Use of Intravenous Peramivir for Treatment of Severe Influenza A(H1N1)pdm09

Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety

Electronic transport in polycrystalline graphene

Most materials in available macroscopic quantities are polycrystalline. Graphene, a recently discovered two-dimensional form of carbon with strong potential for replacing silicon in future electronics, is no exception. There is growing evidence of the polycrystalline nature of graphene samples obtained using various techniques. Grain boundaries, intrinsic topological defects of polycrystalline materials, are expected to dramatically alter the electronic transport in graphene. Here, we develop a theory of charge carrier transmission through grain boundaries composed of a periodic array of dislocations in graphene based on the momentum conservation principle. Depending on the grain boundary structure we find two distinct transport behaviours - either high transparency, or perfect reflection of charge carriers over remarkably large energy ranges. First-principles quantum transport calculations are used to verify and further investigate this striking behaviour. Our study sheds light on the transport properties of large-area graphene samples. Furthermore, purposeful engineering of periodic grain boundaries with tunable transport gaps would allow for controlling charge currents without the need of introducing bulk band gaps in otherwise semimetallic graphene. The proposed approach can be regarded as a means towards building practical graphene electronics.Comment: accepted in Nature Material

Anticipatory governance for social-ecological resilience

Anticipation is increasingly central to urgent contemporary debates, from climate change to the global economic crisis. Anticipatory practices are coming to the forefront of political, organizational, and citizens’ society. Research into anticipation, however, has not kept pace with public demand for insights into anticipatory practices, their risks and uses. Where research exists, it is deeply fragmented. This paper seeks to identify how anticipation is defined and understood in the literature and to explore the role of anticipatory practice to address individual, social, and global challenges. We use a resilience lens to examine these questions. We illustrate how varying forms of anticipatory governance are enhanced by multi-scale regional networks and technologies and by the agency of individuals, drawing from an empirical case study on regional water governance of Malaren, Sweden. Finally, we discuss how an anticipatory approach can inform adaptive institutions, decision making, strategy formation, and societal resilience

Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk factors for hospital mortality

<p>Abstract</p> <p>Background</p> <p>In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection.</p> <p>Methods</p> <p>We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis.</p> <p>Results</p> <p>Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052).</p> <p>Conclusions</p> <p>Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.</p

A Neurophysiologically Plausible Population Code Model for Feature Integration Explains Visual Crowding

An object in the peripheral visual field is more difficult to recognize when surrounded by other objects. This phenomenon is called “crowding”. Crowding places a fundamental constraint on human vision that limits performance on numerous tasks. It has been suggested that crowding results from spatial feature integration necessary for object recognition. However, in the absence of convincing models, this theory has remained controversial. Here, we present a quantitative and physiologically plausible model for spatial integration of orientation signals, based on the principles of population coding. Using simulations, we demonstrate that this model coherently accounts for fundamental properties of crowding, including critical spacing, “compulsory averaging”, and a foveal-peripheral anisotropy. Moreover, we show that the model predicts increased responses to correlated visual stimuli. Altogether, these results suggest that crowding has little immediate bearing on object recognition but is a by-product of a general, elementary integration mechanism in early vision aimed at improving signal quality

Genome-Wide Study of Gene Variants Associated with Differential Cardiovascular Event Reduction by Pravastatin Therapy

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8×10−7). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins

Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams

Natural Intelligence and Anthropic Reasoning

This paper aims to justify the concept of natural intelligence in the biosemiotic context. I will argue that the process of life is (i) a cognitive/semiotic process and (ii) that organisms, from bacteria to animals, are cognitive or semiotic agents. To justify these arguments, the neural-type intelligence represented by the form of reasoning known as anthropic reasoning will be compared and contrasted with types of intelligence explicated by four disciplines of biology – relational biology, evolutionary epistemology, biosemiotics and the systems view of life – not biased towards neural intelligence. The comparison will be achieved by asking questions related to the process of observation and the notion of true observers. To answer the questions I will rely on a range of established concepts including SETI (search for extraterrestrial intelligence), Fermi’s paradox, bacterial cognition, versions of the panspermia theory, as well as some newly introduced concepts including biocivilisations, cognitive/semiotic universes, and the cognitive/semiotic multiverse. The key point emerging from the answers is that the process of cognition/semiosis – the essence of natural intelligence – is a biological universal.Brunel University Londo

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Exclusive breastfeeding (EBF)-giving infants only breast-milk for the first 6 months of life-is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization's Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.This work was primarily supported by grant no. OPP1132415 from the Bill & Melinda Gates Foundation. Co-authors used by the Bill & Melinda Gates Foundation (E.G.P. and R.R.3) provided feedback on initial maps and drafts of this manuscript. L.G.A. has received support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Código de Financiamento 001 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant nos. 404710/2018-2 and 310797/2019-5). O.O.Adetokunboh acknowledges the National Research Foundation, Department of Science and Innovation and South African Centre for Epidemiological Modelling and Analysis. M.Ausloos, A.Pana and C.H. are partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project no. PN-III-P4-ID-PCCF-2016-0084. P.C.B. would like to acknowledge the support of F. Alam and A. Hussain. T.W.B. was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. K.Deribe is supported by the Wellcome Trust (grant no. 201900/Z/16/Z) as part of his international intermediate fellowship. C.H. and A.Pana are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project no. PN-III-P2-2.1-SOL-2020-2-0351. B.Hwang is partially supported by China Medical University (CMU109-MF-63), Taichung, Taiwan. M.Khan acknowledges Jatiya Kabi Kazi Nazrul Islam University for their support. A.M.K. acknowledges the other collaborators and the corresponding author. Y.K. was supported by the Research Management Centre, Xiamen University Malaysia (grant no. XMUMRF/2020-C6/ITM/0004). K.Krishan is supported by a DST PURSE grant and UGC Centre of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M.Kumar would like to acknowledge FIC/NIH K43 TW010716-03. I.L. is a member of the Sistema Nacional de Investigación (SNI), which is supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT), Panamá. M.L. was supported by China Medical University, Taiwan (CMU109-N-22 and CMU109-MF-118). W.M. is currently a programme analyst in Population and Development at the United Nations Population Fund (UNFPA) Country Office in Peru, which does not necessarily endorses this study. D.E.N. acknowledges Cochrane South Africa, South African Medical Research Council. G.C.P. is supported by an NHMRC research fellowship. P.Rathi acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India. Ramu Rawat acknowledges the support of the GBD Secretariat for supporting the reviewing and collaboration of this paper. B.R. acknowledges support from Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal. A.Ribeiro was supported by National Funds through FCT, under the programme of ‘Stimulus of Scientific Employment—Individual Support’ within the contract no. info:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND/02386/2018/CP1538/CT0001/PT. S.Sajadi acknowledges colleagues at Global Burden of Diseases and Local Burden of Disease. A.M.S. acknowledges the support from the Egyptian Fulbright Mission Program. F.S. was supported by the Shenzhen Science and Technology Program (grant no. KQTD20190929172835662). A.Sheikh is supported by Health Data Research UK. B.K.S. acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal for all the academic support. B.U. acknowledges support from Manipal Academy of Higher Education, Manipal. C.S.W. is supported by the South African Medical Research Council. Y.Z. was supported by Science and Technology Research Project of Hubei Provincial Department of Education (grant no. Q20201104) and Outstanding Young and Middle-aged Technology Innovation Team Project of Hubei Provincial Department of Education (grant no. T2020003). The funders of the study had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. All maps presented in this study are generated by the authors and no permissions are required to publish them