Navigating cognitive innovation

This paper revisits the concept of Cognitive Innovation with the aim of helping newcomers appreciate its (intended) demarcating purpose and relevance to the wider literature on cognition and creativity in the humanities, arts, and sciences. Particular emphasis is paid to discussion of the pitfalls of sense-making and the concept's affordance. The main argument presented is that proponents of the concept face the dilemma of seeking to demonstrate its transdisciplinary nature and applicability vis-a-vis retaining its semantic distinctness. Proceeding from a classification of Cognitive Innovation as a dispositional construct, we discuss how it feeds into existing research approaches and opens up new sensibilities in related areas. The perspectives of temporality, interdisciplinary balancing, technology, and metatheories are proposed as promising areas for future elaboration of the function of Cognitive Innovation

The diversity of Porcine Reproductive and Respiratory Syndrome virus type 1 and 2 in Denmark

Session - Viral Heterogeneity and EvolutionBoth Type 1 and Type 2 PRRS viruses are circulating among Danish pigs. The first appearance of Type 1 PRRSV in Denmark was in 1992 whereas the Type 2 PRRSV was introduced in 1996 after the use of a live attenuated vaccine that reverted to virulence. Since then, vaccination to control the disease for both PRRSV genotypes has been widely used in Denmark and it is therefore highly relevant to monitor the diversity of currently circulating PRRSV strains. Only subtype 1 of the Type 1 PRRSV strains and vaccine-like Type 2 PRRSV strains were previously detected in Denmark, however, only few Danish PRRSV strains were sequenced. Denmark exports more than 50.000 living pigs each month. A portion of these pigs inevitably harbor PRRSV. Thus, the diversity of PRRSV in Denmark is of interest to other countries besides Denmark. The main objective of the present study was to close the gap in knowledge on the genetic diversity of currently circulating PRRSV stains in Danish pigs by sequencing ORF5 and ORF7 of approximately 41 Type 1 and 50 Type 2 strains isolated between 2003 and 2013. Furthermore, full genome analysis was performed on nine Type 1 and nine Type 2 selected strains. The preliminary assessment of the results showed that the Type 1 strains all belonged to subtype 1. Based on the ORF5 sequences, the Danish Type 1 viruses clustered into two groups. These two groups shared 84 % to 92 % and 94 % to 99 % nucleotide identity to the Lelystad virus, respectively. The sequenced Type 2 viruses showed a significant higher level of identity in that the ORF5 sequences were 94 - >99 % identical at the nucleotide level. Most of the Type 2 viruses, shared high level of identity to the VR2332 vaccine strain (Ingelvac MLV), but a few more diverse isolates were also identified, including strains with interesting deletions in NSP2 and other genes. The full genome sequences of Danish strains showed an overall nucleotide identity of 88-98 % (Type 1) and 94 % to >99 % (Type 2). The impact of these results will be discussed.postprin

Classifying Alarms: Seeking Durability, Credibility, Consistency, and Simplicity

Alongside the development and testing of new audible alarms intended to support International Electrotechnical Commission 60601-1-8, a global standard concerned with alarm safety, the categories of risk that the standard denotes require further thought and possible updating. In this article, we revisit the origins of the categories covered by the standard. These categories were based on the ways that tissue damage can be caused. We consider these categories from the varied professional perspectives of the authors: human factors, semiotics, clinical practice, and the patient or family (layperson). We conclude that while the categories possess many clinically applicable and defensible features from our range of perspectives, the advances in alarm design now available may allow a more flexible approach. We present a three-tier system with superordinate, basic, and subordinate levels that fit both within the thinking embodied in the current standard and possible new developments

Australian Sphingidae – DNA Barcodes Challenge Current Species Boundaries and Distributions

© 2014 Rougerie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Prostaglandins, masculinization and its disorders:effects of fetal exposure of the rat to the cyclooxygenase inhibitor- indomethacin

Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal ‘masculinization programming window’ (MPW). What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG)-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity) during this period and then examining if androgen production or action (masculinization) was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5–e18.5) to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5), testis weight (e21.5) and testicular PGE2 (e17.5, e21.5), but had no effect on intratesticular testosterone (ITT; e17.5) or anogenital index (AGI; e21.5). Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001) in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Seasonal variation in objectively measured physical activity, sedentary time, cardio-respiratory fitness and sleep duration among 8–11 year-old Danish children: a repeated-measures study

Abstract Background Understanding fluctuations in lifestyle indicators is important to identify relevant time periods to intervene in order to promote a healthy lifestyle; however, objective assessment of multiple lifestyle indicators has never been done using a repeated-measures design. The primary aim was, therefore, to examine between-season and within-week variation in physical activity, sedentary behaviour, cardio-respiratory fitness and sleep duration among 8–11 year-old children. Methods A total of 1021 children from nine Danish schools were invited to participate and 834 accepted. Due to missing data, 730 children were included in the current analytical sample. An accelerometer was worn for 7 days and 8 nights during autumn, winter and spring, from which physical activity, sedentary time and sleep duration were measured. Cardio-respiratory fitness was assessed using a 10-min intermittent running test. Results The children had 5% more sedentary time, 23% less time in moderate-to-vigorous physical activity and 2% longer sleep duration during winter compared to spring and cardio-respiratory fitness was 4% higher during spring compared to autumn (P < 0.001). Sedentary time was higher and total physical activity, moderate-to-vigorous physical activity and sleep duration (boys only) were lower during weekends at all seasons (P ≤ 0.01). Intraclass correlation coefficients between seasons ranged from 0.47-0.74, leaving 45-78% to seasonal variation. Conclusions Overall, sedentary time was higher and physical activity lower during winter and during weekends. The most accurate and unbiased estimates of physical activity came from autumn; however, the considerable intra-individual variation suggests that a single measurement may not adequately characterise children’s habitual sleep and activity

Absence of Host Plasminogen Activator Inhibitor 1 Prevents Cancer Invasion and Vascularization

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats

RATIONALE: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. OBJECTIVE: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. METHODS: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. RESULTS: Only 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 μM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 μM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent. CONCLUSIONS: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability