EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment

Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication

Rapid dynamic activation of a marine-based Arctic ice cap

We use satellite observations to document rapid acceleration and ice loss from a formerly slow-flowing, marine-based sector of Austfonna, the largest ice cap in the Eurasian Arctic. During the past two decades, the sector ice discharge has increased 45-fold, the velocity regime has switched from predominantly slow (~ 101 m/yr) to fast (~ 103 m/yr) flow, and rates of ice thinning have exceeded 25 m/yr. At the time of widespread dynamic activation, parts of the terminus may have been near floatation. Subsequently, the imbalance has propagated 50 km inland to within 8 km of the ice cap summit. Our observations demonstrate the ability of slow-flowing ice to mobilize and quickly transmit the dynamic imbalance inland; a process that we show has initiated rapid ice loss to the ocean and redistribution of ice mass to locations more susceptible to melt, yet which remains poorly understood.This work was supported by the UK Natural Environment Research Council.This article was originally published in Geophysical Research Letters (M McMillan, A Shepherd, N Gourmelen, A Dehecq, A Leeson, A Ridout, T Flament, A Hogg, L Gilbert, T Benham, M van den Broeke, JA Dowdeswell, X Fettweis, B Noël, T Strozzi, Geophysical Research Letters 2014, 41, 8902–8909)

Improving the Efficiency of Psychological Treatment using Outcome Feedback Technology

Aims: This study evaluated the impact of applying computerized outcome feedback (OF) technology in a stepped care psychological service offering low and high intensity therapies for depression and anxiety. Methods: A group of therapists were trained to use OF based on routine outcome monitoring using depression (PHQ-9) and anxiety (GAD-7) measures. Therapists regularly reviewed expected treatment response graphs with patients and discussed cases that were “not on track” in clinical supervision. Clinical outcomes data were collected for all patients treated by this group (N = 594), six months before (controls = 349) and six months after the OF training (OF cases = 245). Symptom reductions in PHQ-9 and GAD-7 were compared between controls and OF cases using longitudinal multilevel modelling. Treatment duration and costs were compared using MANOVA. Qualitative interviews with therapists (N = 15) and patients (N = 6) were interpreted using thematic analysis. Results: OF technology was generally acceptable and feasible to integrate in routine practice. No significant between-group differences were found in post-treatment PHQ-9 or GAD-7 measures. However, OF cases had significantly lower average duration and cost of treatment compared to controls. Conclusions: After adopting OF into their practice, this group of therapists attained similar clinical outcomes but within a shorter space of time and at a reduced average cost per treatment episode. We conclude that OF can improve the efficiency of stepped care

Feedback-informed treatment versus usual psychological treatment for depression and anxiety : a multisite, open-label, cluster randomised controlled trial

Background: Previous research suggests that the use of outcome feedback technology can enable psychological therapists to identify and resolve obstacles to clinical improvement. We aimed to assess the effectiveness of an outcome feedback quality assurance system applied in stepped care psychological services. Methods: This multisite, open-label, cluster randomised controlled trial was done at eight National Health Service (NHS) Trusts in England, involving therapists who were qualified to deliver evidence-based low-intensity or high-intensity psychological interventions. Adult patients (18 years or older) who accessed individual therapy with participating therapists were eligible for inclusion, except patients who accessed group therapies and those who attended less than two individual therapy sessions. Therapists were randomly assigned (1:1) to an outcome feedback intervention group or a treatment-as-usual control group by use of a computer-generated randomisation algorithm. The allocation of patients to therapists was quasi-random, whereby patients on waiting lists were allocated sequentially on the basis of therapist availability. All patients received low-intensity (less than eight sessions) or high-intensity (up to 20 sessions) psychological therapies for the duration of the 1-year study period. An automated computer algorithm alerted therapists in the outcome feedback group to patients who were not on track, and primed them to review these patients in clinical supervision. The primary outcome was symptom severity on validated depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalised Anxiety Disorder-7 [GAD-7]) measures after treatment of varying durations, which were compared between groups with multilevel modelling, controlling for cluster (therapist) effects. We used an intention-to-treat approach. This trial was prospectively registered with ISRCTN, number ISRCTN12459454. Findings: In total, 79 therapists were recruited to the study between Jan 8, 2016, and July 15, 2016, but two did not participate. Of these participants, 39 (51%) were randomly assigned to the outcome feedback group and 38 (49%) to the control group. Overall, 2233 patients were included in the trial (1176 [53%] were treated by therapists in the outcome feedback group, and 1057 [47%] by therapists in the control group). Patients classified as not on track had less severe symptoms after treatment if they were allocated to the outcome feedback group than those in the control group (PHQ-9 d=0·23, B=–1·03 [95% CI −1·84 to −0·23], p=0·012; GAD-7 d=0·19, B=–0·85 [–1·56 to −0·14], p=0·019). Interpretation: Supplementing psychological therapy with low-cost feedback technology can reduce symptom severity in patients at risk of poor response to treatment. This evidence supports the implementation of outcome feedback in stepped care psychological services. Funding: English NHS and Department of Health Sciences, University of York, York, UK

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

Overview of the massive young star-forming complex study in infrared and X-ray (MYStIX) project

The Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) seeks to characterize 20 OB-dominated young clusters and their environs at distances d ≤ 4 kpc using imaging detectors on the Chandra X-ray Observatory, Spitzer Space Telescope, and the United Kingdom InfraRed Telescope. The observational goals are to construct catalogs of star-forming complex stellar members with well-defined criteria and maps of nebular gas (particularly of hot X-ray-emitting plasma) and dust. A catalog of MYStIX Probable Complex Members with several hundred OB stars and 31,784 low-mass pre-main sequence stars is assembled. This sample and related data products will be used to seek new empirical constraints on theoretical models of cluster formation and dynamics, mass segregation, OB star formation, star formation triggering on the periphery of H II regions, and the survivability of protoplanetary disks in H II regions. This paper gives an introduction and overview of the project, covering the data analysis methodology and application to two star-forming regions: NGC 2264 and the Trifid Nebula

The dynamics of stars around spiral arms

Spiral density wave theory attempts to describe the spiral pattern in spiral galaxies in terms of a long-lived wave structure with a constant pattern speed in order to avoid the winding dilemma. The pattern is consequently a rigidly rotating, long-lived feature. We run N-body simulations of a giant disc galaxy consisting of a pure stellar disc and a static dark matter halo, and find that the spiral arms are transient features whose pattern speeds decrease with radius in such a way that the pattern speed is almost equal to the rotation curve of the galaxy. We trace particle motion around the spiral arms. We show that particles from behind and in front of the spiral arm are drawn towards and join the arm. Particles move along the arm in the radial direction and we find a clear trend that they migrate towards the outer (inner) radii on the trailing (leading) side of the arm. Our simulations demonstrate that because the spiral arm feature is corotating, the particles continue to be accelerated (decelerated) by the spiral arm for long periods, which leads to strong and efficient migration, at all radii in the disc

Are 'hot spots' hot spots?

The term ‘hot spot’ emerged in the 1960s from speculations that Hawaii might have its origins in an unusually hot source region in the mantle. It subsequently became widely used to refer to volcanic regions considered to be anomalous in the then-new plate tectonic paradigm. It carried with it the implication that volcanism (a) is emplaced by a single, spatially restricted, mongenetic melt-delivery system, assumed to be a mantle plume, and (b) that the source is unusually hot. This model has tended to be assumed a priori to be correct. Nevertheless, there are many geological ways of testing it, and a great deal of work has recently been done to do so. Two fundamental problems challenge this work. First is the difficulty of deciding a ‘normal’ mantle temperature against which to compare estimates. This is usually taken to be the source temperature of mid-ocean ridge basalts (MORBs). However, Earth's surface conduction layer is ∼200 km thick, and such a norm is not appropriate if the lavas under investigation formed deeper than the 40–50 km source depth of MORB. Second, methods for estimating temperature suffer from ambiguity of interpretation with composition and partial melt, controversy regarding how they should be applied, lack of repeatability between studies using the same data, and insufficient precision to detect the 200–300 °C temperature variations postulated. Available methods include multiple seismological and petrological approaches, modelling bathymetry and topography, and measuring heat flow. Investigations have been carried out in many areas postulated to represent either (hot) plume heads or (hotter) tails. These include sections of the mid-ocean spreading ridge postulated to include ridge-centred plumes, the North Atlantic Igneous Province, Iceland, Hawaii, oceanic plateaus, and high-standing continental areas such as the Hoggar swell. Most volcanic regions that may reasonably be considered anomalous in the simple plate-tectonic paradigm have been built by volcanism distributed throughout hundreds, even thousand of kilometres, and as yet no unequivocal evidence has been produced that any of them have high temperature anomalies compared with average mantle temperature for the same (usually unknown) depth elsewhere. Critical investigation of the genesis processes of ‘anomalous’ volcanic regions would be encouraged if use of the term ‘hot spot’ were discontinued in favour of one that does not assume a postulated origin, but is a description of unequivocal, observed characteristics