Accessibility and integration of HIV, TB and harm reduction services for people who inject drugs in Portugal: a rapid assessment

Executive summary Background: Injecting drug use is associated with high risk of tuberculosis (TB) and reduced retention in treatment. Provision of opioid substitution therapy (OST) improves HIV and TB treatment outcomes among people who inject drugs (PWID) but there is a lack of documented strategies for the effective delivery of integrated HIV, TB and drug dependency treatment. Within a harm reduction framework, Portugal has made concerted efforts to move towards integrated service delivery. We aimed to document existing models of integrated TB and HIV care for PWID in Porto, Portugal. Methods: We undertook a rapid assessment combining the following methods and data sources: a mapping of existing HIV, TB, hepatitis C virus (HCV) and drug dependency treatment services in Porto; a review of existing data on HIV, TB and drug treatment service use and integration; semi-structured interviews with 30 PWID with experience of HIV and/or TB, and with seven providers representing HIV, TB, drug treatment, outreach and prison health services. We analysed quantitative data descriptively and qualitative data thematically, triangulating findings throughout data collection and analysis. Findings: The assessment documented two models of integrated HIV, TB and drug dependency care for PWID. The first ‘combined’ model provides all services within a designated centre staffed by a co-located team of specialists with shared case management protocols. This approach facilitates multidisciplinary care but is resource-intensive, limited to a specific location and offers reduced scope for community/home-based care. The second ‘collaborative’ model is a less formalised, client-centred approach in which multiple and existing health programmes work together to achieve co-located treatment delivery in a location convenient to the patient, with outreach teams often acting as mediators between services. This model allows prompt access and adaptability to clients’ circumstances but is highly dependent on the participation of multiple services. The relative success of integration was shaped by four key factors: the extent of collaborative networks and shared protocols; the central involvement of outreach teams; provision of uninterrupted OST; and flexibility over treatment location. Engagement in services more broadly was shaped by social network and outreach support; recognition of patient autonomy; patient-provider relationships; timing of testing and treatment provision; treatment literacy; and the availability of social care. Few quantitative data were available to assess service integration. Targeted rapid HIV testing in drug treatment centres has achieved high coverage among PWID but rates of TB and HCV screening were low and incompletely reported. Most TB patients knew their HIV status but no equivalent data were available on TB among patients receiving HIV care. Recommendations: Guidelines on integration of HIV, TB and drug dependency care should reflect the importance of: multi-agency collaboration, use of existing professional networks to develop mechanisms for expedited access to integrated care; uninterrupted provision of drug dependency treatment accounting for interactions with anti-TB and anti-retroviral therapy; a client-centred approach recognising service users’ autonomy; and the key role outreach programmes can play in facilitating access. Recommendations specific to Porto include expansion of TB and HCV screening among PWID; improved health information systems; streamlined referral mechanisms; increased user involvement; renewed focus on HCV; tackling stigma in primary care; and addressing PWIDs’ broader social care needs

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Chromosome spreading of associated transposable elements and ribosomal DNA in the fish Erythrinus erythrinus. Implications for genome change and karyoevolution in fish

<p>Abstract</p> <p>Background</p> <p>The fish, <it>Erythrinus erythrinus</it>, shows an interpopulation diversity, with four karyomorphs differing by chromosomal number, chromosomal morphology and heteromorphic sex chromosomes. Karyomorph A has a diploid number of 2n = 54 and does not have differentiated sex chromosomes. Karyomorph D has 2n = 52 chromosomes in females and 2n = 51 in males, and it is most likely derived from karyomorph A by the differentiation of a multiple X₁X₂Y sex chromosome system. In this study, we analyzed karyomorphs A and D by means of cytogenetic approaches to evaluate their evolutionary relationship.</p> <p>Results</p> <p>Conspicuous differences in the distribution of the 5S rDNA and <it>Rex3 </it>non-LTR retrotransposon were found between the two karyomorphs, while no changes in the heterochromatin and 18S rDNA patterns were found between them. <it>Rex3 </it>was interstitially dispersed in most chromosomes. It had a compartmentalized distribution in the centromeric regions of only two acrocentric chromosomes in karyomorph A. In comparison, in karyomorph D, <it>Rex3 </it>was found in 22 acrocentric chromosomes in females and 21 in males. All 5S rDNA sites co-localized with <it>Rex3</it>, suggesting that these are associated in the genome. In addition, the origin of the large metacentric Y chromosome in karyomorph D by centric fusion was highlighted by the presence of internal telomeric sites and 5S rDNA/<it>Rex3 </it>sites on this chromosome.</p> <p>Conclusion</p> <p>We demonstrated that some repetitive DNAs (5S rDNA, <it>Rex3 </it>retroelement and (TTAGGG)_ntelomeric repeats) were crucial for the evolutionary divergence inside <it>E. erythrinus</it>. These elements were strongly associated with the karyomorphic evolution of this species. Our results indicate that chromosomal rearrangements and genomic modifications were significant events during the course of evolution of this fish. We detected centric fusions that were associated with the differentiation of the multiple sex chromosomes in karyomorph D, as well as a surprising increase of associated 5S rDNA/<it>Rex3 </it>loci, in contrast to karyomorph A. In this sense, <it>E. erythrinus </it>emerges as an excellent model system for better understanding the evolutionary mechanisms underlying the huge genome diversity in fish. This organism can also contribute to understanding vertebrate genome evolution as a whole.</p

Comparative chromosome mapping of repetitive sequences. Implications for genomic evolution in the fish, Hoplias malabaricus

<p>Abstract</p> <p>Background</p> <p>Seven karyomorphs of the fish, <it>Hoplias malabaricus </it>(A-G) were previously included in two major groups, Group I (A, B, C, D) and Group II (E, F, G), based on their similar karyotype structure. In this paper, karyomorphs from Group I were analyzed by means of distinct chromosomal markers, including silver-stained nucleolar organizer regions (Ag-NORs) and chromosomal location of repetitive sequences (18S and 5S rDNA, and satellite 5S<it>Hind</it>III-DNA), through fluorescence in situ hybridization (FISH), in order to evaluate the evolutionary relationships among them.</p> <p>Results</p> <p>The results showed that several chromosomal markers had conserved location in the four karyomorphs. In addition, some other markers were only conserved in corresponding chromosomes of karyomorphs A-B and C-D. These data therefore reinforced and confirmed the proposed grouping of karyomorphs A-D in Group I and highlight a closer relationship between karyomorphs A-B and C-D. Moreover, the mapping pattern of some markers on some autosomes and on the chromosomes of the XY and X₁X₂Y systems provided new evidence concerning the possible origin of the sex chromosomes.</p> <p>Conclusion</p> <p>The <it>in situ </it>investigation of repetitive DNA sequences adds new informative characters useful in comparative genomics at chromosomal level and provides insights into the evolutionary relationships among <it>Hoplias malabaricus </it>karyomorphs.</p

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal