism soared afterSeptember 11. How should people approach risk after the events of that day?Clearly, the world needs to protect itself from the acts of terrorists andother disturbed individuals. However, it is also important to address the root causes of such antisocial movements. It is, therefore, suggested thatprograms addressed at combatting ignorance, prejudice, and socialinequalities may be more effective premiums for reducing the risk ofterrosrtism than has been recognized to date.

Sexual behaviour of men that consulted in medical outpatient clinics in Western Switzerland from 2005-2006: risk levels unknown to doctors?

BACKGROUND: To determine male outpatient attenders' sexual behaviours, expectations and experience of talking about their sexuality and sexual health needs with a doctor. METHODS: A survey was conducted among all male patients aged 18-70, recruited from the two main medical outpatient clinics in Lausanne, Switzerland, in 2005-2006. The anonymous self-administered questionnaire included questions on sexual behaviour, HIV/STI information needs, expectations and experiences regarding discussion of sexual matters with a doctor. RESULTS: The response rate was 53.0% (N = 1452). The mean age was 37.7 years. Overall, 13.4% of patients were defined as at STI risk--i.e. having not consistently used condoms with casual partners in the last 6 months, or with a paid partner during the last intercourse--regarding their sexual behaviour in the last year. 90.9% would have liked their physician to ask them questions concerning their sexual life; only 61.4% had ever had such a discussion. The multivariate analysis showed that patients at risk tended to have the following characteristics: recruited from the HIV testing clinic, lived alone, declared no religion, had a low level of education, felt uninformed about HIV/AIDS, were younger, had had concurrent sexual partners in the last 12 months. However they were not more likely to have discussed sexual matters with their doctor than patients not at risk. CONCLUSION: Recording the sexual history and advice on the prevention of the risks of STI should become routine practice for primary health care doctors.

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

BACKGROUND: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. METHODS: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. FINDINGS: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). INTERPRETATION: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Development of a control banding tool for nanomaterials

Control banding (CB) can be a useful tool for managing the potential risks of nanomaterials. The here proposed CB, which should be part of an overall risk control strategy, groups materials by hazard and emission potential. The resulting decision matrix proposes control bands adapted to the risk potential levels and helps define an action plan. If this plan is not practical and financially feasible, a full risk assessment is launched. The hazard banding combines key concepts of nanomaterial toxicology: translocation across biological barriers, fibrous nature, solubility, and reactivity. Already existing classifications specific to the nanomaterial can be used "as is." Otherwise, the toxicity of bulk or analogous substances gives an initial hazard band, which is increased if the substance is not easily soluble or if it has a higher reactivity than the substance. The emission potential bands are defined by the nanomaterials' physical form and process characteristics. Quantities, frequencies, and existing control measures are taken into account during the definition of the action plan. Control strategies range from room ventilation to full containment with expert advice. This CB approach, once validated, can be easily embedded in risk management systems. It allows integrating new toxicity data and needs no exposure data. [Authors]