Sub-cortical and brainstem sites associated with chemo-stimulated increases in ventilation in humans

We investigated the neural basis for spontaneous chemo-stimulated increases in ventilation in awake, healthy humans. Blood oxygen level dependent (BOLD) functional MRI was performed in nine healthy subjects using T2weighted echo planar imaging. Brain volumes (52 transverse slices, cortex to high spinal cord) were acquired every 3.9 s. The 30 min paradigm consisted of six, 5-min cycles, each cycle comprising 45 s of hypoxic-isocapnia, 45 s of isooxic-hypercapnia and 45 s of hypoxic-hypercapnia, with 55 s of non-stimulatory hyperoxic-isocapnia (control) separating each stimulus period. Ventilation was significantly (p < 0.001) increased during hypoxic-isocapnia, isooxic-hypercapnia and hypoxic-hypercapnia (17.0, 13.8, 24.9 L/min respectively) vs. control (8.4 L/min) and was associated with significant (p < 0.05, corrected for multiple comparisons) signal increases within a bilateral network that included the basal ganglia, thalamus, red nucleus, cerebellum, parietal cortex, cingulate and superior mid pons. The neuroanatomical structures identified provide evidence for the spontaneous control of breathing to be mediated by higher brain centres, as well as respiratory nuclei in the brainstem

Fusion of secretory vesicles isolated from rat liver

Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vescle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10–6 m. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesiclesin vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretionin vivo (microtubular inhibitors, local anethetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifications of the vesicle membrane indicate that glycoproteins may account for these differences

Higher order contributions to the effective action of N=2 super Yang-Mills

We apply heat kernel techniques in N=1 superspace to compute the one-loop effective action to order $F^5$ for chiral superfields coupled to a non-Abelian super Yang-Mills background. The results, when combined with those of hep-th/0210146, yield the one-loop effective action to order $F^5$ for any N=2 super Yang-Mills theory coupled to matter hypermultiplets.Comment: 23 pages, references adde

Chiral Rings and Anomalies in Supersymmetric Gauge Theory

Motivated by recent work of Dijkgraaf and Vafa, we study anomalies and the chiral ring structure in a supersymmetric U(N) gauge theory with an adjoint chiral superfield and an arbitrary superpotential. A certain generalization of the Konishi anomaly leads to an equation which is identical to the loop equation of a bosonic matrix model. This allows us to solve for the expectation values of the chiral operators as functions of a finite number of ``integration constants.'' From this, we can derive the Dijkgraaf-Vafa relation of the effective superpotential to a matrix model. Some of our results are applicable to more general theories. For example, we determine the classical relations and quantum deformations of the chiral ring of $\N=1$ super Yang-Mills theory with SU(N) gauge group, showing, as one consequence, that all supersymmetric vacua of this theory have a nonzero chiral condensate.Comment: 67 pages, minor change

Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases

Background Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection. Methods We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001–2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses. Results We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2–1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3–3.1 in Pakistanis and Africans. Conclusions Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19

Risk accuracy of type 2 diabetes in middle aged adults: Associations with sociodemographic, clinical, psychological and behavioural factors

Objective To identify the proportion of individuals with an accurate perception of their risk of type 2 diabetes (T2D) prior to, immediately after and eight weeks after receiving a personalised risk estimate. Additionally, we aimed to explore what factors are associated with underestimation and overestimation immediately post-intervention. Methods Cohort study based on the data collected in the Diabetes Risk Communication Trial. We included 379 participants (mean age 48.9 (SD 7.4) years; 55.1 women) who received a genotypic or phenotypic risk estimate for T2D. Results While only 1.3 of participants perceived their risk accurately at baseline, this increased to 24.7 immediately after receiving a risk estimate and then dropped to 7.3 at eight weeks. Those who overestimated their risk at baseline continued to overestimate it, whereas those who underestimated their risk at baseline improved their risk accuracy. We did not identify any other characteristics associated with underestimation or overestimation immediately after receiving a risk estimate. Conclusion Understanding a received risk estimate is challenging for most participants with many continuing to have inaccurate risk perception after receiving the estimate. Practice implications Individuals who overestimate or underestimate their T2D risk before receiving risk information might require different approaches for altering their risk perception. © 2017 The Author

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Chiral formulation for hyperkaehler sigma-models on cotangent bundles of symmetric spaces

Starting with the projective-superspace off-shell formulation for four-dimensional N = 2 supersymmetric sigma-models on cotangent bundles of arbitrary Hermitian symmetric spaces, their on-shell description in terms of N = 1 chiral superfields is developed. In particular, we derive a universal representation for the hyperkaehler potential in terms of the curvature of the symmetric base space. Within the tangent-bundle formulation for such sigma-models, completed recently in arXiv:0709.2633 and realized in terms of N = 1 chiral and complex linear superfields, we give a new universal formula for the superspace Lagrangian. A closed form expression is also derived for the Kaehler potential of an arbitrary Hermitian symmetric space in Kaehler normal coordinates.Comment: 11 pages, LaTeX, no figue

NS5-Branes, T-Duality and Worldsheet Instantons

The equivalence of NS5-branes and ALF spaces under T-duality is well known. However, a naive application of T-duality transforms the ALF space into a smeared NS5-brane, de-localized on the dual, transverse, circle. In this paper we re-examine this duality, starting from a two-dimensional N=(4,4) gauged linear sigma model describing Taub-NUT space. After dualizing the circle fiber, we find that the smeared NS5-brane target space metric receives corrections from multi-worldsheet instantons. These instantons are identified as Nielsen-Olesen vortices. We show that their effect is to break the isometry of the target space, localizing the NS5-brane at a point. The contribution from the k-instanton sector is shown to be proportional to the weighted integral of the Euler form over the k-vortex moduli space. The duality also predicts the, previously unknown, asymptotic exponential decay coefficient of the BPS vortex solution.Comment: 26 pages. v2: Fourier modes of multi-vortex fermion zero mode corrected. Reference added. v3: typo correcte

Mothers behaving badly: chaotic hedonism and the crisis of neoliberal social reproduction

This article focuses on the significance of the plethora of representations of mothers ‘behaving badly’ in contemporary anglophone media texts, including the films Bad Moms, Fun Mom Dinner and Bad Mom’s Christmas, the book and online cartoons Hurrah for Gin and the recent TV comedy dramas Motherland, The Let Down and Catastrophe. All these media texts include representations of, first, mothers in the midst of highly chaotic everyday spaces where any smooth routine of domesticity is conspicuous by its absence; and second, mothers behaving hedonistically, usually through drinking and partying, behaviour that is more conventionally associated with men or women without children. After identifying the social type of the mother behaving badly (MBB), the article locates and analyses it in relation to several different social and cultural contexts. These contexts are: a neoliberal crisis in social reproduction marked by inequality and overwork; the continual if contested role of women as ‘foundation parents’; and the negotiation of longer-term discourses of female hedonism. The title gestures towards a popular British sitcom of the 1990s, Men Behaving Badly, which popularized the idea of the ‘new lad’; and this article suggests that the new lad’s counterpart, the ladette, is mutating into the mother behaving badly, or the ‘lad mom’. Asking what work this figure does now, in a later neoliberal context, it argues that the mother behaving badly is simultaneously indicative of a widening and liberating range of maternal subject positions and symptomatic of a profound contemporary crisis in social reproduction. By focusing on the classed and racialised dynamics of the MBB – by examining who exactly is permitted to be hedonistic, and how – and by considering the MBB’s limited and partial imagining of progressive social change, the article concludes by emphasizing the urgency of creating more connections between such discourses and ‘parents behaving politically’