Persistent pain after caesarean section and its association with maternal anxiety and socioeconomic background

Background: Pain, both from the surgical site, and from other sources such as musculoskeletal backache, can persist after caesarean section. In this study of a predominantly socially deprived population we have sought to prospectively examine the association between antenatal maternal anxiety and socioeconomic background and the development of persistent pain of all sources after caesarean section. Methods: Demographic details and an anxiety questionnaire were completed by 205 women before elective caesarean section. On the first postoperative day, pain scores were recorded, and at four months patients were asked to complete a Brief Pain Inventory and an Edinburgh Postnatal Depression Score. Results: Of 205 parturients recruited, 186 records were complete at the hospital admission phase and 98 (52.7%) were complete at the four-month follow-up phase. At recruitment, 15.1% reported pain. At four months 41.8% (95% CI 32.1 to 51.6%) reported pain, of whom pain was a new finding in 35.7% (95% CI 26.2 to 45.2%). Antenatal anxiety was not a significant predictor of severity of new pain at four months (P=0.43 for state anxiety, P=0.52 for trait anxiety). However, four-month pain severity did correlate with social deprivation (P=0.011), postnatal depression (P<0.001) and pain at 24 h (P=0.018). Conclusion: Persistent pain from a variety of sources after caesarean section is common. Our findings do not support the use of antenatal anxiety scoring to predict persistent pain in this setting, but suggest that persistent pain is influenced by acute pain, postnatal depression and socioeconomic deprivation

Gait analysis in a <i>Mecp2</i> knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the &lt;i&gt;Mecp2&lt;/i&gt; gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male &lt;i&gt;Mecp2&lt;/i&gt; knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of &lt;i&gt;Mecp2&lt;/i&gt;-dysfunction in future preclinical therapeutic studies

Billiard Systems in Three Dimensions: The Boundary Integral Equation and the Trace Formula

We derive semiclassical contributions of periodic orbits from a boundary integral equation for three-dimensional billiard systems. We use an iterative method that keeps track of the composition of the stability matrix and the Maslov index as an orbit is traversed. Results are given for isolated periodic orbits and rotationally invariant families of periodic orbits in axially symmetric billiard systems. A practical method for determining the stability matrix and the Maslov index is described.Comment: LaTeX, 19 page

Semiclassical Treatment of Diffraction in Billiard Systems with a Flux Line

In billiard systems with a flux line semiclassical approximations for the density of states contain contributions from periodic orbits as well as from diffractive orbits that are scattered on the flux line. We derive a semiclassical approximation for diffractive orbits that are scattered once on a flux line. This approximation is uniformly valid for all scattering angles. The diffractive contributions are necessary in order that semiclassical approximations are continuous if the position of the flux line is changed.Comment: LaTeX, 17 pages, 4 figure

Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing shows that clonal diversity of CAR-T cells is highest in the IPs and declines following infusion. We observe clones that display distinct patterns of clonal kinetics, making variable contributions to the CAR-T cell pool after infusion. Although integration site does not appear to be a key driver of clonal kinetics, scRNA-seq demonstrates that clones that expand after infusion mainly originate from infused clusters with higher expression of cytotoxicity and proliferation genes. Thus, we uncover transcriptional programs associated with CAR-T cell behavior after infusion.Published versio

Restoration of CD28 Expression in CD28− CD8+ Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production

The control of many persistent viral infections by Ag-specific cytolytic CD8+ T cells requires a concurrent virus-specific CD4+ Th cell response. This reflects in part a requirement of activated effector CD8+ T cells for paracrine IL-2 production as a growth and survival factor. In human CMV and HIV infection, the majority of differentiated virus-specific CD8+ T cells notably lose the ability to produce IL-2 but also lose expression of CD28, a costimulatory molecule. Analysis of the fraction of memory CD8+ T cells that continue to express CD28 revealed these cells retain the ability to produce IL-2. Therefore, we examined if IL-2 production by CD28− CD8+ T cells could be restored by introduction of a constitutively expressed CD28 gene. Expression of CD28 in CD28− CD8+ CMV- and HIV-specific CD8+ T cells reconstituted the ability to produce IL-2, which could sustain an autocrine proliferative response after Ag recognition. These results suggest that the loss of CD28 expression during differentiation of memory/effector CD8+ T cells represents a decisive step in establishing regulation of responding CD8+ T cells, increasing the dependence on CD4+ Th for proliferation after target recognition, and has implications for the treatment of viral disease with adoptively transferred CD8+ T cells

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Micronutrient supplement use and diet quality in university students

Many national and international public health organisations recommend achieving nutrient adequacy through consumption of a wide variety of nutritious foods. Despite this, dietary supplement sales continue to increase. Understanding the characteristics of micronutrient supplement users and the relationship with diet quality can help develop effective public health interventions to reduce unnecessary consumption of vitamin and mineral supplements. Participants (n = 1306) were a convenience sample of students studying first year food and nutrition. Data was collected via a Food and Diet Questionnaire (FDQ) and a Food Frequency Questionnaire (FFQ). Supplement users were defined as participants who indicated consuming any listed supplement as frequently as once a month or more. Diet quality was assessed using a Dietary Guideline Index (DGI) score. Prevalence of supplement use was high in this study population with 56% of participants reporting supplement use; the most popular supplements consumed were multivitamins (28%) and vitamin C (28%). A higher DGI score was significantly associated with an increased likelihood of supplement use (mean: 105 &plusmn; 18 vs. 109 &plusmn; 17, p = 0.001). Micronutrient supplement use was associated with a higher DGI score, suggesting that supplements are more likely to be used by those who are less likely to require them

The changing patterns of group politics in Britain

Two interpretations of ways in which group politics in Britain have presented challenges to democracy are reviewed: neo-corporatism or pluralistic stagnation and the rise of single issue interest groups. The disappearance of the first paradigm created a political space for the second to emerge. A three-phase model of group activity is developed: a phase centred around production interests, followed by the development of broadly based 'other regarding' groups, succeeded by fragmented, inner directed groups focusing on particular interests. Explanations of the decay of corporatism are reviewed. Single issue group activity has increased as party membership has declined and is facilitated by changes in traditional media and the development of the internet. Such groups can overload the policy-making process and frustrate depoliticisation. Debates about the constitution and governance have largely ignored these issues and there is need for a debate