3,034 research outputs found
Policy makers, regulators and researchersâ perspectives on genomics research and the capacity of the National Health Research Act of 2013 to regulate genomics research in Zambia
Background: Health research in sub-Saharan Africa takes place against a lengthy history of exploitation and unfair collaboration. This has involved the export of samples and data from the continent for the benefit of institutions and researchers elsewhere. In this paper, we report the perspectives of people involved in conducting genomics research in Zambia and the capacity of the Health Research Act (HRA) of 2013 in regulating genomics research. Methods: We approached 14 purposively selected stakeholders involved in the development or implementation of the HRA in Zambia for in-depth interviews. These were members of research ethics committees, genomics researchers, Ministry of Health policy makers and institutional lawyers. Results: Participants reported that there are benefits in genomics research for Zambia such as diagnosing and treatment of diseases. Participants also expressed concerns, most of which were ethical in nature. Prominent concerns were on consent. Participantsâ main concern was the possible misuse of samples in the future. These concerns resonated with the HRA, which prohibits the use of broad consent for the collection of samples and data for future unspecified research. The implications of this is that Zambians may not participate in any kind of health research for which the storage, sharing and re-use of data or samples is envisaged. The restrictive nature of HRA means that genomics research may be excluded from future health research collaborations, thus isolating the country from potentially beneficial health research. Some policy makers also worried the samples and data that comes from such research may be difficult to access by local scientists. Conclusion: In this article, we describe the views of Zambian policymakers on genomics research and the capacity of HRA in regulating genomics research. Our findings are relevant for the Zambian audience, and other African countries that are aiming to regulate health research, especially genomics research.</ns4:p
Radio Sources in Galaxy Clusters at 28.5 GHz
We present serendipitous detections of radio sources at 28.5 GHz (1 cm),
which resulted from our program to image thermal Sunyaev-Zeldovich (SZ) effect
in 56 galaxy clusters. We find 64 radio sources with fluxes down to 0.4 mJy,
and within 250 arcseconds from the pointing centers. The spectral indices (S ~
\nu^-\alpha) of 54 sources with published low frequency flux densities range
from -0.6 to 2 with a mean of 0.77, and a median of 0.84. Extending low
frequency surveys of radio sources towards galaxy clusters CL 0016+16, Abell
665, and Abell 2218 to 28.5 GHz, and selecting sources with 1.4 GHz flux
density greater than 7 mJy to form an unbiased sample, we find a mean spectral
index of 0.71 and a median of 0.71. We find 4 to 7 times more sources predicted
from a low frequency survey in areas without galaxy clusters. This excess
cannot be accounted for by gravitational lensing of a background radio
population by cluster potentials, indicating most of the detected sources are
associated with galaxy clusters. For the cluster Abell 2218, the presence of
unsubtracted radio sources with 28.5 GHz flux densities less than 0.5 mJy, can
only contribute to temperature fluctuations at a level of 10 to 25 \muK. The
corresponding error due to radio point source contamination in the Hubble
constant derived through a combined analysis of 28.5 GHz SZ images and X-ray
emission observations ranges from 1% to 6%.Comment: 18 pages, 8 figures, to appear in April 1998 issue of A
Genetic background modifies vulnerability to glaucoma related phenotypes in Lmx1b mutant mice
Variants in the LIM homeobox transcription factor 1-beta (LMX1B) gene predispose individuals to elevated intraocular pressure (IOP), a key risk factor for glaucoma. However, the effect of LMX1Bmutations varies widely between individuals. To better understand the mechanisms underlying LMX1B-related phenotypes and individual differences, we backcrossed the Lmx1bV265D (also known as Lmx1bIcst ) allele onto the C57BL/6J (B6), 129/Sj (129), C3A/BLiA-Pde6b+ /J (C3H) and DBA/2J-Gpnmb+ (D2-G) mouse strain backgrounds. Strain background had a significant effect on the onset and severity of ocular phenotypes in Lmx1bV265D/+ mutant mice. Mice of the B6 background were the most susceptible to developing abnormal IOP distribution, severe anterior segment developmental anomalies (including malformed eccentric pupils, iridocorneal strands and corneal abnormalities) and glaucomatous nerve damage. By contrast, Lmx1bV265D mice of the 129 background were the most resistant to developing anterior segment abnormalities, had less severe IOP elevation than B6 mutants at young ages and showed no detectable nerve damage. To identify genetic modifiers of susceptibility to Lmx1bV265D -induced glaucoma-associated phenotypes, we performed a mapping cross between mice of the B6 (susceptible) and 129 (resistant) backgrounds. We identified a modifier locus on Chromosome 18, with the 129 allele(s) substantially lessening severity of ocular phenotypes, as confirmed by congenic analysis. By demonstrating a clear effect of genetic background in modulating Lmx1b-induced phenotypes, providing a panel of strains with different phenotypic severities and identifying a modifier locus, this study lays a foundation for better understanding the roles of LMX1B in glaucoma with the goal of developing new treatments
Spontaneous emission and level shifts in absorbing disordered dielectrics and dense atomic gases: A Green's function approach
Spontaneous emission and Lamb shift of atoms in absorbing dielectrics are
discussed. A Green's-function approach is used based on the multipolar
interaction Hamiltonian of a collection of atomic dipoles with the quantised
radiation field. The rate of decay and level shifts are determined by the
retarded Green's-function of the interacting electric displacement field, which
is calculated from a Dyson equation describing multiple scattering. The
positions of the atomic dipoles forming the dielectrics are assumed to be
uncorrelated and a continuum approximation is used. The associated unphysical
interactions between different atoms at the same location is eliminated by
removing the point-interaction term from the free-space Green's-function (local
field correction). For the case of an atom in a purely dispersive medium the
spontaneous emission rate is altered by the well-known Lorentz local-field
factor. In the presence of absorption a result different from previously
suggested expressions is found and nearest-neighbour interactions are shown to
be important.Comment: 6 pages no figure
Association of Hepcidin-25 with survival after kidney transplantation
Background Hepcidin is considered the master regulator of iron homoeostasis. Novel hepcidin antagonists have recently been introduced as potential treatment for iron-restricted anaemia. Meanwhile, serum hepcidin has been shown to be positively associated with cardiovascular disease and inversely with acute kidney injury. These properties may lead to contrasting effects, especially in renal transplant recipients (RTR), which are prone to cardiovascular diseases and graft failure. To date, the role of serum hepcidin in RTR is unknown. We, therefore, prospectively determined the association of serum hepcidin with risk of graft failure, cardiovascular mortality and all-cause mortality in RTR. Materials and methods Serum hepcidin was assessed in an extensively phenotyped RTR cohort by dual-monoclonal sandwich ELISA specific immunoassay. Statistical analyses were performed using univariate linear regression followed by stepwise backward linear regression. Cox proportional hazard regression models were performed to determine prospective associations. Results We included 561 RTR (age 51 +/- 12 years). Mean haemoglobin (Hb) was 8.6 +/- 1.0 mM. Median [IQR] serum hepcidin was 7.2 [3.2-13.4] ng/mL. Mean estimated glomerular filtration rate was 47 +/- 16 mL/min/ 1.73 m(2). In univariate Cox regression analyses, serum hepcidin was not associated with risk of graft failure, cardiovascular mortality or all-cause mortality. Notably, after adjustment for high sensitivity C-reactive protein and ferritin, serum hepcidin became negatively associated with all-cause mortality (hazard ratio 0.89; 95% confidence interval 0.80-0.99, P = 0.3). Conclusions In this study, we did not find an association between serum hepcidin and outcomes, that is graft failure, cardiovascular mortality or all-cause mortality. Based on our results, it is questionable whether serum hepcidin may be used to predict a beneficial effect of hepcidin antagonists
Multipole interaction between atoms and their photonic environment
Macroscopic field quantization is presented for a nondispersive photonic
dielectric environment, both in the absence and presence of guest atoms.
Starting with a minimal-coupling Lagrangian, a careful look at functional
derivatives shows how to obtain Maxwell's equations before and after choosing a
suitable gauge. A Hamiltonian is derived with a multipolar interaction between
the guest atoms and the electromagnetic field. Canonical variables and fields
are determined and in particular the field canonically conjugate to the vector
potential is identified by functional differentiation as minus the full
displacement field. An important result is that inside the dielectric a dipole
couples to a field that is neither the (transverse) electric nor the
macroscopic displacement field. The dielectric function is different from the
bulk dielectric function at the position of the dipole, so that local-field
effects must be taken into account.Comment: 17 pages, to be published in Physical Review
Performance of the LHCb Vertex Detector Alignment Algorithm determined with Beam Test Data
LHCb is the dedicated heavy flavour experiment at the Large Hadron Collider
at CERN. The partially assembled silicon vertex locator (VELO) of the LHCb
experiment has been tested in a beam test. The data from this beam test have
been used to determine the performance of the VELO alignment algorithm. The
relative alignment of the two silicon sensors in a module and the relative
alignment of the modules has been extracted. This alignment is shown to be
accurate at a level of approximately 2 micron and 0.1 mrad for translations and
rotations, respectively in the plane of the sensors. A single hit precision at
normal track incidence of about 10 micron is obtained for the sensors. The
alignment of the system is shown to be stable at better than the 10 micron
level under air to vacuum pressure changes and mechanical movements of the
assembled system.Comment: accepted for publication in NIM
Gene expression profiling of epithelium-associated FcRL4(+) B cells in primary Sjogren's syndrome reveals a pathogenic signature
In primary Sjögren's syndrome (pSS), FcRL4+ B cells are present in inflamed salivary gland tissue, within or in close proximity to ductal epithelium. FcRL4 is also expressed by nearly all pSS-related mucosa-associated lymphoid tissue (MALT) B cell lymphomas, linking FcRL4 expression to lymphomagenesis. Whether glandular FcRL4+ B cells are pathogenic, how these cells originate, and how they functionally differ from FcRL4- B cells in pSS is unclear. This study aimed to investigate the phenotype and function of FcRL4+ B cells in the periphery and parotid gland tissue of patients with pSS. First, circulating FcRL4+ B cells from 44 pSS and 54 non-SS-sicca patients were analyzed by flow cytometry. Additionally, RNA sequencing of FcRL4+ B cells sorted from parotid gland cell suspensions of 6 pSS patients was performed. B cells were sorted from cell suspensions as mini bulk (5 cells/well) based on the following definitions: CD19+CD27-FcRL4- ('naive'), CD19+CD27+FcRL4- ('memory'), and CD19+FcRL4+ B cells. We found that, although FcRL4+ B cells were not enriched in blood in pSS compared with non-SS sicca patients, these cells generally exhibited a pro-inflammatory phenotype. Genes coding for CD11c (ITGAX), T-bet (TBX21), TACI (TNFRSF13B), Src tyrosine kinases and NF-ÎșB pathway-related genes were, among others, significantly upregulated in glandular FcRL4+ B cells versus FcRL4- B cells. Pathway analysis showed upregulation of B cell activation, cell cycle and metabolic pathways. Thus, FcRL4+ B cells in pSS exhibit many characteristics of chronically activated, pro-inflammatory B cells and their gene expression profile suggests increased risk of lymphomagenesis. We postulate that these cells contribute significantly to the epithelial damage seen in the glandular tissue and that FcRL4+ B cells are an important treatment target in pSS
Deep Underground Science and Engineering Laboratory - Preliminary Design Report
The DUSEL Project has produced the Preliminary Design of the Deep Underground
Science and Engineering Laboratory (DUSEL) at the rehabilitated former
Homestake mine in South Dakota. The Facility design calls for, on the surface,
two new buildings - one a visitor and education center, the other an experiment
assembly hall - and multiple repurposed existing buildings. To support
underground research activities, the design includes two laboratory modules and
additional spaces at a level 4,850 feet underground for physics, biology,
engineering, and Earth science experiments. On the same level, the design
includes a Department of Energy-shepherded Large Cavity supporting the Long
Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates
one laboratory module and additional spaces for physics and Earth science
efforts. With input from some 25 science and engineering collaborations, the
Project has designed critical experimental space and infrastructure needs,
including space for a suite of multidisciplinary experiments in a laboratory
whose projected life span is at least 30 years. From these experiments, a
critical suite of experiments is outlined, whose construction will be funded
along with the facility. The Facility design permits expansion and evolution,
as may be driven by future science requirements, and enables participation by
other agencies. The design leverages South Dakota's substantial investment in
facility infrastructure, risk retirement, and operation of its Sanford
Laboratory at Homestake. The Project is planning education and outreach
programs, and has initiated efforts to establish regional partnerships with
underserved populations - regional American Indian and rural populations
Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis
Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ÎDAS) in the etanercept subset of patients (P = 8Ă10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3âČ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1Ă10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ÎDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al
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