Soft network composite materials with deterministic and bio-inspired designs

Hard and soft structural composites found in biology provide inspiration for the design of advanced synthetic materials. Many examples of bio-inspired hard materials can be found in the literature; far less attention has been devoted to soft systems. Here we introduce deterministic routes to low-modulus thin film materials with stress/strain responses that can be tailored precisely to match the non-linear properties of biological tissues, with application opportunities that range from soft biomedical devices to constructs for tissue engineering. The approach combines a low-modulus matrix with an open, stretchable network as a structural reinforcement that can yield classes of composites with a wide range of desired mechanical responses, including anisotropic, spatially heterogeneous, hierarchical and self-similar designs. Demonstrative application examples in thin, skin-mounted electrophysiological sensors with mechanics precisely matched to the human epidermis and in soft, hydrogel-based vehicles for triggered drug release suggest their broad potential uses in biomedical devices. © 2015 Macmillan Publishers Limited. All rights reservedopen7

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs

BACKGROUND: Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression. METHODS: To identify early markers of VILI, preterm lambs (132 d gestational age; GA, term approximately 147 d) were resuscitated with an injurious ventilation strategy (V(T) 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a V(T) of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses. RESULTS: CTGF, CYR61 and EGR1 lung mRNA levels were increased approximately 25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance. CONCLUSION: CTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes

Estimating the Cost of Type 1 Diabetes in the U.S.: A Propensity Score Matching Method

Diabetes costs represent a large burden to both patients and the health care system. However, few studies that examine the economic consequences of diabetes have distinguished between the two major forms, type 1 and type 2 diabetes, despite differences in underlying pathologies. Combining the two diseases implies that there is no difference between the costs of type 1 and type 2 diabetes to a patient. In this study, we examine the costs of type 1 diabetes, which is often overlooked due to the larger population of type 2 patients, and compare them to the estimated costs of diabetes reported in the literature.Using a nationally representative dataset, we estimate yearly and lifetime medical and indirect costs of type 1 diabetes by implementing a matching method to compare a patient with type 1 diabetes to a similar individual without the disease. We find that each year type 1 diabetes costs this country $14.4 billion (11.5-17.3) in medical costs and lost income. In terms of lost income, type 1 patients incur a disproportionate share of type 1 and type 2 costs. Further, if the disease were eliminated by therapeutic intervention, an estimated$10.6 billion (7.2-14.0) incurred by a new cohort and $422.9 billion (327.2-519.4) incurred by the existing number of type 1 diabetic patients over their lifetime would be avoided.We find that the costs attributed to type 1 diabetes are disproportionately higher than the number of type 1 patients compared with type 2 patients, suggesting that combining the two diseases when estimating costs is not appropriate. This study and another recent contribution provides a necessary first step in estimating the substantial costs of type 1 diabetes on the U.S

Sortase A Substrate Specificity in GBS Pilus 2a Cell Wall Anchoring

Streptococcus agalactiae, also referred to as Group B Streptococcus (GBS), is one of the most common causes of life-threatening bacterial infections in infants. In recent years cell surface pili have been identified in several Gram-positive bacteria, including GBS, as important virulence factors and promising vaccine candidates. In GBS, three structurally distinct types of pili have been discovered (pilus 1, 2a and 2b), whose structural subunits are assembled in high-molecular weight polymers by specific class C sortases. In addition, the highly conserved housekeeping sortase A (SrtA), whose main role is to link surface proteins to bacterial cell wall peptidoglycan by a transpeptidation reaction, is also involved in pili cell wall anchoring in many bacteria. Through in vivo mutagenesis, we demonstrate that the LPXTG sorting signal of the minor ancillary protein (AP2) is essential for pilus 2a anchoring. We successfully produced a highly purified recombinant SrtA (SrtAΔN40) able to specifically hydrolyze the sorting signal of pilus 2a minor ancillary protein (AP2-2a) and catalyze in vitro the transpeptidation reaction between peptidoglycan analogues and the LPXTG motif, using both synthetic fluorescent peptides and recombinant proteins. By contrast, SrtAΔN40 does not catalyze the transpeptidation reaction with substrate-peptides mimicking sorting signals of the other pilus 2a subunits (the backbone protein and the major ancillary protein). Thus, our results add further insight into the proposed model of GBS pilus 2a assembly, in which SrtA is required for pili cell wall covalent attachment, acting exclusively on the minor accessory pilin, representing the terminal subunit located at the base of the pilus

Approachability in Stackelberg Stochastic Games with Vector Costs

The notion of approachability was introduced by Blackwell [1] in the context of vector-valued repeated games. The famous Blackwell's approachability theorem prescribes a strategy for approachability, i.e., for `steering' the average cost of a given agent towards a given target set, irrespective of the strategies of the other agents. In this paper, motivated by the multi-objective optimization/decision making problems in dynamically changing environments, we address the approachability problem in Stackelberg stochastic games with vector valued cost functions. We make two main contributions. Firstly, we give a simple and computationally tractable strategy for approachability for Stackelberg stochastic games along the lines of Blackwell's. Secondly, we give a reinforcement learning algorithm for learning the approachable strategy when the transition kernel is unknown. We also recover as a by-product Blackwell's necessary and sufficient condition for approachability for convex sets in this set up and thus a complete characterization. We also give sufficient conditions for non-convex sets.Comment: 18 Pages, Submitted to Dynamic Games and Application

A systematic review of population health interventions and Scheduled Tribes in India

<p>Abstract</p> <p>Background</p> <p>Despite India's recent economic growth, health and human development indicators of Scheduled Tribes (ST) or <it>Adivasi </it>(India's indigenous populations) lag behind national averages. The aim of this review was to identify the public health interventions or components of these interventions that are effective in reducing morbidity or mortality rates and reducing risks of ill health among ST populations in India, in order to inform policy and to identify important research gaps.</p> <p>Methods</p> <p>We systematically searched and assessed peer-reviewed literature on evaluations or intervention studies of a population health intervention undertaken with an ST population or in a tribal area, with a population health outcome(s), and involving primary data collection.</p> <p>Results</p> <p>The evidence compiled in this review revealed three issues that promote effective public health interventions with STs: (1) to develop and implement interventions that are low-cost, give rapid results and can be easily administered, (2): a multi-pronged approach, and (3): involve ST populations in the intervention.</p> <p>Conclusion</p> <p>While there is a growing body of knowledge on the health needs of STs, there is a paucity of data on how we can address these needs. We provide suggestions on how to undertake future population health intervention research with ST populations and offer priority research avenues that will help to address our knowledge gap in this area.</p