1,725 research outputs found
Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study
Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis.
Methods:
We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models.
Results:
There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001).
Discussion and Conclusion:
A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence
Smeared versus localised sources in flux compactifications
We investigate whether vacuum solutions in flux compactifications that are
obtained with smeared sources (orientifolds or D-branes) still survive when the
sources are localised. This seems to rely on whether the solutions are BPS or
not. First we consider two sets of BPS solutions that both relate to the GKP
solution through T-dualities: (p+1)-dimensional solutions from
spacetime-filling Op-planes with a conformally Ricci-flat internal space, and
p-dimensional solutions with Op-planes that wrap a 1-cycle inside an everywhere
negatively curved twisted torus. The relation between the solution with smeared
orientifolds and the localised version is worked out in detail. We then
demonstrate that a class of non-BPS AdS_4 solutions that exist for IASD fluxes
and with smeared D3-branes (or analogously for ISD fluxes with anti-D3-branes)
does not survive the localisation of the (anti) D3-branes. This casts doubts on
the stringy consistency of non-BPS solutions that are obtained in the limit of
smeared sources.Comment: 23 pages; v2: minor corrections, added references, version published
in JHE
Fractional branes, warped compactifications and backreacted orientifold planes
The standard extremal p-brane solutions in supergravity are known to allow
for a generalisation which consists of adding a linear dependence on the
world-volume coordinates to the usual harmonic function. In this note we
demonstrate that remarkably this generalisation goes through in exactly the
same way for p-branes with fluxes added to it that correspond to fractional
p-branes. We relate this to warped orientifold compactifications by trading the
Dp-branes for Op-planes that solve the RR tadpole condition. This allows us to
interpret the worldvolume dependence as due to lower-dimensional scalars that
flow along the massless directions in the no-scale potential. Depending on the
details of the fluxes these flows can be supersymmetric domain wall flows. Our
solutions provide explicit examples of backreacted orientifold planes in
compactifications with non-constant moduli.Comment: 20 pages, incl. references. v2: small changes required for JHEP
publication. v3: few equation typos correcte
Loss of MIR15A and MIR16-1 at 13q14 is associated with increased TP53 mRNA, de-repression of BCL2 and adverse outcome in chronic lymphocytic leukaemia.
This study was conducted to investigate the possibility that TP53 mRNA is variably expressed in chronic lymphocytic leukaemia (CLL) and that under-expression is associated with TP53 dysfunction and adverse outcome. Although TP53 mRNA levels did indeed vary among the 104 CLL samples examined, this variability resulted primarily from over-expression of TP53 mRNA in 18 samples, all of which lacked TP53 deletion/mutation. These patients had higher lymphocyte counts and shorter overall and treatment-free survival times compared to cases with low TP53 mRNA expression and no TP53 deletion/mutation. Furthermore, TP53 mRNA levels did not correlate with levels of TP53 protein or its transcriptional target CDKN1A. We speculated that the adverse outcome associated with TP53 mRNA over-expression might reflect variation in levels of MIR15A and MIR16-1, which are encoded on chromosome 13q14 and target TP53 and some oncogenes including BCL2. In keeping with our hypothesis, 13q14 copy number and levels of MIR15A/MIR16-1 correlated positively with one another but negatively with levels of TP53 mRNA and BCL2 mRNA. Our findings support a model in which loss of MIR15A/MIR16-1 at chromosome 13q14 results in adverse outcome due to de-repression of oncogenes such as BCL2, and up-regulation of TP53 mRNA as a bystander effect
The perils of contact sport: pathologies of diffuse brain swelling and chronic traumatic encephalopathy neuropathologic change in a 23-year-old rugby union player
New Concepts of Fluorescent Probes for Specific Detection of DNA Sequences: Bis-Modified Oligonucleotides in Excimer and Exciplex Detection
The detection of single base mismatches in DNA is important for diagnostics, treatment of genetic diseases, and identification of single nucleotide polymorphisms. Highly sensitive, specific assays are needed to investigate genetic samples from patients. The use of a simple fluorescent nucleoside analogue in detection of DNA sequence and point mutations by hybridisation in solution is described in this study. The 5′-bispyrene and 3′-naphthalene oligonucleotide probes form an exciplex on hybridisation to target in water and the 5′-bispyrene oligonucleotide alone is an adequate probe to determine concentration of target present. It was also indicated that this system has a potential to identify mismatches and insertions. The aim of this work was to investigate experimental structures and conditions that permit strong exciplex emission for nucleic acid detectors, and show how such exciplexes can register the presence of mismatches as required in SNP analysis. This study revealed that the hybridisation of 5′-bispyrenyl fluorophore to a DNA target results in formation of a fluorescent probe with high signal intensity change and specificity for detecting a complementary target in a homogeneous system. Detection of SNP mutations using this split-probe system is a highly specific, simple, and accessible method to meet the rigorous requirements of pharmacogenomic studies. Thus, it is possible for the system to act as SNP detectors and it shows promise for future applications in genetic testing
Emergence of structural and dynamical properties of ecological mutualistic networks
Mutualistic networks are formed when the interactions between two classes of
species are mutually beneficial. They are important examples of cooperation
shaped by evolution. Mutualism between animals and plants plays a key role in
the organization of ecological communities. Such networks in ecology have
generically evolved a nested architecture independent of species composition
and latitude - specialists interact with proper subsets of the nodes with whom
generalists interact. Despite sustained efforts to explain observed network
structure on the basis of community-level stability or persistence, such
correlative studies have reached minimal consensus. Here we demonstrate that
nested interaction networks could emerge as a consequence of an optimization
principle aimed at maximizing the species abundance in mutualistic communities.
Using analytical and numerical approaches, we show that because of the
mutualistic interactions, an increase in abundance of a given species results
in a corresponding increase in the total number of individuals in the
community, as also the nestedness of the interaction matrix. Indeed, the
species abundances and the nestedness of the interaction matrix are correlated
by an amount that depends on the strength of the mutualistic interactions.
Nestedness and the observed spontaneous emergence of generalist and specialist
species occur for several dynamical implementations of the variational
principle under stationary conditions. Optimized networks, while remaining
stable, tend to be less resilient than their counterparts with randomly
assigned interactions. In particular, we analytically show that the abundance
of the rarest species is directly linked to the resilience of the community.
Our work provides a unifying framework for studying the emergent structural and
dynamical properties of ecological mutualistic networks.Comment: 10 pages, 4 figure
Maximum levels of hepatitis C virus lipoviral particles are associated with early and persistent infection
Background & Aims: Hepatitis C virus (HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance. Methods: LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large >100 nm sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi-LVP). This method correlated with LVP in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi-LVP was measured in a cohort of 180 HCV participants with recent HCV infection and detectable HCV RNA from the Australian Trial in Acute Hepatitis C (ATAHC) and Hepatitis C Incidence and Transmission Study in prison (HITS-p) cohorts. Results: Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi-LVP level was independently associated with spontaneous HCV clearance (≤827 IU/ml; adjusted odds ratio 3.98, 95% CI: 1.02, 15.51, P = 0.047), after adjusting for interferon lambda-3 rs8099917 genotype, estimated duration of HCV infection and total HCV RNA level. Conclusions: Maxi-LVP is a biomarker for the maximum concentration of LVP in non-fasting samples. Low maxi-LVP level is an independent predictor of spontaneous clearance of acute HCV
Stability Constraints on Classical de Sitter Vacua
We present further no-go theorems for classical de Sitter vacua in Type II
string theory, i.e., de Sitter constructions that do not invoke
non-perturbative effects or explicit supersymmetry breaking localized sources.
By analyzing the stability of the 4D potential arising from compactification on
manfiolds with curvature, fluxes, and orientifold planes, we found that
additional ingredients, beyond the minimal ones presented so far, are necessary
to avoid the presence of unstable modes. We enumerate the minimal setups for
(meta)stable de Sitter vacua to arise in this context.Comment: 18 pages; v2: argument improved, references adde
The problematic backreaction of SUSY-breaking branes
In this paper we investigate the localisation of SUSY-breaking branes which,
in the smeared approximation, support specific non-BPS vacua. We show, for a
wide class of boundary conditions, that there is no flux vacuum when the branes
are described by a genuine delta-function. Even more, we find that the smeared
solution is the unique solution with a regular brane profile. Our setup
consists of a non-BPS AdS_7 solution in massive IIA supergravity with smeared
anti-D6-branes and fluxes T-dual to ISD fluxes in IIB supergravity.Comment: 27 pages, Latex2e, 5 figure
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