Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: Beneficial effect of IL-2 and GM-CSF immunotherapy

BACKGROUND: With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1(+ )individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy. METHODS: We assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for naïve and activation markers, and in vitro proliferative responses. Results were compared with those observed in 11 matched, successfully treated asymptomatic clinical progressors (CP) with no evidence of opportunistic infections, and uninfected controls. RESULTS: Median CD4 T-cell counts in IRIS patients rose from 22 cells/μl before initiation of ART, to 70 cells/μl after 8 months of therapy (median 6.5 fold increase). This coincided with IRIS diagnosis, lower levels of naïve CD4 T-cells, increased expression of immune activation markers, and weak CD4 T-cell responses. In contrast, CP had a median CD4 T-cell counts of 76 cells/μl at baseline, which rose to 249 cells/μl 6 months post ART, when strong T-cell responses were seen in > 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC (IRIS > CP > UC). Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery. CONCLUSION: These data suggest that mycobacterial IRIS is associated with inadequate immune reconstitution rather than vigorous specific T-cell responses, and concomitant administration of IL-2 and GM-CSF immunotherapy with effective ART may correct/augment T-cell immunity in such setting resulting in clinical benefit

Entanglement Distribution and Entangling Power of Quantum Gates

Quantum gates, that play a fundamental role in quantum computation and other quantum information processes, are unitary evolution operators $\hat U$ that act on a composite system changing its entanglement. In the present contribution we study some aspects of these entanglement changes. By recourse of a Monte Carlo procedure, we compute the so called "entangling power" for several paradigmatic quantum gates and discuss results concerning the action of the CNOT gate. We pay special attention to the distribution of entanglement among the several parties involved

Conditional q-Entropies and Quantum Separability: A Numerical Exploration

We revisit the relationship between quantum separability and the sign of the relative q-entropies of composite quantum systems. The q-entropies depend on the density matrix eigenvalues p_i through the quantity omega_q = sum_i p_i^q. Renyi's and Tsallis' measures constitute particular instances of these entropies. We perform a systematic numerical survey of the space of mixed states of two-qubit systems in order to determine, as a function of the degree of mixture, and for different values of the entropic parameter q, the volume in state space occupied by those states characterized by positive values of the relative entropy. Similar calculations are performed for qubit-qutrit systems and for composite systems described by Hilbert spaces of larger dimensionality. We pay particular attention to the limit case q --> infinity. Our numerical results indicate that, as the dimensionalities of both subsystems increase, composite quantum systems tend, as far as their relative q-entropies are concerned, to behave in a classical way

Induced measures in the space of mixed quantum states

We analyze several product measures in the space of mixed quantum states. In particular we study measures induced by the operation of partial tracing. The natural, rotationally invariant measure on the set of all pure states of a N x K composite system, induces a unique measure in the space of N x N mixed states (or in the space of K x K mixed states, if the reduction takes place with respect to the first subsystem). For K=N the induced measure is equal to the Hilbert-Schmidt measure, which is shown to coincide with the measure induced by singular values of non-Hermitian random Gaussian matrices pertaining to the Ginibre ensemble. We compute several averages with respect to this measure and show that the mean entanglement of $N \times N$ pure states behaves as lnN-1/2.Comment: 12 latex pages, 2 figures in epsf, submited to J. Phys. A. ver.3, some improvements and a few references adde

Hall Normalization Constants for the Bures Volumes of the n-State Quantum Systems

We report the results of certain integrations of quantum-theoretic interest, relying, in this regard, upon recently developed parameterizations of Boya et al of the n x n density matrices, in terms of squared components of the unit (n-1)-sphere and the n x n unitary matrices. Firstly, we express the normalized volume elements of the Bures (minimal monotone) metric for n = 2 and 3, obtaining thereby "Bures prior probability distributions" over the two- and three-state systems. Then, as an essential first step in extending these results to n > 3, we determine that the "Hall normalization constant" (C_{n}) for the marginal Bures prior probability distribution over the (n-1)-dimensional simplex of the n eigenvalues of the n x n density matrices is, for n = 4, equal to 71680/pi^2. Since we also find that C_{3} = 35/pi, it follows that C_{4} is simply equal to 2^{11} C_{3}/pi. (C_{2} itself is known to equal 2/pi.) The constant C_{5} is also found. It too is associated with a remarkably simple decompositon, involving the product of the eight consecutive prime numbers from 2 to 23. We also preliminarily investigate several cases, n > 5, with the use of quasi-Monte Carlo integration. We hope that the various analyses reported will prove useful in deriving a general formula (which evidence suggests will involve the Bernoulli numbers) for the Hall normalization constant for arbitrary n. This would have diverse applications, including quantum inference and universal quantum coding.Comment: 14 pages, LaTeX, 6 postscript figures. Revised version to appear in J. Phys. A. We make a few slight changes from the previous version, but also add a subsection (III G) in which several variations of the basic problem are newly studied. Rather strong evidence is adduced that the Hall constants are related to partial sums of denominators of the even-indexed Bernoulli numbers, although a general formula is still lackin

Lower healthcare costs associated with the use of a single-pill ARV regimen in the UK, 2004-2008

Aim: Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months. Methods: Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, TruvadaH+EFV or AtriplaH between 1996–2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox’s proportional hazard regression analyses. Use and cost of hospital services were calculated at six and twelve months respectively. Results: All regimens reduced viral load to below the limit of detection and CD4 counts increased to similar levels at six and twelve months for all treatment regimens. No statistically significant differences were observed for rate of treatment failure at six and twelve months. People on AtriplaH generated lower healthcare costs for non-AIDS patients at £5,340 (£5,254 to £5,426) per patient-semester and £9,821 (£9,719 to £9,924) per patient-year that was £1,344 (95%CI £1,222 to £1,465) less per patient-semester and £1,954 (95%CI £1,801 to £2,107) less per patient-year compared with TruvadaH+EFV; healthcare costs for AIDS patients were similar across all regimens. Conclusion: The single pill regimen is as effective as the two- and three-pill regimens of the same drugs, but if started as first-line induction therapy there would be a 20% savings on healthcare costs at six and 17% of costs at twelve months compared with TruvadaH+EFV, that generated the next lowest costs

Global Wheat Head Detection (GWHD) dataset: a large and diverse dataset of high resolution RGB labelled images to develop and benchmark wheat head detection methods

Detection of wheat heads is an important task allowing to estimate pertinent traits including head population density and head characteristics such as sanitary state, size, maturity stage and the presence of awns. Several studies developed methods for wheat head detection from high-resolution RGB imagery. They are based on computer vision and machine learning and are generally calibrated and validated on limited datasets. However, variability in observational conditions, genotypic differences, development stages, head orientation represents a challenge in computer vision. Further, possible blurring due to motion or wind and overlap between heads for dense populations make this task even more complex. Through a joint international collaborative effort, we have built a large, diverse and well-labelled dataset, the Global Wheat Head detection (GWHD) dataset. It contains 4,700 high-resolution RGB images and 190,000 labelled wheat heads collected from several countries around the world at different growth stages with a wide range of genotypes. Guidelines for image acquisition, associating minimum metadata to respect FAIR principles and consistent head labelling methods are proposed when developing new head detection datasets. The GWHD is publicly available at http://www.global-wheat.com/ and aimed at developing and benchmarking methods for wheat head detection.Comment: 16 pages, 7 figures, Dataset pape

A roadmap for gene functional characterisation in wheat

To adapt to the challenges of climate change and the growing world population, it is vital to increase global crop production. Understanding the function of genes within staple crops will accelerate crop improvement by allowing targeted breeding approaches. Despite the importance of wheat, which provides 20 % of the calories consumed by humankind, a lack of genomic information and resources has hindered the functional characterisation of genes in this species. The recent release of a high-quality reference sequence for wheat underpins a suite of genetic and genomic resources that support basic research and breeding. These include accurate gene model annotations, gene expression atlases and gene networks that provide background information about putative gene function. In parallel, sequenced mutation populations, improved transformation protocols and structured natural populations provide rapid methods to study gene function directly. We highlight a case study exemplifying how to integrate these resources to study gene function in wheat and thereby accelerate improvement in this important crop. We hope that this review provides a helpful guide for plant scientists, especially those expanding into wheat research for the first time, to capitalise on the discoveries made in Arabidopsis and other plants. This will accelerate the improvement of wheat, a complex polyploid crop, of vital importance for food and nutrition security