1,799 research outputs found
Test Characteristics of Urinary Lipoarabinomannan and Predictors of Mortality among Hospitalized HIV-Infected Tuberculosis Suspects in Tanzania.
Tuberculosis is the most common cause of death among patients with HIV infection living in tuberculosis endemic countries, but many cases are not diagnosed pre-mortem. We assessed the test characteristics of urinary lipoarabinomannan (LAM) and predictors of mortality among HIV-associated tuberculosis suspects in Tanzania. We prospectively enrolled hospitalized HIV-infected patients in Dar es Salaam, with ≥2 weeks of cough or fever, or weight loss. Subjects gave 2 mLs of urine to test for LAM using a commercially available ELISA, ≥2 sputum specimens for concentrated AFB smear and solid media culture, and 40 mLs of blood for culture. Among 212 evaluable subjects, 143 (68%) were female; mean age was 36 years; and the median CD4 count 86 cells/mm(3). 69 subjects (33%) had culture confirmation of tuberculosis and 65 (31%) were LAM positive. For 69 cases of sputum or blood culture-confirmed tuberculosis, LAM sensitivity was 65% and specificity 86% compared to 36% and 98% for sputum smear. LAM test characteristics were not different in patients with bacteremia but showed higher sensitivity and lower specificity with decreasing CD4 cell count. Two month mortality was 64 (53%) of 121 with outcomes available. In multivariate analysis there was significant association of mortality with absence of anti-retroviral therapy (p = 0.004) and a trend toward association with a positive urine LAM (p = 0.16). Among culture-negative patients mortality was 9 (75%) of 12 in LAM positive patients and 27 (38%) of 71 in LAM negative patients (p = 0.02). Urine LAM is more sensitive than sputum smear and has utility for the rapid diagnosis of culture-confirmed tuberculosis in this high-risk population. Mortality data raise the possibility that urine LAM may also be a marker for culture-negative tuberculosis
Programming gene expression with combinatorial promoters
Promoters control the expression of genes in response to one or more transcription factors (TFs). The architecture of a promoter is the arrangement and type of binding sites within it. To understand natural genetic circuits and to design promoters for synthetic biology, it is essential to understand the relationship between promoter function and architecture. We constructed a combinatorial library of random promoter architectures. We characterized 288 promoters in Escherichia coli, each containing up to three inputs from four different TFs. The library design allowed for multiple −10 and −35 boxes, and we observed varied promoter strength over five decades. To further analyze the functional repertoire, we defined a representation of promoter function in terms of regulatory range, logic type, and symmetry. Using these results, we identified heuristic rules for programming gene expression with combinatorial promoters
Multivariate discrimination and the Higgs + W/Z search
A systematic method for optimizing multivariate discriminants is developed
and applied to the important example of a light Higgs boson search at the
Tevatron and the LHC. The Significance Improvement Characteristic (SIC),
defined as the signal efficiency of a cut or multivariate discriminant divided
by the square root of the background efficiency, is shown to be an extremely
powerful visualization tool. SIC curves demonstrate numerical instabilities in
the multivariate discriminants, show convergence as the number of variables is
increased, and display the sensitivity to the optimal cut values. For our
application, we concentrate on Higgs boson production in association with a W
or Z boson with H -> bb and compare to the irreducible standard model
background, Z/W + bb. We explore thousands of experimentally motivated,
physically motivated, and unmotivated single variable discriminants. Along with
the standard kinematic variables, a number of new ones, such as twist, are
described which should have applicability to many processes. We find that some
single variables, such as the pull angle, are weak discriminants, but when
combined with others they provide important marginal improvement. We also find
that multiple Higgs boson-candidate mass measures, such as from mild and
aggressively trimmed jets, when combined may provide additional discriminating
power. Comparing the significance improvement from our variables to those used
in recent CDF and DZero searches, we find that a 10-20% improvement in
significance against Z/W + bb is possible. Our analysis also suggests that the
H + W/Z channel with H -> bb is also viable at the LHC, without requiring a
hard cut on the W/Z transverse momentum.Comment: 41 pages, 5 tables, 29 figure
Incremental Costs and Cost Effectiveness of Intensive Treatment in Individuals with Type 2 Diabetes Detected by Screening in the ADDITION-UK Trial: An Update with Empirical Trial-Based Cost Data.
BACKGROUND: There is uncertainty about the cost effectiveness of early intensive treatment versus routine care in individuals with type 2 diabetes detected by screening. OBJECTIVES: To derive a trial-informed estimate of the incremental costs of intensive treatment as delivered in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Europe (ADDITION) trial and to revisit the long-term cost-effectiveness analysis from the perspective of the UK National Health Service. METHODS: We analyzed the electronic primary care records of a subsample of the ADDITION-Cambridge trial cohort (n = 173). Unit costs of used primary care services were taken from the published literature. Incremental annual costs of intensive treatment versus routine care in years 1 to 5 after diagnosis were calculated using multilevel generalized linear models. We revisited the long-term cost-utility analyses for the ADDITION-UK trial cohort and reported results for ADDITION-Cambridge using the UK Prospective Diabetes Study Outcomes Model and the trial-informed cost estimates according to a previously developed evaluation framework. RESULTS: Incremental annual costs of intensive treatment over years 1 to 5 averaged £29.10 (standard error = £33.00) for consultations with general practitioners and nurses and £54.60 (standard error = £28.50) for metabolic and cardioprotective medication. For ADDITION-UK, over the 10-, 20-, and 30-year time horizon, adjusted incremental quality-adjusted life-years (QALYs) were 0.014, 0.043, and 0.048, and adjusted incremental costs were £1,021, £1,217, and £1,311, resulting in incremental cost-effectiveness ratios of £71,232/QALY, £28,444/QALY, and £27,549/QALY, respectively. Respective incremental cost-effectiveness ratios for ADDITION-Cambridge were slightly higher. CONCLUSIONS: The incremental costs of intensive treatment as delivered in the ADDITION-Cambridge trial were lower than expected. Given UK willingness-to-pay thresholds in patients with screen-detected diabetes, intensive treatment is of borderline cost effectiveness over a time horizon of 20 years and more.ADDITION-Cambridge was supported by the Wellcome Trust (grant reference No G061895) the Medical Research Council (grant reference no: G0001164), National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks), and the National Institute for Health Research. We received an unrestricted grant from University of Aarhus, Denmark, to support the ADDITION-Cambridge trial. Bio-Rad provided equipment to undertake capillary glucose screening by HbA1c in general practice. SG is a National Institute for Health Research (NIHR) Senior Investigator. The Primary Care Unit is supported by NIHR Research funds. SJG received support from the Department of Health NIHR Programme Grant funding scheme (RP-PG-0606-1259)
Jet vetoing and Herwig++
We investigate the simulation of events with gaps between jets with a veto on
additional radiation in the gap in Herwig++. We discover that the
currently-used random treatment of radiation in the parton shower is generating
some unphysical behaviour for wide-angle gluon emission in QCD 2 to 2
scatterings. We explore this behaviour quantitatively by making the same
assumptions as the parton shower in the analytical calculation. We then modify
the parton shower algorithm in order to correct the simulation of QCD
radiation.Comment: 18 pages, 11 figure
On the breaking of collinear factorization in QCD
We investigate the breakdown of collinear factorization for non-inclusive
observables in hadron-hadron collisions. For pure QCD processes, factorization
is violated at the three-loop level and it has a structure identical to that
encountered previously in the case of super-leading logarithms. In particular,
it is driven by the non-commutation of Coulomb/Glauber gluon exchanges with
other soft exchanges. Beyond QCD, factorization may be violated at the two-loop
level provided that the hard subprocess contains matrix element contributions
with phase differences between different colour topologies.Comment: Version 2: minor improvements for journal publicatio
Household Transmission of Rotavirus in a Community with Rotavirus Vaccination in Quininde, Ecuador
Background: We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era.
Methods: Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (householdcontact
characteristics).
Results: Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was ,18 months and had vomiting, with household contact ,10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission.
Conclusion: Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees
Spin dynamics of molecular nanomagnets fully unraveled by four-dimensional inelastic neutron scattering
Molecular nanomagnets are among the first examples of spin systems of finite
size and have been test-beds for addressing a range of elusive but important
phenomena in quantum dynamics. In fact, for short-enough timescales the spin
wavefunctions evolve coherently according to the an appropriate cluster
spin-Hamiltonian, whose structure can be tailored at the synthetic level to
meet specific requirements. Unfortunately, to this point it has been impossible
to determine the spin dynamics directly. If the molecule is sufficiently
simple, the spin motion can be indirectly assessed by an approximate model
Hamiltonian fitted to experimental measurements of various types. Here we show
that recently-developed instrumentation yields the four-dimensional
inelastic-neutron scattering function S(Q,E) in vast portions of reciprocal
space and enables the spin dynamics to be determined with no need of any model
Hamiltonian. We exploit the Cr8 antiferromagnetic ring as a benchmark to
demonstrate the potential of this new approach. For the first time we extract a
model-free picture of the quantum dynamics of a molecular nanomagnet. This
allows us, for example, to examine how a quantum fluctuation propagates along
the ring and to directly test the degree of validity of the
N\'{e}el-vector-tunneling description of the spin dynamics
Bigger, Better, Faster, More at the LHC
Multijet plus missing energy searches provide universal coverage for theories
that have new colored particles that decay into a dark matter candidate and
jets. These signals appear at the LHC further out on the missing energy tail
than two-to-two scattering indicates. The simplicity of the searches at the LHC
contrasts sharply with the Tevatron where more elaborate searches are necessary
to separate signal from background. The searches presented in this article
effectively distinguish signal from background for any theory where the LSP is
a daughter or granddaughter of the pair-produced colored parent particle
without ever having to consider missing energies less than 400 GeV.Comment: 26 pages, 8 Figures. Minor textual changes, typos fixed and
references adde
An Open-System Quantum Simulator with Trapped Ions
The control of quantum systems is of fundamental scientific interest and
promises powerful applications and technologies. Impressive progress has been
achieved in isolating the systems from the environment and coherently
controlling their dynamics, as demonstrated by the creation and manipulation of
entanglement in various physical systems. However, for open quantum systems,
engineering the dynamics of many particles by a controlled coupling to an
environment remains largely unexplored. Here we report the first realization of
a toolbox for simulating an open quantum system with up to five qubits. Using a
quantum computing architecture with trapped ions, we combine multi-qubit gates
with optical pumping to implement coherent operations and dissipative
processes. We illustrate this engineering by the dissipative preparation of
entangled states, the simulation of coherent many-body spin interactions and
the quantum non-demolition measurement of multi-qubit observables. By adding
controlled dissipation to coherent operations, this work offers novel prospects
for open-system quantum simulation and computation.Comment: Pre-review submission to Nature. For an updated and final version see
publication. Manuscript + Supplementary Informatio
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