3,725 research outputs found

    Plasticity of the Immune System in Children Following Treatment Interruption in HIV-1 Infection

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    It is intriguing that, unlike adults with HIV-1, children with HIV-1 reach a greater CD4+ T cell recovery following planned treatment cessation. The reasons for the better outcomes in children remain unknown but may be related to increased thymic output and diversity of T cell receptor repertoires. HIV-1 infected children from the PENTA 11 trial tolerated planned treatment interruption without adverse long-term clinical, virological, or immunological consequences, once antiretroviral therapy was re-introduced. This contrasts to treatment interruption trials of HIV-1 infected adults, who had rapid changes in T cells and slow recovery when antiretroviral therapy was restarted. How children can develop such effective immune responses to planned treatment interruption may be critical for future studies. PENTA 11 was a randomized, phase II trial of planned treatment interruptions in HIV-1-infected children (ISRCTN 36694210). In this sub-study, eight patients in long-term follow-up were chosen with CD4+ count>500/ml, viral load <50c/ml at baseline: four patients on treatment interruption and four on continuous treatment. Together with measurements of thymic output, we used high-throughput next generation sequencing and bioinformatics to systematically organize memory CD8+ and naïve CD4+ T cell receptors according to diversity, clonal expansions, sequence sharing, antigen specificity, and T cell receptor similarities following treatment interruption compared to continuous treatment. We observed an increase in thymic output following treatment interruption compared to continuous treatment. This was accompanied by an increase in T cell receptor clonal expansions, increased T cell receptor sharing, and higher sequence similarities between patients, suggesting a more focused T cell receptor repertoire. The low numbers of patients included is a limitation and the data should be interpreted with caution. Nonetheless, the high levels of thymic output and the high diversity of the T cell receptor repertoire in children may be sufficient to reconstitute the T cell immune repertoire and reverse the impact of interruption of antiretroviral therapy. Importantly, the effective T cell receptor repertoires following treatment interruption may inform novel therapeutic strategies in children infected with HIV-1

    Stellar Differential Rotation and Coronal Timescales

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    We investigate the timescales of evolution of stellar coronae in response to surface differential rotation and diffusion. To quantify this we study both the formation time and lifetime of a magnetic flux rope in a decaying bipolar active region. We apply a magnetic flux transport model to prescribe the evolution of the stellar photospheric field, and use this to drive the evolution of the coronal magnetic field via a magnetofrictional technique. Increasing the differential rotation (i.e. decreasing the equator-pole lap time) decreases the flux rope formation time. We find that the formation time is dependent upon the geometric mean of the lap time and the surface diffusion timescale. In contrast, the lifetime of flux ropes are proportional to the lap time. With this, flux ropes on stars with a differential rotation of more than eight times the solar value have a lifetime of less than two days. As a consequence, we propose that features such as solar-like quiescent prominences may not be easily observable on such stars, as the lifetimes of the flux ropes which host the cool plasma are very short. We conclude that such high differential rotation stars may have very dynamical coronae

    High-density support matrices: Key to the deep borehole disposal of spent nuclear fuel

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    Deep (4–5 km) boreholes are emerging as a safe, secure, environmentally sound and potentially cost-effective option for disposal of high-level radioactive wastes, including plutonium. One reason this option has not been widely accepted for spent fuel is because stacking the containers in a borehole could create load stresses threatening their integrity with potential for releasing highly mobile radionuclides like 129I before the borehole is filled and sealed. This problem can be overcome by using novel high-density support matrices deployed as fine metal shot along with the containers. Temperature distributions in and around the disposal are modelled to show how decay heat from the fuel can melt the shot within weeks of disposal to give a dense liquid in which the containers are almost weightless. Finally, within a few decades, this liquid will cool and solidify, entombing the waste containers in a base metal sarcophagus sealed into the host rock

    Inferring kangaroo phylogeny from incongruent nuclear and mitochondrial genes

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    The marsupial genus Macropus includes three subgenera, the familiar large grazing kangaroos and wallaroos of M. (Macropus) and M. (Osphranter), as well as the smaller mixed grazing/browsing wallabies of M. (Notamacropus). A recent study of five concatenated nuclear genes recommended subsuming the predominantly browsing Wallabia bicolor (swamp wallaby) into Macropus. To further examine this proposal we sequenced partial mitochondrial genomes for kangaroos and wallabies. These sequences strongly favour the morphological placement of W. bicolor as sister to Macropus, although place M. irma (black-gloved wallaby) within M. (Osphranter) rather than as expected, with M. (Notamacropus). Species tree estimation from separately analysed mitochondrial and nuclear genes favours retaining Macropus and Wallabia as separate genera. A simulation study finds that incomplete lineage sorting among nuclear genes is a plausible explanation for incongruence with the mitochondrial placement of W. bicolor, while mitochondrial introgression from a wallaroo into M. irma is the deepest such event identified in marsupials. Similar such coalescent simulations for interpreting gene tree conflicts will increase in both relevance and statistical power as species-level phylogenetics enters the genomic age. Ecological considerations in turn, hint at a role for selection in accelerating the fixation of introgressed or incompletely sorted loci. More generally the inclusion of the mitochondrial sequences substantially enhanced phylogenetic resolution. However, we caution that the evolutionary dynamics that enhance mitochondria as speciation indicators in the presence of incomplete lineage sorting may also render them especially susceptible to introgression

    The role of transabdominal cervical cerclage techniques in maternity care

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    Key content: The transabdominal cerclage procedure aims to strengthen the cervix by placing a suture at the level of the internal os. The main indications for transabdominal suture are a grossly disrupted cervix, an absent vaginal cervix, and previous failed elective vaginal cerclage. The transabdominal cerclage was first described in 1965 and the laparoscopic modification was first reported in 1998. Published reports suggest very high neonatal survival rates with both approaches. Laparoscopic cerclage has the general advantages of minimal access surgery, such as avoiding a large abdominal incision, short hospital stay and quick recovery. Potential complications include bleeding from uterine vessels and loss of pregnancy for non‐interval procedures. The other reported complications, such as suture migration, rectouterine fistula, uterine rupture and intrauterine growth restriction, are rare. The place of transabdominal cerclage in preventing pregnancy loss and preterm birth remains a subject of debate and there is a need to audit the outcomes. / Learning objectives: To better understand the role of the cervix in miscarriage. To understand the indications for referral for transabdominal cervical cerclage. To understand the obstetric and neonatal outcomes of women after this procedure. / Ethical issues: To consider the place of this invasive procedure, with its consequent possible complications, in the management of cervical weakness in women who often have poor reproductive histories. To consider the lack of national and international availability of this potentially valuable procedure. To consider an effective system of assessment of this procedure in a referral context, and the future of this procedure

    Uterine activity in labour

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    Warm HCN, C2H2, and CO in the disk of GV Tau

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    We present the first high-resolution, ground-based observations of HCN and C2H2 toward the T Tauri binary star system GV Tau. We detected strong absorption due to HCN nu_3 and weak C2H2 (nu_3 and nu_2 + (nu_4 + nu_5)^0_+) absorption toward the primary (GV Tau S) but not the infrared companion. We also report CO column densities and rotational temperatures, and present abundances relative to CO of HCN/CO ~0.6% and C2H2/CO ~1.2% and an upper limit for CH4/CO < 0.37% toward GV Tau S. Neither HCN nor C2H2 were detected toward the infrared companion and results suggest that abundances may differ between the two sources.Comment: 23 pages, 6 figures, accepted by Ap
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