Coupling Optical and Electrical Measurements in Artificial Membranes: Lateral Diffusion of Lipids and Channel Forming Peptides in Planar Bilayers

Planar lipid bilayers (PLB) were prepared by the Montal-Mueller technique in a FRAP system designed to simultaneously measure conductivity across, and lateral diffusion of, the bilayer. In the first stage of the project the FRAP system was used to characterise the lateral dynamics of bilayer lipids with regards to phospholipid composition (headgroup, chain unsaturation etc.), presence of cholesterol and the effect of divalent cations on negatively-charged bilayers. In the second stage of the project, lateral diffusion of two fluorescently-labelled voltage-dependent pore-forming peptides (alamethicin and S4s from Shaker K(+) channel) was determined at rest and in the conducting state. This study demonstrates the feasibility of such experiments with PLBs, amenable to physical constraints, and thus offers new opportunities for systematic studies of structure-function relationships in membrane-associating molecules

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

Emerging Themes and Future Directions of Multi-Sector Nexus Research and Implementation

Water, energy, and food are all essential components of human societies. Collectively, their respective resource systems are interconnected in what is called the “nexus”. There is growing consensus that a holistic understanding of the interdependencies and trade-offs between these sectors and other related systems is critical to solving many of the global challenges they present. While nexus research has grown exponentially since 2011, there is no unified, overarching approach, and the implementation of concepts remains hampered by the lack of clear case studies. Here, we present the results of a collaborative thought exercise involving 75 scientists and summarize them into 10 key recommendations covering: the most critical nexus issues of today, emerging themes, and where future efforts should be directed. We conclude that a nexus community of practice to promote open communication among researchers, to maintain and share standardized datasets, and to develop applied case studies will facilitate transparent comparisons of models and encourage the adoption of nexus approaches in practice

Integrated assessment of urban water supply security and resilience: towards a streamlined approach

Urbanization and competing water demand, as well as rising temperatures and changing weather patterns, are manifesting as gradual processes that increasingly challenge urban water supply security. Cities are also threatened by acute risks arising at the intersection of aging infrastructure, entrenched institutions, and the increasing occurrence of extreme weather events. To better understand these multi-layered, interacting challenges of providing urban water supply for all, while being prepared to deal with recurring shocks, we present an integrated analysis of water supply security in New York City and its resilience to acute shocks and chronic disturbances. We apply a revised version of a recently developed, quantitative framework ('Capital Portfolio Approach', CPA) that takes a social-ecological-technological systems perspective to assess urban water supply security as the performance of water services at the household scale. Using the parameters of the CPA as input, we use a coupled systems dynamics model to investigate the dynamics of services in response to shocks—under current conditions and in a scenario of increasing shock occurrence and a loss of system robustness. We find water supply security to be high and current response to shocks to be resilient thanks to past shock experiences. However, we identify a number of risks and vulnerability issues that, if unaddressed, might significantly impact the city's water services in the mid-term future. Our findings have relevance to cities around the world, and raise questions for research about how security and resilience can and should be maintained in the future

Integrated assessment of urban water supply security and resilience: towards a streamlined approach

Urbanization and competing water demand, as well as rising temperatures and changing weather patterns, are manifesting as gradual processes that increasingly challenge urban water supply security. Cities are also threatened by acute risks arising at the intersection of aging infrastructure, entrenched institutions, and the increasing occurrence of extreme weather events. To better understand these multi-layered, interacting challenges of providing urban water supply for all, while being prepared to deal with recurring shocks, we present an integrated analysis of water supply security in New York City and its resilience to acute shocks and chronic disturbances. We apply a revised version of a recently developed, quantitative framework ('Capital Portfolio Approach', CPA) that takes a social-ecological-technological systems perspective to assess urban water supply security as the performance of water services at the household scale. Using the parameters of the CPA as input, we use a coupled systems dynamics model to investigate the dynamics of services in response to shocks—under current conditions and in a scenario of increasing shock occurrence and a loss of system robustness. We find water supply security to be high and current response to shocks to be resilient thanks to past shock experiences. However, we identify a number of risks and vulnerability issues that, if unaddressed, might significantly impact the city's water services in the mid-term future. Our findings have relevance to cities around the world, and raise questions for research about how security and resilience can and should be maintained in the future