Edaphic factors affecting the toxicity and accumulation of arsenate in the earthworm Lumbricus terrestris

The toxicity and accumulation of arsenate was determined in the earthworm Lumbricus terrestris in soil from different layers of a forest profile. Toxicity increased fourfold between 2 and 10 d. Edaphic factors (pH, soil organic matter, and depth in soil profile) also affected toxicity with a three fold decrease in the concentration that causes 50% mortality with increasing depth in soil (from 0-70 mm to 500-700 mm). In a 4-d exposure study, there was no evidence of arsenic bioconcentration in earthworm tissue, although bioaccumulation was occurring. There was a considerable difference in tissue residues between living and dead earthworms, with dead worms having higher concentrations. This difference was dependent on both soil arsenate concentration and on soil type. Over a wide range of soil arsenate concentrations, earthworm arsenic residues are homeostatically maintained in living worms, but this homeostasis breaks down during death. Alternatively, equilibration with soil residues may occur via accumulation after death. In long-term accumulation studies in soils dosed with a sublethal arsenate concentration (40 μg/g dry weight), bioconcentration of arsenate did not occur until day 12, after which earthworm concentrations rose steadily above the soil concentration, with residues in worms three fold higher than soil concentrations by the termination of the study (23 d). This bioconcentration only occurred in depurated worms over the time period of the study. Initially, depurated worms had lower arsenic concentrations than undepurated until tissue concentrations were equivalent to the soil concentration. Once tissue concentration was greater than soil concentration, depurated worms had higher arsenic residues than undepurated.

Physiological stress in the Eurasian badger (Meles meles): Effects of host, disease and environment

A method for monitoring hypothalamic–pituitary–adrenal (HPA) responses of the Eurasian badger (Meles meles) to stressors was validated by measuring cortisol excretion in serum and faeces. Serum and faecal samples were collected under anaesthesia from live-captured, wild badgers and fresh faeces was collected from latrines at 15 social groups in County Down, Northern Ireland. Variation in levels of cortisol in wild badgers was investigated relative to disease status, season, age, sex, body mass, body condition and reproductive status and environmental factors that might influence stress. Faecal cortisol levels were significantly higher in animals testing culture-positive for Mycobacterium bovis. Prolonged elevation of cortisol can suppress immune function, which may have implications for disease transmission. There was a strong seasonal pattern in both serum cortisol, peaking in spring and faecal cortisol, peaking in summer. Cortisol levels were also higher in adults with poor body condition and low body mass. Faecal samples collected from latrines in grassland groups had significantly higher cortisol than those collected from woodland groups, possibly as a result of greater exposure to sources of environmental stress. This study is the first to investigate factors influencing physiological stress in badgers and indicates that serological and faecal excretion are valid indices of the HPA response to a range of stressors.

Characterization of NKR+ T-cell subsets in human bone marrow:implications for immunosurveillance of neoplasia

In addition to hematopoietic progenitors, human bone marrow contains mature T/NK lymphocytes. Valpha24Vbeta11 NKT-cells, a subset of NK receptor+ (NKR+) T-cells in humans, are rare in bone marrow, suggesting the presence of other NKR+ T-cells which may contribute to tumor surveillance. NKR+/- T-cells were examined in blood (PB), and bone marrow from donors (DM) and patients with active hematopoietic malignancy (PM), or in remission (PR). T-cells in PR & PM were enriched for CD56+ and CD57+ subsets, compared to DM. All marrow NKR+/- T-cell subsets were more activated than PB. PM and, surprisingly, PR marrow contained more activated cells than DM. CD8+ cells were significantly increased in all patient marrows and there was evidence of the formation of an effector/memory pool in malignant marrow. These data suggest that NKR+ T-cell enrichment in human bone marrow that has been exposed to neoplastic transformation is compatible with a role in localized tumor surveillance/eradication.

Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.

Evidential event inference in transport video surveillance

This paper presents a new framework for multi-subject event inference in surveillance video, where measurements produced by low-level vision analytics usually are noisy, incomplete or incorrect. Our goal is to infer the composite events undertaken by each subject from noise observations. To achieve this, we consider the temporal characteristics of event relations and propose a method to correctly associate the detected events with individual subjects. The Dempster–Shafer (DS) theory of belief functions is used to infer events of interest from the results of our vision analytics and to measure conflicts occurring during the event association. Our system is evaluated against a number of videos that present passenger behaviours on a public transport platform namely buses at different levels of complexity. The experimental results demonstrate that by reasoning with spatio-temporal correlations, the proposed method achieves a satisfying performance when associating atomic events and recognising composite events involving multiple subjects in dynamic environments.

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.

Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12–1.28, P = 1.9·10−7), heart failure (HR = 1.47, 95% CI, 1.35–1.60, P = 9·10−19) and ischaemic stroke (HR = 1.15, 95% CI, 1.06–1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028–0.033, P = 3·10−107). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12–3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05–3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.

Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome.

METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone.

FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions.

INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Exploring inequities in child welfare and child protection services: Explaining the ‘inverse intervention law’

Attempts to record, understand and respond to variations in child welfare and protection reporting, service patterns and outcomes are international, numerous and longstanding. Reframing such variations as an issue of inequity between children and between families opens the way to a new approach to explaining the profound difference in intervention rates between and within countries and administrative districts. Recent accounts of variation have frequently been based on the idea that there is a binary division between bias and risk (or need). Here we propose seeing supply (bias) and demand (risk) factors as two aspects of a single system, both framed, in part, by social structures. A recent finding from a study of intervention rates in England, the 'inverse intervention law', is used to illustrate the complex ways in which a range of factors interact to produce intervention rates. In turn, this analysis raises profound moral, policy, practice and research questions about current child welfare and child protection services.

Experimental Saltwater Intrusion in Coastal aquifers Using Automated Image Analysis: Applications to Homogeneous Aquifers.

This paper presents the applications of a novel methodology to quantify saltwater intrusion parameters in laboratory-scale experiments. The methodology uses an automated image analysis procedure, minimizing manual inputs and the subsequent systematic errors that can be introduced. This allowed the quantification of the width of the mixing zone which is difficult to measure in experimental methods that are based on visual observations. Glass beads of different grain sizes were tested for both steady-state and transient conditions. The transient results showed good correlation between experimental and numerical intrusion rates. The experimental intrusion rates revealed that the saltwater wedge reached a steady state condition sooner while receding than advancing. The hydrodynamics of the experimental mixing zone exhibited similar
traits; a greater increase in the width of the mixing zone was observed in the receding saltwater wedge, which indicates faster fluid velocities and higher dispersion. The angle of intrusion analysis revealed the formation of a volume of diluted saltwater at the toe position when the saltwater wedge is prompted to recede. In addition, results of different physical repeats of the experiment produced an average coefficient of variation less than 0.18 of the measured toe length and width of the mixing zone.

The effect of preferential paw usage on dogs' (Canis familiaris) performance in a manipulative problem-solving task

In a number of species, individuals showing lateralized hand/paw usage (i.e. the preferential use of either the right or left paw) compared to ambilateral individuals have been shown to be more proactive in novel situations. In the current study we used an established test to assess preferential paw usage in dogs (the Kong test) and then compared the performance of ambilateral and lateralized dogs as well as left- vs. right-pawed dogs in a novel manipulative problem solving task. Results showed an equal proportion of ambilateral and lateralized dogs but contrary to predictions non-lateralized dogs were faster at accessing the apparatus in test trials. No differences emerged between right- and left-pawed dogs. Results are discussed in relation to previous studies on lateralization. © 2013 Elsevier B.V.

Validity of model devices used to assess canine temperament in behavioral tests

Temperament tests are widely accepted as instruments for profiling behavioral variability in dogs, and they are applied in numerous areas of investigation (e.g. suitability for adoption or for breeding). During testing, to elicit a dog's reaction toward novel stimuli and predict its behavior in everyday life, model devices such as a child-like doll, or a fake dog, are often employed. However, the reliability of these devices to accurately stimulate dogs' reactions to children or dogs, is unknown and perhaps overestimated. This may be a particular concern in the case of aggressive behavior toward humans, a significant public health issue. The aim of this study was to: (1) evaluate the correlation between dogs' reactions to these devices, and owners' reports of their dog's aggression history (using the C-BARQ ??); (2) compare reactions toward the devices of dogs with and without histories of aggression. Subjects were selected among those visiting for behavioral consultation at the Veterinary Hospital of the University of Pennsylvania, and previously categorized as aggressive toward unfamiliar children, conspecifics, or as non-aggressive dogs (control). The test consisted of different components: an unfamiliar female tester approaching the dog; the presentation of a child-like doll, an ambiguous object, and a fake plastic dog. All tests were videotaped and durations of behaviors were later analyzed on the basis of a specified ethogram. Dogs' reactions were compared to C-BARQ scores, and interesting correlations emerged for 'dog-directed aggression/fear' (R = 0.48, P = 0.004), and 'stranger-directed aggression' (R = 0.58, P <0.001) factors. Dogs differed in their reactions toward the devices: the child-like doll and the fake dog elicited more social behaviors than the ambiguous object used as a control stimulus. Issues concerning the reliability of these tools to assess canine temperament are discussed. ?? 2012 Elsevier B.V. All rights reserved.

Determinants and heritability of intraocular pressure and cup-to-disc ratio in a defined older population.

PURPOSE:

To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population.

DESIGN:

Family-based cohort study.

PARTICIPANTS:

Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships.

METHODS:

Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glaucoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP.

MAIN OUTCOME MEASURES:

Heritability and determinants of IOP and CDR, and impact of siblings' glaucoma status on IOP and CDR.

RESULTS:

We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12-0.46) for IOP and 0.56 (95% CI, 0.35-0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004).

CONCLUSIONS:

In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands.

Validation of a high-throughput immunobead array technique for multiplex detection of three foodborne pathogens in chicken products

This study rigorously evaluated a previously developed immunobead array method to simultaneously detect three important foodborne pathogens, Campylobacter jejuni, Listeria monocytogenes, and Salmonella spp., for its actual application in routine food testing. Due to the limitation of the detection limit of the developed method, an enrichment step was included in this study by using Campylobacter Enrichment Broth for C. jejuni and Universal Pre-enrichment Broth for L. monocytogenes and Salmonella spp.. The findings show that the immunobead array method was capable of detecting as low as 1 CFU of the pathogens spiked in the culture media after being cultured for 24 hours for all three pathogens. The immunobead array method was further evaluated for its pathogen detection capabilities in ready-to-eat (RTE) and ready-to-cook (RTC) chicken samples and proven to be able to detect as low as 1 CFU of the pathogens spiked in the food samples after being cultured for 24 hours in the case of Salmonella spp., and L. monocytogenes and 48 hours in the case of C. jejuni. The method was subsequently validated with three types of chicken products (RTE, n=30; RTC, n=20; raw chicken, n=20) and was found to give the same results as the conventional plating method. Our findings demonstrated that the previously developed immunobead array method could be used for actual food testing with minimal enrichment period of only 52 hours, whereas the conventional ISO protocols for the same pathogens take 90-144 hours. The immunobead array was therefore an inexpensive, rapid and simple method for the food testing.