Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response

Objective: Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated the COX-2 gene for functional variants that may influence susceptibility to disease. Methods and results: The promoter of COX-2 was screened for variants in healthy subjects by use of polymerase chain reaction-based methods. Promoter activity was investigated by using reporter expression experiments in human lung fibroblasts. Patients undergoing coronary artery bypass graft surgery, with measurements of plasma markers linked to COX-2 activity, were genotyped for association studies. A common COX-2 promoter variant, -765G>C, was found and shown to be carried by >25% of a group of healthy UK subjects. The -765C allele had significantly lower promoter activity compared with -765G, basally (28±3% lower, P<0.005) and in serum-stimulated cells (31±2% lower, P<0.005). In patients subjected to coronary artery bypass graft surgery, the magnitude of rise in levels of C-reactive protein (CRP) was strongly genotype dependent. Compared with -765G homozygotes, patients carrying the -765C allele had significantly lower plasma CRP levels at 1 to 4 days after surgery (14% lower at the peak of CRP levels on day 3, P<0.05 for all time points). Conclusions: For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed

Integrating wild and agrobiodiversity conservation

This research shows that both wild biodiversity and agrobiodiversity provide multiple ecosystem services that support food production, underpin food security and human wellbeing. We consider that biodiversity conservation efforts in agricultural contexts should better integrate wild and agrobiodiversity approache

A Novel Culture-Dependent Gesture Selection System for a Humanoid Robot Performing Greeting Interaction

In human-robot interaction, it is important for the robots to adapt to our ways of communication. As humans, rules of non-verbal communication, including greetings, change depending on our culture. Social robots should adapt to these specific differences in order to communicate effectively, as a correct way of approaching often results into better acceptance of the robot. In this study, a novel greeting gesture selection system is presented and an experiment is run using the robot ARMAR-IIIb. The robot performs greeting gestures appropriate to Japanese culture; after interacting with German participants, the selection should become appropriate to German culture. Results show that the mapping of gesture selection evolves successfully

Building an Assessment Use Argument for sign language: the BSL Nonsense Sign Repetition Test

In this article, we adapt a concept designed to structure language testing more effectively, the Assessment Use Argument (AUA), as a framework for the development and/or use of sign language assessments for deaf children who are taught in a sign bilingual education setting. By drawing on data from a recent investigation of deaf children's nonsense sign repetition skills in British Sign Language, we demonstrate the steps of implementing the AUA in practical test design, development and use. This approach provides us with a framework which clearly states the competing values and which stakeholders hold these values. As such, it offers a useful foundation for test-designers, as well as for practitioners in sign bilingual education, for the interpretation of test scores and the consequences of their use

Optimizing the impact of medications for opioid use disorder at release from prison and jail settings: A microsimulation modeling study

Background: We examined the impact of expanded access to medications for opioid use disorder (MOUD) in a unified prison and jail system on post-release, opioid-related overdose mortality. Methods: We developed a microsimulation model to simulate a population of 55,000 persons at risk of opioid-related overdose mortality in Rhode Island. The effect of an extended-release (XR) naltrexone only intervention and the effect of providing access to all three MOUD (i.e., methadone, buprenorphine, and XR-naltrexone) at release from incarceration on cumulative overdose death over eight years (2017–2024) were compared to the standard of care (i.e., limited access to MOUD). Results: In the standard of care scenario, the model predicted 2385 opioid-related overdose deaths between 2017 and 2024. An XR-naltrexone intervention averted 103 deaths (4.3% reduction), and access to all three MOUD averted 139 deaths (5.8% reduction). Among those with prior year incarceration, an XR-naltrexone only intervention and access to all three MOUD reduced overdose deaths by 22.8% and 31.6%, respectively. Conclusions: Expanded access to MOUD in prison and jail settings can reduce overdose mortality in a general, at-risk population. However, the real-world impact of this approach will vary by levels of incarceration, treatment enrollment, and post-release retention

The institutional shaping of management: in the tracks of English individualism

Globalisation raises important questions about the shaping of economic action by cultural factors. This article explores the formation of what is seen by some as a prime influence on the formation of British management: individualism. Drawing on a range of historical sources, it argues for a comparative approach. In this case, the primary comparison drawn is between England and Scotland. The contention is that there is a systemic approach to authority in Scotland that can be contrasted to a personal approach in England. An examination of the careers of a number of Scottish pioneers of management suggests the roots of this systemic approach in practices of church governance. Ultimately this systemic approach was to take a secondary role to the personal approach engendered by institutions like the universities of Oxford and Cambridge, but it found more success in the different institutional context of the USA. The complexities of dealing with historical evidence are stressed, as is the value of taking a comparative approach. In this case this indicates a need to take religious practice as seriously as religious belief as a source of transferable practice. The article suggests that management should not be seen as a simple response to economic imperatives, but as shaped by the social and cultural context from which it emerges

Reconceptualising adaptation to climate change as part of pathways of change and response

The need to adapt to climate change is now widely recognised as evidence of its impacts on social and natural systems grows and greenhouse gas emissions continue unabated. Yet efforts to adapt to climate change, as reported in the literature over the last decade and in selected case studies, have not led to substantial rates of implementation of adaptation actions despite substantial investments in adaptation science. Moreover, implemented actions have been mostly incremental and focused on proximate causes; there are far fewer reports of more systemic or transformative actions. We found that the nature and effectiveness of responses was strongly influenced by framing. Recent decision-oriented approaches that aim to overcome this situation are framed within a "pathways" metaphor to emphasise the need for robust decision making within adaptive processes in the face of uncertainty and inter-temporal complexity. However, to date, such "adaptation pathways" approaches have mostly focused on contexts with clearly identified decision-makers and unambiguous goals; as a result, they generally assume prevailing governance regimes are conducive for adaptation and hence constrain responses to proximate causes of vulnerability. In this paper, we explore a broader conceptualisation of "adaptation pathways" that draws on 'pathways thinking' in the sustainable development domain to consider the implications of path dependency, interactions between adaptation plans, vested interests and global change, and situations where values, interests, or institutions constrain societal responses to change. This re-conceptualisation of adaptation pathways aims to inform decision makers about integrating incremental actions on proximate causes with the transformative aspects of societal change. Case studies illustrate what this might entail. The paper ends with a call for further exploration of theory, methods and procedures to operationalise this broader conceptualisation of adaptation

Long term follow up of persistence of immunity following quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children

Background: Human Papillomavirus (HPV) causes significant burden of HPV-related diseases, which are more prevalent in immunosuppressed compared to immunocompetent people. We conducted a multi-centre clinical trial to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. Here we present the immunogenicity results 5 years post vaccination. Methods: We followed up immunocompromised children (5-18 years) with a range of specified underlying conditions who were previously recruited from three Australian paediatric hospitals. Participants received three doses of quadrivalent HPV vaccine (Gardasil Quadrivalent HPV Types 6, 11, 16, 18) and were followed up between 2007 and 2016 (60 months post-vaccination). The immunogenicity primary outcome was seroconversion and geometric mean titres (GMT) of the quadrivalent HPV vaccine serotypes in the study. Results: Of the 59 original participants, 37 were followed up at 60 months. The proportion of participants who seroconverted were: 86.5%, 89.2%, 89.2%, 91.9% by competitive Luminex immunoassay (cLIA) and 83.8%, 83.8%, 94.6%, 78.4% by total immunoglobulin G assays (IgG) for serotypes 6, 11, 16 and 18 respectively. GMT values ranged from 118 (95%CI: 79-177) for serotype 11, to 373 (95%CI: 215-649) for serotype 16 by cLIA. For IgG, serotype 16 had the highest GMT of 261 (95%CI: 143-477) and serotype 18 had the lowest value of 37 (95%CI: 21-68). All antibody titres were lower in females compared to males but the difference was not statistically significant except for serotype 16. No serious adverse event was reported during this follow-up period. Conclusion: Our evidence, although limited by small numbers, is reassuring that a three dose schedule of HPV vaccine remains immunogenic in immunocompromised children to five years post vaccination. Large scale studies are required to determine long term protection in immunocompromised children.C. Raina MacIntyre, Peter J. Shaw, Fiona E. Mackie, Christina Boros, Helen Marshall, Holly Seale, Sean E. Kennedy, Aye Moa, Abrar Ahmad Chughtai, Mallory Trent, Edward V O’Loughlin, Michael Stormo

Quantum magnetism in two dimensions: From semi-classical N\'eel order to magnetic disorder

This is a review of ground-state features of the s=1/2 Heisenberg antiferromagnet on two-dimensional lattices. A central issue is the interplay of lattice topology (e.g. coordination number, non-equivalent nearest-neighbor bonds, geometric frustration) and quantum fluctuations and their impact on possible long-range order. This article presents a unified summary of all 11 two-dimensional uniform Archimedean lattices which include e.g. the square, triangular and kagome lattice. We find that the ground state of the spin-1/2 Heisenberg antiferromagnet is likely to be semi-classically ordered in most cases. However, the interplay of geometric frustration and quantum fluctuations gives rise to a quantum paramagnetic ground state without semi-classical long-range order on two lattices which are precisely those among the 11 uniform Archimedean lattices with a highly degenerate ground state in the classical limit. The first one is the famous kagome lattice where many low-lying singlet excitations are known to arise in the spin gap. The second lattice is called star lattice and has a clear gap to all excitations. Modification of certain bonds leads to quantum phase transitions which are also discussed briefly. Furthermore, we discuss the magnetization process of the Heisenberg antiferromagnet on the 11 Archimedean lattices, focusing on anomalies like plateaus and a magnetization jump just below the saturation field. As an illustration we discuss the two-dimensional Shastry-Sutherland model which is used to describe SrCu2(BO3)2.Comment: This is now the complete 72-page preprint version of the 2004 review article. This version corrects two further typographic errors (three total with respect to the published version), see page 2 for detail

Spin-Charge Separation in the t−Jt-J Model: Magnetic and Transport Anomalies

A real spin-charge separation scheme is found based on a saddle-point state of the $t-J$ model. In the one-dimensional (1D) case, such a saddle-point reproduces the correct asymptotic correlations at the strong-coupling fixed-point of the model. In the two-dimensional (2D) case, the transverse gauge field confining spinon and holon is shown to be gapped at {\em finite doping} so that a spin-charge deconfinement is obtained for its first time in 2D. The gap in the gauge fluctuation disappears at half-filling limit, where a long-range antiferromagnetic order is recovered at zero temperature and spinons become confined. The most interesting features of spin dynamics and transport are exhibited at finite doping where exotic {\em residual} couplings between spin and charge degrees of freedom lead to systematic anomalies with regard to a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic fluctuation with a small, doping-dependent energy scale is found, which is characterized in momentum space by a Gaussian peak at ($\pi/a$, $\pi/a$) with a doping-dependent width ($\propto \sqrt{\delta}$, $\delta$ is the doping concentration). This commensurate magnetic fluctuation contributes a non-Korringa behavior for the NMR spin-lattice relaxation rate. There also exits a characteristic temperature scale below which a pseudogap behavior appears in the spin dynamics. Furthermore, an incommensurate magnetic fluctuation is also obtained at a {\em finite} energy regime. In transport, a strong short-range phase interference leads to an effective holon Lagrangian which can give rise to a series of interesting phenomena including linear-$T$ resistivity and $T^2$ Hall-angle. We discuss the striking similarities of these theoretical features with those found in the high-$T_c$ cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request; minor revisions in the text and references have been made; To be published in July 1 issue of Phys. Rev. B52, (1995