3,514 research outputs found
Quantum Dynamics in Atomic-Fountain Experiments for Measuring the Electric Dipole Moment of the Electron with Improved Sensitivity
An improved measurement of the electron electric dipole moment (EDM) appears feasible using groundstate alkali atoms in an atomic fountain in which a strong electric field, which couples to a conceivable EDM, is applied perpendicular to the fountain axis. In a practical fountain, the ratio of the atomic tensor Stark shift to the Zeeman shift is a factor μ ~ 100.We expand the complete time-evolution operator in inverse powers of this ratio; complete results are presented for atoms of total spin F = 3, 4, and 5. For a specific set of entangled hyperfine sublevels (coherent states), potential systematic errors enter only as even powers of 1/μ, making the expansion rapidly convergent. The remaining EDM-mimicking effects are further suppressed in a proposed double-differential setup, where the final state is interrogated in a differential laser configuration, and the direction of the strong electric field also is inverted. Estimates of the signal available at existing accelerator facilities indicate that the proposed apparatus offers the potential for a drastic improvement in EDM limits over existing measurements, and for constraining the parameter space of supersymmetric (SUSY) extensions of the Standard Model
Dust Temperatures in the Infrared Space Observatory Atlas of Bright Spiral Galaxies
We examine far-infrared and submillimeter spectral energy distributions for
galaxies in the Infrared Space Observatory Atlas of Bright Spiral Galaxies. For
the 71 galaxies where we had complete 60-180 micron data, we fit blackbodies
with lambda^-1 emissivities and average temperatures of 31 K or lambda^-2
emissivities and average temperatures of 22 K. Except for high temperatures
determined in some early-type galaxies, the temperatures show no dependence on
any galaxy characteristic. For the 60-850 micron range in eight galaxies, we
fit blackbodies with lambda^-1, lambda-2, and lambda^-beta (with beta variable)
emissivities to the data. The best results were with the lambda^-beta
emissivities, where the temperatures were ~30 K and the emissivity coefficient
beta ranged from 0.9 to 1.9. These results produced gas to dust ratios that
ranged from 150 to 580, which were consistent with the ratio for the Milky Way
and which exhibited relatively little dispersion compared to fits with fixed
emissivities.Comment: AJ, 2003, in pres
The socioeconomic profile of alcohol-attributable mortality in South Africa : a modelling study
CITATION: Probst, C. et al. 2018. The socioeconomic profile of alcohol-attributable mortality in South Africa : a modelling study. BMC Medicine, 16:97, doi:10.1186/s12916-018-1080-0.The original publication is available at https://bmcmedicine.biomedcentral.comBackground: Globally, illness and life expectancy follow a social gradient that puts people of lower socioeconomic status (SES) at higher risk of dying prematurely. Alcohol consumption has been shown to be a factor contributing to socioeconomic differences in mortality. However, little evidence is available from low- and middle-income countries. The objective of this study was to quantify mortality attributable to alcohol consumption in the adult (15+ years) general population of South Africa in 2015 by SES, age, and sex.
Methods : A comparative risk assessment was performed using individual and aggregate data from South Africa and risk relations reported in the literature. Alcohol-attributable fractions (AAFs) and alcohol-attributable mortality rates were estimated for cause-specific mortality by SES, sex, and age. Monte Carlo simulation techniques were used to calculate 95% uncertainty intervals (UI).
Results: Overall, approximately 62,300 (95% UI 27,000–103,000) adults died from alcohol-attributable causes in South Africa in 2015, with 60% of deaths occurring in people in the low and 15% in the high SES groups. Age-standardized, alcohol-attributable mortality rates per 100,000 adults were highest for the low SES group (727 deaths, 95% UI 354–1208 deaths) followed by the middle (377 deaths, 95% UI 165–687 deaths) and high SES groups (163 deaths, 95% UI 71–289 deaths). The socioeconomic differences were highest for mortality from infectious diseases.
People of low SES had a lower prevalence of current alcohol use but heavier drinking patterns among current drinkers. Among men, AAFs were elevated at low and middle SES, particularly for the middle and higher age groups (35+). Among women, AAFs differed less across SES groups and, in the youngest age group (15–34), women of high SES had elevated AAFs.
Conclusions: Alcohol use contributed to vast socioeconomic differences in mortality. Where observed, elevated AAFs for people of low and middle SES arose from higher levels of consumption among current drinkers and not from the prevalence of current alcohol use per se. The findings can direct preventive measures and interventions on those at highest risk. Future research is needed to investigate socioeconomic differences in the risk functions relating alcohol use to cause-specific mortality.https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1080-0Publisher's versio
Listeria monocytogenes Infection in Macrophages Induces Vacuolar-Dependent Host miRNA Response
Listeria monocytogenes is a Gram-positive facultative intracellular pathogen, causing serious illness in immunocompromised individuals and pregnant women. Upon detection by macrophages, which are key players of the innate immune response against infection, L. monocytogenes induces specific host cell responses which need to be tightly controlled at transcriptional and post-transcriptional levels. Here, we ask whether and how host miRNAs, which represent an important mechanism of post-transcriptional regulation in a wide array of biological processes, are altered by a model pathogen upon live infection of murine bone marrow derived macrophages. We first report that L. monocytogenes subverts the host genome-wide miRNA profile of macrophages in vitro. Specifically, we show that miR-155, miR-146a, miR-125a-3p/5p and miR-149 were amongst the most significantly regulated miRNAs in infected macrophages. Strikingly, these miRNAs were highly upregulated upon infection with the Listeriolysin-deficient L. monocytogenes mutant Δhly, that cannot escape from the phagosome thus representing a vacuolar-contained infection. The vacuolar miRNA response was significantly reduced in macrophages deficient for MyD88. In addition, miR-146a and miR-125a-3p/5p were regulated at transcriptional levels upon infection, and miR-125a-3p/5p were found to be TLR2 responsive. Furthermore, miR-155 transactivation in infection was regulated by NF-κB p65, while miR-146a and miR-125a-3p/5p expression was unaffected in p65-deficient primary macrophages upon L. monocytogenes infection. Our results demonstrate that L. monocytogenes promotes significant changes in the miRNA expression profile in macrophages, and reveal a vacuolar-dependent miRNA signature, listeriolysin-independent and MyD88-dependent. These miRNAs are predicted to target immune genes and are therefore most likely involved in regulation of the macrophage innate immune response against infection at post-transcriptional levels
In Pursuit of New Physics with B_s Decays
The presence of a sizeable CP-violating phase in B_s^0-B_s^0-bar mixing would
be an unambiguous signal of physics beyond the Standard Model. We analyse
various possibilities to detect such a new phase considering both tagged and
untagged decays. The effects of a sizeable width difference Delta Gamma between
the B_s mass eigenstates, on which the untagged analyses rely, are included in
all formulae. A novel method to find this phase from simple measurements of
lifetimes and branching ratios in untagged decays is proposed. This method does
not involve two-exponential fits, which require much larger statistics. For the
tagged decays, an outstanding role is played by the observables of the
time-dependent angular distribution of the B_s -> J/psi [-> l^+ l^-] \phi [->
K^+K^-] decay products. We list the formulae needed for the angular analysis in
the presence of both a new CP-violating phase and a sizeable Delta Gamma, and
propose methods to remove a remaining discrete ambiguity in the new phase. This
phase can therefore be determined in an unambiguous way.Comment: minor changes, lattice prediction of Delta Gamma updated, appears in
PR
Pharmacogenetic Analysis of INT 0144 Trial: Association of Polymorphisms with Survival and Toxicity in Rectal Cancer Patients Treated with 5-FU and Radiation
PURPOSE
We tested whether 18 polymorphisms in 16 genes (GSTP1, COX2, IL10, EGFR, EGF, FGFR4, CCDN1, VEGFR2, VEGF, CXCR2, IL8, MMP3, ICAM1, ERCC1, RAD51, and XRCC3) would predict disease-free survival (DFS), overall survival (OS), and toxicity in the INT0144 trial, which was designed to investigate different postoperative regimens of 5-fluorouracil (5-FU)-based chemoradiation (CRT) in locally advanced rectal cancers: Arm 1 consisted of bolus 5-FU followed by 5-FU protracted venous infusion (PVI) with radiotherapy; arm 2 was induction and concomitant PVI 5-FU with radiotherapy and arm 3 was induction and concomitant bolus 5-FU with radiotherapy.
EXPERIMENTAL DESIGN
DNA from 746 stage II/III rectal patients enrolled in the Southwest Oncology Group (SWOG) S9304 phase III trial was analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue. The polymorphisms were analyzed using direct DNA-sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTS
GSTP1-Ile105Val (rs1695) was significantly associated with DFS and OS and its effect did not vary by treatment arm. The five-year DFS and OS were 53% and 58%, respectively, for G/G, 66% and 72% for G/A, and 57% and 66% for A/A patients. In arm 2, IL8-251A/A genotype (rs4073) was associated with a lower risk of toxicities (P = 0.04). The VEGFR2 H472Q Q/Q genotype (rs1870377) was associated with a higher risk of grade 3-5 proximal upper gastrointestinal tract (PUGIT) mucositis (P = 0.04) in arm 2. However, in arm 1, this genotype was associated with a lower risk of PUGIT mucositis (P = 0.004).
CONCLUSION
rs1695 may be prognostic in patients with rectal cancer treated with adjuvant CRT. rs4073 and rs1870377 may exhibit different associations with toxicity, according to the 5-FU schedule
DNM1 encephalopathy: A new disease of vesicle fission.
ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention
In search of the authentic nation: landscape and national identity in Canada and Switzerland
While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration
Translating the BDI and BDI-II into the HAMD and vice versa with equipercentile linking
Abstract
Aims
The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.
Methods
We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.
Results
The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.
Conclusions
The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research
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