531 research outputs found

    Fiscal Multipliers and Public Debt Dynamics in Consolidations

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    The success of a consolidation in reducing the debt ratio depends crucially on the value of the multiplier, which measures the impact of consolidation on growth, and on the reaction of sovereign yields to such a consolidation. We present a theoretical framework that formalizes the re spo nse of the public debt ratio to fiscal consolidations in relation to the value of fiscal multipliers, the starting debt level and the cyclical elasticity of the budget balance. We also assess the role of markets confidence to fiscal consolidations under al ternative scenarios. We find that with high levels of public debt and sizeable fiscal multipliers , debt ratios are likely to increase in the short term in response to fiscal consolidations. Hence, the typical horizon for a consolidation during crises episo des to reduce the debt ratio is two - three years , although this horizon depends critically on the size and persistence of fiscal multipliers and the reaction of financial markets. Anyway, such undesired debt responses are mainly short - lived. This effect is very unlikely in non - crisis times, as it requires a number of conditions difficult to observe at the same time , especially high fiscal multipliers

    Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.

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    In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24-59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7. Several interferon-stimulated genes are differentially expressed in children with pre-LAIV asymptomatic respiratory viral infections and negatively correlated with LAIV VLs. Upregulation of genes enriched in macrophages, neutrophils, and eosinophils is associated with lower VLs and found more commonly in children with asymptomatic viral infections. Variability in pre-infection mucosal interferon gene expression in children may impact the course of subsequent influenza infections. This variability may be due to frequent respiratory viral infections, demonstrating the potential importance of mucosal virus-virus interactions in children

    Comparative Analysis of Cervical Spine Management in a Subset of Severe Traumatic Brain Injury Cases Using Computer Simulation

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    BACKGROUND: No randomized control trial to date has studied the use of cervical spine management strategies in cases of severe traumatic brain injury (TBI) at risk for cervical spine instability solely due to damaged ligaments. A computer algorithm is used to decide between four cervical spine management strategies. A model assumption is that the emergency room evaluation shows no spinal deficit and a computerized tomogram of the cervical spine excludes the possibility of fracture of cervical vertebrae. The study's goal is to determine cervical spine management strategies that maximize brain injury functional survival while minimizing quadriplegia. METHODS/FINDINGS: The severity of TBI is categorized as unstable, high risk and stable based on intracranial hypertension, hypoxemia, hypotension, early ventilator associated pneumonia, admission Glasgow Coma Scale (GCS) and age. Complications resulting from cervical spine management are simulated using three decision trees. Each case starts with an amount of primary and secondary brain injury and ends as a functional survivor, severely brain injured, quadriplegic or dead. Cervical spine instability is studied with one-way and two-way sensitivity analyses providing rankings of cervical spine management strategies for probabilities of management complications based on QALYs. Early collar removal received more QALYs than the alternative strategies in most arrangements of these comparisons. A limitation of the model is the absence of testing against an independent data set. CONCLUSIONS: When clinical logic and components of cervical spine management are systematically altered, changes that improve health outcomes are identified. In the absence of controlled clinical studies, the results of this comparative computer assessment show that early collar removal is preferred over a wide range of realistic inputs for this subset of traumatic brain injury. Future research is needed on identifying factors in projecting awakening from coma and the role of delirium in these cases

    PUS3 mutations are associated with intellectual disability, leukoencephalopathy, and nephropathy

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    Mutations in PUS3, which encodes a highly conserved enzyme responsible for posttranscriptional modification of tRNA, have been shown in a single family to be a cause of nonsyndromic intellectual disability (ID).1 In this study, we used whole-exome sequencing (WES) to identify biallelic mutations in PUS3 associated with syndromic ID with dysmorphic features, white matter disease (WMD), and renal abnormalities in a nonconsanguineous family from Brazil

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

    Identification of Methanoculleus spp. as active methanogens during anoxic incubations of swine manure storage tank samples

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    Methane emissions represent a major environmental concern associated with manure management in the livestock industry. A more thorough understanding of how microbial communities function in manure storage tanks is a prerequisite for mitigating methane emissions. Identifying the microorganisms that are metabolically active is an important first step. Methanogenic archaea are major contributors to methanogenesis in stored swine manure, and we investigated active methanogenic populations by DNA stable isotope probing (DNA-SIP). Following a preincubation of manure samples under anoxic conditions to induce substrate starvation, [U-¹³C] acetate was added as a labeled substrate. Fingerprint analysis of density-fractionated DNA, using length-heterogeneity analysis of PCR-amplified mcrA genes (encoding the alpha subunit of methyl coenzyme M reductase), showed that the incorporation of ¹³C into DNA was detectable at in situ acetate concentrations (~7g/liter). Fingerprints of DNA retrieved from heavy fractions of the ¹³C treatment were primarily enriched in a 483-bp amplicon and, to a lesser extent, in a 481-bp amplicon. Analyses based on clone libraries of the mcrA and 16S rRNA genes revealed that both of these heavy DNA amplicons corresponded to Methanoculleus spp. Our results demonstrate that uncultivated methanogenic archaea related to Methanoculleus spp. were major contributors to acetate-C assimilation during the anoxic incubation of swine manure storage tank samples. Carbon assimilation and dissimilation rate estimations suggested that Methanoculleus spp. were also major contributors to methane emissions and that the hydrogenotrophic pathway predominated during methanogenesis

    Assessing early memories of threat and subordination: Confirmatory factor analyisis of the early life experiences scale for adolescents.

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    The Early Life Experiences Scale (ELES) is a self-report questionnaire that assesses personal feelings of perceived threat and submissiveness in interactions within family. This paper presents the adaptation and validation of the ELES in Portuguese language for adolescents. The sample was composed of 771 adolescents from community schools with ages between 13 and 18 years old. Along with ELES, participants also answered the Early Memories of Warmth and Safeness Scale and the Positive and Negative Affect Schedule for Children and Adolescents. Confirmatory factor analysis (CFA) was performed to test the factor structure of the ELES and results confirm a three-factor structure, composed by Threat, Submissiveness and Unvalued dimensions. These emotional memories focused on perceived threat, submissiveness and unvalued seem to have a distinct nature. The scale also showed adequate internal consistency, good test-retest reliability and convergent validity with measures of positive emotional memories, positive and negative affect. There were sex differences for threat subscale and age differences for submissiveness subscale. Overall, these findings suggest that the ELES in its Portuguese version for adolescents may be a useful tool for research, educational and clinical contexts with school-aged adolescents
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