Changes in body composition during and after adjuvant or neo-adjuvant chemotherapy in women with breast cancer stage I-IIIB compared with changes over a similar timeframe in women without cancer.

PURPOSE: Body weight and body composition may change during and after adjuvant or neo-adjuvant chemotherapy for breast cancer. However, most studies did not include a comparison group of women without cancer, thus could not assess whether observed changes differed from age-related fluctuations in body weight and body composition over time. We assessed changes in body composition during and after chemotherapy in breast cancer patients compared with age-matched women not diagnosed with cancer. METHODS: We recruited 181 patients with stage I-IIIb breast cancer and 180 women without cancer. In patients, we assessed body composition using a dual-energy X-ray scan before start of chemotherapy (T1), shortly after chemotherapy (T2), and 6 months after chemotherapy (T3); for the comparison group, the corresponding time points were recruitment (T1) and 6 (T2) and 12 (T3) months. RESULTS: Fifteen percent of patients and 8% of the comparison group gained at least 5% in body weight between T1 and T3. Among the comparison group, no statistically significant changes in body weight, or body composition were observed over time. Body weight of patients significantly increased from baseline (72.1 kg ± 0.4 kg) to T2 (73.3 kg ± 0.4 kg), but decreased to 73.0 kg ± 0.4 kg after chemotherapy (T3). Lean mass of patients significantly increased from 43.1 kg ± 0.5 kg at baseline to 44.0 kg ± 0.5 kg at T2, but returned to 43.1 kg ± 0.5 kg at T3. There were no differential changes in fat mass over time between patients and the comparison group. CONCLUSIONS: Changes in body weight and body composition during and after chemotherapy for early stage breast cancer were modest, and did not differ substantially from changes in body weight and body composition among women without cancer.

[Postoperative remote monitoring]. / Postoperatives "remote monitoring".

During the course of surgical interventions, complications mostly occur in the postoperative period. Slight clinical indications can be observed, which precede a significant deterioration of the patient's condition. On the general ward vital parameters, such as heart and breathing frequencies are measured every 4-8 h. Even if the monitoring of critically ill patients is increased to every 2 h and the measurement of vital functions takes 10 min, the patient is only monitored for 120 min in a 24 h period and remains postoperatively on the general ward without monitoring for 22 out of 24 h. New wireless monitoring systems are available to continuously register some vital functions with the aid of wearable sensors. These systems can alert and alarm ward personnel if the patient's condition deteriorates. Although the optimal monitoring system does not yet exist and implementation of these new wireless monitoring systems might involve some risks, these new methods offer a great opportunity to optimize surveillance of postoperative patients on the general ward.

The regulatory challenge of chemicals in the environment: Toxicity testing, risk assessment, and decision-making models.

Environmental assessment for chemicals relies on models of fate, exposure, toxicity, risk, and impacts. Together, these models should provide scientific support for regulatory risk management decision-making, assuming that progress through the data-information-knowledge-wisdom (DIKW) hierarchy is both appropriate and sufficient. Improving existing regulatory processes necessitates continuing enhancement of interpretation and evaluation of key data for use in decision-making schemes, including ecotoxicity testing data, physical-chemical properties, and environmental fate processes. Yet, as environmental objectives also increase in scope and sophistication to encompass a safe chemical economy, testing, risk assessment, and decision-making are subject to additional complexity due to the ongoing interaction between science and policy models. Problems associated with existing design and implementation choices in science and policy have both limited needed development beyond chemo-centric environmental risk assessment modeling and constrained needed improvements in environmental decision-making. Without a thorough understanding of either the scientific foundations or the disparate evaluation processes for validation, quality, and relevance, this results in complex technical and philosophical problems that increase costs and decrease productivity. Both over- and under-management of chemicals are consequences of failure to validate key model assumptions, unjustified standardized views on data selection, and inordinate reification (i.e., abstract concepts are wrongly treated as facts).

Method selection for sustainability assessments: The case of recovery of resources from waste water.

Sustainability assessments provide scientific support in decision procedures towards sustainable solutions. However, in order to contribute in identifying and choosing sustainable solutions, the sustainability assessment has to fit the decision context. Two complicating factors exist. First, different stakeholders tend to have different views on what a sustainability assessment should encompass. Second, a plethora of sustainability assessment methods exist, due to the multi-dimensional characteristic of the concept. Different methods provide other representations of sustainability. Based on a literature review, we present a protocol to facilitate method selection together with stakeholders. The protocol guides the exploration of i) the decision context, ii) the different views of stakeholders and iii) the selection of pertinent assessment methods. In addition, we present an online tool for method selection. This tool identifies assessment methods that meet the specifications obtained with the protocol, and currently contains characteristics of 30 sustainability assessment methods. The utility of the protocol and the tool are tested in a case study on the recovery of resources from domestic waste water. In several iterations, a combination of methods was selected, followed by execution of the selected sustainability assessment methods. The assessment results can be used in the first phase of the decision procedure that leads to a strategic choice for sustainable resource recovery from waste water in the Netherlands.

Regional ecotoxicological hazards associated with anthropogenic enrichment of heavy metals.

Regional geochemical data of heavy metals are commonly used for environmental risk assessment and management. Often these data are based on so-called total concentrations, whereas the exposure to the mobile or reactive fraction of these elements finally determines whether the exposed ecosystem is at risk and to which extent. The objective of our research was to develop a wider applicable method for quantitative hazard assessment of soil metal contamination attributable to the activity of man, based on and illustrated with data from the Netherlands. Since chemical availability (0.43 M HNO3 extractable concentrations) of Cd, Cu, Pb and Zn appeared strongly related to the estimated anthropogenic enrichment, we used these concentrations to assess the hazard of human-induced enrichment of these metals. We expressed the enrichment hazard using the toxic pressure concept, which estimates the fraction of biological species (varying between 0 and 1) potentially affected due to the level of exposure to single metals or their local mixtures. This is done using logistic (enrichment) concentration/response models parameterized with ecotoxicological effect data from toxicity tests and mixture models. Hazards varied from very low toxic pressures (lower than 0.01) to (most often) toxic pressure less than 0.05, whereby the latter relates to the so-called 95%-protection criterion used in some soil protection legislations. In rare cases, the toxic pressure exceeded the value of 0.05, to an upper limit of 0.054 for Cd. The rank order of metal enrichment hazards suggests that Cd enrichment induces the largest hazard increase. There are limited (rank order) differences in enrichment hazards between soil types. Comparing the judgement of soils based on soil screening levels and based on toxic pressure of anthropogenic Cd, Cu, Pb and Zn enrichments, the soil screening values appear to more conservative. This exemplifies the use of soil screening values as a method to note regulatory concern, but not always indicating an actual hazard or risk. When screening values are exceeded, refined hazard insights can be obtained, as illustrated in this paper. This provides a more refined insight in the ecotoxic implications of human-induced metal enrichments in soils, as refined basis for risk management decisions.

Remote wireless vital signs monitoring on the ward for early detection of deteriorating patients: A case series.

INTRODUCTION: Remote wireless monitoring is a new technology that allows the continuous recording of ward patients' vital signs, supporting nurses by measuring vital signs frequently and accurately. A case series is presented to illustrate how these systems might contribute to improved patient surveillance. METHODS AND RESULTS: Five hospitals in three European countries installed a remote wireless vital signs monitoring system on medical or surgical wards. Heart rate, respiratory rate and temperature were measured by the system every 2 min. Four cases of (paroxysmal) atrial fibrillation are presented, two cases of sepsis and one case each of pyrexia, cardiogenic pulmonary edema and pulmonary embolisms. All cases show that the remote monitoring system revealed the first signs of ventilatory and circulatory deterioration before a change in the trends of the respective values became obvious by manual vital signs measurement. DISCUSSION: This case series illustrates that a wireless remote vital signs monitoring system on medical and surgical wards has the potential to reduce time to detect deteriorating patients.

Impact of metal pools and soil properties on metal accumulation in Folsomia candida (Collembola).

Soil-dwelling organisms are exposed to metals in different ways. Evidence exists for predominant pore water uptake of metals by soft-bodied oligochaete species. In the present research, uptake kinetics of metals and the metalloid As by the semi-soft-bodied springtail Folsomia candida were studied, for which uptake via the pore water is less obvious. Springtails were exposed in 16 field soils and in metal-spiked artificial Organization for Economic Cooperation and Development (Paris, France) soil (OECD soil). Subsequently, accumulation parameters were statistically related to soil metal pools and soil properties. In Cd-spiked OECD soil, internal Cd levels were linearly related to external Cd concentrations, whereas the springtails maintained fixed internal levels of Cu and Zn regardless of spiked concentrations. In the field soils, all body concentrations of the elements As, Cr, and Ni were below detection limit. The essential metals Cu and Zn were presumably regulated, and no influence of soil characteristics could be demonstrated. For Cd and Pb, accumulation patterns were correlated mainly to solid-phase soil characteristics. The presence of these explanatory variables in the multiple correlations suggests that an uptake mechanism that is solely determined by pore water concentrations should not be taken as a universally applicable principle in risk assessments of metals for soil invertebrates. Cadmium in OECD soils was more available for uptake than in the field soils. The difference remained when extractability was taken into account. The results suggest that experiments in OECD soil cannot be used directly in risk assessment for nonessential metals (at least for F. candida), although a reduction of uncertainties in metal risk assessment can be reached by consistent use of body residues rather than external concentrations.

State of the art of contaminated site management in The Netherlands: policy framework and risk assessment tools.

This paper presents the policy framework of contaminated site management in The Netherlands and the corresponding risk assessment tools, including innovations that have taken place since an overview was published in 1999. According to the Dutch Soil Protection Act assessment framework, soils are subdivided into three quality classes: clean, slightly contaminated and seriously contaminated. Historic cases of slightly contaminated soils are managed in a sustainable way by re-use of soil material within a region on the basis of risk-based and land use specific Maximal Values and Background Values. In case of serious soil contamination remediation is in principle necessary and the urgency of remediation has to be determined based on site-specific risks for human health, the ecosystem and groundwater. The major risk assessment tools in The Netherlands are the CSOIL exposure model (human health risks and food safety), Species Sensitivity Distributions and the Soil Quality Triad (ecological risks), along with a procedure to assess the risks due to contaminant spreading to and in the groundwater. Following the principle 'simple if possible, complex when necessary', tiered approaches are used. Contaminated site practices are supported with web-based decision support systems.

Adaptation to soil pollution by cadmium excretion in natural populations of Orchesella cincta (L.) (Collembola).

Population differentiation in Orchesella cincta (L.) (Collembola) populations, from various heavy metal contaminated sites, was studied by comparing cadmium excretion efficiency in first generation (F1) laboratory individuals. Animals from sites with high metal concentrations in the litter and with a long history of contamination showed significantly higher excretion efficiencies than animals from low pollution, or reference sites. Differences found in the F1 laboratory animals suggest evidence for genetic differences between the populations. Beneficial and detrimental effects of cadmium excretion were studied in relation to body growth and cadmium concentrations. In chronically exposed animals from an unpolluted site, no physiological acclimation was observed. Excretion efficiency was negatively correlated with body concentrations of cadmium. No detrimental effects were found. Whole-body equilibrium concentrations of cadmium and lead were similar in F1 animals from the reference site and polluted sites. Significant differences in excretion efficiencies imply that the distribution of toxic metals over body compartments differs, tolerant populations having a higher proportion deposited in the gut. Body concentrations of zinc were consistently higher in animals from the polluted site, during both cadmium and zinc exposure. No detrimental effects of increased cadmium excretion on body concentrations of zinc were observed. Population comparisons of cadmium excretion efficiency data and growth reduction in F1 laboratory animals showed that both parameters were inversely related. Cadmium and lead contamination were not the sole factors determining tolerance differentiation.

A conceptual framework for implementation of bioavailability of metals for environmental management purposes.

Although bioavailability is an important issue, the scientific basis for its adequate use in the assessment of ecological risks is weak. What is often ignored is that bioavailability should be handled as a dynamic process that comprises two distinct phases: a physicochemically driven desorption process (also referred to as "environmental availability") and a physiologically driven uptake process (also referred to as "environmental bioavailability"). Since the internal concentration of the organism (also referred to as "toxicological bioavailability") is related with organ-effect levels, it is the latter that is determinant for the actual bioavailability. On the basis of contemporary ideas on equilibrium partitioning both within soils and between soils and organisms combined with a detailed literature review, in this contribution a framework is presented aimed at providing a guidance to necessary components of risk assessment procedures that take bioavailability into account. The framework provides suggestions with regard to the design and scope of studies to be carried out. It is based on knowledge on physico-chemical metal partitioning, in combination with models and concepts applied to analyse toxico-kinetics in exposed organisms. The conceptual dynamic framework boils down to a description of the system in the form of equilibria. It is assumed that each biotic species can be considered as one of the soil phases next to the particulate phase and the liquid phase. Each phase has a characteristic set of exposure routes. Equilibration processes are assumed to take place between all phases present. Essential is that the plan should result in validated procedures that, because they will explicitly address the issue of availability, will be predictive of effects in systems that have not been biologically tested.

ADHD: sibling interaction or dominance: an evaluation of statistical power.

Sibling interaction effects are suggested by a difference in phenotypic variance between monozygotic (MZ) twins and dizygotic (DZ) twins, and a pattern of twin correlations that is inconsistent with additive genetic influences. Notably, negative sibling interaction will result in MZ correlations which are more than twice as high as DZ correlations, a pattern also seen in the presence of genetic dominance. Negative sibling interaction effects have been reported in most genetic studies on Attention Deficit Hyperactivity Disorder (ADHD) and related phenotypes, while the presence of genetic dominance is not always considered in these studies. In the present paper the statistical power to detect both negative sibling interaction effects and genetic dominance is explored. Power calculations are presented for univariate models including sources of variation due to additive genetic influences, unique environmental influences, dominant genetic influences and a negative sibling interaction (i.e., contrast effect) between phenotypes of twins. Parameter values for heritability and contrast effects are chosen in accordance with published behavior genetic studies on ADHD and associated phenotypes. Results show that when both genetic dominance and contrast effects are truly present and using a classical twin design, genetic dominance is more likely to go undetected than the contrast effect. Failure to detect the presence of genetic dominance consequently gives rise to slightly biased estimates of additive genetic effects, unique environmental effects, and the contrast effect. Contrast effects are more easily detected in the absence of genetic dominance. If the significance of the contrast effect is evaluated while also including genetic dominance, small contrast effects are likely to go undetected, resulting in a relatively large bias in estimates of the other parameters. Alternative genetic designs, such as adding pairs of unrelated siblings reared together to a classical twin design, or adding non-twin siblings to twin pairs, greatly enhances the statistical power to detect contrast effects as well as the power to distinguish between genetic dominance and contrast effects.

Single and joint toxic effects of copper and zinc on reproduction of Enchytraeus crypticus in relation to sorption of metals in soils.

Joint toxic effects of copper and zinc were studied in the terrestrial worm Enchytraeus crypticus (Westheide and Graefe) (Oligochaeta, Annelida). Animals were exposed in OECD artificial soil. Sublethal toxicity was judged by effects on reproduction. Metals were applied singly or in binary mixtures. Observed effects were compared with effects expected from simple similar action (concentration addition), by recalculation of metal concentrations in toxic units. Exposure of the worms was quantified with body concentrations and with external concentrations (total, extractable, soluble). The observed joint effect was similar to concentration additive when judged by external concentrations and less than concentration additive for body concentrations. This difference is attributable to interactions among metals during sorption to soil and during uptake. Copper reduced the sorption of zinc to soil, but copper sorption was inert for zinc addition. Zinc uptake from the soil solution was stimulated by copper, but copper uptake was not stimulated by zinc. Joint effects of toxicants to soil biota are partly determined by interactions outside the organism, as a result of dissimilarity between total and bioavailable concentrations. The design of joint toxicity studies in terrestrial systems is discussed with special reference to metal sorption in soils, experimental methodology, and laboratory practice. The joint toxic effect of copper and zinc for E. crypticus was of similar magnitude as found in studies with aquatic species exposed to metal mixtures.

Quantification of metal bioavailability for lettuce (Lactuca sativa L.) in field soils.

Understanding metal bioavailability of plants in soils requires, apart from physiological processes and symbiosis with arbuscular mycorrhizal fungi, the consideration of the chemical availability in the soil solution (the intensity of the toxic exposure) and the soil's capacity to supply the metal (capacity). In this contribution we report on the time-dependent accumulation of As, Cd, Cr, Cu, Ni, Pb, and Zn in lettuce (Lactuca sativa L.). Bioassays with 17 Dutch field soils and two artificially metal-contaminated soils were carried out. Phytotoxicity was observed in soils with pH (pore water) <4.8. Metal uptake is shown to be both metal- and soil-dependent and strongly depends on the amount of water the plant transpired and the available concentration in the water. No net accumulation of As, Pb, Ni, and especially Cr was observed in most soils tested. The latter observation is in agreement with findings of Zayed et al. (Planta, 1998 206:293-299), who reported that translocation of Cr from roots to shoots is extremely limited. Internal Cd levels in the plants varied greatly among soils, whereas plant tissue concentrations of Zn and especially Cu appear to be regulated at more or less fixed levels. The 0.01 M CaCl(2)-extractable metal pool provides the best descriptor for the capacity of the soil to supply Cd and Zn. This enabled the development of models that are suited to predict Zn and Cd uptake by lettuce in both field soils (weathered soils) and soils to which metal salts were added, which is common practice in toxicity testing of chemicals. It is concluded that of all metals included in this study, Cd is the metal of most concern due to bioaccumulation through the soil-plant-animal food chain as Cd is the only metal that might pose human or animal health risks at plant tissue concentrations that are not directly phytotoxic. Finally, application of the models for risk assessment purposes is discussed.

Relating environmental availability to bioavailability: soil-type-dependent metal accumulation in the oligochaete Eisenia andrei.

Body residues are often better estimates of the amount of a chemical at the sites of toxic action in an organism than ambient soil concentrations, because bioavailability differences among soils are explicitly taken into account in considerations of body residues. Often, however, insufficient attention is paid to the rate and extent at which tissue concentrations respond to soil concentrations and soil characteristics. In this contribution the impact of soil characteristics on the environmental bioavailability of heavy metals for the oligochaete worm Eisenia andrei is reported. Uptake of As, Cd, Cr, Cu, Ni, Pb, and Zn in 20 Dutch field soils and in OECD artificial soil was quantified as a function of time. Internal metal concentrations varied less than the corresponding external levels. Metal uptake and elimination were both metal- and species-dependent. Worms typically attained steady-state concentrations rapidly for Cr, Cu, Ni, and Zn. Internal concentrations similar to those in the cultivation medium, linearly increasing body concentrations, or steady-state internal concentrations well above those in the cultivation medium were found for As, Cd, and Pb. Multivariate expressions were derived to describe uptake rate constants, steady-state concentrations, and bioaccumulation factors as a function of soil characteristics. Soil acidity is the most important solid-phase characteristic modulating the availability of As, Cd, and Pb. Although additional semimechanistic calculations yielded evidence of pore-water-related uptake of Cd and Pb modulated by competition between H(+) and metal ions at the active sites of the membranes, the findings for Cr, Cu, Ni, and Zn point to additional influences, among which is probably regulation.

Effects of zinc contamination on a natural nematode community in outdoor soil mesocosms.

The effect of zinc on the indigenous nematode fauna of a sandy soil was determined in an experimentally contaminated outdoor field plot. The aims of the study were to describe and quantify the changes in density of separate nematode taxa and total nematodes, and the changes in the number of taxa, species diversity, community maturation, and species composition in response to zinc exposure with time, and to compare the observed responses with benchmark concentrations for soil as derived from the species sensitivity distribution (SSD) for zinc toxicity. Speciation of zinc in pore water was considered and CaCl2-exchangeable zinc concentrations were used as a measure of the bioavailable zinc fraction. After contamination, a reduction of total zinc and an increase of labile sorbed zinc over time occurred, concurrent with various changes in soil and biological characteristics. Data analyses on the nematode species revealed different sensitivity levels for several population and community endpoints to zinc exposure. Based on no observed effect concentration (NOEC) values, the most sensitive community-level response was obtained with principal response curve (PRC) analysis, which incorporates all density data in a single analysis. The PRC-based community NOECs were 56, 100, and 100 mg total Zn/kg dry soil after 3, 10, and 22 months of exposure, respectively. Based on 0.01 M CaCl2-exchangeable zinc, the community response appeared to increase, as NOECs were 4.9, 4.4, and 0.67 mg exchangeable Zn/kg dry weight. Total density was least sensitive, followed by diversity of taxa and the Shannon-Wiener index. NOECs for separate species covered a broad range from sensitive to tolerant species. This range of sensitivities was similar to the one found for other species groups tested in the field plot soil. A comparison was made between benchmark concentrations HC5 and HC50 derived from the general SSD of soil organisms for zinc and the nematode response data. These comparisons roughly confirm the predictions of the SSD model, that is, the community NOEC is in agreement with the benchmark that should protect the soil ecosystem's integrity, and large adverse effects were found at the benchmark derived for setting remediation urgency.

Prediction of metal bioavailability in Dutch field soils for the oligochaete Enchytraeus crypticus.

Current risk assessment procedures ignore that variation in soil properties results in substantial differences for uptake and effects in organisms in different soils. In this contribution is presented the results of a study on the soil-related factors that modulate metal uptake and elimination by the oligochaete worm Enchytraeus crypticus. Uptake of Cd, Cu, Pb, and Zn was quantified in 20 Dutch field soils as a function of time. Uptake rate constants and equilibrium concentrations were estimated using compartment modeling. Internal metal concentrations varied less than the corresponding external levels. Zn and especially Cu provided the most extreme examples of this general behavior, which suggests regulation by the organism. Body residues by Cd increased linearly over time in 11 of the 20 soils studied, whereas in the remaining 9 soils equilibration of internal Cd levels was observed. CaCl2 extraction could be used to discriminate the 9 soils in which there is Pb accumulation from the 11 soils in which bioavailable Pb levels were too low to allow for uptake. Multivariate expressions that describe uptake rate constants and bioaccumulation factors as a function of soil characteristics were derived. pH and cation exchange capacity were the most important parameters. The formulae were very similar to those describing partitioning of metals over the solid and liquid phase of the soils, which suggests pore water-mediated uptake. A semi-mechanistic approach yielded further evidence of pore water-related uptake, modulated by competition between H+ and metal ions at the active sites of the membranes.