Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial

Objectives To determine the effects of adding an oxytocin infusion to bolus oxytocin on blood loss at elective caesarean section

Reduced thymic output in elite athletes

Athletes undergoing intensive training schedules have chronic exposure to stress-induced hormones such as cortisol that can depress immune function. We compared the circulating levels of T cell receptor excision circles (TREC), a marker of recent thymic emigrants, as well as the levels of naïve and memory subsets in a group of elite endurance athletes and in controls. The athletes showed a reduction in absolute numbers of naïve T cells, particularly in CD4 T cells. In contrast, memory cells were increased. TREC levels in the athletes were significantly reduced compared to age-matched controls. Such changes resemble premature ageing of the T cell component of the immune system. Since thymic production of T cells naturally decline with age, these results raise the concern that prolonging high intensity exercise into the 4th decade of life may have deleterious consequences for athletes' health. © 2014 Elsevier Inc

The influence of exercise training status on antigen-stimulated IL-10 production in whole blood culture and numbers of circulating regulatory T cells

Highly trained athletes are associated with high resting antigen-stimulated whole blood culture interleukin (IL)-10 production. The purpose of the present study was to examine the effects of training status on resting circulating T regulatory (T) cell counts and antigen-stimulated IL-10 production and the effect of acute bout of exercise on the T response. Forty participants volunteered to participate and were assigned to one of the four groups: sedentary (SED), recreationally active (REC), sprint-trained athletes and endurance-trained athletes (END). From the resting blood sample, CD4CD25CD127 T cells and in vitro antigen-stimulated IL-10 production were assessed. Ten REC subjects performed 60 min cycling at 70 % of maximal oxygen uptake and blood samples for T analysis were collected post- and 1 h post-exercise. IL-10 production was greater in END compared with the other groups (P  0.05). Our results demonstrate that high training loads in END are associated with greater resting IL-10 production and T cell count and suggest a possible mechanism for depression of immunity commonly reported in athletes engaged in high training loads. © 2013 Springer-Verlag Berlin Heidelberg

Constraints on the behaviour and content of volatiles in Galápagos magmas from melt inclusions and nominally anhydrous minerals

Despite their relatively low concentration in most oceanic basalts, volatile species (e.g. H2O, CO2 and S) have a disproportionately large influence on a wide range of mantle and magmatic processes. However, constraining the concentration of H2O (and other volatiles) in basaltic magmas is not straightforward as submarine glass analyses are influenced by assimilation of hydrothermal brines, and the melt inclusion record is often reset by post-entrapment processes. Nevertheless, in this study we show that it is possible to reconstruct a detailed history of the volatile content of basaltic magmas through integration of multiple discreet volatile records and careful consideration of secondary processes. We present new analyses of volatiles in olivine-hosted melt inclusions, melt embayments and nominally anhydrous minerals (NAMS, clinopyroxene and orthopyroxene) found in basalts erupted on Floreana Island in the south-eastern Galápagos Archipelago. Our results indicate that the Floreana magmas, which are characterised by the most radiogenic Pb and Sr isotope signatures in the Galápagos Archipelago, contain H2O concentrations between 0.4 and 0.8 wt% (at a melt Mg# of 0.65, where Mg# = Mg/(Mg + Fe) molar). These are marginally greater than the H2O contents of magmas beneath Fernandina in the western Galápagos Archipelago (cf. 0.2–0.7 wt% H2O at Mg# = 0.65). While the volatile content of magmas from the western archipelago follow trends defined by concurrent mixing and crystallisation, NAMs from Floreana reveal the presence of rare, volatile-rich magmas (~2 wt% H2O) that form as a consequence of reactive porous flow in mush-dominated magmatic systems beneath the south-eastern Galápagos. Furthermore, the Floreana magmas have similar H2O/light Rare Earth Element ratios to basalts from the western Galápagos but contain F/Nd and Cl/K ratios that are ~2 – 3 times greater, indicating that the mantle source of the Floreana lavas might represent an important halogen reservoir in the Galápagos mantle plume

Upper mantle mush zones beneath low melt flux ocean island volcanoes: insights from Isla Floreana, Galápagos

The physicochemical characteristics of sub-volcanic magma storage regions have important implications for magma system dynamics and pre-eruptive behaviour. The architecture of magma storage regions located directly above high buoyancy flux mantle plumes (such as Kīlauea, Hawai’i and Fernandina, Galápagos) are relatively well understood. However, far fewer constraints exist on the nature of magma storage beneath ocean island volcanoes that are distal to the main zone of mantle upwelling or above low buoyancy flux plumes, despite these systems representing a substantial proportion of ocean island volcanism globally. To address this, we present a detailed petrological study of Isla Floreana in the Galápagos Archipelago, which lies at the periphery of the upwelling mantle plume and is thus characterised by an extremely low flux of magma into the lithosphere. Detailed in situ major and trace element analyses of crystal phases within exhumed cumulate xenoliths, lavas and scoria deposits, indicate that the erupted crystal cargo is dominated by disaggregated crystal-rich material (i.e., mush or wall rock). Trace element disequilibria between cumulus phases and erupted melts, as well as trace element zoning within the xenolithic clinopyroxenes, reveals that reactive porous flow (previously identified beneath mid-ocean ridges) is an important process of melt transport within crystal-rich magma storage regions. In addition, application of three petrological barometers reveal that the Floreana mush zones are located in the upper mantle, at a depth of 23.7±5.1 km. Our barometric results are compared to recent studies of high melt flux volcanoes in the western Galápagos, and other ocean island volcanoes worldwide, and demonstrate that the flux of magma from the underlying mantle source represents a first-order control on the depth and physical characteristics of magma storage

Asymmetry of balance responses to monaural galvanic vestibular stimulation in subjects with vestibular schwannoma

h i g h l i g h t s Galvanic vestibular stimulation is used to study vestibulospinal asymmetry. Responses to monaural stimulation of left and right healthy ears are not different. In schwannoma the unaffected-ear response is larger than the affected-ear response. The asymmetry ratio of right and left-ear responses is elevated in schwannoma. The method provides a lateralising test of vestibulospinal pathways for balance. a b s t r a c t Objective: We investigated the potential of galvanic vestibular stimulation (GVS) to quantify lateralised asymmetry of the vestibulospinal pathways by measuring balance responses to monaural GVS in 10 subjects with vestibular schwannoma and 22 healthy control subjects. Methods: Subjects standing without vision were stimulated with 3 s, 1 mA direct current stimuli delivered monaurally. The mean magnitude and direction of the evoked balance responses in the horizontal plane were measured from ground-reaction forces and from displacement and velocity of the trunk. Vestibular-evoked myogenic potentials (VEMPs) to 500 Hz air and bone-conducted tones were also recorded. Results: In healthy subjects, the magnitudes of the force, velocity and displacement responses were not significantly different for left compared to right ear stimulation. Their individual asymmetry ratios were always <30%. Subjects with vestibular schwannoma had significantly smaller force, velocity and displacement responses to stimulation of the affected compared with non-affected ear. Their mean asymmetry ratios were significantly elevated for all three measures (41.2 ± 10.3%, 40.3 ± 15.1% and 21.9 ± 14.6%). Conclusions: Asymmetry ratios of balance responses to monaural GVS provide a quantitative and clinically applicable lateralising test of the vestibulospinal pathways. Significance: This method offers a more clinically relevant measure of standing balance than existing vestibular function tests which assess only vestibuloocular and vestibulocollic pathways

How should we discuss genetic testing with women newly diagnosed with breast cancer? Design and implementation of a randomized controlled trial of two models of delivering education about treatment-focused genetic testing to younger women newly diagnosed with breast cancer

BACKGROUND: Germline BRCA1 and BRCA2 mutation testing offered shortly after a breast cancer diagnosis to inform women's treatment choices - treatment-focused genetic testing 'TFGT' - has entered clinical practice in specialist centers and is likely to be soon commonplace in acute breast cancer management, especially for younger women. Yet the optimal way to deliver information about TFGT to younger women newly diagnosed with breast cancer is not known, particularly for those who were not suspected of having a hereditary breast cancer syndrome prior to their cancer diagnosis. Also, little is known about the behavioral and psychosocial impact or cost effectiveness of educating patients about TFGT. This trial aims to examine the impact and efficiency of two models of educating younger women newly diagnosed with breast cancer about genetic testing in order to provide evidence for a safe and effective future clinical pathway for this service. DESIGN/METHODS: In this non-inferiority randomized controlled trial, 140 women newly diagnosed with breast cancer (aged less than 50 years) are being recruited from nine cancer centers in Australia. Eligible women with either a significant family history of breast and/or ovarian cancer or with other high risk features suggestive of a mutation detection rate of > 10% are invited by their surgeon prior to mastectomy or radiotherapy. After completing the first questionnaire, participants are randomized to receive either: (a) an educational pamphlet about genetic testing (intervention) or (b) a genetic counseling appointment at a family cancer center (standard care). Each participant is offered genetic testing for germline BRCA mutations. Decision-related and psychosocial outcomes are assessed over 12 months and include decisional conflict (primary outcome);uptake of bilateral mastectomy and/or risk-reducing salpingo-oophorectomy; cancer-specific- and general distress; family involvement in decision making; and decision regret. A process-oriented retrospective online survey will examine health professionals' attitudes toward TFGT; a health economic analysis will determine the cost effectiveness of the intervention. DISCUSSION: This trial will provide crucial information about the impact, efficiency and cost effectiveness of an educational pamphlet designed to inform younger women newly diagnosed with breast cancer about genetic testing. Issues regarding implementation of the trial are discussed

A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding

Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug-resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism