Simplicial gauge theory on spacetime

We define a discrete gauge-invariant Yang-Mills-Higgs action on spacetime simplicial meshes. The formulation is a generalization of classical lattice gauge theory, and we prove consistency of the action in the sense of approximation theory. In addition, we perform numerical tests of convergence towards exact continuum results for several choices of gauge fields in pure gauge theory.Comment: 18 pages, 2 figure

Development of microdialysis methodology for interstitial insulin measurement in rodents.

INTRODUCTION: Accurate assessment of muscle insulin sensitivity requires measurement of insulin concentration in interstitial fluid (ISF), but has proved difficult. We aimed to optimise measurement of ISF insulin concentrations in rat muscles in vivo using microdialysis. METHODS: Factorial experimental design experiments were performed in vitro to determine optimal conditions for insulin recovery with microdialysis probes. These conditions were tested in vivo, adjusted appropriately and used in lean and obese Zucker rats to compare ISF insulin concentrations basally and during hyperinsulinaemic-euglycaemic (HE) clamp. RESULTS: Optimal conditions in vivo were: a 100kDa microdialysis probe inserted in muscle, perfused with 1% BSA, 1.5mM glucose in 0.9% sodium chloride at 1μl/min. Samples were collected into siliconised glass microvials. As a reference for insulin, we established a protocol of inulin infusion, beginning at -80min and reaching equilibrium within 60min. HE clamp, beginning at 0min, increased ISF insulin concentration from 122±56 basally to 429±180pmol/l (P<0.05) in lean rats and from 643±165 to 1087±243pmol/l (P=0.07) in obese rats; ISF insulin concentrations were significantly higher throughout in obese rats. The difference between ISF and plasma insulin concentration (ISF:plasma ratio) was substantially higher in obese rats, but fell to similar values in obese and lean rats during HE clamp. DISCUSSION: Optimising insulin recovery with microdialysis allowed accurate measurement of basal ISF insulin in muscle of lean and obese Zucker rats and indicates insulin transport across capillaries is impaired in obese rats, basally and during hyperinsulinaemia

Competition law and policy and the food value chain

This On-Topic revisits the complex issues rising in the food sector and its value chain. Both the European Union and the US competition authorities have scrutinized relationships between food chain actors. The increasing market concentration raises new challenges for competition enforcement authorities dealing with the creation of new powerful actors at the distribution but also at the factor of production (input) levels. The concept of superior bargaining power has played a key role, sometimes criticised, in order to assess these relationships. The papers also discuss the critical intersection of competition law with public policy, with the aim to preserve sustainability, food safety and the stability of agricultural markets

Persistence in diving American mink

Background: American mink forage on land and in water, with aquatic prey often constituting a large proportion of their diet. Their long, thin body shape and relatively poor insulation make them vulnerable to heat loss, particularly in water, yet some individuals dive over 100 times a day. At the level of individual dives, previous research found no difference in dive depth or duration, or the total number of dives per day between seasons, but mink did appear to make more dives per active hour in winter than in summer. There was also no difference in the depth or duration of individual dives between the sexes, but there was some evidence that females made more dives per day than males. However, because individual mink dives tend to be extremely short in duration, persistence (quantified as the number of consecutive dives performed) may be a more appropriate metric with which to compare diving behaviour under different scenarios. Results: Mink performed up to 28 consecutive dives, and dived continually for up to 36 min. Periods of more loosely aggregated diving (termed ‘aquatic activity sessions’) comprised up to 80 dives, carried out over up to 162.8 min. Contrary to our predictions, persistence was inversely proportional to body weight, with small animals more persistent than large ones, and (for females, but not for males) increased with decreasing temperature. For both sexes, persistence was greater during the day than during the night. Conclusions: The observed body weight effect may point to inter-sexual niche partitioning, since in mink the smallest animals are females and the largest are males. The results may equally point to individual specialism’s, since persistence was also highly variable among individuals. Given the energetic costs involved, the extreme persistence of some animals observed in winter suggests that the costs of occasional prolonged activity in cold water are outweighed by the energetic gains. Analysing dive persistence can provide information on an animal’s physical capabilities for performing multiple dives and may reveal how such behaviour is affected by different conditions. Further development of monitoring and biologging methodology to allow quantification of hunting success, and thus the rewards obtained under alternative scenarios, would be insightful.Fil: Bagniewska, Joanna M.. University Of Oxford; Reino Unido. University Of Reading; Reino UnidoFil: Harrington, Lauren A.. University Of Oxford; Reino UnidoFil: Hart, Tom. University Of Oxford; Reino UnidoFil: Harrington, Andrew L.. University Of Oxford; Reino UnidoFil: Fasola, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Macdonald, David W.. University Of Oxford; Reino Unid

The relationship between quality of life (EORTC QLQ-C30) and survival in patients with gastro-oesopohageal cancer

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P &#60; 0.01), tumour length (P &#60; 0.0001), TNM stage (P&#60;0.0001), weight loss (P&#60;0.0001), dysphagia score (P&#60;0.001), performance status (P&#60;0.1) and treatment (P&#60;0.0001) were significantly associated with cancer-specific survival. EORTC QLQ-C30, physical functioning (P&#60;0.0001), role functioning (P&#60;0.001), cognitive functioning (P&#60;0.01), social functioning (P&#60;0.0001), global quality of life (P&#60;0.0001), fatigue (P&#60;0.0001), nausea/vomiting (P&#60;0.01), pain (P&#60;0.001), dyspnoea (P&#60;0.0001), appetite loss (P&#60;0.0001) and constipation (P&#60;0.05) were also significantly associated with cancer-specific survival. On multivariate survival analysis, tumour stage (P&#60;0.0001), treatment (P&#60;0.001) and appetite loss (P&#60;0.0001) were significant independent predictors of cancer-specific survival. The present study highlights the importance of quality of life (EORTC QLQ-C30) measures, in particular appetite loss, as a prognostic factor in these patients

A powerful intervention: general practitioners' use of sickness certification in depression

&lt;b&gt;Background&lt;/b&gt; Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Prevention programmes for children of problem drinkers: a review

It is well established that children of problem drinkers have an increased risk of developing mental health problems, including drinking and drug misuse problems, depression, eating disorders, conduct disorders, and delinquency. However, compared to the hundreds of studies that have examined the effects of parental problem drinking on their children, the genetics of problem drinking, and the physical and mental problems of these children, it is disappointing that so few studies have explored the possibilities of prevention. Despite all the research on children of problem drinkers, we have no usable operationalizations of what problem drinking is, or when a child can be defined as a child of a problem drinker. Furthermore, no valid screening or severity assessment instruments are available; there is no solution for the ethical dilemma of the need to involve parents while these parents are at the same time the problem; very few theory-driven prevention programmes have been developed; very little is known about protective factors that could be the focus of prevention programmes; and we have no programmes that can be considered to be ‘evidence based’. This paper describes these problems, presents an overview of the prevention research in this area, and gives some directions for future research

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

THE α1 and α2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS. CDS is important in the selection of T cells as anti-CDS antibody injected into perinatal mice interfers with this process. We previously used a hybrid class I molecule with the α1/α2 domains from L^d and the α3 domain from Q7^b and showed that this molecule binds an L^d-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-L^d cytotoxic T lymphocytes. In addition, positive selection of virus-specific L^d-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells

Diseño y Evaluación de un programa informático para la educación musical de maestros no especialistas. El caso de EMOLAB.

Este trabajo expone el diseño, desarrollo y evaluación de un software como apoyo docente en una materia de formación musical básica para futuros maestros generalistas. La evaluación del programa fue realizada por estudiantes de primer año del Grado de Maestro en Educación Primaria. Cumplimentaron un cuestionario que recogió sus opiniones (versatilidad, eficacia, facilidad de uso, calidad del entorno gráfico, adecuación, interés, facilitación del aprendizaje, feedback, funcionalidad) y percepciones sobre aspectos más generales (control, orientación, afectividad, consulta, verificación, seguimiento). Los resultados sugieren que el alumnado percibe EMOLab como herramienta de gran ayuda en el desarrollo de sus habilidades musicales