986 research outputs found

    Feynman diagrams versus Fermi-gas Feynman emulator

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    Precise understanding of strongly interacting fermions, from electrons in modern materials to nuclear matter, presents a major goal in modern physics. However, the theoretical description of interacting Fermi systems is usually plagued by the intricate quantum statistics at play. Here we present a cross-validation between a new theoretical approach, Bold Diagrammatic Monte Carlo (BDMC), and precision experiments on ultra-cold atoms. Specifically, we compute and measure with unprecedented accuracy the normal-state equation of state of the unitary gas, a prototypical example of a strongly correlated fermionic system. Excellent agreement demonstrates that a series of Feynman diagrams can be controllably resummed in a non-perturbative regime using BDMC. This opens the door to the solution of some of the most challenging problems across many areas of physics

    Physiologically based modeling of lisofylline pharmacokinetics following intravenous administration in mice

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    Lisofylline (LSF), is the R-(−) enantiomer of the metabolite M1 of pentoxifylline, and is currently under development for the treatment of type 1 diabetes. The aim of the study was to develop a physiologically based pharmacokinetic (PBPK) model of LSF in mice and to perform simulations in order to predict LSF concentrations in human serum and tissues following intravenous and oral administration. The concentrations of LSF in serum, brain, liver, kidneys, lungs, muscle, and gut were determined at different time points over 60 min by a chiral HPLC method with UV detection following a single intravenous dose of LSF to male CD-1 mice. A PBPK model was developed to describe serum pharmacokinetics and tissue distribution of LSF using ADAPT II software. All pharmacokinetic profiles were fitted simultaneously to obtain model parameters. The developed model characterized well LSF disposition in mice. The estimated intrinsic hepatic clearance was 5.427 ml/min and hepatic clearance calculated using the well-stirred model was 1.22 ml/min. The renal clearance of LSF was equal to zero. On scaling the model to humans, a good agreement was found between the predicted by the model and presented in literature serum LSF concentration–time profiles following an intravenous dose of 3 mg/kg. The predicted LSF concentrations in human tissues following oral administration were considerably lower despite the twofold higher dose used and may not be sufficient to exert a pharmacological effect. In conclusion, the mouse is a good model to study LSF pharmacokinetics following intravenous administration. The developed PBPK model may be useful to design future preclinical and clinical studies of this compound

    Validating the Time and Change test to screen for dementia in elderly Koreans

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    BACKGROUND: We assessed the applicability of the T&C test as an accurate and convenient means to screen for dementia in primary care and community settings. METHODS: The study group comprised 59 patients and 405 community participants, all of who were aged 65 years and over. The time component of the T&C test evaluated the ability of a subject to comprehend clock hands that indicated a time of 11:10, while the change component of the T&C test evaluated the ability of a subject to make 1,000 Won from a group of coins with smaller denominations (one 500, seven 100, and seven 50 Won coins). RESULTS: The T&C test had a sensitivity and specificity of 73.0 and 90.9%, respectively, and positive and negative predictive values of 93.1, and 66.7%, respectively. The test-retest and interobserver agreement rates were both 95% (κ = 0.91) (time interval, 24 hours). The association between the T&C test and K-MMSE test was modest, while significant (r = 0.422, p < 0.001). The T&C test scores were not influenced by educational status. CONCLUSIONS: We conclude that the T&C test is useful as supplemental testing of important domains (e.g., calculation, conceptualization, visuospatial) to traditional measures such as the MMSE. However, because T&C test is simple, rapid, and easy to use, it can be applied conveniently to elderly subjects by non-specialist personnel who receive training

    Introduction: locating gentrification in the Global East

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    This special issue, a collection of papers presented and debated at an Urban Studies Foundation-funded workshop on Global Gentrification in London in 2012, attempts to problematise contemporary understandings of gentrification, which is all too often confined to the experiences of the so-called Global North, and sometimes too narrowly understood as classic gentrification. Instead of simply confirming the rise of gentrification in places outside of the usual suspects of North America and Western Europe, a more open-minded approach is advocated so as not to over-generalise distinctive urban processes under the label of gentrification, thus understanding gentrification as constitutive of diverse urban processes at work. This requires a careful attention to the complexity of property rights and tenure relations, and calls for a dialogue between gentrification and non-gentrification researchers to understand how gentrification communicates with other theories to capture the full dynamics of urban transformation. Papers in this special issue have made great strides towards these goals, namely theorising, distorting, mutating and bringing into question the concept of gentrification itself, as seen from the perspective of the Global East, a label that we have deliberately given in order to problematise the existing common practices of grouping all regions other than Western European and North American ones into the Global South

    Unidimensional scales for fears of cancer recurrence and their psychometric properties : the FCR4 and FCR7

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    Funding: Support was received from SUPAC (NCRI) Early Career Fund to complete this study. NCRI Supportive & Palliative Care (SuPaC) Research Collaboratives Capacity Building Grant Scheme: G Ozakinci (PI), G Humphris, M Sharpe.Background:  The assessment of fear of recurrence (FCR) is crucial for understanding an important psychological state in patients diagnosed and treated for cancer. The study aim was to determine psychometric details of a seven question self-report scale (FCR7) and a short form (FCR4) based upon items already used in various extensive measures of FCR. Methods:  Two consecutive samples of patients (breast and colorectal) were recruited from a single specialist cancer centre. The survey instrument contained the FCR7 items, Hospital Anxiety and Depression Scale (HADS), and demographic details. Clinical information was obtained from patient hospital records. Statistical analyses were performed using classical test and item response theory approaches, to demonstrate unidimensional factor structure and testing key parameters. Construct validity was inspected through nomological and theoretical prediction. Results:  Internal consistency was demonstrated by alpha coefficients (FCR4: 0.93 and FCR7: 0.92). Both scales (FCR7 & FCR4) were associated with the HADs subscales as predicted. Patients who experienced chemotherapy, minor aches/pains, thought avoidance of cancer and high cancer risk belief were more fearful. Detailed inspection of item responses profile provided some support for measurement properties of scales. Conclusion: The internal consistency, and pattern of key associations and discriminability indices provided positive psychometric evidence for these scales. The brief measures of FCR may be considered for audit, screening or routine use in clinical service and research investigations.Publisher PDFPeer reviewe

    Gene Flow between the Korean Peninsula and Its Neighboring Countries

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    SNP markers provide the primary data for population structure analysis. In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry using 320 subjects covering 24 regional groups including Northern ( = 16) and Southern ( = 3) Asians, Amerindians ( = 1), and four HapMap populations (YRI, CEU, JPT, and CHB). Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs with various clustering methods, along with their dependencies on recombination hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific markers. The RH- and LD-free multi-dimensional scaling (MDS) method showed a broad picture of human migration from Africa to North-East Asia on our genome map, supporting results from previous haploid DNA studies. Of the Asian groups, the East Asian group showed greater differentiation than the Northern and Southern Asian groups with respect to Fst statistics. By extension, the analysis of monomorphic markers implied that nine out of ten historical regions in South Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later settlement of East Asia (South Korea, Japan and China), while Gyeongju in South East Korea showed signs of the earliest settlement in East Asia. In the genome map, the gene flow to the Korean Peninsula from its neighboring countries indicated that some genetic signals from Northern populations such as the Siberians and Mongolians still remain in the South East and West regions, while few signals remain from the early Southern lineages

    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

    A Non-coding RNA of Insect HzNV-1 Virus Establishes Latent Viral Infection through MicroRNA

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    Heliothis zea nudivirus-1 (HzNV-1) is an insect virus previously known as Hz-1 baculovirus. One of its major early genes, hhi1, is responsible for the establishment of productive viral infection; another gene, pag1, which expresses a non-coding RNA, is the only viral transcript detectable during viral latency. Here we showed that this non-coding RNA was further processed into at least two distinct miRNAs, which targeted and degraded hhi1 transcript. This is a result strikingly similar to a recent report that herpes simplex virus produces tightly-regulated latent specific miRNAs to silence its own key early transcripts. Nevertheless, proof for the establishment of viral latency by miRNA is still lacking. We further showed that HzNV-1 latency could be directly induced by pag1-derived miRNAs in cells infected with a pag1-deleted, latency-deficient virus. This result suggests the existence of a novel mechanism, where miRNAs can be functional for the establishment of viral latency
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