A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor

Herein, we present the use of a single gold nanorod sensor for detection of diseases on an antibody-functionalized surface, based on antibody–antigen interaction and the localized surface plasmon resonance (LSPR) ?max shifts of the resonant Rayleigh light scattering spectra. By replacing the cetyltrimethylammonium bromide (CTAB), a tightly packed self-assembled monolayer of HS(CH2)11(OCH2CH2)6OCH2COOH(OEG6) has been successfully formed on the gold nanorod surface prior to the LSPR sensing, leading to the successful fabrication of individual gold nanorod immunosensors. Using prostate specific antigen (PSA) as a protein biomarker, the lowest concentration experimentally detected was as low as 111 aM, corresponding to a 2.79 nm LSPR ?max shift. These results indicate that the detection platform is very sensitive and outperforms detection limits of commercial tests for PSA so far. Correlatively, its detection limit can be equally compared to the assays based on DNA biobarcodes. This study shows that a gold nanorod has been used as a single nanobiosensor to detect antigens for the first time; and the detection method based on the resonant Rayleigh scattering spectrum of individual gold nanorods enables a simple, label-free detection with ultrahigh sensitivity.

Harnessing the power of personality assessment:Subjective assessment predicts behaviour in horses

Objective assessment of animal personality is typically time consuming, requiring the repeated measure of behavioural responses. By contrast, subjective assessment of personality allows information to be collected quickly by experienced caregivers. However, subjective assessment must predict behaviour to be valid. Comparisons of subjective assessments and behaviour have been made but often with methodological weaknesses and thus, limited success. Here we test the validity of a subjective assessment against a battery of behaviour tests in 146 horses (Equus caballus). Our first aim was to determine if subjective personality assessment could predict behaviour during behaviour testing. We made specific a priori predictions for how subjectively measured personality should relate to behaviour testing. We found that Extroversion predicted time to complete a handling test and refusal behaviour during this test. It also predicted minimum distance to a novel object. Neuroticism predicted how reactive an individual was to a sudden visual stimulus but not how quickly it recovered from this. Agreeableness did not predict any behaviour during testing. There were several unpredicted correlations between subjective measures and behaviour tests which we explore further. Our second aim was to combine data from the subjective assessment and behaviour tests to gain a more comprehensive understanding of personality. We found that the combination of methods provides new insights into horse behaviour. Furthermore, our data are consistent with the idea of horses showing different coping styles, a novel finding for this species. © 2013 Elsevier B.V.

An Excess of Risk-Increasing Low-Frequency Variants Can Be a Signal of Polygenic Inheritance in Complex Diseases

In most complex diseases, much of the heritability remains unaccounted for by common variants. It has been postulated that lower-frequency variants contribute to the remaining heritability. Here, we describe a method to test for polygenic inheritance from lower-frequency variants by using GWAS summary association statistics. We explored scenarios with many causal low-frequency variants and showed that there is more power to detect risk variants than to detect protective variants, resulting in an increase in the ratio of detected risk to protective variants (R/P ratio). Such an excess can also occur if risk variants are present and kept at lower frequencies because of negative selection. The R/P ratio can be falsely elevated because of reasons unrelated to polygenic inheritance, such as uneven sample sizes or asymmetric population stratification, so precautions to correct for these confounders are essential. We tested our method on published GWAS results and observed a strong signal in some diseases (schizophrenia and type 2 diabetes) but not others. We also explored the shared genetic component in overlapping phenotypes related to inflammatory bowel disease (Crohn disease [CD] and ulcerative colitis [UC]) and diabetic nephropathy (macroalbuminuria and end-stage renal disease [ESRD]). Although the signal was still present when both CD and UC were jointly analyzed, the signal was lost when macroalbuminuria and ESRD were jointly analyzed, suggesting that these phenotypes should best be studied separately. Thus, our method may also help guide the design of future genetic studies of various traits and diseases.

Pain expression is linked to personality in horses

Tissue damage may result in pain, inducing protective behaviour such as lameness. Because we cannot directly measure an animal's subjective experience, pain research and veterinary assessment rely on these behavioural indicators when quantifying pain. This assumes that pain expression is proportional to damage but this has not been tested in animals and ignores the possible effects of personality and coping style. First, we assessed whether lameness accurately predicted the severity of tissue damage, or whether there is variance in how "stoical" individuals are. An experienced equine veterinarian scored horses for lameness and then the severity of tissue damage using either x-ray or ultrasound during the course of normal diagnostics in a clinical setting. Contrary to assumptions, we found no relation between scores for lameness and severity. Consequently, "stoicism" was calculated as severity score minus lameness score. We tested hypotheses founded on previous work concerning how personality would be expected to link with stoicism and pain behaviour. Personality was quantified using a validated questionnaire, completed by owners. Owners also gave their subjective opinion on how tolerant the horse was to pain using a 1-5 likert scale. This is the first paper to assess the relationships between pain behaviour and personality in animals. We found that neuroticism is negatively related to "stoicism" whereas extroversion was positively related to levels of lameness, which may mean that pain in more easily identified in highly extrovert individuals. Future work to clarify these findings and their major implications for accurate assessment of damage and pain in animals are discussed. © 2013 Elsevier B.V.

Periodontitis and systemic diseases:A record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases

Background There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions. Aim To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4. Results Working group 4 recognized that the studies performed to date were largely cross-sectional or case-control with few prospective cohort studies and no randomized clinical trials. The best current evidence suggests that periodontitis is characterized by both infection and pro-inflammatory events, which variously manifest within the systemic diseases and disorders discussed. Diseases with at least minimal evidence of an association with periodontitis include COPD, pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. The working group agreed that there is insufficient evidence to date to infer causal relationships with the exception that organisms originating in the oral microbiome can cause lung infections. Conclusions The group was unanimous in their opinion that the reported associations do not imply causality, and establishment of causality will require new studies that fulfil the Bradford Hill or equivalent criteria. Precise and community-agreed case definitions of periodontal disease states must be implemented systematically to enable consistent and clearer interpretations of studies of the relationship to systemic diseases. The members of the working group were unanimous in their opinion that to develop data that best inform clinicians, investigators and the public, studies should focus on robust disease outcomes and avoid surrogate endpoints. It was concluded that because of the relative immaturity of the body of evidence for each of the purported relationships, the field is wide open and the gaps in knowledge are large. © 2013 European Federation of Periodontology and American Academy of Periodontology.

Integrated care pathways for airway diseases (AIRWAYS-ICPs)

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).