Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge up to 20 times the weight of a normal kidney due to the growth of renal cysts, and patients with ADPKD have an increased risk of morbidity, premature mortality, and other life-time complications including renal and hepatic cyst and urinary tract infection, intracranial aneurysm, diverticulosis, and kidney pain which impair quality of life. Despite some therapeutic advances and the growing number of clinical trials in ADPKD, the outcomes that are relevant to patients and clinicians, such as symptoms and quality of life, are infrequently and inconsistently reported. This potentially limits the contribution of trials to inform evidence-based decision-making. The Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based set of core outcomes for trials in PKD (with an initial focus on ADPKD but inclusive of all stages) that patients and health professionals identify as critically important. METHODS: The five phases of SONG-PKD are: a systematic review to identify outcomes that have been reported in existing PKD trials; focus groups with nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choices; qualitative stakeholder interviews with health professionals to elicit individual values and perspectives on outcomes for trials involving patients with PKD; an international three-round Delphi survey with all stakeholder groups (including patients, caregivers, healthcare providers, policy makers, researchers, and industry) to gain consensus on critically important core outcome domains; and a consensus workshop to review and establish a set of core outcome domains and measures for trials in PKD. DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency and completeness of outcome reporting across ADPKD trials, leading to improvements in the reliability and relevance of trial-based evidence to inform decisions about treatment and ultimately improve the care and outcomes for people with ADPKD

A discrete latent factor model of smoking, cancer and mortality

This paper investigates the relationship between smoking and ill-health, with a focus on the onset of cancer. A discrete latent factor model for smoking and health outcomes, allowing for these to be commonly affected by unobserved factors, is jointly estimated, using the British Health and Lifestyle Survey (HALS) dataset. Post-estimation predictions suggest the reduction in time-to-cancer to be 5.7 years for those with an exposure of 30 pack-years, compared to never-smokers. Estimation of posterior probabilities for class membership shows that individuals in certain classes exhibit similar observables but highly divergent health outcomes, suggesting that unobserved factors influence outcomes. The use of a joint model changes the results substantially. The results show that failure to account for unobserved heterogeneity leads to differences in survival times between those with different smoking exposures to be overestimated by more than 50% (males, with 30 pack-years of exposure)

School-based physical education programs: evidence-based physical activity interventions for youth in Latin America

This article focuses on results of the systematic review from the Guide for Useful Interventions for Activity in Latin America project related to school-based physical education (PE) programs in Latin America. The aims of the article are to describe five school-based PE programs from Latin America, discuss implications for effective school-based PE recommendations, propose approaches for implementing these interventions, and identify gaps in the research literature related to physical activity promotion in Latin American youth. Following the US Community Guide systematic review process, five school-based PE intervention studies with sufficient quality of design, execution and detail of intervention and outcomes were selected for full abstraction. One study was conducted in Brazil, two studies were conducted in Chile and two studies were conducted on the US/Mexico border. While studies presented assorted outcomes, methods and duration of interventions, there were consistent positive increases in physical activity levels for all outcomes measured during PE classes, endurance and active transportation to school in all three randomized studies. Except for one cohort from one study, the non-randomized studies showed positive intervention effects for moderate and vigorous physical activity levels during PE classes. The core elements of these five interventions included capacity building and staff training (PE specialists and/or classroom teachers); changes in the PE curricula; provision of equipment and materials; and adjustment of the interventions to specific target populations. In order to translate the strong evidence for school-based PE into practice, systematic attention to policy and implementation issues is required. (Global Health Promotion, 2010; 17(2): pp. 05–15

Functional characterization of the PHT1 family transporters of foxtail millet with development of a novel Agrobacterium-mediated transformation procedure

Phosphate is an essential nutrient for plant growth and is acquired from the environment and distributed within the plant in part through the action of phosphate transporters of the PHT1 family. Foxtail millet (Setaria italica) is an orphan crop essential to the food security of many small farmers in Asia and Africa and is a model system for other millets. A novel Agrobacterium-mediated transformation and direct plant regeneration procedure was developed from shoot apex explants and used to downregulate expression of 3 members of the PHT1 phosphate transporter family SiPHT1;2 SiPHT1;3 and SiPHT1;4. Transformants were recovered with close to 10% efficiency. The downregulation of individual transporters was confirmed by RT-PCR. Downregulation of individual transporters significantly reduced the total and inorganic P contents in shoot and root tissues and increased the number of lateral roots and root hairs showing they have non-redundant roles. Downregulation of SiPHT1;2 had the strongest effect on total and inorganic P in shoot and root tissues. Complementation experiments in S. cerevisiae provide evidence for the ability of SiPHT1;1, 1;2, 1;3, 1;7 and 1;8 to function as high affinity Pi transporters. This work will aid development of improved millet varieties for global food security

Livelihoods, conflict and aid programming: Is the evidence base good enough?

In conflict-affected situations, aid-funded livelihood interventions are often tasked with a dual imperative: to generate material welfare benefits and to contribute to peacebuilding outcomes. There may be some logic to such a transformative agenda, but does the reality square with the rhetoric? Through a review of the effectiveness of a range of livelihood promotion interventions—from job creation to microfinance—this paper finds that high quality empirical evidence is hard to come by in conflict-affected situations. Many evaluations appear to conflate outputs with impacts and numerous studies fail to include adequate information on their methodologies and datasets, making it difficult to appraise the reliability of their conclusions. Given the primary purpose of this literature—to provide policy guidance on effective ways to promote livelihoods— this silence is particularly concerning. As such, there is a strong case to be made for a restrained and nuanced handling of such interventions in conflict-affected settings.Department for International Development - PO511

Contour models of cellular adhesion

The development of traction-force microscopy, in the past two decades, has created the unprecedented opportunity of performing direct mechanical measurements on living cells as they adhere or crawl on uniform or micro-patterned substrates. Simultaneously, this has created the demand for a theoretical framework able to decipher the experimental observations, shed light on the complex biomechanical processes that govern the interaction between the cell and the extracellular matrix and offer testable predictions. Contour models of cellular adhesion, represent one of the simplest and yet most insightful approach in this problem. Rooted in the paradigm of active matter, these models allow to explicitly determine the shape of the cell edge and calculate the traction forces experienced by the substrate, starting from the internal and peripheral contractile stresses as well as the passive restoring forces and bending moments arising within the actin cortex and the plasma membrane. In this chapter I provide a general overview of contour models of cellular adhesion and review the specific cases of cells equipped with isotropic and anisotropic actin cytoskeleton as well as the role of bending elasticity.Comment: 24 pages, 9 figures. arXiv admin note: text overlap with arXiv:1304.107

Management and valorisation of wastes through use in producing alkali-activated cement materials

There is a growing global interest in maximising the re-use and recycling of waste, to minimise the environmental impacts associated with waste treatment and disposal. Use of high-volume wastes in the production of blended or novel cements (including alkali-activated cements) is well known as a key pathway by which these wastes can be re-used. This paper presents a critical overview of the urban, agricultural, mining and industrial wastes that have been identified as potential precursors for the production of alkali-activated cement materials, or that can be effectively stabilised/solidified via alkali activation, to assure their safe disposal. The central aim of this review is to elucidate the potential advantages and pitfalls associated with the application of alkali-activation technology to a wide variety of wastes that have been claimed to be suitable for the production of construction materials. A brief overview of the generation and characteristics of each waste is reported, accompanied by identification of opportunities for the use of alkali-activation technology for their valorisation and/or management

Prevalence of disability in a composite ≥75 year-old population in Spain: A screening survey based on the International Classification of Functioning

<p>Abstract</p> <p>Background</p> <p>The prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF.</p> <p>Methods</p> <p>Nine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2^ndedition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100).</p> <p>Results</p> <p>The age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32).</p> <p>Conclusions</p> <p>Disability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.</p