Curvaton Scenario with Affleck-Dine Baryogenesis

We discuss the curvaton scenario with the Affleck-Dine baryogenesis. In this scenario, non-vanishing baryonic entropy fluctuation may be generated even without primordial fluctuation of the Affleck-Dine field. Too large entropy fluctuation is inconsistent with the observations and hence constraints on the curvaton scenario with the Affleck-Dine baryogenesis are obtained. We calculate the baryonic entropy fluctuation (as well as other cosmological density fluctuations) in this case and derive constraints. Implications to some of the models of the curvaton are also discussed.Comment: 16 pages,2 figure

Bigger is fitter? Quantitative genetic decomposition of selection reveals an adaptive evolutionary decline of body mass in a wild rodent population

This is the final version of the article. Available from the publisher via the DOI in this record.In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called "stasis paradox" highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is superior to purely phenotypic estimates of selection and evolutionary change.The study was funded by a Swiss National Science Foundation (http://www.snf.ch) project grant (31003A_141110) awarded to EP

Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD

Dirkje S Postma,1 Nicolas Roche,2 Gene Colice,3 Elliot Israel,4 Richard J Martin,5 Willem MC van Aalderen,6 Jonathan Grigg,7 Anne Burden,8 Elizabeth V Hillyer,8 Julie von Ziegenweidt,8 Gokul Gopalan,9 David Price8,10 1University of Groningen, Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 2Respiratory and Intensive Care Medicine, Cochin Hospital Group, APHP, Paris-Descartes University (EA2511), Paris, France; 3Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center and George Washington University School of Medicine, Washington DC, USA; 4Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, National Jewish Health, Denver, CO, USA; 6Dept of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital AMC, Amsterdam, the Netherlands; 7Blizard Institute, Queen Mary University London, London, UK; 8Research in Real Life, Ltd, Cambridge, UK; 9Respiratory, Global Scientific Affairs, Teva Pharmaceuticals, Frazer, PA, USA; 10Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2–4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD. Patients and methods: Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection. Results: Mean patient age was 67 years, 57%–60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32–4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 µg/day versus 436 µg/day for initiation, 438 µg/day versus 534 µg/day for step-up patients). Conclusion: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up. Keywords: COPD exacerbation, extrafine particle, matched cohort analysis, real life, small airway

Safety and immunogenicity of live viral vaccines in a multicenter cohort of pediatric transplant recipients

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. EXPOSURES: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. MAIN OUTCOME AND MEASURE: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. RESULTS: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. CONCLUSIONS AND RELEVANCE: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella

M-flation and its spectators

M-flation is an implementation of assisted inflation, in which the inflaton fields are three N_c x N_c non-abelian hermitean matrices. The model can be consistently truncated to an effectively single field inflation model, with all ``spectator'' fields fixed at the origin. We show that starting with random initial conditions for all fields the truncated sector is not a late-time attractor, but instead the system evolves towards quadratic assisted inflation with all fields mass degenerate. Demanding the energy density during inflation to be below the effective quantum gravity scale, we find that the number of fields, and thus the assisted effect, is bounded N_c < 10^2.Comment: 26 pages, published versio

Bodemweerbaarheid als alternatief voor chemie

Bodems die planten beschermen tegen bodemziekten en -plagen? Ze bestaan. De kunst is om dit verschijnsel in alle bodems op te roepen. Stap voor stap ontrafelen onderzoekers van Wageningen UR het mechanisme en ontwikkelen ze praktische toepassingen

The impact of introducing patient co-payments in Germany on the use of IVF and ICSI:a price-elasticity of demand assessment

BACKGROUND: Authorities concerned by rising healthcare costs have a tendency to target reproductive treatments because of the perception that infertility is a low priority. In 2004 German health authorities introduced a 50% co-payment for patients, in an effort to save cost. We explored the impact of this pricing policy on the utilization of reproductive treatments in Germany. METHODS: Using aggregated annual in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycle data in Germany, we evaluated the relationship between changes in the number of cycles in relation to changes in costs faced by consumers following the introduction of a patient co-payment from 'no fees' to (sic)1500-2000 by estimating the short-run price-elasticity of demand. The impact of introducing patient co-payments for IVF/ICSI on the likelihood of switching to other low-cost fertility treatments was evaluated using the cross-price elasticity methodology. RESULTS: The reduction in demand for IVF and ICSI cycles in the year following the introduction of patient co-payments resulted in elasticities of -0.41 and -0.34, respectively. The price-elasticity for the combined reduction of IVF/ICSI in relation to the co-payment was estimated to be -0.36. The cross-price elasticity for clomifene was close to zero (-0.01) suggesting that demand for these interventions are independent of each other and no substitution occurred. CONCLUSIONS: We report price elasticities for IVF and ICSI of -0.41 and -0.34 after introducing a (sic)1500-2000 co-payment. These findings likely represent short-run elasticities that are likely to vary over time as factors that influence the supply and demand for fertility treatments change

Spin effects in transport through non-Fermi liquid quantum dots

The current-voltage characteristic of a one dimensional quantum dot connected via tunnel barriers to interacting leads is calculated in the region of sequential tunneling. The spin of the electrons is taken into account. Non-Fermi liquid correlations implying spin-charge separation are assumed to be present in the dot and in the leads. It is found that the energetic distance of the peaks in the linear conductance shows a spin-induced parity effect at zero temperature T. The temperature dependence of the positions of the peaks depends on the non-Fermi liquid nature of the system. For non-symmetric tunnel barriers negative differential conductances are predicted, which are related to the participation in the transport of collective states in the quantum dot with larger spins. Without spin-charge separation the negative differential conductances do not occur. Taking into account spin relaxation destroys the spin-induced conductance features. The possibility of observing in experiment the predicted effects are briefly discussed.Comment: 15 pages, 16 figures, accepted for publication on Physical Review