238 research outputs found
Government Size, Fiscal Policy and the Level and Growth of Output: A Review of Recent Evidence
Theoretical developments, improved methodologies and more extensive data have helped generate a dramatic increase in the literature testing for the impact of government size and fiscal policy on economic growth in recent years. We review a range of the more recent evidence and examine (1) the consistency or robustness of the results; (2) how these results differ from the earlier literature and (3) their usefulness as a guide to policy reform in practice. We find that the last decade has produced more robust evidence and more plausible orders of magnitude on the impact of fiscal policy on growth. However, the value of this evidence remains limited as a basis for quantifying macroeconomic responses to fiscal policy reform in practice
Effects of Triton X-100 concentration and incubation temperature on carboxyfluorescein release from multilamellar liposomes
Carboxyfluorescein is the most commonly used probe to measure the rate of release of vesicle contents. The validity of the data obtained by this method depends on obtaining an end point based on the complete release of the dye on treatment of the liposomes with a detergent, usually Triton X-100. However, Triton does not completely release entrapped carboxyfluorescein from multilamellar liposomes and the amount and rate of release of marker upon detergent treatment is a function of lipid composition of the liposome, Triton concentration and temperature and duration of detergent incubation. The fluorescence `end point' for distearoyl--[alpha]-phosphatidylcholine/cholesterol (2:1, mol%) multilamellar liposomes treated with 0.5% Triton at 22[deg]C (a condition often used) is only about one-fifth the value for liposomes treated with 5% Triton at 72[deg]C. The conditions of treatment appear to affect the release of carboxyfluorescein from the lipid of the partially or completely disrupted liposome and the subsequent partitioning of the free dye into the aqueous phase. This effect can lead to serious errors in the interpretation of multilamellar liposome stability data. However, Triton allows complete release of entrapped dye from small unilamellar vesicles under all conditions tested.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26095/1/0000171.pd
Aminoglycoside antibiotics preferentially increase permeability in phosphoinositide-containing membranes: a study with carboxyfluorescein in liposomes
The rate of release from multilamellar liposomes of the fluoroscent probe carboxyfluorescein was determined as a measure of membrane permeability. Liposomes of phosphatidylcholine and different anionic phospholipids were incubated with low (1 [mu]M) and high (3 mM) concentrations of calcium in the absence or presence of aminoglycoside antibiotics. The leakage of carboxyfluorescein into the medium was not caused by liposomal fusion as no vesicle fusion was observed in experiments with terbium and dipicolinic acid-loaded liposomes. The basal rate of carboxyfluorescein release (in the absence or presence of 1 [mu]M calcium) from all types of liposomes ranged from 0.1 to 0.3% of trapped carboxyfluorescein per hour. The presence of 3 mM calcium caused the greatest increase in the rate of carboxyfluorescein release (about 9-fold) in liposomes containing phosphatidylinositol 4,5-bisphosphate (PIP2) whereas liposomes containing the other anionic phospholipids (phosphatidylserine, phosphatidylinositol and phosphatidylinositol 4-phosphate) showed an approximate 5-fold increase. In the presence of 1 [mu]M calcium, the aminoglycosides neomycin and gentamicin also increased the rate of carboxyfluorescein release, with PIP2-containing liposomes showing a 3-5-times greater response than the other liposomes, releasing up to 4.6% of trapped carboxyfluorescein per hour. This drug-induced release was dose-dependent and antagonized by calcium. In the presence of 3 mM calcium, 0.1 mM gentamicin or neomycin were ineffective while the drug at 1 mM affected carboxyfluorescein release from PIP2-liposomes only. The aminoglycoside antibiotics, neomycin, gentamicin, tobramycin, kanamycin, amikacin, netilmicin, as well as neamine and spectinomycin (all at 0.1 mM) showed a graded effect on the rate of carboxyfluorescein release from PIP2-containing vesicles in the presence of 0.1 mM calcium. The magnitude of the effect correlated well with the ototoxicity of the drugs previously determined directly in cochlear perfusions in the guinea pig. The study demonstrates that aminoglycoside antibiotics are capable of altering membrane permeabilities and that this effect is most pronounced if PIP2 is present in the bilayers. The excellent correlation between this membrane action and the in-situ toxicity of the drugs further establishes the specific role of PIP2 in the molecular mechanism of aminoglycoside-induced hearing loss. Moreover, it confirms the usefulness of such physicochemical models for the screening and prediction of aminoglycoside toxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26611/1/0000152.pd
Membrane effects of aminoglycoside antibiotics measured in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate
The mechanism of membrane disturbance by aminoglycoside antibiotics was investigated in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate (ANS). Liposomes of PC and different anionic phospholipids (1:1 to 15:1 molar ratios) were challenged with aminoglycosides in the presence of low (1 [mu]M) and high (3 mM) concentrations of calcium. Liposomes containing PIP2 showed the greatest drug-induced changes in ANS fluorescence in the presence of high and low concentrations of calcium and at all PC:PIP2 molar ratios tested. Liposomes containing other anionic phospholipids (PS, PI and PIP2) were not reactive toward aminoglycosides in the presence of 3 mM calcium or when the ratio of PC to anionic lipid was increased to 10:1. The aminoglycoside-induced changes of ANS flouorescence were not due to any changes in the emission spectrum of ANS, nor to changes in quantum yield, nor to a change in the binding affinity of ANS. It is concluded that a specific aminoglycoside-PIP2 interaction results in phase separation of PC and PIP2 and thus increases the number of available ANS binding sites in PC:PIP2 liposomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25983/1/0000049.pd
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
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
The Ecological Conditions That Favor Tool Use and Innovation in Wild Bottlenose Dolphins (Tursiops sp.)
Dolphins are well known for their exquisite echolocation abilities, which enable them to detect and discriminate prey species and even locate buried prey. While these skills are widely used during foraging, some dolphins use tools to locate and extract prey. In the only known case of tool use in free-ranging cetaceans, a subset of bottlenose dolphins (Tursiops sp.) in Shark Bay, Western Australia habitually employs marine basket sponge tools to locate and ferret prey from the seafloor. While it is clear that sponges protect dolphins' rostra while searching for prey, it is still not known why dolphins probe the substrate at all instead of merely echolocating for buried prey as documented at other sites. By ‘sponge foraging’ ourselves, we show that these dolphins target prey that both lack swimbladders and burrow in a rubble-littered substrate. Delphinid echolocation and vision are critical for hunting but less effective on such prey. Consequently, if dolphins are to access this burrowing, swimbladderless prey, they must probe the seafloor and in turn benefit from using protective sponges. We suggest that these tools have allowed sponge foraging dolphins to exploit an empty niche inaccessible to their non-tool-using counterparts. Our study identifies the underlying ecological basis of dolphin tool use and strengthens our understanding of the conditions that favor tool use and innovation in the wild
Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy
Critical thinking for 21st-century education: A cyber-tooth curriculum?
It is often assumed that the advent of digital technologies requires fundamental change to the curriculum and to the teaching and learning approaches used in schools around the world to educate this generation of “digital natives” or the “net generation”. This article analyses the concepts of 21st-century skills and critical thinking, to understand how these aspects of learning might contribute to a 21st-century education. The author argues that, although both critical thinking and 21st-century skills are indeed necessary in a curriculum for a 21st-century education, they are not sufficient, even in combination. The role of knowledge and an understanding of differing cultural perspectives and values indicate that education should also fit local contexts in a global world and meet the specific needs of students in diverse cultures. It should also fit the particular technical and historical demands of the 21st century in relation to digital skills
Reply to Komatsu et al.: From local social mindfulness to global sustainability efforts?
Komatsu et al. (1) argue that Van Doesum et al. (2)
may have overlooked the role of GDP in reporting a
positive association between social mindfulness
(SoMi) and the Environmental Performance Index
(EPI) at country level. Although the relationship
between EPI and SoMi is relatively weaker for countries with higher GDP, that does not imply that the
overall observed relationship is a statistical artifact.
Rather, it implies that GDP may be a moderator of
the relationship between EPI and SoMi. The
observed correlation is a valid result on average
across countries, and the actual effect size would, at
least to some degree, depend on GDP
Reply to Nielsen et al.: Social mindfulness is associated with countries' environmental performance and individual environmental concern.
Nielsen et al. (1) argue that Van Doesum et al. (2)
need to consider three points for their interpretation
of a positive association between individual-level
social mindfulness (SoMi) and environmental performance (EPI) at the country level (3). The association
is weaker when 1) it is controlled for GDP and 2)
when the data of three countries are removed; also,
3) the data do not address the association between
SoMi and individual-level environmental concern.
We discuss these points in turn
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