28 research outputs found

    Challenges for Developing Complex System Governance

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    This paper examines the challenges and practice implications for Complex System Governance (CSG). CSG is presented as an emerging field focused on the design, execution, and evolution of the higher order (metasystem) functions necessary to provide control, communication, coordination, and integration of a complex system. This paper is focused on three primary objectives. First, we introduce the complex system problem domain that the CSG field is being designed to address. The pervasiveness of this problem domain is demonstrated by a short examination of the water utilities sector. Second, we expound the nature of CSG and an emerging reference model that defines the functions of CSG. These functions must be performed by any system that maintains viability (continued existence). The CSG reference model rests on the underlying conceptual foundations built from Systems Theory (axioms and propositions governing system integration and coordination) and Management Cybernetics (communication and control for effective system organization). Third, we explore the particular challenges that must be addressed if the potential of the emerging CSG field is to be realized. The paper concludes by suggesting the potential that the CSG field brings for enhancing practitioner capabilities to more effectively deal with complex systems and their associated problems

    Jean-François Kosta-Théfaine, Le Chant de la douleur dans les poésies de Christine de Pizan

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    Cet essai propose un examen du thème de la douleur dans les poésies de Christine de Pizan. On sait combien le deuil marque l’œuvre de Christine et est la clé de voûte de son entrée en écriture. Deuil triple en quelque sorte avec la disparition première du roi modèle, Charles V, puis du père Thomas de Bologne, enfin de l’époux, Étienne du Castel. Peu à peu s’effondre la stabilité matérielle de Christine et, selon ce qu’elle dit, son univers affectif, puisque – fait rare à l’époque – elle prése..

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

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    Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

    High resolution and contrast 7 tesla MR brain imaging of the neonate

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    IntroductionUltra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system.MethodsImages were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM).ResultsThere was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy.DiscussionWe demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life

    Mechanistic target of rapamycin signaling in human nervous system development and disease

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    Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates fundamental cellular processes including growth control, autophagy and metabolism. mTOR has key functions in nervous system development and mis-regulation of mTOR signaling causes aberrant neurodevelopment and neurological diseases, collectively called mTORopathies. In this mini review we discuss recent studies that have deepened our understanding of the key roles of the mTOR pathway in human nervous system development and disease. Recent advances in single-cell transcriptomics have been exploited to reveal specific roles for mTOR signaling in human cortical development that may have contributed to the evolutionary divergence from our primate ancestors. Cerebral organoid technology has been utilized to show that mTOR signaling is active in and regulates outer radial glial cells (RGCs), a population of neural stem cells that distinguish the human developing cortex. mTOR signaling has a well-established role in hamartoma syndromes such as tuberous sclerosis complex (TSC) and other mTORopathies. New ultra-sensitive techniques for identification of somatic mTOR pathway mutations have shed light on the neurodevelopmental origin and phenotypic heterogeneity seen in mTORopathy patients. These emerging studies suggest that mTOR signaling may facilitate developmental processes specific to human cortical development but also, when mis-regulated, cause cortical malformations and neurological disease

    Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis

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    Mechanistic target of rapamycin (mTOR) is a protein kinase that integrates multiple inputs to regulate anabolic cellular processes. For example, mTOR complex 1 (mTORC1) has key functions in growth control, autophagy, and metabolism. However, much less is known about the signaling components that act downstream of mTORC1 to regulate cellular morphogenesis. Here, we show that the RNA-binding protein Unkempt, a key regulator of cellular morphogenesis, is a novel substrate of mTORC1. We show that Unkempt phosphorylation is regulated by nutrient levels and growth factors via mTORC1. To analyze Unkempt phosphorylation, we immunoprecipitated Unkempt from cells in the presence or the absence of the mTORC1 inhibitor rapamycin and used mass spectrometry to identify mTORC1-dependent phosphorylated residues. This analysis showed that mTORC1-dependent phosphorylation is concentrated in a serine-rich intrinsically disordered region in the C-terminal half of Unkempt. We also found that Unkempt physically interacts with and is directly phosphorylated by mTORC1 through binding to the regulatory-associated protein of mTOR, Raptor. Furthermore, analysis in the developing brain of mice lacking TSC1 expression showed that phosphorylation of Unkempt is mTORC1 dependent in vivo. Finally, mutation analysis of key serine/threonine residues in the serine-rich region indicates that phosphorylation inhibits the ability of Unkempt to induce a bipolar morphology. Phosphorylation within this serine-rich region thus profoundly affects the ability of Unkempt to regulate cellular morphogenesis. Taken together, our findings reveal a novel molecular link between mTORC1 signaling and cellular morphogenesis

    Student Pharmacists Target the Million Hearts Initiative for Potentially at-risk Medicare Beneficiaries

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    Background: The Centers for Disease Control and Prevention (CDC) and Centers for Medicare & Medicaid Services (CMS) are sponsoring partners of Million Hearts, a national initiative to prevent 1 million heart attacks and strokes over the next 5 years. Million Hearts targets the ABCS of clinical prevention (appropriate Aspirin therapy, Blood pressure control, Cholesterol management, and Smoking cessation). Objective: This study measured ABCS outcomes and provided education to a Medicare population. Methods: Twelve healthcare outreach events were offered to Medicare beneficiaries in Northern/Central California between October and November 2012. Student pharmacists, under supervision of pharmacists, provided medication therapy management (MTM) services, along with blood pressure, cholesterol and other healthcare screenings with corresponding education. Data collection included beneficiary demographics, medication, systolic (SBP) and diastolic (DBP) blood pressure and cholesterol measurement, and smoking status. Results: 586 beneficiaries received MTM services, with 286 (49%) reporting daily aspirin use. Of those with self-reported hypertension who had their blood pressure measured, 103/239 (43%) were uncontrolled (defined as SBP ≥ 140 or DBP ≥ 90). Of those without self-reported hypertension whose blood pressure was measured, 40/131 (31%) were uncontrolled. Four-hundred sixteen (86%) indicated having their cholesterol checked within the last year. Of the 204 beneficiaries in whom cholesterol was measured onsite, 49 (24%) had a total cholesterol level ≥ 200 mg/dL. In total 414 (71%) were non-smokers and 144 (25%) were former smokers. Conclusion: Student pharmacists can assist in identifying at-risk Medicare beneficiaries through ABCS health screenings and provide education to improve beneficiary outcomes

    Student Pharmacists Target the Million Hearts Initiative for Potentially at-risk Medicare Beneficiaries

    No full text
    Background: The Centers for Disease Control and Prevention (CDC) and Centers for Medicare & Medicaid Services (CMS) are sponsoring partners of Million Hearts, a national initiative to prevent 1 million heart attacks and strokes over the next 5 years. Million Hearts targets the ABCS of clinical prevention (appropriate Aspirin therapy, Blood pressure control, Cholesterol management, and Smoking cessation). Objective: This study measured ABCS outcomes and provided education to a Medicare population. Methods: Twelve healthcare outreach events were offered to Medicare beneficiaries in Northern/Central California between October and November 2012. Student pharmacists, under supervision of pharmacists, provided medication therapy management (MTM) services, along with blood pressure, cholesterol and other healthcare screenings with corresponding education. Data collection included beneficiary demographics, medication, systolic (SBP) and diastolic (DBP) blood pressure and cholesterol measurement, and smoking status. Results: 586 beneficiaries received MTM services, with 286 (49%) reporting daily aspirin use. Of those with self-reported hypertension who had their blood pressure measured, 103/239 (43%) were uncontrolled (defined as SBP ≥ 140 or DBP ≥ 90). Of those without self-reported hypertension whose blood pressure was measured, 40/131 (31%) were uncontrolled. Four-hundred sixteen (86%) indicated having their cholesterol checked within the last year. Of the 204 beneficiaries in whom cholesterol was measured onsite, 49 (24%) had a total cholesterol level ≥ 200 mg/dL. In total 414 (71%) were non-smokers and 144 (25%) were former smokers. Conclusion: Student pharmacists can assist in identifying at-risk Medicare beneficiaries through ABCS health screenings and provide education to improve beneficiary outcomes
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