Endocrine disrupters and human health: Could oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women? A review of evidence and call for further research

In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of. data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application of body care products (unlike diffuse environmental chemical exposures) should be amenable to evaluation, quantification and control. The exposure issues are clear and the exposed population is large, and these factors should provide the necessary impetus to investigate this potential issue of public health. Copyright (C) 2004 John Wiley Sons, Ltd.

Effect of improving representation of horizontal and vertical cloud structure on the Earth's global radiation budget. Part I: review and parametrization

A poor representation of cloud structure in a general circulation model (GCM) is widely recognised as a potential source of error in the radiation budget. Here, we develop a new way of representing both horizontal and vertical cloud structure in a radiation scheme. This combines the ‘Tripleclouds’ parametrization, which introduces inhomogeneity by using two cloudy regions in each layer as opposed to one, each with different water content values, with ‘exponential-random’ overlap, in which clouds in adjacent layers are not overlapped maximally, but according to a vertical decorrelation scale. This paper, Part I of two, aims to parametrize the two effects such that they can be used in a GCM. To achieve this, we first review a number of studies for a globally applicable value of fractional standard deviation of water content for use in Tripleclouds. We obtain a value of 0.75 ± 0.18 from a variety of different types of observations, with no apparent dependence on cloud type or gridbox size. Then, through a second short review, we create a parametrization of decorrelation scale for use in exponential-random overlap, which varies the scale linearly with latitude from 2.9 km at the Equator to 0.4 km at the poles. When applied to radar data, both components are found to have radiative impacts capable of offsetting biases caused by cloud misrepresentation. Part II of this paper implements Tripleclouds and exponential-random overlap into a radiation code and examines both their individual and combined impacts on the global radiation budget using re-analysis data.

Chess endgame knowledge advances

This review of recent developments starts with the publication of Harold van der Heijden's Study Database Edition IV, John Nunn's second trilogy on the endgame, and a range of endgame tables (EGTs) to the DTC, DTZ and DTZ50 metrics. It then summarises data-mining work by Eiko Bleicher and Guy Haworth in 2010. This used CQL and pgn2fen to find some 3,000 EGT-faulted studies in the database above, and the Type A (value-critical) and Type B-DTM (DTM-depth-critical) zugzwangs in the mainlines of those studies. The same technique was used to mine Chessbase's BIG DATABASE 2010 to identify Type A/B zugzwangs, and to identify the pattern of value-concession and DTM-depth concession in sub-7-man play.

Proposed best practice for statisticians in the reporting and publication of pharmaceutical industry-sponsored clinical trials

In this paper we set out what we consider to be a set of best practices for statisticians in the reporting of pharmaceutical industry-sponsored clinical trials. We make eight recommendations covering: author responsibilities and recognition; publication timing; conflicts of interest; freedom to act; full author access to data; trial registration and independent review. These recommendations are made in the context of the prominent role played by statisticians in the design, conduct, analysis and reporting of pharmaceutical sponsored trials and the perception of the reporting of these trials in the wider community.

Policies to promote healthy eating in Europe: a structured review of policies and their effectiveness

This review provides a classification of public policies to promote healthier eating as well as a structured mapping of existing measures in Europe. Complete coverage of alternative policy types was ensured by complementing the review with a selection of major interventions from outside Europe. Under the auspices of the Seventh Framework Programme's Eatwell Project, funded by the European Commission, researchers from five countries reviewed a representative selection of policy actions based on scientific papers, policy documents, grey literature, government websites, other policy reviews, and interviews with policy-makers. This work resulted in a list of 129 policy interventions, 121 of which were in Europe. For each type of policy, a critical review of its effectiveness was conducted, based on the evidence currently available. The results of this review indicate a need exists for a more systematic and accurate evaluation of government-level interventions as well as for a stronger focus on actual behavioral change rather than changes in attitude or intentions alone. The currently available evidence is very heterogeneous across policy types and is often incomplete.

Review of R&D progress and practical application of the solar photovoltaic/thermal (PV/T) technologies

In this paper, the global market potential of solar thermal, photovoltaic (PV) and combined photovoltaic/thermal (PV/T) technologies in current time and near future was discussed. The concept of the PV/T and the theory behind the PV/T operation were briefly introduced, and standards for evaluating technical, economic and environmental performance of the PV/T systems were addressed. A comprehensive literature review into R&D works and practical application of the PV/T technology was illustrated and the review results were critically analysed in terms of PV/T type and research methodology used. The major features, current status, research focuses and existing difficulties/barriers related to the various types of PV/T were identified. The research methods, including theoretical analyses and computer simulation, experimental and combined experimental/theoretical investigation, demonstration and feasibility study, as well as economic and environmental analyses, applied into the PV/T technology were individually discussed, and the achievement and problems remaining in each research method category were described. Finally, opportunities for further work to carry on PV/T study were identified. The review research indicated that air/water-based PV/T systems are the commonly used technologies but their thermal removal effectiveness is lower. Refrigerant/heat-pipe-based PV/Ts, although still in research/laboratory stage, could achieve much higher solar conversion efficiencies over the air/water-based systems. However, these systems were found a few technical challenges in practice which require further resolutions. The review research suggested that further works could be undertaken to (1) develop new feasible, economic and energy efficient PV/T systems; (2) optimise the structural/geometrical configurations of the existing PV/T systems; (3) study long term dynamic performance of the PV/T systems; (4) demonstrate the PV/T systems in real buildings and conduct the feasibility study; and (5) carry on advanced economic and environmental analyses. This review research helps finding the questions remaining in PV/T technology, identify new research topics/directions to further improve the performance of the PV/T, remove the barriers in PV/T practical application, establish the standards/regulations related to PV/T design and installation, and promote its market penetration throughout the world.

A critical review of methodologies for measuring rental depreciation applied to UK commercial real estate

Real estate depreciation continues to be a critical issue for investors and the appraisal profession in the UK in the 1990s. Depreciation-sensitive cash flow models have been developed, but there is a real need to develop further empirical methodologies to determine rental depreciation rates for input into these models. Although building quality has been found to be an important explanatory variable in depreciation it is very difficult to incorporate it into such models or to analyse it retrospectively. It is essential to examine previous depreciation research from real estate and economics in the USA and UK to understand the issues in constructing a valid and pragmatic way of calculating rental depreciation. Distinguishing between 'depreciation' and 'obsolescence' is important, and the pattern of depreciation in any study can be influenced by such factors as the type (longitudinal or crosssectional) and timing of the study, and the market state. Longitudinal studies can analyse change more directly than cross-sectional studies. Any methodology for calculating rental depreciation rate should be formulated in the context of such issues as 'censored sample bias', 'lemons' and 'filtering', which have been highlighted in key US literature from the field of economic depreciation. Property depreciation studies in the UK have tended to overlook this literature, however. Although data limitations and constraints reduce the ability of empirical property depreciation work in the UK to consider these issues fully, 'averaging' techniques and ordinary least squares (OLS) regression can both provide a consistent way of calculating rental depreciation rates within a 'cohort' framework.

Input type and parameter resetting: is naturalistic input necessary?

It has been argued that extended exposure to naturalistic input provides L2 learners with more of an opportunity to converge of target morphosyntactic competence as compared to classroom-only environments, given that the former provide more positive evidence of less salient linguistic properties than the latter (e.g., Isabelli 2004). Implicitly, the claim is that such exposure is needed to fully reset parameters. However, such a position conflicts with the notion of parameterization (cf. Rothman and Iverson 2007). In light of two types of competing generative theories of adult L2 acquisition – the No Impairment Hypothesis (e.g., Duffield and White 1999) and so-called Failed Features approaches (e.g., Beck 1998; Franceschina 2001; Hawkins and Chan 1997), we investigate the verifiability of such a claim. Thirty intermediate L2 Spanish learners were tested in regards to properties of the Null-Subject Parameter before and after study-abroad. The data suggest that (i) parameter resetting is possible and (ii) exposure to naturalistic input is not privileged.

A review of urban roughness sublayer turbulence

It is becoming increasingly important that we can understand and model flow processes in urban areas. Applications such as weather forecasting, air quality and sustainable urban development rely on accurate modelling of the interface between an urban surface and the atmosphere above. This review gives an overview of current understanding of turbulence generated by an urban surface up to a few building heights, the layer called the roughness sublayer (RSL). High quality datasets are also identified which can be used in the development of suitable parameterisations of the urban RSL. Datasets derived from physical and numerical modelling, and full-scale observations in urban areas now exist across a range of urban-type morphologies (e.g. street canyons, cubes, idealised and realistic building layouts). Results show that the urban RSL depth falls within 2 – 5 times mean building height and is not easily related to morphology. Systematic perturbations away from uniform layouts (e.g. varying building heights) have a significant impact on RSL structure and depth. Considerable fetch is required to develop an overlying inertial sublayer, where turbulence is more homogeneous, and some authors have suggested that the “patchiness” of urban areas may prevent inertial sublayers from developing at all. Turbulence statistics suggest similarities between vegetation and urban canopies but key differences are emerging. There is no consensus as to suitable scaling variables, e.g. friction velocity above canopy vs. square root of maximum Reynolds stress, mean vs. maximum building height. The review includes a summary of existing modelling practices and highlights research priorities.

Endophytic bacterial community composition in wheat (Triticum aestivum) is determined by plant tissue type, developmental stage and soil nutrient availability

Aims: To understand effects of tissue type, growth stage and soil fertilisers on bacterial endophyte communities of winter wheat (Triticum aestivum cv. Hereward). Methods: Endophytes were isolated from wheat grown under six fertiliser conditions in the long term Broadbalk Experiment at Rothamsted Research, UK. Samples were taken in May and July from root and leaf tissues. Results: Root and leaf communities differed in abundance and composition of endophytes. Endophytes were most abundant in roots and the Proteobacteria were most prevalent. In contrast, Firmicutes and Actinobacteria, the Gram positive phyla, were most prevalent in the leaves. Both fertiliser treatment and sample time influenced abundance and relative proportions of each phylum and genus in the endosphere. A higher density of endophytes was found in the Nil input treatment plants. Conclusions: Robust isolation techniques and stringent controls are critical for accurate recovery of endophytes. The plant tissue type, plant growth stage, and soil fertiliser treatment all contribute to the composition of the endophytic bacterial community in wheat. These results should help facilitate targeted development of endophytes for beneficial applications in agriculture.

Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice

Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations, often leading to uninterpretable or invalid outcomes. If the statistical concepts identified within this review are considered and addressed during the design of a trial amendment, it is possible to effectively assess a new treatment arm within an ongoing trial without compromising the original trial outcomes.

Cancer patients taking herbal medicines: a review of clinical purposes, associated factors, and perceptions of benefit or harm

Ethnopharmacological relevance: Cancer patients in all cultures are high consumers of herbal medicines (HMs) usually as part of a regime consisting of several complementary and alternative medicine (CAM) modalities, but the type of patient, the reasons for choosing such HM-CAM regimes, and the benefits they perceive from taking them are poorly understood. There are also concerns that local information may be ignored due to language issues. This study investigates aspects of HM-CAM use in cancer patients using two different abstracting sources: Medline, which contains only peer-reviewed studies from SCI journals, and in order to explore whether further data may be available regionally, the Thai national databases of HM and CAM were searched as an example. Materials and methods: the international and Thai language databases were searched separately to identify relevant studies, using key words chosen to include HM use in all traditions. Analysis of these was undertaken to identify socio-demographic and clinical factors, as well as sources of information, which may inform the decision to use HMs. Results: Medline yielded 5,638 records, with 49 papers fitting the criteria for review. The Thai databases yielded 155, with none relevant for review. Factors associated with HM-CAM usage were: a younger age, higher education or economic status, multiple chemotherapy treatment, late stage of disease. The most common purposes for using HM-CAM cited by patients were to improve physical symptoms, support emotional health, stimulate the immune system, improve quality of life, and relieve side-effects of conventional treatment. Conclusions: Several indicators were identified for cancer patients who are most likely to take HM-CAM. However, interpreting the clinical reasons why patients decide to use HM-CAM is hampered by a lack of standard terminology and thematic coding, because patients' own descriptions are too variable and overlapping for meaningful comparison. Nevertheless, fears that the results of local studies published regionally are being missed, at least in the case of Thailand, appeared to be unfounded.

Application of biochar for soil remediation

Research into the use of biochar for the remediation of contaminated soils has expanded rapidly over the past 5 yr. We review recent developments in the field and present the findings emanating from small-scale batch sorption experiments, through soil incubations and bioassays, to large-scale field experiments. We discuss the evidence that these experiments have contributed toward a mechanistic understanding of how biochar is capable of remediating soils contaminated with both organic and inorganic contaminants. The effects of biochar pyrolysis temperature, biochar source material, soil type, and contaminant type on the performance of biochars for remediation are identified. The risks associated with applying biochar to uncontaminated agricultural soils are discussed. Knowledge gaps and questions are identified which, if addressed, will considerably advance the application of biochar as a soil remediation tool in the future.

Meta-analysis to integrate effect sizes within a paper: Possible misuse and Type-1 error inflation

In recent years an increasing number of papers have employed meta-analysis to integrate effect sizes of researchers’ own series of studies within a single paper (“internal meta-analysis”). Although this approach has the obvious advantage of obtaining narrower confidence intervals, we show that it could inadvertently inflate false-positive rates if researchers are motivated to use internal meta-analysis in order to obtain a significant overall effect. Specifically, if one decides whether to stop or continue a further replication experiment depending on the significance of the results in an internal meta-analysis, false-positive rates would increase beyond the nominal level. We conducted a set of Monte-Carlo simulations to demonstrate our argument, and provided a literature review to gauge awareness and prevalence of this issue. Furthermore, we made several recommendations when using internal meta-analysis to make a judgment on statistical significance.

Are visual threats prioritized without awareness? A critical review and meta analysis involving 3 behavioral paradigms and 2696 observers

Given capacity limits, only a subset of stimuli 1 give rise to a conscious percept. Neurocognitive models suggest that humans have evolved mechanisms that operate without awareness and prioritize threatening stimuli over neutral stimuli in subsequent perception. In this meta analysis, we review evidence for this ‘standard hypothesis’ emanating from three widely used, but rather different experimental paradigms that have been used to manipulate awareness. We found a small pooled threat-bias effect in the masked visual probe paradigm, a medium effect in the binocular rivalry paradigm and highly inconsistent effects in the breaking continuous flash suppression paradigm. Substantial heterogeneity was explained by the stimulus type: the only threat stimuli that were robustly prioritized across all three paradigms were fearful faces. Meta regression revealed that anxiety may modulate threat biases, but only under specific presentation conditions. We also found that insufficiently rigorous awareness measures, inadequate control of response biases and low level confounds may undermine claims of genuine unconscious threat processing. Considering the data together, we suggest that uncritical acceptance of the standard hypothesis is premature: current behavioral evidence for threat-sensitive visual processing that operates without awareness is weak.