2,471 research outputs found

    Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants

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    Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log10 rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33–3.27), and increased 1.6-fold for each log10 rise in maternal cytomegalovirus viral load (aHR 1.62; 95% CI 1.11–2.36). In girls, mortality was more strongly associated with maternal C-reactive protein than cytomegalovirus; in boys, mortality was more strongly associated with cytomegalovirus than C-reactive protein. At age one month, HIV-exposed uninfected infants had a distinct immune milieu, characterised by raised soluble CD14 and an altered CD8 + T-cell compartment. Alterations in immunophenotype and systemic inflammation were generally greater in boys than girls. Collectively, these findings show how the pregnancy immune environment in women with HIV underlies mortality and immune development in their offspring in a sex-differentiated manner, and highlights potential new intervention strategies to transform outcomes of HIV-exposed children. ClinicalTrials.gov/NCT01824940

    Systematic review and meta-analysis of therapeutic alliance, engagement and outcome in psychological therapies for psychosis

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    Aim: The moderate association between therapeutic alliance (TA) and psychological therapy outcome is well established. Historically, the field has not focused on people with a severe mental illness. This is the first review to conduct a meta-analysis of associations between TA and therapeutic engagement as well as outcome in psychological therapy for psychosis. / Eligibility criteria: Eligible studies conducted a quantitative investigation of the relationship between TA during a psychological therapy and outcome at a subsequent time-point. / Method: A systematic review examined the relationship between TA and engagement as well as outcome measures within psychological therapy for psychosis. Correlational meta-analyses using an aggregate random effects model were conducted. / Results: Twenty-four studies were eligible for inclusion (n = 1,656) of which 13 were included in the meta-analyses. Client- and therapist-rated TA were associated with engagement in therapy (rclient (c) = 0.36, p = .003; rtherapist (t) = 0.40, p = .0053). TA was also associated with reduction in global (rc = 0.29, p = .0005; rt = 0.24, p = .0015) and psychotic symptoms (rc = 0.17, p = .0115; rt = 0.30, p = .0003). The systematic review identified no evidence or limited evidence for a relationship between TA during therapy and depression, substance use, physical health behaviours, global as well as social functioning, overall mental health recovery, and self-esteem at follow-up. Although number of studies was small, TA was related to a reduced risk of subsequent hospitalization in 40% of analyses (across two studies) and improved cognitive outcome in 50% of analyses (across three studies). / Conclusions: The observed TA-therapy engagement and TA-outcome associations were broadly consistent with those identified across non-psychotic diagnostic groups. Well-powered studies are needed to investigate the relationship between TA and process as well as outcome in psychological therapy for psychosis specifically. / Practitioner points: This is the first review to conduct a meta-analytic synthesis of the association between therapeutic alliance (TA) and both engagement and change in outcome in psychological therapies for psychosis. TA (as rated by therapist and client) was associated with the extent of therapeutic engagement as well as reduction in global mental health symptoms and psychotic symptoms. The significant associations between TA and engagement as well as change in outcome identified in the current review are broadly consistent with those observed across non-psychotic diagnostic groups. We consider factors that could impact upon the dynamic and potentially interdependent relationships between TA and therapeutic techniques, including attachment security and severity of paranoid ideation

    The Spitzer c2d Survey of Nearby Dense Cores. IX. Discovery of a Very Low Luminosity Object Driving a Molecular Outflow in the Dense Core L673-7

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    We present new infrared, submillimeter, and millimeter observations of the dense core L673-7 and report the discovery of a low-luminosity, embedded Class 0 protostar driving a molecular outflow. L673-7 is seen in absorption against the mid-infrared background in 5.8, 8, and 24 micron Spitzer images, allowing for a derivation of the column density profile and total enclosed mass of L673-7, independent of dust temperature assumptions. Estimates of the core mass from these absorption profiles range from 0.2-4.5 solar masses. Millimeter continuum emission indicates a mass of about 2 solar masses, both from a direct calculation assuming isothermal dust and from dust radiative transfer models constrained by the millimeter observations. We use dust radiative transfer models to constrain the internal luminosity of L673-7, defined to be the luminosity of the central source and excluding the luminosity from external heating, to be 0.01-0.045 solar luminosities, with 0.04 solar luminosities the most likely value. L673-7 is thus classified as a very low luminosity object (VeLLO), and is among the lowest luminosity VeLLOs yet studied. We calculate the kinematic and dynamic properties of the molecular outflow in the standard manner, and we show that the expected accretion luminosity based on these outflow properties is greater than or equal to 0.36 solar luminosities. The discrepancy between this expected accretion luminosity and the internal luminosity derived from dust radiative transfer models indicates that the current accretion rate is much lower than the average rate over the lifetime of the outflow. Although the protostar embedded within L673-7 is consistent with currently being substellar, it is unlikely to remain as such given the substantial mass reservoir remaining in the core.Comment: 19 pages, 14 figures. Accepted by Ap

    Acquired immune heterogeneity and its sources in human helminth infection

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    Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations

    Observations of Global and Local Infall in NGC 1333

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    We report ``infall asymmetry'' in the HCO+^+ (1--0) and (3--2) lines toward NGC 1333, extended over 0.39pc2\sim 0.39 {\rm pc}^2, a larger extent than has been reported be fore, for any star-forming region. The infall asymmetry extends over a major portion of the star-forming complex, and is not limited to a single protostar, or to a single dense core, or to a single spectral line. It seems likely that the infall asymmetry represents inward motions, and that these motions are physically associated with the complex. Both blue-asymmetric and red-asymmetric lines are seen, but in both the (3--2) and (1--0) lines of HCO+^+ the vast majority of the asymmetric lines are blue, indicating inward motions. The (3--2) line, tracing denser gas, has the spectra with the strongest asymmetry and these spectra are associated with the protostars IRAS 4A and 4B, which most likely indicates a warm central source is affecting the line profiles. The (3--2) and (1--0) lines usually have the same sense of asymmetry in common positions, but their profiles differ significantly, and the (1--0) line appears to trace motions on much larger spatial scales than does the (3--2) line. Line profile models fit the spectra well, but do not strongly constrain their parameters. The mass accretion rate of the inward motions is of order 104^{-4} M_\odot/yr, similar to the ratio of stellar mass to cluster age.Comment: 28 pages, 11 figures, 1 colour figur

    Capturing Hiproofs in HOL Light

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    Hierarchical proof trees (hiproofs for short) add structure to ordinary proof trees, by allowing portions of trees to be hierarchically nested. The additional structure can be used to abstract away from details, or to label particular portions to explain their purpose. In this paper we present two complementary methods for capturing hiproofs in HOL Light, along with a tool to produce web-based visualisations. The first method uses tactic recording, by modifying tactics to record their arguments and construct a hierarchical tree; this allows a tactic proof script to be modified. The second method uses proof recording, which extends the HOL Light kernel to record hierachical proof trees alongside theorems. This method is less invasive, but requires care to manage the size of the recorded objects. We have implemented both methods, resulting in two systems: Tactician and HipCam
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