Analysis and Functional Consequences of Increased Fab-Sialylation of Intravenous Immunoglobulin (IVIG) after Lectin Fractionation

It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab’)2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation

Multiscale scenarios for nature futures

Targets for human development are increasingly connected with targets for nature, however, existing scenarios do not explicitly address this relationship. Here, we outline a strategy to generate scenarios centred on our relationship with nature to inform decision-making at multiple scales

Introduction: exploring and explaining the Asia-Pacific Partnership on Clean Development and Climate

This introduction lays the groundwork for this Special Issue by providing an overview of the Asia-Pacific Partnership on Clean Development and Climate (APP), and by introducing three main analytical themes. The first theme concerns the emergence and continuation of the APP. The contributions show that the emergence of the APP can be attributed to international factors, including the United States' rejection of the Kyoto Protocol, and its search for an alternative arena for global climate governance, and other countries' wish to maintain good relations with the US; as well as domestic factors, such as the presence of bureaucratic actors in favour of the Partnership, alignment with domestic priorities, and the potential for reaping economic benefits through participation. The second theme examines the nature of the Partnership, concluding that it falls on the very soft side of the hard-soft law continuum and that while being branded as a public-private partnership, governments remain in charge. Under the third theme, the influence which the APP exerts on the post-2012 United Nations (UN) climate change negotiations is scrutinised. The contributions show that at the very least, the APP is exerting some cognitive influence on the UN discussions through its promotion of a sectoral approach. The introduction concludes with outlining areas for future research. © Springer Science+Business Media B.V. 2009

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Faecalibacterium prausnitzii : from microbiology to diagnostics and prognostics

We thank Dr Xavier Aldeguer and MD David Busquets from the Hospital Dr Josep Trueta (Girona, Spain) and M.D Míriam Sabat Mir from the Hospital Santa Caterina (Salt, Spain) for their help and critical discussion concerning clinical aspects. This work was partially funded by the Spanish Ministry of Education and Science through the projects SAF2010-15896 and SAF2013-43284-P, which has been co-financed with FEDER funds. Dr Sylvia H Duncan acknowledges support from the Scottish Government Food, Land and People program.Peer reviewedPostprin

Read all about it!? Public accountability, fragmented global climate governance and the media

The way that the media reports and comments on key events in the fragmented global climate governance landscape is one important route to strengthening public accountability of such governance. Editorials and other opinion pieces provide key contributions to the public sphere, but have been almost entirely neglected in media research on climate change. Another understudied aspect in such research is the reporting on the fragmentation of global climate governance across numerous forums. This article provides an exploratory approach to address these two research gaps. It presents a quantitative analysis of how often leading newspapers in seven countries (Finland, India, Laos, Norway, South Africa, UK and USA) wrote about 18 meetings in six different global climate governance forums between 2004–2009 and whether they provided commentaries about them. The study shows that media coverage (articles and opinion pieces) is limited or absent for many meetings that are not attended by heads of state, are the launch of a new process or do not have the convening power of the United Nations Framework Convention on Climate Change. The pattern of coverage differs significantly among individual newspapers and there is no clear distinction between developed and developing country newspapers. The article concludes that overall news coverage, and editorial commentary in particular, of global climate meetings in the selected newspapers is too low and too patchy to significantly support domestic publics to hold their own (and indirectly other) governments accountable with regard to fragmented global climate governance

Enhancing implementation of the Convention on Biological Diversity : A novel peer-review mechanism aims to promote accountability and mutual learning

The Convention on Biological Diversity (CBD) – the main international environmental agreement (IEA) for securing our planet's life-supporting systems – is far from delivering its commitments: the 2010 Biodiversity Target was not met, and states are already failing to achieve the Aichi Biodiversity Targets by the 2020 deadline. Whilst this is not an uncommon outcome in IEAs and other internationally adopted environmental goals, the important question is: how to transform this situation? Review processes on implementation of international norms are one important means for this, as resulting information has potential to mobilise criticism, praise and/or feedback from peers and civil society organisations. Criticism may in turn put pressure on and/or encourage states to justify their behaviour and to take actions. In this context, beyond normative considerations as a practice of good governance, accountability is conceptualised as an active practice of giving and demanding of reason of conduct with transformative potential. Our starting argument is that review processes that enable account-holding dynamics have potential to promote implementation of IEAs. In order to assess whether the CBD enables such dynamics, we characterise the CBD's review system, and analyse its review mechanisms from the relational perspective of accountability. In particular, we focus on a novel voluntary peer-review mechanism (VPR) that is to be applied in a pilot phase, as requested by the Conference of the Parties at its thirteenth meeting held in December 2016. We then discuss the potential of the VPR to enable transformative accountability dynamics and enhance national implementation in the CBD