Case study part 1: how to calculate appropriate deterministic long-term toxicity to exposure rates (TERs) for birds and mammals

In the European Union, first-tier assessment of the long-term risk to birds and mammals from pesticides is based on calculation of a deterministic long-term toxicity/exposure ratio(TERlt). The ratio is developed from generic herbivores and insectivores and applied to all species. This paper describes two case studies that implement proposed improvements to the way long-term risk is assessed. These refined methods require calculation of a TER for each of five identified phases of reproduction (phase-specific TERs) and use of adjusted No Observed Effect Levels (NOELs)to incorporate variation in species sensitivity to pesticides. They also involve progressive refinement of the exposure estimate so that it applies to particular species, rather than generic indicators, and relates spraying date to onset of reproduction. The effect of using these new methods on the assessment of risk is described. Each refinement did not necessarily alter the calculated TER value in a way that was either predictable or consistent across both case studies. However, use of adjusted NOELs always reduced TERs, and relating spraying date to onset of reproduction increased most phase-specific TERs. The case studies suggested that the current first-tier TERlt assessment may underestimate risk in some circumstances and that phase-specific assessments can help identify appropriate risk-reduction measures. The way in which deterministic phase-specific assessments can currently be implemented to enhance first-tier assessment is outlined.

Case study part 2: probabilistic modelling of long-term effects of pesticides on individual breeding success in birds and mammals

Abstract: Long-term exposure of skylarks to a fictitious insecticide and of wood mice to a fictitious fungicide were modelled probabilistically in a Monte Carlo simulation. Within the same simulation the consequences of exposure to pesticides on reproductive success were modelled using the toxicity-exposure-linking rules developed by R.S. Bennet et al. (2005) and the interspecies extrapolation factors suggested by R. Luttik et al.(2005). We built models to reflect a range of scenarios and as a result were able to show how exposure to pesticide might alter the number of individuals engaged in any given phase of the breeding cycle at any given time and predict the numbers of new adults at the season’s end.

The short- and long-term fitness consequences of natal dispersal in a wild bird population

Dispersal is a key process in population and evolutionary ecology. Individual decisions are affected by fitness consequences of dispersal, but these are difficult to measure in wild populations. A long-term dataset on a geographically closed bird population, the Mauritius kestrel, offers a rare opportunity to explore fitness consequences. Females dispersed further when the availability of local breeding sites was limited, whereas male dispersal correlated with phenotypic traits. Female but not male fitness was lower when they dispersed longer distances compared to settling close to home. These results suggest a cost of dispersal in females. We found evidence of both short- and long-term fitness consequences of natal dispersal in females, including reduced fecundity in early life and more rapid aging in later life. Taken together, our results indicate that dispersal in early life might shape life history strategies in wild populations.

Environmental oestrogens and breast cancer: long-term low-dose effects of mixtures of various chemical combinations

The incidence of breast cancer has risen worldwide to unprecedented levels in recent decades, making it now the major cancer of women in many parts of the world.1 Although diet, alcohol, radiation and inherited loss of BRCA1/2 genes have all been associated with increased incidence, the main identified risk factors are life exposure to hormones including physiological variations associated with puberty/pregnancy/menopause,1 personal choice of use of hormonal contraceptives2 and/or hormone replacement therapy.3–6 On this basis, exposure of the human breast to the many environmental pollutant chemicals capable of mimicking or interfering with oestrogen action7 should also be of concern.8 Hundreds of such environmental chemicals have now been measured in human breast tissue from a range of dietary and domestic exposure sources7 ,9 including persistent organochlorine pollutants (POPs),10 polybrominated diphenylethers and polybromobiphenyls,11 polychlorinated biphenyls,12 dioxins,13 alkyl phenols,14 bisphenol-A and chlorinated derivatives,15 as well as other less lipophilic compounds such as parabens (alkyl esters of p-hydroxybenzoic acid),16 but studies investigating any association between raised levels of such compounds and the development of breast cancer remain inconclusive.7–16 However, the functionality of these chemicals has continued to be assessed on the basis of individual chemicals rather than the environmental reality of long-term low-dose exposure to complex mixtures. This misses the potential for individuals to have high concentrations of different compounds but with a common mechanism of action. It also misses the complex interactions between chemicals and physiological hormones which together may act to alter the internal homeostasis of the oestrogenic environment of mammary tissue.

Acute and long-term effects of dietary fatty acids on vascular function in health and disease

Purpose of review: Vascular function is recognized as an early and integrative marker of cardiovascular disease. While there is consistent evidence that the quantity of dietary fat has significant effects on vascular function, the differential effects of individual fatty acids is less clear. This review summarizes recent evidence from randomly controlled dietary studies on the impact of dietary fatty acids on vascular function, as determined by flow-mediated dilatation (FMD). Recent findings: Critical appraisal is given to five intervention studies (one acute, four chronic) which examined the impact of long-chain n-3 polyunsaturated fatty acid [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] on FMD. In the acute setting, a high dose of long-chain n-3 polyunsaturated fatty acid (4.9 g per 70 kg man) improved postprandial FMD significantly, compared with a saturated fatty acid-rich meal in healthy individuals. In longer-term studies, there was limited evidence for a significant effect of EPA/DHA on FMD in diseased groups. Summary: The strongest evidence for the benefits of EPA/DHA on vascular function is in the postprandial state. More evidence from randomly controlled intervention trials with foods will be required to substantiate the long-term effects of EPA/DHA, to inform public health and clinical recommendations.

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD.

Risking the ire of investors in pursuit of long-term value: an interview with Cynthia Carroll, the CEO of Anglo American plc

Purpose – The purpose of this paper is to demonstrate how key strategic decisions are made in practice at successful FTSE 100 companies. Design/methodology/approach – The paper is based on a semi-structured interview with Ms Cynthia Carroll, Chief Executive of Anglo American plc. Findings – The interview outlines a number of important factors on: the evolution of strategy within Anglo American, strategy execution, leadership at board and executive levels, and capturing synergies within the company. Originality/value – The paper bridges the gap between theory and practice. It provides a practical view and demonstrates how corporate leaders think about key strategic issues

The interactive responses of water quality and hydrology to changes in multiple stressors, and implications for the long-term effective management of phosphorus

Soluble reactive phosphorus (SRP) plays a key role in eutrophication, a global problem decreasing habitat quality and in-stream biodiversity. Mitigation strategies are required to prevent SRP fluxes from exceeding critical levels, and must be robust in the face of potential changes in climate, land use and a myriad of other influences. To establish the longevity of these strategies it is therefore crucial to consider the sensitivity of catchments to multiple future stressors. This study evaluates how the water quality and hydrology of a major river system in the UK (the River Thames) respond to alterations in climate, land use and water resource allocations, and investigates how these changes impact the relative performance of management strategies over an 80-year period. In the River Thames, the relative contributions of SRP from diffuse and point sources vary seasonally. Diffuse sources of SRP from agriculture dominate during periods of high runoff, and point sources during low flow periods. SRP concentrations rose under any future scenario which either increased a) surface runoff or b) the area of cultivated land. Under these conditions, SRP was sourced from agriculture, and the most effective single mitigation measures were those which addressed diffuse SRP sources. Conversely, where future scenarios reduced flow e.g. during winters of reservoir construction, the significance of point source inputs increased, and mitigation measures addressing these issues became more effective. In catchments with multiple point and diffuse sources of SRP, an all-encompassing effective mitigation approach is difficult to achieve with a single strategy. In order to attain maximum efficiency, multiple strategies might therefore be employed at different times and locations, to target the variable nature of dominant SRP sources and pathways.

Predicting long-term growth in students' mathematics achievement: the unique contributions of motivation and cognitive strategies

This research examined how motivation (perceived control, intrinsic motivation, and extrinsic motivation), cognitive learning strategies (deep and surface strategies), and intelligence jointly predict long-term growth in students' mathematics achievement over 5 years. Using longitudinal data from six annual waves (Grades 5 through 10; Mage = 11.7 years at baseline; N = 3,530), latent growth curve modeling was employed to analyze growth in achievement. Results showed that the initial level of achievement was strongly related to intelligence, with motivation and cognitive strategies explaining additional variance. In contrast, intelligence had no relation with the growth of achievement over years, whereas motivation and learning strategies were predictors of growth. These findings highlight the importance of motivation and learning strategies in facilitating adolescents' development of mathematical competencies.

Controlled adhesion and growth of long term glial and neuronal cultures on Parylene-C

This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1–P7) rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C) in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF). We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures.

An assessment of observed vertical flux divergence in long-term eddy-covariance measurements over two Midwestern forest ecosystems

Vertical divergence of CO2 fluxes is observed over two Midwestern AmeriFlux forest sites. The differences in ensemble averaged hourly CO2 fluxes measured at two heights above canopy are relatively small (0.2–0.5 μmol m−2 s−1), but they are the major contributors to differences (76–256 g C m−2 or 41.8–50.6%) in estimated annual net ecosystem exchange (NEE) in 2001. A friction velocity criterion is used in these estimates but mean flow advection is not accounted for. This study examines the effects of coordinate rotation, averaging time period, sampling frequency and co-spectral correction on CO2 fluxes measured at a single height, and on vertical flux differences measured between two heights. Both the offset in measured vertical velocity and the downflow/upflow caused by supporting tower structures in upwind directions lead to systematic over- or under-estimates of fluxes measured at a single height. An offset of 1 cm s−1 and an upflow/downflow of 1° lead to 1% and 5.6% differences in momentum fluxes and nighttime sensible heat and CO2 fluxes, respectively, but only 0.5% and 2.8% differences in daytime sensible heat and CO2 fluxes. The sign and magnitude of both offset and upflow/downflow angle vary between sonic anemometers at two measurement heights. This introduces a systematic and large bias in vertical flux differences if these effects are not corrected in the coordinate rotation. A 1 h averaging time period is shown to be appropriate for the two sites. In the daytime, the absolute magnitudes of co-spectra decrease with height in the natural frequencies of 0.02–0.1 Hz but increase in the lower frequencies (<0.01 Hz). Thus, air motions in these two frequency ranges counteract each other in determining vertical flux differences, whose magnitude and sign vary with averaging time period. At night, co-spectral densities of CO2 are more positive at the higher levels of both sites in the frequency range of 0.03–0.4 Hz and this vertical increase is also shown at most frequencies lower than 0.03 Hz. Differences in co-spectral corrections at the two heights lead to a positive shift in vertical CO2 flux differences throughout the day at both sites. At night, the vertical CO2 flux differences between two measurement heights are 20–30% and 40–60% of co-spectral corrected CO2 fluxes measured at the lower levels of the two sites, respectively. Vertical differences of CO2 flux are relatively small in the daytime. Vertical differences in estimated mean vertical advection of CO2 between the two measurement heights generally do not improve the closure of the 1D (vertical) CO2 budget in the air layer between the two measurement heights. This may imply the significance of horizontal advection. However, a reliable assessment of mean advection contributions in annual NEE estimate at these two AmeriFlux sites is currently an unsolved problem.

Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events

Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward. (PsycINFO Database Record (c) 2013 APA, all rights reserved)(journal abstract)

Energy exchange in a dense urban environment – part I: temporal variability of long-term observations in central London

Though anthropogenic impacts on boundary layer climates are expected to be large in dense urban areas, to date very few studies of energy flux observations are available. We report on 3.5 years of measurements gathered in central London, UK. Radiometer and eddy covariance observations at two adjacent sites, at different heights, were analysed at various temporal scales and with respect to meteorological conditions, such as cloud cover. Although the evaporative flux is generally small due to low moisture availability and a predominately impervious surface, the enhancement following rainfall usually lasts for 12–18 h. As both the latent and sensible heat fluxes are larger in the afternoon, they maintain a relatively consistent Bowen ratio throughout the middle of the day. Strong storage and anthropogenic heat fluxes sustain high and persistently positive sensible heat fluxes. At the monthly time scale, the urban surface often loses more energy by this turbulent heat flux than is gained from net all-wave radiation. Auxiliary anthropogenic heat flux information suggest human activities in the study area are sufficient to provide this energy.