Rephasing Invariants of CP and T Violation in the Four-Neutrino Mixing Models

We calculate the rephasing invariants of CP and T violation in a favorable parametrization of the 4x4 lepton flavor mixing matrix. Their relations with the CP- and T-violating asymmetries in neutrino oscillations are derived, and the matter effects are briefly discussed.Comment: RevTex 9 pages. Slight changes. Phys. Rev. D (in press

CP violation effect in long-baseline neutrino oscillation in the four-neutrino model

We investigate CP-violation effect in the long-baseline neutrino oscillation in the four-neutrino model with mass scheme of the two nearly degenerate pairs separated with the order of 1 eV, by using the data from the solar neutrino deficit, the atmospheric neutrino anomaly and the LSND experiments along with the other accelerator and reactor experiments. By use of the most general parametrization of the mixing matrix with six angles and six phases, we show that the genuine CP-violation effect could attain as large as 0.3 for $\Delta P(\nu_\mu\to\nu_\tau) \equiv P(\nu_\mu\to\nu_\tau) - P(\bar{\nu_\mu}\to\bar{\nu_\tau})$ and that the matter effect is negligibly small such as at most 0.01 for $\Delta P(\nu_\mu\to\nu_\tau)$ for $\Delta m^2 = (1-5)\times 10^{-3} {\rm eV}^2$, which is the mass-squared difference relevant to the long-baseline oscillation.Comment: 21 pages in LaTeX, 9 ps figures. Some changes in the Introduction and Reference

Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449]

BACKGROUND: Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. METHODS: Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline). They were then assigned to either placebo (56 days) followed by experimental (56 days) or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health) were obtained and analysed by repeated measures ANOVAs. RESULTS: Symptom severity for all symptoms (except constipation) were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 – 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p < .05 level. There were no significant differences between the conditions for any of the psychological measures. CONCLUSION: Dietary nucleotide supplementation improves some of the symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed

Flavor Mixing and CP Violation of Massive Neutrinos

We present an overview of recent progress in the phenomenological study of neutrino masses, lepton flavor mixing and CP violation. We concentrate on the model-independent properties of massive neutrinos, both in vacuum and in matter. Current experimental constraints on the neutrino mass spectrum and the lepton flavor mixing parameters are summarized. The Dirac- and Majorana-like phases of CP violation, which are associated respectively with the long-baseline neutrino oscillations and the neutrinoless double beta decay, are discussed in detail. The seesaw mechanism, the leptogenesis scenario and the strategies to construct lepton mass matrices are briefly described. The features of flavor mixing between one sterile neutrino and three active neutrinos are also explored.Comment: Invited review. LaTex 76 pages (14 PS figures included

Human oral isolate Lactobacillus fermentum AGR1487 induces a proinflammatory response in germ-free rat colons

Lactobacilli are thought to be beneficial for human health, with lactobacilli-associated infections being confined to immune-compromised individuals. However, Lactobacillus fermentum AGR1487 negatively affects barrier integrity in vitro so we hypothesized that it caused a pro-inflammatory response in the host. We compared germ-free rats inoculated with AGR1487 to those inoculated with another L. fermentum strain, AGR1485, which does not affect in vitro barrier integrity. We showed that rats inoculated with AGR1487 had more inflammatory cells in their colon, higher levels of inflammatory biomarkers, and increased colonic gene expression of pro-inflammatory pathways. In addition, our in vitro studies showed that AGR1487 had a greater capacity to activate TLR signaling and induce pro-inflammatory cytokines in immune cells. This study indicates the potential of strains of the same species to differentially elicit inflammatory responses in the host and highlights the importance of strain characterization in probiotic approaches to treat inflammatory disorders

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

<p>Abstract</p> <p>Background</p> <p>Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model.</p> <p>Methods</p> <p>To address this issue, we determined the effects of 6 week <it>in vivo </it>acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG) lesions in the transgenic polyomavirus middle T (PyMT) breast cancer mouse model.</p> <p>Results</p> <p>We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the <it>in vivo </it>exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs), demonstrating a relationship between hypoxia and macrophages in an experimental model.</p> <p>Conclusion</p> <p>These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.</p

Clinical practice: Breastfeeding and the prevention of allergy

The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fuelled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4–6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations

Intestinal microbiota in human health and disease: the impact of probiotics

The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestinal microbiota to human health. Moreover, we review the association between dysbiosis of the microbiota and both intestinal and extra-intestinal diseases. Finally, we discuss the potential of probiotic microorganism to modulate the intestinal microbiota and thereby contribute to health and well-being. The effects of probiotic consumption on the intestinal microbiota are addressed, as well as the development of tailor-made probiotics designed for specific aberrations that are associated with microbial dysbiosis

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe