845 research outputs found

    Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic ischemic encephalopathy: a non-randomised cohort study

    Get PDF
    Objective To examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE). Design Non-randomised cohort study. Setting Eight tertiary neonatal units in the UK and the USA. Patients 47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth. Interventions Whole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours). Main outcome measures MRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years. Results The baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09). Conclusions Therapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials

    Discovering Polarized Communities in Signed Networks

    Full text link
    Signed networks contain edge annotations to indicate whether each interaction is friendly (positive edge) or antagonistic (negative edge). The model is simple but powerful and it can capture novel and interesting structural properties of real-world phenomena. The analysis of signed networks has many applications from modeling discussions in social media, to mining user reviews, and to recommending products in e-commerce sites. In this paper we consider the problem of discovering polarized communities in signed networks. In particular, we search for two communities (subsets of the network vertices) where within communities there are mostly positive edges while across communities there are mostly negative edges. We formulate this novel problem as a "discrete eigenvector" problem, which we show to be NP-hard. We then develop two intuitive spectral algorithms: one deterministic, and one randomized with quality guarantee n\sqrt{n} (where nn is the number of vertices in the graph), tight up to constant factors. We validate our algorithms against non-trivial baselines on real-world signed networks. Our experiments confirm that our algorithms produce higher quality solutions, are much faster and can scale to much larger networks than the baselines, and are able to detect ground-truth polarized communities

    Neurotransmitters Drive Combinatorial Multistate Postsynaptic Density Networks

    Get PDF
    The mammalian postsynaptic density (PSD) comprises a complex collection of ~1100 proteins. Despite extensive knowledge of individual proteins, the overall organization of the PSD is poorly understood. Here, we define maps of molecular circuitry within the PSD based on phosphorylation of postsynaptic proteins. Activation of a single neurotransmitter receptor, the N-methyl-D-aspartate receptor (NMDAR), changed the phosphorylation status of 127 proteins. Stimulation of ionotropic and metabotropic glutamate receptors and dopamine receptors activated overlapping networks with distinct combinatorial phosphorylation signatures. Using peptide array technology, we identified specific phosphorylation motifs and switching mechanisms responsible for the integration of neurotransmitter receptor pathways and their coordination of multiple substrates in these networks. These combinatorial networks confer high information-processing capacity and functional diversity on synapses, and their elucidation may provide new insights into disease mechanisms and new opportunities for drug discover

    Hypothermia for encephalopathy in low-income and middle-income countries: feasibility of whole-body cooling using a low-cost servo-controlled device

    No full text
    Although therapeutic hypothermia (TH) is the standard of care for hypoxic ischaemic encephalopathy in high-income countries, the safety and efficacy of this therapy in low-income and middle-income countries (LMICs) is unknown. We aimed to describe the feasibility of TH using a low-cost servo-controlled cooling device and the short-term outcomes of the cooled babies in LMIC. Design: We recruited babies with moderate or severe hypoxic ischaemic encephalopathy (aged <6 hours) admitted to public sector tertiary neonatal units in India over a 28-month period. We administered whole-body cooling (set core temperature 33.5°C) using a servo-controlled device for 72 hours, followed by passive rewarming. We collected the data on short-term neonatal outcomes prior to hospital discharge. Results: Eighty-two babies were included-61 (74%) had moderate and 21 (26%) had severe encephalopathy. Mean (SD) hypothermia cooling induction time was 1.7 hour (1.5) and the effective cooling time 95% (0.08). The mean (SD) hypothermia induction time was 1.7 hour (1.5 hour), core temperature during cooling was 33.4°C (0.2), rewarming rate was 0.34°C (0.16°C) per hour and the effective cooling time was 95% (8%). Twenty-five (51%) babies had gastric bleeds, 6 (12%) had pulmonary bleeds and 21 (27%) had meconium on delivery. Fifteen (18%) babies died before discharge from hospital. Heart rate more than 120 bpm during cooling (P=0.01) and gastric bleeds (P<0.001) were associated with neonatal mortality. Conclusions: The low-cost servo-controlled cooling device maintained the core temperature well within the target range. Adequately powered clinical trials are required to establish the safety and efficacy of TH in LMICs. Clinical trial registration number: NCT01760629

    Specific-Heat Exponent of Random-Field Systems via Ground-State Calculations

    Full text link
    Exact ground states of three-dimensional random field Ising magnets (RFIM) with Gaussian distribution of the disorder are calculated using graph-theoretical algorithms. Systems for different strengths h of the random fields and sizes up to N=96^3 are considered. By numerically differentiating the bond-energy with respect to h a specific-heat like quantity is obtained, which does not appear to diverge at the critical point but rather exhibits a cusp. We also consider the effect of a small uniform magnetic field, which allows us to calculate the T=0 susceptibility. From a finite-size scaling analysis, we obtain the critical exponents \nu=1.32(7), \alpha=-0.63(7), \eta=0.50(3) and find that the critical strength of the random field is h_c=2.28(1). We discuss the significance of the result that \alpha appears to be strongly negative.Comment: 9 pages, 9 figures, 1 table, revtex revised version, slightly extende

    Maximum gradient embeddings and monotone clustering

    Full text link
    Let (X,d_X) be an n-point metric space. We show that there exists a distribution D over non-contractive embeddings into trees f:X-->T such that for every x in X, the expectation with respect to D of the maximum over y in X of the ratio d_T(f(x),f(y)) / d_X(x,y) is at most C (log n)^2, where C is a universal constant. Conversely we show that the above quadratic dependence on log n cannot be improved in general. Such embeddings, which we call maximum gradient embeddings, yield a framework for the design of approximation algorithms for a wide range of clustering problems with monotone costs, including fault-tolerant versions of k-median and facility location.Comment: 25 pages, 2 figures. Final version, minor revision of the previous one. To appear in "Combinatorica

    Stress perfusion cardiovascular magnetic resonance and serial fractional flow reserve assessment of the left anterior descending artery in patients undergoing right coronary artery chronic total occlusion revascularization

    Get PDF
    Background: Fractional flow reserve (FFR) assessment of remote arteries, in the context of a bystander chronic total occlusion (CTO), can lead to false positive results. Adenosine stress cardiovascular magnetic resonance (CMR) evaluates perfusion defects across the entire myocardium and may therefore be a reliable tool in the work-up of remote lesions in CTO patients. The IMPACT-CTO study investigated donor artery invasive physiology before, immediately post, and at 4 months following right coronary artery (RCA) CTO percutaneous coronary intervention (PCI). The aim of this subanalysis was to assess the concordance between baseline perfusion CMR and serial FFR evaluation of left anterior descending artery (LAD) ischemia in patients from the IMPACT-CTO study.Methods: Baseline adenosine stress CMR examinations from 26 patients were analyzed for qualitative evidence of LAD ischemia. The results were correlated with the serial LAD FFR measurements.Results: The present findings demonstrated that before RCA CTO PCI, there was 62% agreement between perfusion CMR and FFR (ischemic threshold £ 0.8) in the assessment of LAD ischemia (k = 0.29; fair concordance). At 4 months after revascularization, there was 77% agreement (k = 0.52; moderate concordance) between the index CMR assessment of LAD ischemia and the follow-up LAD FFR. Concordance was improved at a LAD FFR ischemic threshold of £ 0.75.Conclusions: In this hypothesis generating study, baseline CMR assessment of LAD ischemia correlated better with the 4 months LAD FFR data (threshold £ 0.8) as compared to the FFR measurements taken prior to RCA CTO revascularization

    Kurt Symanzik - a stable fixed point beyond triviality

    Full text link
    In 1970 Kurt Symanzik proposed a "precarious" phi**4-theory with a negative quartic coupling constant as a valid candidate for an asymptotically free theory of strong interactions. Symanzik's deep insight in the non-trivial properties of this theory has been overruled since then by the Hermitian intuition of generations of scientists, who considered or consider this actually non-Hermitian highly important theory to be unstable. This short - certainly controversial - communication tries to shed some light on the historical and formalistic context of Symanzik's theory in order to sharpen our (quantum) intuition about non-perturbative theoretical physics between (non)triviality and asymptotic freedom.Comment: 6 pages, no figures, new style files, revised for typos, improved discussion, new references adde
    • …
    corecore