3,668 research outputs found
Setting implementation research priorities to reduce preterm births and stillbirths at the community level.
Asha George and colleagues from the GAPPS group report the implementation research priorities to address prematurity and stillbirths at the community level that resulted from their recent expert consensus exercise
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Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice.
Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity
Fine mapping of candidate effector genes for heart rate
An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality
Risk and sensitivity quantification of fracture failure employing cohesive zone elements
Many structures are subjected to the risk of fatigue failure. For their reliability-based design, it is thus important to calculate the probability of fatigue failure and assess the relative importance of the involved parameters. Although various studies have analyzed the fatigue failure, the stage of fracture failure has been less focused. In particular, the risk analysis of fracture failure needs to be conducted considering its importance in actual structures. This article proposes a new probabilistic framework for the risk and sensitivity analysis of structural fatigue failure employing cohesive zone elements. The proposed framework comprises three steps, namely finite element analysis using cohesive zone elements, response surface construction, and risk and sensitivity analysis of fatigue failure, which require several mathematical techniques and algorithms. The proposed framework is tested by applying it to an illustrative example, and the corresponding analysis results of fracture failure probability with different threshold values of a limit-state function are presented. In addition, the sensitivities of failure risk with respect to the statistical parameters of random variables are presented and their relative importance is discussed
Utilization of outpatient services in refugee settlement health facilities: a comparison by age, gender, and refugee versus host national status
<p>Abstract</p> <p>Background</p> <p>Comparisons between refugees receiving health care in settlement-based facilities and persons living in host communities have found that refugees have better health outcomes. However, data that compares utilization of health services between refugees and the host population, and across refugee settlements, countries and regions is limited. The paper will address this information gap. The analysis in this paper uses data from the United Nations High Commissioner of Refugees (UNHCR) Health Information System (HIS).</p> <p>Methods</p> <p>Data about settlement populations and the use of outpatient health services were exported from the UNHCR health information system database. Tableau Desktop was used to explore the data. STATA was used for data cleaning and statistical analysis. Differences in various indicators of the use of health services by region, gender, age groups, and status (host national vs. refugee population) were analyzed for statistical significance using generalized estimating equation models that adjusted for correlated data within refugee settlements over time.</p> <p>Results</p> <p>Eighty-one refugee settlements were included in this study and an average population of 1.53 million refugees was receiving outpatient health services between 2008 and 2009. The crude utilization rate among refugees is 2.2 visits per person per year across all settlements. The refugee utilization rate in Asia (3.5) was higher than in Africa on average (1.8). Among refugees, females have a statistically significant higher utilization rate than males (2.4 visits per person per year vs. 2.1). The proportion of new outpatient attributable to refugees is higher than that attributable to host nationals. In the Asian settlements, only 2% outpatient visits, on average, were attributable to host community members. By contrast, in Africa, the proportion of new outpatient (OPD) visits by host nationals was 21% on average; in many Ugandan settlements, the proportion of outpatient visits attributable to host community members was higher than that for refugees. There was no statistically significant difference between the size of the male and female populations across refugee settlements. Across all settlements reporting to the UNHCR database, the percent of the refugee population that was less than five years of age is 16% on average.</p> <p>Conclusions</p> <p>The availability of a centralized database of health information across UNHCR-supported refugee settlements is a rich resource. The SPHERE standard for emergencies of 1-4 visits per person per year appears to be relevant for Asia in the post-emergency phase, but not for Africa. In Africa, a post-emergency standard of 1-2 visits per person per year should be considered. Although it is often assumed that the size of the female population in refugee settlements is higher than males, we found no statistically significant difference between the size of the male and female populations in refugee settlements overall. Another assumption---that the under-fives make up 20% of the settlement population during the emergency phase---does not appear to hold for the post-emergency phase; under-fives made up about 16% of refugee settlement populations.</p
Molecular Characterization and Expression Analysis of Pathogenesis related Protein 6 from Panax ginseng
Panax ginseng Meyer is one of the important medicinal plants in the world, particularly in Asian
countries. Ginseng encounters many stress exposure during its long cultivation period. However, the molecular
mechanism of stress resistance is still poorly understood in spite of its importance. In this study, pathogenesis-
related protein 6 (PR6), also called proteinase inhibitor (PI), was isolated from ginseng embryogenic
callus, named PgPR6. The small size of PR6, containing an open reading frame of 219 bp encoding 72 amino
acids, the typical characteristic of PR6 protein, shares the highest sequence similarity to PR6 of Theobroma
cacao (69% identity). Sequence and structural analysis indicated that PgPR6 belongs to class Kunitz-type PI
family. This is the first report pertaining to the identification of PR6 gene from the P. ginseng genome. The
high-level expression of PgPR6 was observed in root as revealed by quantitative real-time PCR. The temporal
expression analysis demonstrated that PgPR6 expression was highly up-regulated by signaling molecules,
heavy metals, mechanical wounding, chilling, salt, sucrose, and mannitol stress, indicating that PgPR6 may
play an important role in the molecular defense response of ginseng to a various range of environmental
stresses
Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases
Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid
Chiral primary one-point functions in the D3-D7 defect conformal field theory
JHEP is an open-access journal funded by SCOAP3 and licensed under CC BY 4.0archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2012-81 slaccitation: %%CITATION = ARXIV:1210.7015;%%archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2012-81 slaccitation: %%CITATION = ARXIV:1210.7015;%%C.F.K. and D.Y. were supported in part by FNU through grant number 272-08-0329.
G.W.S. is supported by NSERC of Canada and by the Villum foundation through their
Velux Visiting Professor program
Rupture by damage accumulation in rocks
The deformation of rocks is associated with microcracks nucleation and
propagation, i.e. damage. The accumulation of damage and its spatial
localization lead to the creation of a macroscale discontinuity, so-called
"fault" in geological terms, and to the failure of the material, i.e. a
dramatic decrease of the mechanical properties as strength and modulus. The
damage process can be studied both statically by direct observation of thin
sections and dynamically by recording acoustic waves emitted by crack
propagation (acoustic emission). Here we first review such observations
concerning geological objects over scales ranging from the laboratory sample
scale (dm) to seismically active faults (km), including cliffs and rock masses
(Dm, hm). These observations reveal complex patterns in both space (fractal
properties of damage structures as roughness and gouge), time (clustering,
particular trends when the failure approaches) and energy domains (power-law
distributions of energy release bursts). We use a numerical model based on
progressive damage within an elastic interaction framework which allows us to
simulate these observations. This study shows that the failure in rocks can be
the result of damage accumulation
Quantitative nanoscale vortex-imaging using a cryogenic quantum magnetometer
Microscopic studies of superconductors and their vortices play a pivotal role
in our understanding of the mechanisms underlying superconductivity. Local
measurements of penetration depths or magnetic stray-fields enable access to
fundamental aspects of superconductors such as nanoscale variations of
superfluid densities or the symmetry of their order parameter. However,
experimental tools, which offer quantitative, nanoscale magnetometry and
operate over the large range of temperature and magnetic fields relevant to
address many outstanding questions in superconductivity, are still missing.
Here, we demonstrate quantitative, nanoscale magnetic imaging of Pearl vortices
in the cuprate superconductor YBCO, using a scanning quantum sensor in form of
a single Nitrogen-Vacancy (NV) electronic spin in diamond. The sensor-to-sample
distance of ~10nm we achieve allows us to observe striking deviations from the
prevalent monopole approximation in our vortex stray-field images, while we
find excellent quantitative agreement with Pearl's analytic model. Our
experiments yield a non-invasive and unambiguous determination of the system's
local London penetration depth, and are readily extended to higher temperatures
and magnetic fields. These results demonstrate the potential of quantitative
quantum sensors in benchmarking microscopic models of complex electronic
systems and open the door for further exploration of strongly correlated
electron physics using scanning NV magnetometry.Comment: Main text (5 pages, 4 figures) plus supplementary material (5 pages,
6 figures). Comments welcome. Further information under
http://www.quantum-sensing.c
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