946 research outputs found

    Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy.

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    BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34-1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66-2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth

    Identification of a Core Amino Acid Motif within the α Subunit of GABAARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures

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    The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the α1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic neurotransmission, and seizure sensitivity. The Gabra1-2 mutation rescues seizure-induced lethality in Gabra2-1 mice, which lack axo-axonic synapses due to the deletion of the ISTM from the α2 subunit. Taken together, our data demonstrate that the ISTM plays a critical role in promoting inhibitory synapse formation, both in the axonic and somatodendritic compartments

    eParticipation Evaluation and Impact

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    This booklet investigates how to evaluate eParticipation. Our main objective is to identify the relevant elements of existing approaches to evaluation and to develop them on the basis of a coherent and comprehensive eParticipation evaluation framework. The document describes the key issues and questions that evaluation research must address, and presents a layered model of eParticipation evaluation, which includes three important perspectives (project, socio-technical, and democratic perspectives), related evaluation criteria, and possible research indicators and methods. The main factors that influence evaluation will be outlined and three general types of evaluation design discussed. Moreover, common methods used in evaluation research are described and some salient quality issues are addressed. Selected items from three case examples of evaluation research in this area are used to illustrate how different parts of our framework might operate in practice.

    Cytomegalovirus is associated with depression and anxiety in older adults

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    Infection with cytomegalovirus (CMV), a β-herpesvirus, is common within the population. Although asymptomatic, infection is associated with increased serum concentrations of cytokines such as TNFα and IL-6, which are also related to mood and wellbeing. The present study examined whether infection with CMV was associated with mood in a community-based sample of olderadults. Blood samples and scores on the General Health Questionnaire were available for 137 participants. Serum was analysed for the presence of CMV-specific IgG and the antibody titre was used as an indirect measure of viral load. The majority of the participants (66%) were CMV-seropositive and seropositive status was not associated with psychological morbidity. However, within the CMV-positive group, individuals with higher CMV-specific antibody titres were more likely to be depressed, anxious, and suffer more overall psychological morbidity. This association could be mediated by the impact of affect-moderating cytokines secreted through the CMV-specific immune response.\ud \u

    What Sets the Initial Rotation Rates of Massive Stars?

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    The physical mechanisms that set the initial rotation rates in massive stars are a crucial unknown in current star formation theory. Observations of young, massive stars provide evidence that they form in a similar fashion to their low-mass counterparts. The magnetic coupling between a star and its accretion disk may be sufficient to spin down low-mass pre-main sequence (PMS) stars to well below breakup at the end stage of their formation when the accretion rate is low. However, we show that these magnetic torques are insufficient to spin down massive PMS stars due to their short formation times and high accretion rates. We develop a model for the angular momentum evolution of stars over a wide range in mass, considering both magnetic and gravitational torques. We find that magnetic torques are unable to spin down either low or high mass stars during the main accretion phase, and that massive stars cannot be spun down significantly by magnetic torques during the end stage of their formation either. Spin-down occurs only if massive stars' disk lifetimes are substantially longer or their magnetic fields are much stronger than current observations suggest.Comment: 12 pages, 10 figures, Accepted for publication in Ap

    Transformation in a changing climate: a research agenda

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    The concept of transformation in relation to climate and other global change is increasingly receiving attention. The concept provides important opportunities to help examine how rapid and fundamental change to address contemporary global challenges can be facilitated. This paper contributes to discussions about transformation by providing a social science, arts and humanities perspective to open up discussion and set out a research agenda about what it means to transform and the dimensions, limitations and possibilities for transformation. Key focal areas include: (1) change theories, (2) knowing whether transformation has occurred or is occurring; (3) knowledge production and use; (4), governance; (5) how dimensions of social justice inform transformation; (6) the limits of human nature; (7) the role of the utopian impulse; (8) working with the present to create new futures; and (9) human consciousness. In addition to presenting a set of research questions around these themes the paper highlights that much deeper engagement with complex social processes is required; that there are vast opportunities for social science, humanities and the arts to engage more directly with the climate challenge; that there is a need for a massive upscaling of efforts to understand and shape desired forms of change; and that, in addition to helping answer important questions about how to facilitate change, a key role of the social sciences, humanities and the arts in addressing climate change is to critique current societal patterns and to open up new thinking. Through such critique and by being more explicit about what is meant by transformation, greater opportunities will be provided for opening up a dialogue about change, possible futures and about what it means to re-shape the way in which people live

    The STAGES view of red spirals and dusty red galaxies: Mass-dependent quenching of star-formation in cluster infall

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    We investigate the properties of optically passive spirals and dusty red galaxies in the A901/2 cluster complex at redshift ~0.17 using restframe near-UV-optical SEDs, 24 micron IR data and HST morphologies from the STAGES dataset. The cluster sample is based on COMBO-17 redshifts with an rms precision of sigma_cz~2000 km/sec. We find that 'dusty red galaxies' and 'optically passive spirals' in A901/2 are largely the same phenomenon, and that they form stars at a substantial rate, which is only 4x lower than that in blue spirals at fixed mass. This star formation is more obscured than in blue galaxies and its optical signatures are weak. They appear predominantly in the stellar mass range of log M*/Msol=[10,11] where they constitute over half of the star-forming galaxies in the cluster; they are thus a vital ingredient for understanding the overall picture of star formation quenching in clusters. We find that the mean specific SFR of star-forming galaxies in the cluster is clearly lower than in the field, in contrast to the specific SFR properties of blue galaxies alone, which appear similar in cluster and field. Such a rich red spiral population is best explained if quenching is a slow process and morphological transformation is delayed even more. At log M*/Msol<10, such galaxies are rare, suggesting that their quenching is fast and accompanied by morphological change. We note, that edge-on spirals play a minor role; despite being dust-reddened they form only a small fraction of spirals independent of environment.Comment: Accepted for publication in MNRA

    Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo

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    Malaria remains a major global health problem. Emerging resistance to existing antimalarial drugs drives the search for new antimalarials, and protein translation is a promising pathway to target. Here we explore the potential of the aminoacyl-tRNA synthetase (ARS) family as a source of antimalarial drug targets. First, a battery of known and novel ARS inhibitors was tested against Plasmodium falciparum cultures, and their activities were compared. Borrelidin, a natural inhibitor of threonyl-tRNA synthetase (ThrRS), stands out for its potent antimalarial effect. However, it also inhibits human ThrRS and is highly toxic to human cells. To circumvent this problem, we tested a library of bioengineered and semisynthetic borrelidin analogs for their antimalarial activity and toxicity. We found that some analogs effectively lose their toxicity against human cells while retaining a potent antiparasitic activity both in vitro and in vivo and cleared malaria from Plasmodium yoelii-infected mice, resulting in 100% mice survival rates. Our work identifies borrelidin analogs as potent, selective, and unexplored scaffolds that efficiently clear malaria both in vitro and in vivo.Human Frontier Science Program (Strasbourg, France) (Postdoctoral Fellowship LT000307/2013

    Disordered eating behaviour is associated with blunted cortisol and cardiovascular reactions to acute psychological stress

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    Research suggests a potential dysregulation of the stress response in individuals with bulimia nervosa. This study measured both cardiovascular and cortisol reactions to a standardised laboratory stress task in individuals identified as showing disordered eating behaviour to determine whether dysregulation of the stress response is characteristic of the two branches of the stress response system. Female students (N = 455) were screened using two validated eating disorder questionnaires. Twelve women with disordered eating, including self-induced vomiting, and 12 healthy controls were selected for laboratory stress testing. Salivary cortisol and cardiovascular activity, via Doppler imaging and semi-automatic blood pressure monitoring, were measured at resting baseline and during and after exposure to a 10-min mental arithmetic stress task. Compared to controls the disordered eating group showed blunted cortisol, cardiac output, heart rate, and stroke volume reactions to the acute stress, as well as an attenuated vasodilatory reaction. These effects could not be accounted for in terms of group differences in stress task performance, subjective task impact/engagement, age, BMI, neuroticism, cardiorespiratory fitness, or co-morbid exercise dependence. Our findings suggest that disordered eating is characterised by a dysregulation of the autonomic stress-response system. As such, they add further weight to the general contention that blunted stress reactivity is characteristic of a number of maladaptive behaviours and states
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