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

Regulation of <i>Salmonella</i>-induced membrane ruffling by SipA differs in strains lacking other effectors

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Achieving food and environmental security: new approaches to close the gap

IntroductionAchieving food security in a ‘perfect storm’ scenario is a grand challenge for society. Unless 50% more food, 50% more energy and 30% more freshwater are available by 2030, a ‘perfect storm’ is envisaged where there would be simultaneous shortages of all of these on a global scale [1]. This becomes an even more ‘wicked problem’ when climate change and an expanding global population act in concert, making the challenge of achieving global food security even more complex and demanding.Food security ‘exists when all people, at all times, have physical and economic access to sufficient, safe and nutritious food to meet their dietary needs and food preferences for an active and healthy life’ [2, Plan of Action no. 1]. It is determined by four factors: (i) availability (from agricultural production and land-use or exchange); (ii) stability of supplies (e.g. seasonally and from year to year); (iii) access (dependent on financial means but also physical access and social factors); and (iv) biological utilization of food (e.g. nutritional diversity and food safety issues) [3]. It is estimated that almost one billion people face hunger through lack of macronutrients [4], and a further one billion lack sufficient micronutrients, leading to both negative health and development outcomes [5].Millennium development goal (MDG) number 1 (eradicate hunger and poverty) is effectively coupled to many of the other MDGs; it is imperative that we develop mechanisms to meet MDG 1 and other goals that are complementary and which do not oppose one another. For example, sustainable intensification (SI) of agriculture has been proposed as a way to address hunger while also minimizing further environmental impact. However, the desire to raise productivity and yields has led historically to environmental degradation, reduced biodiversity and limitations to ecosystem services, with the greatest impacts falling upon the poor. Addressing MDGs in isolation can, therefore, be at the expense of others, and improved integration of actions is required. We must increase food security sustainably and in a climate change-resilient manner, while also reducing greenhouse gas emissions, alleviating poverty and conserving biodiversity [4–7]: perhaps the greatest challenge that we have ever faced.The relationship between food security outcomes and the environment is complex and multidimensional [8]. Food security is dependent not only on (non-provisioning) ecosystem services, but it is also one of the greatest drivers of the loss of ecosystem services. The pursuit of food security through increased agricultural production may include changes in land use, land cover, management practices and agricultural inputs, and it a key driver of landscape change [9].The concepts of planetary boundaries and ‘safe operating space’ have already had a significant influence on the international discourse about global sustainability [10]. Nine interlinked ecological boundaries have been defined at the planetary scale, and it is argued that society should remain within these if it is to avoid ‘disastrous consequences for humanity’. Three of these (biodiversity loss, climate change and nitrogen cycling) have all been exceeded, and all are linked to agricultural intensification. A recent and novel framework for considering this concept has been proposed by economists from Oxfam [11]. The ‘safe and just operating spaces’ (doughnut) idea argues for the need to live within the ‘space’ that lies beneath the planetary boundary, yet above the social floor of basic and just needs for food, energy and water security, and social goods such as education and healthcare.How do we deliver food security for all, without further exceeding planetary boundaries that have already been breached? Many of these social and just boundaries are linked to the MDGs and will undoubtedly be within the emerging sustainable development goals planned for post-2015. Science must play a central role in providing innovative solutions to these challenges, and this special issue of the Philosophical Transactions of the Royal Society B captures a Discussion Meeting (‘Achieving food and environmental security: new approaches to close the gap’) that took place at the Royal Society, in London between 3 and 4 December 2012, to explore some of avenues that science is currently pursuing. It invited prominent speakers to report on (i) the challenges that we face in achieving food and environmental security, (ii) research and extension in pursuit of sustainable production intensification, (iii) innovation for sustainable agriculture and (iv) using the ecosystem services framework for managing agricultural ecosystems.Following the London meeting, a workshop was held at the Kavli International Centre between 5 and 6 December 2012. Discussions at this meeting focused on reviewing the key issues, barriers and opportunities for science to contribute towards the new global agricultural systems that are needed to deliver food security. From this workshop, a statement ‘The Kavli Declaration: a vision for agriculture in 2050’ was developed. All of the attendees at the Kavli workshop have signed the declaration, which is presented in box 1

Co-culture Of Two Mdck Strains With Distinct Junctional Protein Expression: A Model For Intercellular Junction Rearrangement And Cell Sorting

Distinct epithelial MDCK cell strains displaying extremes in transepithelial electrical resistance (paracellular permeability) have been established in co-culture and the subsequent cellular behaviour and formation of junctional complexes investigated. After high-density seeding, MDCK strain I and II cells in co-culture are initially randomly distributed but subsequently sort themselves out in a time-dependent manner to form separate homotypic aggregates. The final pattern of cell arrangement of homotypic aggregates depends on the relative seeding proportion of each cell type. Immunostaining of established marker proteins for junctional complexes has revealed that MDCK I and II cells differ in the degree of expression of the zonula-adherens-associated protein, E-cadherin, their cytoskeletal architecture and the junctional distribution of a desmosomal protein, and by showing subtle differences in tight junction staining for the zona-occludens-associated proteins, ZO-1 and occludin. The distinct pattern of junctional protein expression is maintained when the two MDCK strains are co-cultured; however, morphologically atypical intercellular junctions between heterotypic cells at the boundary of homotypic cell aggregates have been observed. It has been suggested that cell sorting, a phenomenon yet to be completely understood, is involved in important morphogenetic processes. 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