Nanomaterials in the aquatic environment: A European Union-United States perspective on the status of ecotoxicity testing, research priorities, and challenges ahead

The US-EU Community of Research (CoR) was established in 2012 to provide a platform for scientists to develop a ‘shared repertoire of protocols and methods to overcome nanotechnology environmental health and safety (nanoEHS) research gaps and barriers’ (www.us-eu.org/). Based on work within the Ecotoxicology CoR (2012–2015) we provide here an overview of the state-of-the-art of nanomaterials (NMs) in the aquatic environment by addressing different research questions with a focus on ecotoxicological test systems and the challenges faced when assessing nanomaterial (NM) hazards (e.g., uptake routes, bioaccumulation, toxicity, test protocols and model organisms). Our recommendation is to place particular importance on studying the ecological effects of aged/weathered NMs, as-manufactured NMs, as well as NMs released from consumer products in addressing the following overarching research topics: i) NM characterization and quantification in environmental and biological matrices, ii) NM transformation in the environment and consequences for bioavailability and toxicity, iii) alternative methods to assess exposure, iv) influence of exposure scenarios on bioavailability and toxicity, v) development of more environmentally realistic bioassays and vi) uptake, internal distribution, and depuration of NMs. Research addressing these key topics will reduce uncertainty in ecological risk assessment and support the sustainable development of nanotechnology

Capacitated Center Problems with Two-Sided Bounds and Outliers

In recent years, the capacitated center problems have attracted a lot of research interest. Given a set of vertices $V$, we want to find a subset of vertices $S$, called centers, such that the maximum cluster radius is minimized. Moreover, each center in $S$ should satisfy some capacity constraint, which could be an upper or lower bound on the number of vertices it can serve. Capacitated $k$-center problems with one-sided bounds (upper or lower) have been well studied in previous work, and a constant factor approximation was obtained. We are the first to study the capacitated center problem with both capacity lower and upper bounds (with or without outliers). We assume each vertex has a uniform lower bound and a non-uniform upper bound. For the case of opening exactly $k$ centers, we note that a generalization of a recent LP approach can achieve constant factor approximation algorithms for our problems. Our main contribution is a simple combinatorial algorithm for the case where there is no cardinality constraint on the number of open centers. Our combinatorial algorithm is simpler and achieves better constant approximation factor compared to the LP approach

Concern-driven integrated approaches to nanomaterial testing and assessment - report of the NanoSafety Cluster Working Group

Abstract Bringing together topic-related European Union (EU)-funded projects, the so-called "NanoSafety Cluster" aims at identifying key areas for further research on risk assessment procedures for nanomaterials (NM). The outcome of NanoSafety Cluster Working Group 10, this commentary presents a vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM. Such approaches should start out by determining concerns, i.e., specific information needs for a given NM based on realistic exposure scenarios. Recognised concerns can be addressed in a set of tiers using standardised protocols for NM preparation and testing. Tier 1 includes determining physico-chemical properties, non-testing (e.g., structure-activity relationships) and evaluating existing data. In tier 2, a limited set of in vitro and in vivo tests are performed that can either indicate that the risk of the specific concern is sufficiently known or indicate the need for further testing, including details for such testing. Ecotoxicological testing begins with representative test organisms followed by complex test systems. After each tier, it is evaluated whether the information gained permits assessing the safety of the NM so that further testing can be waived. By effectively exploiting all available information, IATA allow accelerating the risk assessment process and reducing testing costs and animal use (in line with the 3Rs principle implemented in EU Directive 2010/63/EU). Combining material properties, exposure, biokinetics and hazard data, information gained with IATA can be used to recognise groups of NM based upon similar modes of action. Grouping of substances in return should form integral part of the IATA themselves

Evaluation of the implementation of a clinical pharmacy service on an acute internal medicine ward in Italy

© 2018 The Author(s). Published by Springer Nature. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background: Successful implementation of clinical pharmacy services is associated with improvement of appropriateness of prescribing. Both high clinical significance of pharmacist interventions and their high acceptance rate mean that potential harm to patients could be avoided. Evidence shows that low acceptance rate of pharmacist interventions can be associated with lack of communication between pharmacists and the rest of the healthcare team. The objective of this study was to evaluate the effect of a structured communication strategy on acceptance rate of interventions made by a clinical pharmacist implementing a ward-based clinical pharmacy service targeting elderly patients at high risk of drug-related problems. Characteristics of interventions made to improve appropriateness of prescribing, their clinical significance and intervention acceptance rate by doctors were recorded. Methods: A clinical pharmacy intervention study was conducted between September 2013 and December 2013 in an internal medicine ward of a teaching hospital. A trained clinical pharmacist provided pharmaceutical care to 94 patients aged over 70 years. The clinical pharmacist used the following communication and marketing tools to implement the service described: Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis; Specific, Measurable, Achievable, Realistic and Timely (SMART) goals; Awareness, Interest, Desire, Action (AIDA) model. Results: A total of 740 interventions were made by the clinical pharmacist. The most common drug classes involved in interventions were: antibacterials for systemic use (11.1%) and anti-parkinson drugs (10.8%). The main drug-related problem categories triggering interventions were: no specific problem (15.9%) and prescription writing error (12.0%). A total of 93.2% of interventions were fully accepted by physicians. After assessment by an external panel 63.2% of interventions (96 interventions/ per month) were considered of moderate clinical significance and 23.4% (36 interventions/ per month) of major clinical significance. The most frequent interventions were to educate a healthcare professional (20.4%) and change dose (16.1%). Conclusions: To our knowledge this is the first study evaluating the effect of a structured communication strategy on acceptance rate of pharmacist interventions. Pharmaceutical care delivered by the clinical pharmacist is likely to have had beneficial outcomes. Clinical pharmacy services like the one described should be implemented widely to increase patient safety.Peer reviewedFinal Published versio

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Yellow fever control in Cameroon: Where are we now and where are we going?

<p>Abstract</p> <p>Background</p> <p>Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan.</p> <p>Methods</p> <p>In January 2003, case-based surveillance of suspected yellow fever cases was instituted in the whole country. A year later, yellow fever immunisation at nine months of age (the same age as routine measles immunisation) was introduced. Supplementary immunisation activities (SIAs), both preventive and in response to outbreaks, also formed an integral part of the yellow fever control plan. Each level of the national health system makes a synthesis of its activities and sends this to the next higher level at defined regular intervals; monthly for routine data and daily for SIAs.</p> <p>Results</p> <p>From 2004 to 2006 the national routine yellow fever vaccination coverage rose from 58.7% to 72.2%. In addition, the country achieved parity between yellow fever and measles vaccination coverage in 2005 and has since maintained this performance level. The number of suspected yellow fever cases in the country increased from 156 in 2003 to 859 in 2006, and the proportion of districts that reported at least one suspected yellow fever case per year increased from 31.4% to 68.2%, respectively. Blood specimens were collected from all suspected cases (within 14 days of onset of symptoms) and tested at a central laboratory for yellow fever IgM antibodies; leading to confirmation of yellow fever outbreaks in the health districts of Bafia, Méri and Ntui in 2003, Ngaoundéré Rural in 2004, Yoko in 2005 and Messamena in 2006. Owing to constraints in rapidly mobilising the necessary resources, reactive SIAs were only conducted in Bafia and Méri several months after confirmation of the outbreak. In both districts, a total of 60,083 people (representing 88.2% of the 68,103 targeted) were vaccinated. Owing to the same constraints, SIAs were not conducted promptly in response to the outbreaks in Ntui, Ngaoundéré Rural, Yoko and Messamena. However, these four and two other health districts at high risk of yellow fever outbreaks (i.e. Maroua Urban and Ngaoundéré Urban) conducted preventive SIAs in November 2006, vaccinating a total of 752,195 people (92.8% of target population). In both the reactive and preventive SIAs, the mean wastage rates for vaccines and injection material were less than 5% and there was no report of a serious adverse event following immunisation.</p> <p>Conclusion</p> <p>Amidst other competing health priorities, over the past four years Cameroon has successfully planned and implemented evidence-based strategies for preventing yellow fever outbreaks and for detecting and responding to the outbreaks when they occur. In order to sustain these initial successes, the country will have to attain and sustain high routine vaccination coverage in each successive birth cohort in every district. This would require fostering and sustaining high-level political commitment, improving the planning and monitoring of immunisation services at all levels, adequate community mobilisation, and efficient coordination of current and future immunisation partners.</p